Ventricular arrhythmias and K+ transfer during myocardial ischemia and intervention with procaine amide, insulin, or glucose solution.

To assess the relation of ventricular arrhythmias to myocardial K(+) movement during ischemia, we placed an electrode catheter in the left anterior descending coronary artery for thrombus production in intact anesthetized dogs. (85)Kr injections distal to the thrombus permitted serial coronary blood flow measurements. Animals of Group I with a moderate flow reduction exhibited no arrhythmia or myocardial egress of K(+). In Group II, marked flow reduction was accompanied by an injury potential and loss of K(+) from the ischemic site, before and during ventricular tachycardia. Therapeutic interventions were performed in animals having the same degree of ischemia as Group II. Systemic procaine amide in Group III interrupted the tachycardia and egress of K(+), despite persistent ischemia. Group IV did not respond to intracoronary insulin with K(+) uptake, as did normal dogs, and progressed to fibrillation. During the production of hyperglycemia in Group V, myocardial loss of K(+) ceased with maintenance of sinus rhythm. Hemodynamic factors did not appear to have a major role in the genesis of the arrhythmia.Since intracoronary infusion of K(+) in normal dogs similarly altered repolarization and produced fibrillation, it would appear that during ischemia egress of K(+) before development of the arrhythmia indicates a major role of the ion in pathogenesis. This view is supported by the myocardial loss of K(+) and arrhythmia induced in normal dogs by strophanthidin and by the fact that pharmacologic regulation of K(+) loss is associated with correction of the arrhythmia, despite persistence of low blood flow.

Metabolic responses to fructose-1,6-diphosphate in healthy subjects.

Fructose-1,6-diphosphate (FDP) is an important naturally occurring intracellular metabolite with a direct regulatory role in many metabolic pathways. The most important and widely studied of the FDP effects has been its regulation of glycolysis, particularly the enzyme that synthesizes FDP--phosphofructokinase (PFK). Since it was observed experimentally that FDP does indeed modulate carbohydrate metabolism, we investigated whether FDP would similarly enhance carbohydrate utilization in man. The study used indirect calorimetry and was open to healthy adults (N = 45) of either sex and above legal age. After a steady metabolic state was obtained, 5 g of FDP (10%) was infused into a brachial vein. In 10 subjects, glucose (5 g) or FDP (5 g) was sequentially infused. The rapid intravenous infusion of FDP produced a slight but significant decrease in heart and respiration rates (P < .05). A significant increase in the serum concentration of inorganic phosphate (P < .0001) and the intraerythrocytic concentration of adenosine triphosphate (ATP) (P < .01) was also observed. The FDP infusion produced a decrease in plasma cholesterol and triglycerides (P < .001 and P < .01, respectively). The indirect calorimetric data indicate that the infusion produced a highly significant increase in the respiratory quotient ([RQ] P < .0001) and the energy derived from carbohydrates (P < .0001) and a significant decrease in the energy derived from lipids (P < .0001). Glucose infusion did not cause changes in any of the parameters. These data indicate that carbohydrate metabolism is stimulated by FDP.

Effect of fructose-1, 6-diphosphate versus diphenhydramine on mortality in compound 48/80-induced shock.

Fructose-1,6-diphosphate (FDP) has a salutary effect on hemorrhagic, traumatic and endotoxic shock. The role of FDP on compound 48/80-induced shock was therefore investigated. Sprague Dawley aged male rats (448+/-7.4 gm body weight) were randomly assigned into three groups and treated intraperitoneally with diphenhydramine (DPHM) 15 mg/kg (n=11), 12.5 ml of 10% FDP (n=10) and 12.5 ml saline (n=10). The rats were injected with compound 48/80 (5 mg/kg) 30 min later, and monitored every 10 min for 60 min. Arterial pressure was higher in FDP rats than in DPHM (P<0.01) or saline (P<0.005) groups. Plasma potassium (K(+)) was lower in the FDP group (P<0.01). Arterial pO2 and pCO2 were within physiological range in all groups. A profound decrease in arterial pH and bicarbonate (HCO3(-)) was also observed in all groups. Mortality at 48 h in the saline group was 100%, in the DPHM group 91%, and in the FDP group 20% (P<0.001 and P<0.005, respectively). FDP improved survival significantly in this study.

Plasma oxidase assay for screening of myocardial infarction.

The availability of techniques such as surgical reperfusion, angioplasty, and thrombolysis for the treatment of acute myocardial infarction (AMI) has revived interest in seeking an early detectable biochemical marker diagnostic for AMI. Therefore, we investigated whether an unidentified oxidase that is released by activated neutrophils at the onset of AMI could be used as an early diagnostic assay. The conversion by plasma oxidase of 1 microM of adrenaline to 1 microM of adrenochrome represents the plasma oxidase activity (POA) of 1 U/L. Fifty patients suspected of having AMI, 40% of whose electrocardiograms were nondiagnostic for AMI, were admitted to the coronary care unit, and venous blood samples were obtained for determination of the POA and creatine phosphokinase-MB levels. Healthy volunteers (n = 12) served as control subjects, and 8 patients with pneumonia whose leukocyte counts were greater than 15,000 microL were included in the study. In those with AMI (n = 22), as determined by serial creatine phosphokinase-MB, the mean POA (+/- standard error of the mean) was 233 +/- 13 U/L, and in those with angina and no AMI (n = 28) was 127 +/- 5 U/L (P < 0.0001). In the control group, mean POA (+/- standard error of the mean) was 84 +/- 5 U/L (control versus angina; P < 0.01) and for those with infection was 214 +/- 10 U/L. At admission, the creatine phosphokinase-MB was diagnostic for only 12 of the 22 patients with AMI (sensitivity rate of 54%), whereas in 21 of those patients, the POA values were diagnostic for AMI (sensitivity rate of 95%).(ABSTRACT TRUNCATED AT 250 WORDS)

Reversal of acute myocardial ischemia in closed chest animals by retrograde perfusion of the coronary sinus with arterial blood.

The fundamental objective of this study was to develop a technique for salvaging aco the ischemic muscle segment is the coronary venous system. We have been able to ration) in closed chest dogs by placing a double lumen balloon catheter in the coronary sinus, and perfusing it with blood derived from a peripheral artery. We have been able to partially reverse these same manifestations in similar dogs with an ischemic period of 30-60 minutes.