We conducted a multicenter, double-blind, placebo-controlled randomized trial of aspirin treatment (324 mg in buffered solution daily) for 12 weeks in 1266 men with unstable angina (625 taking aspirin and 641 placebo). The principal end points were death and acute myocardial infarction diagnosed by the presence of creatine kinase MB or pathologic Q-wave changes on electrocardiograms. The incidence of death or acute myocardial infarction was 51 per cent lower in the aspirin group than in the placebo group: 31 patients (5.0 per cent) as compared with 65 (10.1 per cent); P = 0.0005. Nonfatal acute myocardial infarction was 51 per cent lower in the aspirin group: 21 patients (3.4 per cent) as compared with 44 (6.9 per cent); P = 0.005. The reduction in mortality in the aspirin group was also 51 per cent--10 patients (1.6 per cent) as compared with 21 (3.3 per cent)--although it was not statistically significant; P = 0.054. There was no difference in gastrointestinal symptoms or evidence of blood loss between the treatment and control groups. Our data show that aspirin has a protective effect against acute myocardial infarction in men with unstable angina, and they suggest a similar effect on mortality.

Two patients with mitochondrial encephalomyopathy due to complexes I and IV deficiencies received 150 mg/d of coenzyme Q10 (CoQ). We studied them with a bicycle ergometer exercise test and 31P NMR spectroscopy before and after 10 months of treatment. Before treatment, we observed a low phosphocreatine/inorganic phosphate (PCr/P(i)) resting value along with abnormally high resting lactate concentration. During exercise, there was a pronounced acidosis with delayed kinetics of postexercise recovery for blood lactate, pH, PCr, and PCr/P(i) ratio. Oxygen uptake during exercise was reduced while the lowering of the ventilatory threshold indicated an early activation of glycolysis. After treatment, the bicycle ergometer exercise test indicated a significant improvement with a decrease in resting blood lactate level, an increase in oxygen consumption during exercise, and an increase in the kinetics of lactate disappearance during the recovery period. A shift of the ventilatory threshold to higher workload was present. 31P NMR spectroscopy confirmed the improvement, showing a significant increase in the PCr/P(i) ratio at rest and in the kinetics of recovery for pH, PCr, and PCr/P(i) ratio following exercise in patient 1. For patient 2, we observed a less pronounced acidosis correlated with a lesser amount of Pi produced during exercise. These observations indicate an improvement of mitochondrial function and a shift from high to low glycolytic activity in both patients consequent to CoQ treatment.

Systolic time intervals (STI) were measured in ten healthy male volunteers before and after intravenous (i.v.) administration of 25 mug/kg delta-9-tetrahydrocannabinol (delta-9-THC). Mean +/- SEM heart rate increased 32 +/- 7 beats/min, while systolic and diastolic blood pressures were unchanged after delta-9-THC. Total electromechanical systole lengthened 17 +/- 4.2 msec, left ventricular ejection time (LVETc) prolonged 24 +/- 4.0 msec and pre-ejection period (PEP) shortened 17 +/- 5.1 msec after delta-9-THC. All of these changes were significant (P less than 0.01). In nine other subjects who underwent prior beta adrenergic blockade, similar but less marked changes were noted in heart rate, blood pressure, and STI after delta-9-THC. The shortening of PEP after delta-9-THC was only 9 msec (NS) in beta blocked subjects. Thus, delta-9-THC significantly increased heart rate, shortened PEP and prolonged LVETc without any change in afterload. Beta adrenergic blockade prevented significant shortening of PEP and blunted other responses. These findings suggest that delta-9-THC enhanced cardiac performance. Partial inhibition of this effect was achieved with prior beta adrenergic blockade.

We have previously reported that 25 micrograms/kg of intravenous (i.v.) delta-9-tetrahydrocannabinol (delta-9-THC) produces marked increases in heart rate, prolongation of left ventricular ejection time corrected for heart rate (LVETc), and a shortening of the pre-ejection period in normal volunteers. Beta-adrenergic blockade partially attenuates these responses. To elucidate further the mechanism of action of delta-9-THC, we gave 10 normal volunteers 0.1 mg/kg of i.v. propranolol and 2 mg of i.v. atropine before they received 25 micrograms/kg of i.v. delta-9-THC. Systolic time intervals were compared in the denervated subjects before and after delta-9-THC. Post delta-9-THC responses were measured at a time approximating peak psychologic high. Mean +/- SEM heart rate before and after delta-9-THC was 89 +/- 4 and 87 +/- 3 beats/min (NS); mean +/- SEM pre-ejection period before and after delta-9-TCH was 107 +/- 5 and 109 +/- 4 ms (NS); and mean +/- SEM LVETc before and after delta-9-THC was 433 +/- 6 and 429 +/- 6 ms (NS). Since previous denervation of our subjects with atropine and propranolol totally abolished changes in heart rate and systolic time intervals, the cardiac effects of delta-9-THC appear to be mediated totally via the autonomic nervous system, probably reflecting direct central nervous system stimulation.

SUMMARYThirty-three patients with severe hypertension were treated with rapidly injected intravenous diazoxide. Renal function was measured in nine patients and four underwent cardiac catheterization during renal function studies. Diazoxide had a rapid, profound hypotensive effect. Average Thirty-three patients with severe or malignant hypertension were studied. All patients had sustained diastolic blood pressures of 120 mm Hg or more. The patients were separated into two groups.Group 1 consisted of 24 patients, age 10 months to 57 years, who were studied clinically. Many had severe renal disease. Mean blood urea nitrogenwas 82 mg% and mean serum creatinine was 7.7 mg%. The patients were given 300 mg of diazoxide intravenously by the rapid-injection technique described by Finnerty The intra-aortic systolic, diastolic, and mean blood pressure, before, during, and after rapid intravenous injection of 300 mg of diazoxide.