Huey G. McDaniel

Enhancement of left ventricular function by glucose-insulin-potassium infusion in acute myocardial infarction

Abstract Twenty-eight patients admitted to the hospital with suspected acute myocardial infarction underwent baseline studies within 12 hours of onset of symptoms. Patients were then randomized to receive control infusion (0.45 percent sodium chloride at 20 ml/hour) (15 patients) or glucoseinsulin-potassium infusion (300 g glucose, 50 units regular insulin, 80 mEq KCl/liter water at 1.5 ml/kg per hour) (13 patients) for 48 hours. All patients received 0.45 percent sodium chloride for 2 more days. Coronary arteriograms and left ventriculograms were obtained in 26 (93 percent) of 28 patients 2 to 3 weeks after infarction. Radionuclide ejection fraction improved during glucose-insulin-potassium infusion (49 ± 4 to 55 ± 5 percent, p During experimental infusion pulmonary arterial end-diastolic pressure decreased in the glucose-insulin-potassium group (17 ± 2 to 12 ± 2 mm Hg, p These data suggest that glucose-insulin-potassium infusion after acute myocardial infarction in human beings (1) increases global ejection fraction, (2) Increases ejection fraction in the “infarcted zone” without changing ejection fraction in the “noninfarcted zone”, and (3) decreases pulmonary arterial end-diastolic pressure and end-diastolic and end-systolic volumes.

Clinical effects of glucose-insulin-potassium on left ventricular function in acute myocardial infarction: Results from a randomized clinical trial

Abstract The effects of glucose-insulin-potassium (GIK) on hemodynamics and left ventricular (LV) function in patients with acute myocardial infarction (AMI) were investigated in a prospective randomized study. Patients who presented with suspected AMI were candidates for this study if prerandomization evaluation was completed within 12 hours from onset of chest pain. Patients over 75 years of age, insulin-dependent diabetics, patients with renal insufficlency, and comatose patients were excluded. Following completion of baseline hemodynamic measurements, patients were randomly allocated to 48-hour infusion of 300 gm G, 500 units I, and 80 mEq KCl per liter at rate of 1.5 ml/kg/hr or to conventional therapy. In addition to serial hemodynamic measurements, dextran LV function curves (LVFC) were constructed during the second and third days to assess extent of LV injury. Eighty-five of 118 patients who were initially randomized into this study had AMI documented by diagnostic rise and fall of CK-MB isoenzyme. Baseline characteristics and hemodynamics were similar for GIK and control patients with AMI. GIK patients who presented with their initial AMI had significant reduction in pulmonary arterial end-diastolic pressure from prerandomization value of 16 ± 1 to 10 ± 1 by day 3, compared to 18 ± 1 to 16 ± 1 mm Hg for control patients ( p 2 for control patients ( p p p

Myocardial Fuel and Energy Balance, Acute Ischemia and Diabetes

When glucose-insulin-potassium (GIK) is infused, glucose supplies most of the energy demands of the heart. Fatty acid becomes the major substrate during fasting, pathologically increased work loads or insulin deficiency. Myocardial purine breakdown reflects myocardial energy status and influences coronary tone. Ischemia accelerates breakdown of ATP to AMP, which is further metabolized to adenosine, which causes vasodilatation and a blunted response to catecholamines. If normal circulation is restored, ADP and AMP are rapidly converted to ATP and purine metabolism is changed from degradation to salvage and de novo synthesis of purines. Ischemia impairs mitochondrial function, causing decreased capacity to oxidize fatty acids once aerobic conditions return. Thus, reperfusion with elevated plasma free fatty acids results in acyl-CoA accumulation in the heart. In diabetic animals, phosphorylation of AMP to ATP is defective in the heart, and AMP degradation is increased. Therefore, careful regulation of the blood sugar with concomitant lowering of plasma free fatty acids in diabetics with ischemic heart disease should improve myocardial salvage by preserving and repleting myocardial ATP. Thus, along with reestablishment of coronary flow and reduction in myocardial oxygen demands, may significantly reduce the morbidity of acute ischemia in diabetics.

Demonstration of the adenosine reservoirs with nitrobenzylthioinosine in liver and diaphragm by high-performance liquid chromatography.

Purine nucleotides, nucleosides, nucleobases, dinucleotides and nucleosides derivatives from acid-extracted rat liver and diaphragm were separated and quantitated by reversed-phase ion-pair high-performance liquid chromatography with a mobile phase composed of 90 mM potassium phosphate, 15 mM tetrabutylammonium hydroxide and a 1-30% methanol gradient. During 5 min of ischemia, adenine and guanine nucleotides decreased along with significant declines in NAD and increases in adenosine, inosine, hypoxanthine, xanthine, NADP and adenylosuccinate. Nitrobenzylthioinosine by gavage (5 mg/kg per day for five days) increased adenosine levels but without any alteration in nucleobase levels. Adenosine was shuttled to every available intracellular reservoir which included in declining order of magnitude GDP greater than adenosylhomocysteine greater than adenosine greater than ADP greater than AMP greater than IMP = XMP = GMP.

Experimental hyperthermia: protective effect of oxygen carrying fluorocarbon and crystalloids intraperitoneally.

The treatment of hyperthermia produced by passive warming was studied in anesthetized rats weighing 250-300 grams. In the first set of seven experiments, the authors found that venous blood oxygen fell as core temperature rose. Intraperitoneal injection of 20 ml of the oxygen carrying fluorocarbon (perfluorotributylamine, FC-43) emulsion in three of the animals shifted the curve to the right improving venous oxygen content (p less than 0.1). In the second series of experiments, a catheter was placed in the carotid artery. This catheter was attached to a pressure transducer for continuous recording of blood pressure and heart rate. Periodic blood samples were removed for measurement of blood gases, pH, and lactate. Four of the animals received 20 ml of isotonic saline, three received 20 ml of FC-43 emulsion both given intraperitoneally, and four served as controls. In the control group, there was an increase in systolic blood pressure and heart rate which peaked at a colon temperature of 42 degrees C, followed by cardiovascular collapse and death around 43 degrees C. Arterial PO2 (corrected for temperature) remained relatively constant up to 42 degrees C, and then fell. The arterial PCO2 rose sharply when the core temperature exceeded 43 degrees C. Arterial lactate content began to increase at 42 degrees C and above 43 degrees C was 2.5 fold elevated. Isotonic saline provided circulatory support but did not change the hypoxia or mixed acidosis from CO2 and lactate above 43 degrees C. FC-43 emulsion decreased hypoxia and improved circulatory performance but was associated with a mild respiratory alkalosis as arterial PCO2 fell.(ABSTRACT TRUNCATED AT 250 WORDS)