Inotropic effects of tolbutamide in man

The hemodynamic responses of normal subjects to intravenous injections of tolbutamide, 250 mg., and 1,000 mg., were assessed by measurements of serial systolic time intervals. Analysis of results, compared to saline control, revealed evidence of minor inotropic effects during the period five to 10 minutes after infusion. Small but statistically significant (p less than 0.05) decreases in pre-ejection phase and electromechanical systole were noted. The time response of these changes did not correlate with dose of blood level of tolbutamide, and appeared to coincide with peak insulin levels. No inotropic or chronotropic effects were seen during the first four minutes after infusion, suggesting that the myocardial adenyl cyclase-stimulating properties of the drug, previously demonstrated in vitro, are not significant in intact man. The minor late inotropic effects are of doubtful clinical significance, and cannot be invoked to explain the reported increased cardiovascular mortality of patients treated with tolbutamide.