Glucose-insulin-potassium
imaging: the past and the future?
C.M.C. van Campen, Lucas J. Klein, Frans
C. Visser
Department of Cardiology, Vrije Universiteit Medical Center,
Amsterdam, The Netherlands
Correspondence: Dr C.M.C. van Campen, Department of Cardiology,
Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV
Amsterdam, The Netherlands. Tel: +31 20 4442244, fax: +31 20
4442446, e-mail: cardiol@azvu.nl
Introduction
Recently, renewed interest has been shown in the use of glucose-insulin-potassium
(GIK) infusion in acute myocardial infarction. A metaanalysis
of acute myocardial infarction studies in the prethrombolytic
era showed a reduction in mortality by GIK.[1]
Also, a pilot study in South America showed a significant reduction
in inhospital mortality in patients treated with GIK and reperfusion
therapy.[2] In experimental myocardial infarction
and ischemia studies, GIK preserved oxidative metabolism,[3]
reduced infarct size,[4] and improved recovery
of left ventricular function.[5,6]
The exact mechanism behind the potential beneficial effect of
GIK in acute myocardial infarction is unclear. Proposed explanations
include reduction in plasma free fatty acid levels, optimization
of calcium handling, stimulation of Na,K-ATPase, and improvement
of glucose availability, with effects on intracellular ATP levels.[7]
Because GIK and dobutamine may share a similar mechanism of action,
we hypothesized that GIK infusion improves left ventricular function
and detects viable tissue to a similar extent as dobutamine. We
therefore studied the use of GIK in comparison with dobutamine
in patients with recent myocardial infarction.
Patients and methods
Twenty patients with acute myocardial infarction were enrolled
in the study. Myocardial infarction and its complications were
treated in a standard fashion. In the subacute phase, patients
underwent low-dose dobutamine (LDD) and GIK echocardiography on
the same day. Exclusion criteria were severe ventricular arrhythmias,
atrial fibrillation, pacemaker rhythm, overt heart failure, severe
primary valvular disease, and insulin-dependent diabetes mellitus.
Patients underwent LDD echocardiography in the morning and GIK
echocardiography in the afternoon. This order was fixed to prevent
a possible carryover effect of GIK.
Echocardiography
A 2D echocardiogram was obtained including the parasternal long-
and short-axis views, and the apical 2-, 3-, and 4-chamber long-axis
views, while simultaneously monitoring cardiac rhythm.
LDD echocardiography
Echocardiograms were obtained at baseline and at a dose of 15
mg/kg per min. None of the patients experienced significant side
effects such as serious ventricular arrhythmias or chest pain.
GIK echocardiography
Patients were studied during a hyperinsulinemic-euglycemic clamp
as described previously.[8] In brief, cannulas
were introduced into the left and right antecubital veins. One
cannula was used for GIK infusion, and the contralateral cannula
was used for blood sampling. Twenty units of insulin (Human Velosulin,
100 U/mL; Novo Nordisk, Alphen a/d Rijn, The Netherlands) were
added to 50 mL 0.65% NaCl and infused at a constant rate of 100
mU/kg per h. Glucose infusion (500 mL 20% glucose with 20 mL 14.9%
KCl to prevent hypokalemia) was started at a rate of 6 mg/kg per
min and was adjusted to maintain normoglycemia, based on instantly
determined plasma glucose levels, using a GlucoTouch (Lifescan,
Beerse, Belgium) apparatus, adjusted for whole blood samples.
Echocardiography was performed prior to and at 60 min of GIK infusion.
Thereafter the infusion was stopped. None of the patients had
signs or symptoms of heart failure during or after the study.
Echocardiographic data analysis
The LDD and GIK echocardiograms were scored by two independent
observers, unaware of the clinical data of patients and type of
intervention (LDD or GIK). Echocardiograms at baseline and after
intervention were reviewed side by side. The LDD and GIK studies
of the same patient were analyzed on two separate occasions, at
least 1 month apart, and in random order. In case of disagreement,
consensus was obtained by combined reading.
The left ventricle was divided into 13 segments (six basal, six
distal, and one apical segment) as described previously.[9]
Each segment was scored on a four-point scale assessing both inward
wall motion and wall thickening: 0 = normal contraction; 1 = hypokinesis
(decreased endocardial excursion and systolic wall thickening);
2 = akinesis (absence of endocardial excursion and systolic wall
thickening); and 3 = dyskinesias (paradoxic outward movement during
systole). This resulted in the wall motion score. Contractile
reserve was considered present if the score of a dysfunctional
segment at baseline decreased at least one point during LDD or
GIK infusion. Dyskinetic segments at baseline had to show at least
hypokinesia to have contractile reserve (decrease of the score
by 2).[10] In a similar manner, functional
recovery during follow-up was identified by comparing the score
of the dysfunctional baseline segments with the scores during
follow-up.
Results
Twenty patients were enrolled in the study. The mean age was 60
± 15 years. There were 17 male and three female patients. The
location of the myocardial infarction was anterior in nine patients
(45%) and inferior in 11 patients (55%). Four patients had had
a previous myocardial infarction. Nine patients were treated conservatively,
and 11 with revascularization therapy (including three PTCA procedures).
All patients were treated with aspirin or Coumadin derivates,
and 85% of the patients were treated with b-blockers. The time
between the myocardial infarction and the echocardiography protocol
was 6.1 ± 2.7 days.
Figure 1 shows the improvement of regional function: the wall
motion score improved from 7.15 ± 3.65 to 4.70 ± 2.77 (P <
0.0001) during LDD echocardiography, and from 7.30 ± 3.66 to 4.65
± 2.64 (P < 0.0001) during GIK infusion.
| Figure 1. Improvement of regional left ventricular
function expressed by wall motion score (WMS) before and after
LDD echocardiography and GIK infusion.*P <0.05. |
 |
| Table I. Agreement between LDD and GIK echocardiography
to detect contractile reserve. |
 |
Table I shows the agreement between LDD and GIK
echocardiography (to detect contractile reserve). During LDD echocardiography,
50 dysfunctional segments showed contractile reserve whereas 57
did not. During GIK echocardiography, 53 showed contractile reserve
and 55 did not. Of the segments with contractile reserve, none
showed a biphasic response. Overall agreement was 87%, with a
kappa value of 0.75.
Figure 2 shows an example of improvement of left ventricular function
during LDD and GIK infusion.
 Figure
2. Example of global left ventricular function improvement.
The upper example is the end-diastolic and end-systolic frame
during baseline. The middle example is the end-diastolic and end-systolic
frame during dobutamine 15 µg/kg per min, and the lower example
is the end-diastolic and end-systolic frame after 1 h of GIK infusion.
Discussion
This study shows that GIK infusion results in improvement of left
ventricular function, and that GIK echocardiography can detect
contractile reserve soon after myocardial infarction. These effects
are not different from those during LDD stimulation. In addition,
GIK administration was safe.
Our data are in line with those of previous studies. In studies
of experimental cardiac ischemia, GIK exerted beneficial effects
on regional and global left ventricular function peri- and post-ischemia.[5,6,11,12]
One study attributed the salutary effect of GIK to insulin alone.[12]
In patients undergoing cardiac surgery, GIK infusion resulted
in higher postoperative cardiac indices.[13,14]
A comparison of GIK and LDD infusion in postoperative patients
showed an increase in cardiac index and stroke work index during
both interventions, but the rate-pressure product and the tension-time
index increased only in the dobutamine group, suggesting that
myocardial oxygen consumption was not changed during GIK.[15]
Furthermore, whole body oxygen consumption was increased with
LDD whereas it was unchanged in GIK infusion.
LDD echocardiography is a well-established technique to assess
contractile reserve,[16] and can reliably predict
left ventricular function improvement in patients with acute myocardial
infarction[17,18,19]
irrespective of the treatment strategy. Also, in patients with
chronic ischemic left ventricular dysfunction, LDD echocardiography
can predict improvement of function after revascularization.[16,20]
The present study shows a high agreement of GIK echocardiography
with LDD echocardiography to detect contractile reserve, with
a kappa value of 0.75. The diagnostic value of LDD echocardiography
we observed is in line with that of previously published studies.[17,18,19]
The positive effects of GIK have been attributed to several mechanisms.
These include enhanced availability of glucose to the cell, reduction
of plasma free fatty acid levels, effects on Na+,K+-ATPase, decrease
in myocardial oxygen consumption, and improved Ca2+ handling.[7]
As a result of GIK infusion, the availability of substrate for
glycolysis is enhanced in ischemic cells, with a possibility for,
albeit low, anaerobic ATP production.[21] The
ATP produced by glycolysis is preferentially used to maintain
membrane functions, such as ATP-sensitive K+ channels[22]
and the sarcolemmal Ca2+ pump,[23] but may
also become available for contraction. The functional impairment
observed in postischemic myocardium is related to cellular Ca2+
overload.[23] In this view, GIK infusion with
subsequent enhancement of glycolysis may reduce the Ca2+ overload
present in postischemic myocardial cells. This reduction may be
responsible for the enhanced contractility of dysfunctional myocardium
observed in the present study.
Methodological considerations
The dosage of GIK used in this study (100 mU/kg per h insulin)
was higher than in GIK interventions in acute myocardial infarction.[1,2]
It is, however, an accepted and widely used dosage in diagnostic
FDG imaging.[8] In addition, it has been observed
that low-dose GIK infusion is not effective after acute myocardial
infarction.[24]
The order of the LDD and GIK echocardiography was fixed in this
study and performed on the same day. The order was fixed because
the duration of the positive effects of GIK is not known, in contrast
to the short-lasting effects of dobutamine. To avoid bias, the
observers were blinded to the intervention strategy (LDD or GIK),
and echocardiograms were reviewed in a totally random order. The
studies were performed on the same day to avoid influence of spontaneous
recovery after the acute ischemic event. The use of echocardiography
to compare LDD and GIK interventions rules out possible methodological
differences between two different imaging modalities.
GIK echocardiography proved to be safe in this patient group,
as no patients experienced significant side effects of GIK infusion
(eg, signs of heart failure or ischemia, deterioration of serum
potassium levels, or severe hypoglycemia).
Summary
We clearly demonstrated that GIK infusion results in improvement
of left ventricular function, and that the improvement is related
to the improvement of function of viable segments. Moreover, the
magnitude of improvement is similar to that of dobutamine infusion.
Therefore GIK can be used as an alternative to dobutamine both
for functional improvement and for the detection of viable tissue.
Its major advantage over dobutamine is that GIK does not increase
oxygen consumption25 and the risk of ventricular arrhythmias.
REFERENCES
-
Comment in:
 |
Circulation. 1997 Aug 19;96(4):1074-7 |
|
Circulation. 1998 Jun 9;97(22):2278-9 |
Glucose-insulin-potassium therapy for treatment of acute
myocardial infarction: an overview of randomized placebo-controlled
trials.
Fath-Ordoubadi F, Beatt KJ.
Medical Research Council Clinical Sciences Centre, Postgraduate
Medical School, and Department of Cardiology, Hammersmith Hospital,
London, UK. 100412.3302@compuserve.com
BACKGROUND: Glucose-insulin-potassium (GIK) therapy has been
advocated for the treatment of acute myocardial infarction.
However, the results from the clinical trials have been inconclusive,
largely because of the small number of patients recruited and
discrepancies between protocols used in these studies. METHOD
AND RESULTS: A systematic MEDLINE search for all the randomized
placebo-controlled studies of GIK therapy in acute myocardial
infarction was made, and a meta-analysis of the mortality data
was performed. Fifteen trials were identified, 5 were excluded
because of poor randomization, and 1 was excluded because recruitment
was limited to diabetic patients. The 9 remaining trials with
a total of 1932 patients were included in the analysis. Hospital
mortality was reduced from 21% (205 of 972 patients) in the
placebo group to 16.1% (154 of 956) in the GIK group (P=.004;
odds ratio, 0.72; 95% confidence interval [CI], 0.57 to 0.90).
The proportional mortality reduction was 28% (CI, 10% to 43%).
The number of lives saved per 1000 patients treated was 49 (95%
CI, 14 to 83). CONCLUSIONS: The findings indicate that GIK therapy
may have an important role in reducing the in-hospital mortality
after acute myocardial infarction. The value of this therapy
in the era of thrombolysis and acute revascularization by primary
angioplasty can be fully resolved only by conducting a large
randomized mortality study.
Publication Types:
|
Meta-analysis |
PMID: 9286943 [PubMed - indexed for MEDLINE]
-
-
Metabolic modulation of acute myocardial infarction. The
ECLA (Estudios Cardiologicos Latinoamerica) Collaborative Group.
Diaz R, Paolasso EA, Piegas LS, Tajer CD, Moreno MG, Corvalan
R, Isea JE, Romero G.
Department of Cardiology, Instituto Cardiovascular de Rosario,
Rosario, Argentina.
BACKGROUND: Several trials have been performed in the past using
glucose, insulin, and potassium infusion (GIK) for the treatment
of acute myocardial infarction (AMI). Because of continuing
uncertainty about the potential role of this therapeutic intervention,
we conducted a randomized trial to evaluate the impact of a
GIK solution during the first hours of AMI. METHODS AND RESULTS:
Four hundred seven patients with suspected AMI admitted within
24 hours of symptoms onset were enrolled. In a ratio of 2:1,
268 patients were allocated to receive GIK (high- or low-dose)
and 139 to receive control. Phlebitis and serum changes in the
plasma concentration of glucose or potassium were observed more
often with GIK. A trend toward a nonsignificant reduction in
major and minor in-hospital events was observed in patients
allocated to GIK. In 252 patients (61.9%) treated with reperfusion
strategies, a statistically significant reduction in mortality
(relative risk [RR] 0.34; 95% CI: 0.15 to 0.78; 2P=0.008) and
a consistent trend toward fewer in-hospital events in the GIK
group were observed. CONCLUSIONS: Our results confirm that a
metabolic modulation strategy in the first hours of an AMI is
feasible, applicable worldwide, and has mild side effects. The
statistically significant mortality reduction in patients who
underwent a reperfusion strategy might have important implications
for the management of AMI patients. It is now essential to perform
a large-scale trial to reliably determine the magnitude of benefit.
Publication Types:
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Clinical trial |
|
Multicenter study |
|
Randomized controlled trial |
PMID: 9867443 [PubMed - indexed for MEDLINE]
-
Effects of glucose, insulin and potassium infusion on tissue
metabolic changes within first hour of myocardial infarction
in the baboon.
Opie LH, Bruyneel K, Owen P.
The effects of infusions of glucose, insulin and potassium (GIK)
on the heart tissue metabolic changes found in adult baboons
60 min after coronary artery ligation were studied. Biopsies
taken from 11 baboons without coronary artery ligation gave
control values. A second group of 46 baboons had coronary artery
ligation. A third group of 17 baboons received an infusion of
KCl after coronary artery ligation. A fourth group of 26 baboons
received infusion of GIK. Coronary artery ligation resulted
in the expected fall of ATP, creatine phosphate, glycogen, tissue
(K+/Na+) ratio, and tissue pH, and rise of inorganic phosphate,
lactare, lactate/pyruvate ratio and alpha-glycerophosphate in
the infarction zones. Compared with ligation, additional infusions
of GIK approximately doubled the contents of creatine phosphate
and glycogen in the infarct zones, increased the content of
ATP in the central infarct zone, and decreased the content of
inorganic phosphate in the peripheral infarct zone. Other GIK
effects were that the tissue (K+/Na+) ratio rose in the peripheral
infarct zone, and the content of both glycogen and lactate rose
in the peri-infarct and non-ischemic zones; the pH of tissue
homogenates did not decrease. KCl infusions had few effects
compared with the ligation group. GIK infusions exerted a beneficial
effect when compared with infusions of KCl in that tissue creatine
phosphate rose in the peripheral infarct and nonischemic zones;
the tissue K+/Na+ ratio rose in the peripheral infarct, peri-infarct,
and nonischemic zones; and the lactate/pyruvate ratio fell in
the infarct zone. It is proposed that GIK counteracted early
tissue metabolic deterioration in the infarcting baboon heart.
PMID: 236843 [PubMed - indexed for MEDLINE]-
Effect of glucose-insulin-potassium infusion on myocardial
infarction following experimental coronary artery occlusion.
Maroko PR, Libby P, Sobel BE, Bloor CM, Sybers HD, Shell
WE, Covell JW, Braunwald E.
PMID: 5032816 [PubMed - indexed for MEDLINE]-
Effect of insulin on the performance and metabolism of the
anoxic isolated perfused rat heart.
Weissler AM, Altschuld RA, Gibb LE, Pollack ME, Kruger FA.
PMID: 4684123 [PubMed - indexed for MEDLINE]-
Glucose-insulin-potassium preserves systolic and diastolic
function in ischemia and reperfusion in pigs.
Zhu P, Lu L, Xu Y, Greyson C, Schwartz GG.
Cardiovascular Research Institute, University of California,
San Francisco, California 94121, USA.
Clinical and experimental studies have suggested benefit of
treatment with intravenous glucose-insulin-potassium (GIK) in
acute myocardial infarction. However, patients hospitalized
with acute coronary syndromes often experience recurrent myocardial
ischemia without infarction that may cause progressive left
ventricular (LV) dysfunction. This study tested the hypothesis
that anticipatory treatment with GIK attenuates both systolic
and diastolic LV dysfunction resulting from ischemia and reperfusion
without infarction in vivo. Open-chest, anesthetized pigs underwent
90 min of moderate regional ischemia (mean subendocardial blood
flow 0.3 ml x g(-1) x min(-1)) and 90 min reperfusion. Eight
pigs were treated with GIK (300 g/l glucose, 50 U/l insulin,
and 80 meq/l KCl; infused at 2 ml x kg(-1) x h(-1)) beginning
30 min before ischemia and continuing through reperfusion. Eight
untreated pigs comprised the control group. Regional LV wall
area was measured with orthogonal pairs of sonomicrometry crystals.
GIK significantly increased myocardial glucose uptake and lactate
release during ischemia. After reperfusion, indexes of regional
systolic function (external work and fractional systolic wall
area reduction), regional diastolic function (maximum rate of
diastolic wall area expansion), and global LV function (LV positive
and negative maximum rate of change in pressure with respect
to time) recovered to a significantly greater extent in GIK-treated
pigs than in control pigs (all P < 0.05). The findings suggest
that the clinical utility of GIK may extend beyond treatment
of acute myocardial infarction to anticipatory metabolic protection
of myocardium in patients at risk for recurrent episodes of
ischemia.
PMID: 10666092 [PubMed - indexed for MEDLINE]-
-
Glucose-insulin-potassium for acute myocardial infarction:
remarkable results from a new prospective, randomized trial.
Apstein CS.
Publication Types:
|
Editorial |
|
Review |
|
Review, tutorial |
PMID: 9826307 [PubMed - indexed for MEDLINE]
-
-
Comment in:
|
J Nucl Med. 1992 Jul;33(7):1263,
1266-8 |
|
J Nucl Med. 1992 Jul;33(7):1263-6 |
Euglycemic hyperinsulinemic clamp and oral glucose load in
stimulating myocardial glucose utilization during positron emission
tomography.
Knuuti MJ, Nuutila P, Ruotsalainen U, Saraste M, Harkonen
R, Ahonen A, Teras M, Haaparanta M, Wegelius U, Haapanen A,
et al.
Department of Clinical Physiology, University of Turku, Finland.
To enable assessment of myocardial viability, myocardial glucose
utilization has commonly been stimulated by oral glucose loading.
To compare the effects of glucose loading and insulin and glucose
infusion (insulin clamp) on PET fluorodeoxyglucose ([18F]FDG)
myocardial scan image quality and regional myocardial glucose
utilization rate (rMGU), eight patients with angiographically
documented coronary artery disease and previous myocardial Q-wave
infarction were studied twice, once during insulin clamp and
once 1 hr after oral glucose loading. The rMGU rates were derived
by graphic Patlak analysis in 33 normal, 10 scar and 6 "hot
spot" myocardial segments. Infusion of insulin and glucose
gave stable plasma-glucose and serum-insulin levels during imaging.
In contrast, glucose loading caused marked changes in plasma-glucose
and insulin concentrations. The image quality was clearly superior
and the fractional utilization rates of [18F]FDG were twice
as high during insulin clamp than after glucose loading (p less
than 0.0001). Due to the higher plasma-glucose levels after
glucose loading, the calculated rMGU in normal, scar and hot
spot myocardial segments was comparable between the two protocols.
The insulin clamp technique makes it possible to adjust and
maintain a metabolic steady state during the PET study. It does
not alter [18F]FDG uptake patterns in different myocardial areas
when compared to the standard glucose loading protocol, but
this technique results in superior image quality and permits
the use of smaller [18F] FDG patient doses.
PMID: 1613561 [PubMed - indexed for MEDLINE]
-
Short and long term predictive value of admission wall motion
score in acute myocardial infarction. A cross sectional echocardiographic
study of 345 patients.
Kan G, Visser CA, Koolen JJ, Dunning AJ.
A score of left ventricular segmental wall motion was used as
a convenient rapid way to assess overall left ventricular function
in acute myocardial infarction. Its success in risk stratification
at admission was assessed by a blind review of cross sectional
echocardiographic tape recordings from multiple acoustic windows.
Sixty nine (20%) of the 345 patients died during hospital stay
or within a one year follow up. The mean (SD) wall motion score
in those who died was significantly higher than in those who
survived (16.2 (5.9) vs 5.7 (3.9)). There were no differences
between the group that died in hospital within three months
of discharge and the group that died between three months and
one year after discharge. Among the 31 patients who died in
hospital, however, wall motion score was highest in 15 patients
dying of cardiogenic shock (19.2 (4.2)). In 16 patients with
lethal ruptures it was 13.5 (6.1). The nine patients with free
wall ruptures had higher wall motion scores than those with
ventricular septal rupture or papillary muscle rupture (15.7
(6.9) vs 8.5 (5.3)). Eight (3.3%) of 245 patients with a score
less than 10 died, compared with 61 (61%) of 100 scoring greater
than or equal to 10. The sensitivity of a score of greater than
or equal to 10 in predicting death within one year was 88%,
the specificity was 86%, the positive predictive value was 61%,
and the negative predictive value was 97%.
PMID: 3790378 [PubMed - indexed for MEDLINE]-
Prediction of recovery of myocardial dysfunction after revascularization.
Comparison of fluorine-18 fluorodeoxyglucose/thallium-201 SPECT,
thallium-201 stress-reinjection SPECT and dobutamine echocardiography.
Bax JJ, Cornel JH, Visser FC, Fioretti PM, van Lingen A,
Reijs AE, Boersma E, Teule GJ, Visser CA.
Department of Cardiology, Free University Hospital Amsterdam,
The Netherlands.
OBJECTIVES: We compared three techniques to predict functional
recovery after revascularization. BACKGROUND: Recently, fluorine-18
(F-18) fluorodeoxyglucose in combination with single-photon
emission computed tomography (SPECT) has been proposed to identify
viable myocardium, Thallium-201 reinjection and low dose dobutamine
echocardiography are used routinely for this purpose. METHODS:
Seventeen patients (mean [+/- SD] left ventricular ejection
fraction 36 +/- 11%) were studied. Regional and global ventricular
function were evaluated before and 3 months after revascularization
by echocardiography and radionuclide ventriculography, respectively.
Myocardial F-18 fluorodeoxyglucose uptake (during hyperinsulinemic
glucose clamping) was compared with rest perfusion assessed
with early thallium-201 SPECT. On a separate day, low dose dobutamine
echocardiography and post-stress thallium-201 reinjection SPECT
were simultaneously performed. RESULTS: The sensitivities for
F-18 fluorodeoxyglucose/thallium-201, thallium-201 reinjection
and low dose dobutamine echocardiography to assess recovery
were 89%, 93% and 85%, respectively; specificities were 77%,
43% and 63%, respectively. Stepwise logistic regression indicated
that F-18 fluorodeoxyglucose/ thallium-201 was the best predictor.
In hypokinetic segments, the combination of F-18 fluorodeoxyglucose/thallium-201
and low dose dobutamine echocardiography was the best predictor.
Global function improved (left ventricular ejection fraction
increased > 5%) in 6 patients and remained unchanged in 11.
All three techniques correctly identified five of six patients
with improvement. Fluorine-18 fluorodeoxyglucose/thallium-201
identified all patients without improvement; low dose dobutamine
echocardiography identified 9 of 11 without improvement; and
thallium-201 reinjection identified 6 of 11 patients without
improvement. CONCLUSIONS: Fluorine-18 fluorodeoxyglucose/thallium-201
SPECT was superior to the other techniques in assessing functional
recovery. Integration of metabolic and functional data is necessary,
particularly in hypokinesia, for optimal prediction of improvement
of regional function.
PMID: 8772739 [PubMed - indexed for MEDLINE]-
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Comment in:
|
Hypertension. 1999 Dec;34(6):e12-3 |
Vasodilator response to systemic but not to local hyperinsulinemia
in the human forearm.
Cardillo C, Kilcoyne CM, Nambi SS, Cannon RO 3rd, Quon MJ,
Panza JA.
Cardiology Branch, Hypertension-Endocrine Branch, National Heart,
Lung,and Blood Institute, National Institutes of Health, Bethesda,
MD, USA.
Insulin-mediated vasodilation has been proposed as an important
determinant of whole-body insulin-stimulated glucose disposal.
However, it is not clear whether the vasodilator effect of insulin
results from a direct action of the hormone or whether alternative
mechanisms are involved. To better characterize the mechanism
of insulin-mediated vasorelaxation, we compared forearm blood
flow (FBF) responses to local (intra-arterial) and systemic
(intravenous, euglycemic clamp) hyperinsulinemia in 10 healthy
lean subjects using venous occlusion plethysmography. In addition,
we assessed the effect of nitric oxide (NO) synthase inhibition
by NG-monomethyl-L-arginine (L-NMMA) on the vasodilator and
metabolic responses to hyperinsulinemia. Similar forearm concentrations
of insulin were achieved during local and systemic infusion
(231+/-39 versus 265+/-22 microU/mL; P=0.54). Of note, FBF did
not change significantly in response to local hyperinsulinemia
(from 2.6+/-0.3 to 2.4+/-0.3 mL . min-1 . dL-1; P=0.50). In
contrast, systemic hyperinsulinemia caused a 52% increase in
FBF (from 2.5+/-0.2 to 3. 8+/-0.5 mL . min-1 . dL-1; P<0.004),
which was reversed by L-NMMA (FBF decreased from 3.8+/-0.5 to
2.3+/-0.2 mL . min-1 . dL-1; P=0. 004). We conclude that systemic,
but not local, hyperinsulinemia induces vasodilation in the
forearm. Our findings suggest that insulin-mediated vasodilation
is not due solely to a direct stimulatory effect of insulin
but involves additional mechanisms activated only during systemic
hyperinsulinemia.
Publication Types:
|
Clinical trial |
PMID: 9774373 [PubMed - indexed for MEDLINE]
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Insulin improves functional and metabolic recovery of reperfused
working rat heart.
Doenst T, Richwine RT, Bray MS, Goodwin GW, Frazier OH, Taegtmeyer
H.
Department of Medicine, The University of Texas-Houston Medical
School, 77030, USA.
BACKGROUND: Glucose, insulin, and potassium solution improves
left ventricular function in refractory pump failure. Direct
effects of insulin on the heart cannot be determined in vivo.
We hypothesized that insulin has a direct positive inotropic
effect on the reperfused heart. METHODS: Isolated working rat
hearts were perfused with buffer containing glucose (5 mmol/L)
plus oleate (1.2 mmol/L). Hearts were subjected to 15 minutes
of ischemia and reperfused with or without insulin (100 microU/mL)
for 40 minutes. Epinephrine (1 micromol/L) was added for the
last 20 minutes. RESULTS: Hearts recovered 51.1% of preischemic
cardiac power in the absence and 76.4% in the presence of insulin
(p < 0.05). Whereas oleate oxidation remained unchanged,
glucose uptake and oxidation increased during reperfusion with
epinephrine (p < 0.01). This increase was significantly greater
when hearts were reperfused in the presence of insulin (p <
0.01). Insulin also prevented an epinephrine-induced glycogen
breakdown during reperfusion (p < 0.05). CONCLUSIONS: Insulin
has a direct positive inotropic effect on postischemic rat heart.
This effect is additive to epinephrine and occurs without delay.
Increased rates of glucose oxidation and net glycogen synthesis
are more protracted.
PMID: 10391275 [PubMed - indexed for MEDLINE]-
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Efficacy of metabolic support with glucose-insulin-potassium
for left ventricular pump failure after aortocoronary bypass
surgery.
Coleman GM, Gradinac S, Taegtmeyer H, Sweeney M, Frazier
OH.
University of Texas Medical School, Division of Cardiology,
Houston 77030.
Refractory pump failure after cardiopulmonary bypass carries
a high mortality. To assess the effectiveness of metabolic support
for the heart in patients with refractory heart failure after
hypothermic ischemic arrest for aortocoronary bypass surgery,
we randomly assigned 22 patients to receive either intravenous
glucose (50%), insulin (80 units/I), and potassium (100 meq/l)
(GIK) infused at a rate of 1 ml/kg/hr for up to 48 hours or
glucose (5%) and NaCl (0.225%) infused at the same rate (control).
All patients required inotropic drug support, received intra-aortic
balloon pump assistance, and had an initial mean cardiac index
(CI) of 2.5 l/min/m2. At 12 and 24 hours, CI had risen significantly
in the GIK but not in the control group (3.6 and 3.4 l/min/m2
vs. 2.5 and 2.7 l/min/m2, p less than 0.005). Time on the intra-aortic
balloon pump (39 vs. 61 hours) and requirements for inotropic
drug support were also significantly less in the GIK compared
with the control group. Although the number of patients was
relatively small, the GIK group also showed a trend for improved
long-term survival: at 60 days after surgery, there were 10
of 11 survivors in the GIK-treated group compared with seven
of 11 survivors in the control group. Although the exact mechanism
for the beneficial effects of GIK on myocardial contractility
remains to be elucidated, we conclude that GIK is safe and effective
in the treatment of refractory left ventricular failure after
aortocoronary bypass surgery.
Publication Types:
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Clinical trial |
|
Randomized controlled trial |
PMID: 2670331 [PubMed - indexed for MEDLINE]
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-
Glucose-insulin-potassium solutions enhance recovery after
urgent coronary artery bypass grafting.
Lazar HL, Philippides G, Fitzgerald C, Lancaster D, Shemin
RJ, Apstein C.
Department of Cardiothoracic Surgery, Boston University Medical
Center, Mass, USA.
OBJECTIVE: This prospective, randomized, clinical study was
undertaken to determine whether glucose-insulin-potassium solutions
would benefit patients undergoing coronary artery bypass grafting
because of unstable angina. METHODS: The study group consisted
of 30 patients with unstable angina who required coronary artery
bypass grafting. In 15 patients, glucose-insulin-potassium solution
(30% dextrose in water; K+, 80 mEq/L: regular insulin, 50 units)
was given intravenously at 1 ml/kg per hour after induction
of anesthesia and administration continued for 12 hours after
aortic unclamping. Fifteen patients in a separate group received
5% dextrose in water intravenously at 50 ml/hr. RESULTS: Patients
treated with glucose-insulin-potassium solution had higher cardiac
indices (2.8 +/- 0.1 vs 2.0 +/- 1 L/min per square meter; p
< 0.001), lower inotrope scores (0.06 +/- 0.01 vs 0.46 +/-
0.19; p = 0.041), and less weight gain (6.4 +/- 9 vs 11.6 +/-
1.1 pounds; p < 0.001) and had shorter times of ventilator
support (8.3 +/- 0.6 vs 14.2 +/- 0.2 hours; p = 0.003). They
had a significantly lower incidence of atrial fibrillation (13.3%
vs 53.3%; p = 0.020) and had shorter stays in the intensive
care unit (14.8 +/- 1.3 vs 31.6 +/- 5.2 hours; p = 0.002) and
in the hospital (6.0 +/- 0.4 vs 8.0 +/- 0.7 days; p = 0.010).
CONCLUSIONS: We conclude that glucose insulin-potassium therapy
enhances myocardial performance and results in faster recovery
from urgent coronary artery bypass grafting.
Publication Types:
|
Clinical trial |
|
Randomized controlled trial |
PMID: 9040630 [PubMed - indexed for MEDLINE]
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Effects of dobutamine versus insulin on cardiac performance,
myocardial oxygen demand, and total body metabolism after coronary
artery bypass grafting.
Hiesmayr M, Haider WJ, Grubhofer G, Heilinger D, Keznickl
FP, Mares P, Rajek AM, Coraim F, Semsroth M.
Department of Cardiothoracic and Vascular Anesthesia, University
of Vienna, Austria.
OBJECTIVE: The purpose was to study whether the hemodynamic
benefit of a catabolic catecholamine (dobutamine) induces a
certain oxygen cost for the myocardial energy demand and whether
this effect would be less pronounced if an anabolic intervention,
such as the administration of insulin, was used. DESIGN: A prospective
and randomized study. SETTING: A university hospital. PARTICIPANTS:
Investigation of two comparable groups of cardiac patients.
INTERVENTIONS: The interventions were postoperative infusions
of dobutamine, 7 micrograms/kg/min, and of insulin, 1.5 U/kg/h,
respectively, over a period of 30 minutes. MEASUREMENTS AND
MAIN RESULTS: The effects of the interventions were measured
using parameters relating to cardiac work and myocardial oxygen
demand. Moreover, parameters relating to total body metabolism
were also recorded. In the dobutamine group, cardiac index (CI)
and left ventricular stroke work index (LVSWI) increased significantly
(p < 0.05) during therapy by 30% and 40%, respectively. Cardiac
effort index (CEI) and tension time index (TTI) also increased
(p < 0.05) during therapy by 41% and 30%, respectively. However,
in the insulin group, CI and LVSWI also increased (p < 0.01
and p < 0.05) during therapy, although to a lesser extent
(16% and 14%), but CEI and TTI did not change at all during
therapy. Total body CO2 production (VCO2) and O2 consumption
(VO2) in the dobutamine group increased (p < 0.05) during
therapy by 9% and 11%, respectively, whereas in the insulin
group only CO2 production increased (p < 0.05) by 13%. O2
consumption remained unchanged in this group. CONCLUSIONS: It
is concluded that dobutamine as well as insulin administration
increase cardiac performance. However, in contrast to dobutamine,
insulin does not appear to increase myocardial oxygen demand.
Therefore, the anabolic insulin administration may represent
a more economic pattern of energy-consuming hemodynamic intervention
than does the catabolic catecholamine administration.
Publication Types:
|
Clinical trial |
|
Randomized controlled trial |
PMID: 8664455 [PubMed - indexed for MEDLINE]
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Accuracy of currently available techniques for prediction
of functional recovery after revascularization in patients with
left ventricular dysfunction due to chronic coronary artery
disease: comparison of pooled data.
Bax JJ, Wijns W, Cornel JH, Visser FC, Boersma E, Fioretti
PM.
Department of Cardiology, Academic Hospital, Leiden, The Netherlands.
bax@cardio.azl.nl
OBJECTIVES: This study evaluated the relative merits of the
most frequently used techniques for predicting improvement in
regional contractile function after coronary revascularization
in patients with left ventricular dysfunction due to chronic
coronary artery disease. BACKGROUND: Several techniques have
been proposed for predicting improvement in regional contractile
function after revascularization, including thallium-201 (Tl-201)
stress-redistribution-reinjection, Tl-201 rest-redistribution,
fluorine-18 fluorodeoxyglucose with positron emission tomography,
technetium-99m sestamibi imaging and low dose dobutamine echocardiography
(LDDE). METHODS: A systematic review of all reports on prediction
of functional recovery after revascularization in patients with
chronic coronary artery disease (published between 1980 and
March 1997) revealed 37 with sufficient details for calculating
the sensitivity and specificity of each imaging modality. From
the pooled data, 95% and 99% confidence intervals were also
calculated. RESULTS: Sensitivity for predicting regional functional
recovery after revascularization was high for all techniques.
The specificity of both Tl-201 protocols was significantly lower
(p < 0.05) and LDDE significantly higher (p < 0.01) than
that of the other techniques. CONCLUSIONS: Pooled analysis of
37 studies showed that although all techniques accurately identify
segments with improved contractile function after revascularization,
the Tl-201 protocols may overestimate functional recovery. The
evidence available thus far indicates that LDDE appears to have
the highest predictive accuracy.
Publication Types:
|
Meta-analysis |
PMID: 9362401 [PubMed - indexed for MEDLINE]
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Time course of myocardial viability after acute myocardial
infarction: an echocardiographic study.
Knudsen AS, Darwish AZ, Norgaard A, Gotzsche O, Thygesen
K.
Department of Medicine and Cardiology, Aarhus University, Denmark.
The recognition of dysfunctional but viable myocardium after
acute myocardial infarction (MI) may be of importance for both
patient prognostication and the decision for revascularization.
Low-dose dobutamine echocardiography (LDDE) has been shown to
be a reliable technique in detecting reversibility of dysfunctional
myocardium. The aim of the present study was to assess by LDDE
possible time-dependent changes in myocardial viability and
to evaluate the value of LDDE used in the postinfarction period.
Twenty-seven patients with acute MI underwent LDDE on day 6,
30, and 90. At LDDE day 6, 41% of the affected segments showed
a positive response to LDDE. At later examination on day 30
and 90, only 32% and 18%, respectively, of the dysfunctioning
segments responded to dobutamine stimulation, with a significant
decline in response (p < 0.0001), indicating loss of viability.
Spontaneous segmental outcome was significantly better for LDDE-responding
segments than for nonresponding segments (p = 0.0001). This
study indicated that myocardial viability may be temporary and
that a time-dependent loss of viability may take place during
the first months after MI.
PMID: 9453521 [PubMed - indexed for MEDLINE]-
Myocardial viability assessed by dobutamine echocardiography
in acute myocardial infarction after successful primary coronary
angioplasty.
Leclercq F, Messner-Pellenc P, Moragues C, Rivalland F, Carabasse
D, Davy JM, Grolleau-Raoux R.
Department of Cardiology, University Hospital, Montpellier,
France.
Dobutamine echocardiography (5 and 10 microg/kg/ min) was performed
in 40 patients 4 +/- 1 days after acute myocardial infarction
reperfused by primary coronary angioplasty. The left ventricle
was divided into 11 segments. Reversible myocardial dysfunction
was indicated by a decrease in at least 2 grades in the total
segmental score. Follow-up echocardiography was performed 2
months later. Contractile reserve was documented in 18 patients
with dobutamine echocardiography (45%). Sensitivity, specificity,
positive, and negative predictive value of dobutamine echocardiography
in predicting improvement in contractile function at follow-up
were 82%, 83%, 78%, and 86%, respectively. Negative predictive
value was high in all dyssynergic segments (86%). Positive predictive
value was higher in hypokinetic than in akinetic segments (73%
vs 21%; p <0.05). Recovery of wall motion at follow-up was
statistically associated with higher left ventricular ejection
fraction (p <0.04), collateral blood flow before reperfusion
(p = 0.007), and dobutamine responsiveness (p = 0.0001), and
was more frequently observed in hypokinetic than in akinetic
segments (p <0.05). Thus, low-dose dobutamine echocardiography
accurately predicts the extent of irreversibly damaged myocardium
early after successful direct coronary angioplasty in acute
myocardial infarction.
PMID: 9205011 [PubMed - indexed for MEDLINE]-
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Comment in:
|
Circulation. 1993 Aug;88(2):797-9 |
Low-dose dobutamine echocardiography detects reversible dysfunction
after thrombolytic therapy of acute myocardial infarction.
Smart SC, Sawada S, Ryan T, Segar D, Atherton L, Berkovitz
K, Bourdillon PD, Feigenbaum H.
Krannert Institute of Cardiology, Department of Medicine, Indiana
University School of Medicine, Indianapolis.
BACKGROUND. Dysfunction after thrombolytic therapy of acute
myocardial infarction (MI) may be reversible. Early after myocardial
infarction, both reversible and irreversible injury may be manifested
by regional wall motion abnormalities. Improved wall thickening
during dobutamine infusion (dobutamine-responsive wall motion)
may accurately identify reversibly injured segments. METHODS
AND RESULTS. To determine whether dobutamine-responsive wall
motion accurately detects reversible postischemic dysfunction
irrespective of infarct location, multistage (baseline, 4 and
12 micrograms.kg-1.min-1, and peak) dobutamine echocardiography
(DE) was performed within 7 days of thrombolytic therapy. Resting
echocardiography was repeated > or = 4 weeks after MI, and
reversible dysfunction was defined as improved wall motion.
The accuracy of dobutamine-responsive wall motion was compared
with that of signs of early reperfusion, non-Q-wave MI, and
peak creatine kinase (CK). Sixty-three patients underwent DE
without complications. Follow-up echocardiograms were done in
51 (81%) of these patients, and wall motion improved in 22 (41%).
Dobutamine-responsive wall motion during all stages of DE was
very specific for reversible dysfunction (90% to 93%) but sensitive
(86%) only when hemodynamics were not altered (low dose, 4 micrograms.kg-1.min-1).
Non-Q-wave MI and a low peak CK (< 1000 IU/mL) were also
specific (89% to 93%) but less sensitive (64% [P = .16] and
55% [P < .05], respectively). Signs of early reperfusion
did not identify postischemic dysfunction. Low-dose dobutamine-responsive
wall motion and non-Q-wave MI independently identified reversible
dysfunction, but only dobutamine-responsive wall motion was
sensitive in all infarct locations. Non-Q-wave MI was sensitive
only in anterior infarction. CONCLUSIONS. Multistage dobutamine
echocardiography can be performed safely early after thrombolytic
therapy. Low-dose dobutamine-responsive wall motion accurately
detected reversible dysfunction in all infarct locations. Dobutamine-responsive
wall motion and non-Q-wave infarction may be very useful for
accurately identifying reversible dysfunction early after thrombolytic
therapy for acute MI.
PMID: 8339404 [PubMed - indexed for MEDLINE]
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Echocardiography during infusion of dobutamine for identification
of reversibly dysfunction in patients with chronic coronary
artery disease.
La Canna G, Alfieri O, Giubbini R, Gargano M, Ferrari R,
Visioli O.
Cattedra di Cardiologia, Universita degli Studi di Brescia,
Italy.
OBJECTIVES. The aim of this study was to test whether the contractile
response of akinetic myocardium to low dose dobutamine is useful
for detecting myocardial viability in patients with coronary
artery disease and persistent left ventricular dysfunction.
BACKGROUND. In some patients with chronic coronary artery disease,
persistent abnormalities of left ventricular wall motion can
be reversed by successful coronary artery bypass surgery. Thus,
identification of potentially reversible dysfunction has important
therapeutic and prognostic implications. Echocardiography during
infusion of low dose dobutamine can detect viable myocardium
in patients after thrombolytic therapy. However, there is no
detailed information on the use of this method in patients with
chronic left ventricular dysfunction without reperfusion. METHODS.
We studied 33 selected patients with angiographically proved
coronary artery disease and persistent left ventricular dysfunction.
The effect of dobutamine infusion (5 micrograms/kg body weight
per min, followed by 10 micrograms/kg per min) on left ventricular
wall motion was evaluated by transthoracic echocardiography
before coronary artery bypass grafting and compared with that
obtained immediately after the operation (evaluated by intraoperative
epicardial echocardiography) and both 2 weeks and 3 months later.
Left ventricular wall motion was analyzed qualitatively by dividing
the left ventricle into 16 segments, and a score was assigned
to each region. RESULTS. Before coronary artery bypass surgery,
314 segments were akinetic. Of these, 183 became normokinetic
immediately after revascularization, and 15 became hypokinetic.
Dobutamine infusion was able to predict improvement in 178 of
the 205 segments that recovered function after revascularization
(sensitivity 86.8%) and to identify 89 of the 109 segments that
did not recover postoperatively (specificity 81.6%). Mean (+/-
SD) segment scores were 2.24 +/- 0.35 at baseline, 1.49 +/-
0.34 (p < 0.001) after dobutamine infusion, 1.51 +/- 0.38
(p < 0.001) immediately after and 1.51 +/- 0.38 (p < 0.001)
2 weeks after coronary artery bypass and 1.55 +/- 0.37 (p <
0.001) at 3-month follow-up. CONCLUSIONS. Echocardiography during
infusion of low dose dobutamine is a safe and accurate method
for identifying reversible dysfunctioning myocardium and predicts
early reversibility of wall motion after surgical revascularization
in selected patients with coronary artery disease with chronic
left ventricular dysfunction.
PMID: 8113543 [PubMed - indexed for MEDLINE]-
ATP synthesis during low-flow ischemia: influence of increased
glycolytic substrate.
Cave AC, Ingwall JS, Friedrich J, Liao R, Saupe KW, Apstein
CS, Eberli FR.
Cardiac Muscle Research Laboratory, Whitaker Cardiovascular
Institute, Boston University School of Medicine, Boston, MA,
USA.
BACKGROUND: Our goals were to (1) simulate the degree of low-flow
ischemia and mixed anaerobic and aerobic metabolism of an acutely
infarcting region; (2) define changes in anaerobic glycolysis,
oxidative phosphorylation, and the creatine kinase (CK) reaction
velocity; and (3) determine whether and how increased glycolytic
substrate alters the energetic profile, function, and recovery
of the ischemic myocardium in the isolated blood-perfused rat
heart. METHODS AND RESULTS: Hearts had 60 minutes of low-flow
ischemia (10% of baseline coronary flow) and 30 minutes of reperfusion
with either control or high glucose and insulin (G+I) as substrate.
In controls, during ischemia, rate-pressure product and oxygen
consumption decreased by 84%. CK velocity decreased by 64%;
ATP and phosphocreatine (PCr) concentrations decreased by 51%
and 63%, respectively; inorganic phosphate (P(i)) concentration
increased by 300%; and free [ADP] did not increase. During ischemia,
relative to controls, the G+I group had similar CK velocity,
oxygen consumption, and tissue acidosis but increased glycolysis,
higher [ATP] and [PCr], and lower [P(i)] and therefore had a
greater free energy yield from ATP hydrolysis. Ischemic systolic
and diastolic function and postischemic recovery were better.
CONCLUSIONS: During low-flow ischemia simulating an acute myocardial
infarction region, oxidative phosphorylation accounted for 90%
of ATP synthesis. The CK velocity fell by 66%, and CK did not
completely use available PCr to slow ATP depletion. G+I, by
increasing glycolysis, slowed ATP depletion, maintained lower
[P(i)], and maintained a higher free energy from ATP hydrolysis.
This improved energetic profile resulted in better systolic
and diastolic function during ischemia and reperfusion. These
results support the clinical use of G+I in acute MI.
PMID: 10790352 [PubMed - indexed for MEDLINE]
Glycolysis preferentially inhibits ATP-sensitive K+ channels
in isolated guinea pig cardiac myocytes.
Weiss JN, Lamp ST.
Department of Medicine, UCLA School of Medicine 90024.
In heart, glycolysis may be a preferential source of adenosine
triphosphate (ATP) for membrane functions. In this study the
patch-clamp technique was used to study potassium channels
sensitive to intracellular ATP levels in permeabilized ventricular
myocytes. Activation of these K+ channels has been implicated
in marked cellular K+ loss leading to electrophysiological
abnormalities and arrhythmias during myocardial ischemia.
The results showed that glycolysis was more effective than
oxidative phosphorylation in preventing ATP-sensitive K+ channels
from opening. Experiments in excised inside-out patches suggested
that key glycolytic enzymes located in the membrane or adjacent
cytoskeleton near the channels may account for their preference
for glycolytic ATP.
PMID: 2443972 [PubMed - indexed for MEDLINE]-
Relation between glycolysis and calcium homeostasis in
postischemic myocardium.
Jeremy RW, Koretsune Y, Marban E, Becker LC.
Department of Medicine, Johns Hopkins Medical Institutions,
Baltimore, Md.
This study examined the hypothesis that glycolysis is required
for functional recovery of the myocardium during reperfusion
by facilitating restoration of calcium homeostasis. [Ca2+]i
was measured in isolated perfused rabbit hearts by using the
Ca2+ indicator 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic
acid (5F-BAPTA) and 19F nuclear magnetic resonance spectroscopy.
In nonischemic control hearts, inhibition of glycolysis with
iodoacetate did not alter [Ca2+]i. In hearts subjected to
20 minutes of global zero-flow ischemia, [Ca2+]i increased
from 260 +/- 80 nM before ischemia to 556 +/- 44 nM after
15 minutes of ischemia (p less than 0.05). After reperfusion
with 5 mM pyruvate as a carbon substrate, [Ca2+]i increased
further in hearts with intact glycolysis to 851 +/- 134 nM
(p less than 0.05 versus ischemia) during the first 10 minutes
of reperfusion, before returning to preischemic levels. In
contrast, inhibition of glycolysis during the reperfusion
period resulted in persistent severe calcium overload ([Ca2+]i,
1,380 +/- 260 nM after 15 minutes of reperfusion, p less than
0.02 versus intact glycolysis group). Furthermore, despite
the presence of pyruvate and oxygen, inhibition of glycolysis
during early reperfusion resulted in greater impairment of
functional recovery (rate/pressure product, 3,722 +/- 738
mm Hg/min) than did reperfusion with pyruvate and intact glycolysis
(rate/pressure product, 9,851 +/- 590 mm Hg/min, p less than
0.01). Inhibition of glycolysis during early reperfusion was
also associated with a marked increase in left ventricular
end-diastolic pressure during reperfusion (41 +/- 5 mm Hg)
compared with hearts with intact glycolysis (16 +/- 2 mm Hg,
p less than 0.01). The detrimental effects of glycolytic inhibition
during early reperfusion were, however, prevented by initial
reperfusion with a low calcium solution ([Ca]o, 0.63 mM for
30 minutes, then 2.50 mM for 30 minutes). In these hearts,
the rate/pressure product after 60 minutes of reperfusion
was 12,492 +/- 1,561 mm Hg/min (p less than 0.01 versus initial
reflow with [Ca]o of 2.50 mM). These findings indicate that
the functional impairment observed in postischemic myocardium
is related to cellular Ca2+ overload. Glycolysis appears to
play an important role in restoration of Ca2+ homeostasis
and recovery of function of postischemic myocardium.
PMID: 1576739 [PubMed - indexed for MEDLINE]-
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Comment in:
|
Cardiovasc Drugs Ther. 1999
May;13(3):185-9 |
Low-dose glucose-insulin-potassium is ineffective in acute
myocardial infarction: results of a randomized multicenter
Pol-GIK trial.
Ceremuzynski L, Budaj A, Czepiel A, Burzykowski T, Achremczyk
P, Smielak-Korombel W, Maciejewicz J, Dziubinska J, Nartowicz
E, Kawka-Urbanek T, Piotrowski W, Hanzlik J, Cieslinski A,
Kawecka-Jaszcz K, Gessek J, Wrabec K.
Postgraduate Medical School, Grochowski Hospital, Warsaw,
Poland. proclin@warman.com.pl
We aimed to assess the clinical efficacy of glucose-insulin-potassium
(GIK) in acute myocardial infarction. Experimental data provided
evidence of the beneficial effects of GIK on ischemic myocardium.
The clinical trials, mostly uncontrolled and conducted mainly
before the thrombolytic era, were inconclusive due to the
small number of patients and discrepancies in protocols. In
order to evaluate the efficacy of this intervention, we have
performed a prospective multicenter randomized study. The
study consisted of 954 patients with acute myocardial infarction
(MI) randomized within 24 hours from the onset of symptoms
to low-dose GIK (n = 494), which consisted of 1000 mL 10%
dextrose, 32-20 U insulin, and 80 mEq K-, or to the control
group (n = 460), which was given 1000 mL 0.89% sodium chloride,
by intravenous 24-hour infusion at a rate of 42 mL/h. Cardiac
mortality and the occurrence of cardiac events at 35 days
did not differ between GIK and control-allocated patients
(32 (6.5%) vs. 21 (4.6%), respectively; OR 1.45, 95% CI 0.79-2.68,
P = 0.20; and 214 (43.3%) vs. 192 (41.7%), OR 1.07, 95% CI
0.82-1.38, P = 0.62). Total mortality at 35 days was significantly
higher in the GIK than in the control group (44 (8.9%) vs.
22 (4.8%), respectively, OR 1.95, 95% CI 1.12-3.47, P = 0.01).
The excess of non-cardiac deaths in the GIK group may have
occurred by chance. Low-dose GIK treatment does not improve
the survival and clinical course in acute MI.
Publication Types:
|
Clinical trial |
|
Multicenter study |
|
Randomized controlled trial |
PMID: 10439881 [PubMed - indexed for MEDLINE]
-
Acute effects of glucose-insulin-potassium infusion on
myocardial substrates, coronary blood flow and oxygen consumption
in man.
Rogers WJ, Russell RO Jr, McDaniel HG, Rackley CE.
PMID: 900041 [PubMed - indexed for MEDLINE]
|
