Hemodynamic Changes Associated With Angina Pectoris Induced By Maximal Treadmill Exercise: Effect of Sublingual Isosorbide Dinitrate On Systolic Time Intervals

Abstract

A technique for the study of patients with angina pectoris has been described, in which systolic time interval (STI) measurements are obtained at intervals after the onset of stress-induced angina. The technique is uniquely suited to the evaluation of anti-anginal drugs. Sublingual isosorbide dinitrate (SISD) was randomly alternated with a placebo (P) tablet in a double-blind study of 20 patients with stable angina pectoris. After SISD, compared to placebo, a highly significant shortening of Q-S2 and LVET occurred (p less than 0.001) which lasted throughout the entire 120 minute study period. The hemodynamic basis for these differences was felt to be improved myocardial contractility secondary to a reduction in systemic vascular resistance and reduced venous return induced by the SISD. A significant prolongation of PEP occurred at 60 minutes post-SISD (p less than 0.01). This was attributed to an increase in the gradient between LVEDP and aortic diastolic pressure resulting from reduced venous return after SISD. The PEP/LVET ratio was significantly increased up to 60 minutes after SISD (P less than 0.05). Heart rate was uniformly higher post-SISD, compared to post-placebo values; the differences were highly significant up to 60 minutes (P less than 0.001) and remained significant at 120 minutes (p less than 0.05). The time to angina was significantly longer (immediately post SISD, p less than 0.05; 30 min, p less than 0.001; 60 mins, p less than 0.05; 120 mins, p less than 0.05); and the work load greater, for 120 minutes following SISD: the increase in the latter was highly significant for 30 minutes after SISD (p less than 0.001) and remained significant up to 120 minutes (60 mins, p less than 0.05; 120 mins, p less than 0.05). These observations were attributed to an improvement in myocardial function due to the sublingual isosorbide dinitrate. A high degree of correlation was found to exist between heart rate and the STI. This correlation was negative for the QS2 interval (-0.996) and LVET (-0.993) and positive for PEP (+0.817) and the PEP/LVET ratio (+0.950).