Ineffectiveness of Glucose, Potassium, and Insulin Infusion During Pacing Stress in Chronic Ischemic Heart Disease

Lesch, Michael; Teichholz, Louis E.; Soeldner, J S; Gorlin, Richard

doi:10.1161/01.cir.49.6.1028

Cited by 31 publications

(28 citation statements)

References 28 publications

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“…During ischemia and hypoxia, glycolysis is accelerated and glucose utilization is enhanced (4)(5)(6)(7)(8). Glucose-insulin-potassium infusions have been advocated for patients with acute myocardial infarctions and chronic ischemic heart disease; however, the efficacy of this treatment for limiting myocardial infarct size and left ventricular dysfunction still remains to be determined (3,(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Metabolic fate of extracted glucose in normal human myocardium.

Wisneski¹,

Gertz²,

Neese³

et al. 1985

J. Clin. Invest.

182

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Glucose is an important substrate for myocardial metabolism. This study was designed to determine the effect of circulating metabolic substrates on myocardial glucose extraction and to determine the metabolic fate of glucose in normal human myocardium. Coronary sinus and arterial catheters were placed in 23 healthy male volunteers. 16-"'CjGlucose was infused as a tracer in 10 subjects. 16-'CiGlucose and IU-_3Cilactate were simultaneously infused in the other 13 subjects. Simultaneous blood samples were obtained for chemical analyses of glucose, lactate, and free fatty acids and for the isotopic analyses of glucose and lactate. Glucose oxidation was assessed by measuring myocardial 4 CO2 production. The amount of glucose extracted and oxidized by the myocardium was inversely correlated with the arterial level of free fatty acids (r = -0.71; P < 0.0001). 20% (range, 0-63%) of the glucose extraction underwent immediate oxidation. Chemical lactate analysis showed a net extraction of 26.0±16.4%. However, isotopic analysis demonstrated that lactate was being released by the myocardium. In the 13 subjects receiving the dual-carbon-labeled isotopes, the lactate released was 0.09±0.04 ,mol/ml and 49.5±29.5% of this lactate was from exogenous glucose. This study demonstrates that the circulating level of free fatty acids plays a major role in determining the amount of glucose extracted and oxidized by the normal human myocardium. Only 20.1±19.4% of the glucose extracted underwent oxidation, and 13.0±9.0% of the glucose extracted was metabolized to lactate and released by the myocardium. Thus, 60-70% of the glucose extracted by the normal myocardium is probably stored as glycogen in the fasting, resting state.

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Section: Introductionmentioning

confidence: 99%

Metabolic fate of extracted glucose in normal human myocardium.

Wisneski¹,

Gertz²,

Neese³

et al. 1985

J. Clin. Invest.

182

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“…Failure to consider the importance of potassium in the genesis of either the QRS or TQ-ST alterations may result in the inappropriate classification of certain interventions as efficacious when, in fact, they may be harmful. The observation that glucose-potassium-insulin administration reduced TQ-ST deflections (45) and histologic evidence of ischemic necrosis (46) is contrary to the clinical findings of Lesch et al (47) in which it was concluded that tolerance to ischemia was not extended but instead adversely affected by glucose-potassium-insulin administration.…”

Section: Discussionmentioning

confidence: 86%

The QRS complex during myocardial ischemia. An experimental analysis in the porcine heart.

Holland¹,

Brooks²

1976

J. Clin. Invest.

169

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A B S T R A C T Although ST segment deflections have been widely utilized as a means of assessing the degree of underlying ischemic injury, the relationship of QRS complex alterations to the ischemic process is poorly understood. In this study we made a beat-to-beat analysis of the QRS complex in terms of ventricular activation time (CT) and R wave voltage (V) in the acutely ischemic porcine myocardium and analyzed the relationship of these responses to changes in the area of ischemic involvement, altered myocardial energy demands, and plasma [K+]o levels.With the onset of ischemia the QRS complex underwent a specific and reproducible biphasic sequence with an initial decrease in CT and V indicating a transient increase in the conduction velocity of the ischemic tissue. Subsequently both CT and V returned briefly to control and then increased dramatically, now indicating a marked decrease in conduction velocity. The time when CT first began to increase (Tc) was shortened by enlarging the area of ischemia or after an inotropic intervention and was lengthened by decreasing the area of ischemia or with administration of propranolol. Moreover Tc was found to be inversely proportional to plasma [K+]o in the range 3.4-8.8 mM, above which the initial decrease in CT and V was no longer present.We conclude that this biphasic sequence of QRS alterations in early myocardial ischemia is attributable to a progressive leakage of potassium out of the ischemic cells which in turn alters both the time-course and transmural pathway of the activation process through the ischemic tissue. These changes are related to both inotropic state and the area of ischemic involvement. INTRODUCTIONAlthough ST segment deflections have been widely utilized as a means of assessing the degree of underlying ischemic injury (1, 2) the relationship of QRS complex alterations to the ischemic process is poorly understood. The casual observations of changes in R wave amplitude noticed by some ST segment investigators after coronary artery occlusion in the dog (3-5) as well as the more specific studies of , Scher (9), and Durrer and van der Tweel (10) in the dog and goat suggest that ischemic QRS complex alterations may bear characteristic temporal and/or spatial relationships to the underlying ischemic process.In the present study we have characterized the temporal sequence of QRS complex alterations during early myocardial ischemia in the intact porcine heart, their modification by changes in the area of ischemic involvement, and altered myocardial energy demands, as well as the important role of potassium in their genesis.

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“…Intracellular metabolites, primarily glycogen and glutamate, were labeled with I3 C by addition of [l- 13 C]glucose to the perfusate during a normoxk, preischemic period. 13 C and 31 P NMR spectroscopy was used to observe the metabolism of "C-labeled metabolites simultaneously with high-energy phosphorus metabolites and pH. The extent of acidosis and the rate and amount of labeled lactate accumulation during ischemia were the same in control (3 mM glucose + insulin) and GIK-treated hearts.…”

Section: I P Nuclear Magnetic Resonance Studymentioning

confidence: 99%

“…We report here the use of I3 C and 3I P NMR spectroscopy to correlate in time the metabolism of labeled carbon metabolites with changes in high energy phosphorus metabolites and pH during ischemia and reflow in the isolated Langendorff-perfused guinea pig heart. 13 C and 31 P spectra were collected on an alternate scan by guest on May 10, 2018 http://circres.ahajournals.org/ Downloaded from basis, 19 allowing us to observe metabolites containing phosphorus and carbon simultaneously on each heart. This combination is much more powerful than observation of either nucleus alone.…”

Section: I P Nuclear Magnetic Resonance Studymentioning

confidence: 99%

Rates of glycolysis and glycogenolysis during ischemia in glucose-insulin-potassium-treated perfused hearts: A 13C, 31P nuclear magnetic resonance study.

Hoekenga

Brainard

Hutson

1988

Circulation Research

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The effects of 11.7 mM glucose, insulin, and potassium (GIK) on metabolism during ischemia were investigated in the perfused guinea pig heart using magnetic resonance spectroscopy. Intracellular metabolites, primarily glycogen and glutamate, were labeled with I3 C by addition of [l-13 C]glucose to the perfusate during a normoxk, preischemic period. 13C and 31 P NMR spectroscopy was used to observe the metabolism of "C-labeled metabolites simultaneously with high-energy phosphorus metabolites and pH. The extent of acidosis and the rate and amount of labeled lactate accumulation during ischemia were the same in control (3 mM glucose + insulin) and GIK-treated hearts. In contrast, the rate of labeled glycogen mobilization during ischemia in GIK-treated hearts was one third the rate observed in control hearts. These observations suggest that GIK decreased the rate of glycogenolysis during ischemia without affecting the rate of glycolysis. We propose that glucose contributed as a glycolytic substrate to a greater extent during ischemia in GIK-treated hearts than in hearts perfused with 3 mM glucose and insulin. The glycogen-sparing effect of GIK demonstrated in these studies could delay the onset of ischemic damage in a clinical setting by prolonging the availability of glycolytic substrate necessary for production of high-energy phosphate. (Circulation Research 1988;62:1065-1074 M yocardial ischemia is a common and important clinical problem. Although metabolism of the ischemic myocardium has been an area of active investigation for many years, the metabolic changes resulting from the inadequate oxygen and substrate supply and product removal associated with ischemia are incompletely understood. However, it is clear that one of the important metabolic events leading to cellular damage during ischemia is failure of the rate of energy production to meet the demands for energy utilization.Several therapeutic strategies have been introduced to alter cardiac metabolism during ischemia. A mixture of glucose, insulin, and potassium (GIK) was initially used 25 years ago as a means of eliminating the electrocardiographic abnormalities of myocardial infarction.1 Since that time GIK has been used in numerous studies of coronary artery occlusion in animals and man. Nearly all of the animal studies, using a variety of measures of recovery, have shown reduced infarct size and improved tissue metabolism.2 " 3 Studies in man have been less conclusive. Infusion of GIK in patients Received November 6, 1986; accepted January 6, 1988. with acute myocardial infarction has resulted in improved left ventricular function, 6 improved electrical stability, 7 clinical improvement, 8 and reduced mortality. 9 Other studies have found no reduction in mortality.l 0 " In patients with stable angina pectoris and coronary artery disease, administration of GIK, together with cardiac pacing, was beneficial in some studies 12 and detrimental in others.13M A better understanding of the metabolic action of GDC may explain many of these contradicto...

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Ineffectiveness of Glucose, Potassium, and Insulin Infusion During Pacing Stress in Chronic Ischemic Heart Disease

Abstract: SUMMARYEight patients with coronary artery disease and positive exercise electrocardiograms undergoing cardiac catheterization were subjected to periods of atrial pacing-induced tachycardia at identical rates, before and during a glucose, potassium, and insulin (GKI) infusion.

Cited by 31 publications

References 28 publications

Metabolic fate of extracted glucose in normal human myocardium.

Metabolic fate of extracted glucose in normal human myocardium.

The QRS complex during myocardial ischemia. An experimental analysis in the porcine heart.

Rates of glycolysis and glycogenolysis during ischemia in glucose-insulin-potassium-treated perfused hearts: A 13C, 31P nuclear magnetic resonance study.

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