The effect of nitroglycerin on myocardial release of inosine, hypoxanthine and lactate during pacing-induced angina

Abstract

The efficacy of nitroglycerin as an antianginal drug has been evaluated by calculation of myocardial extraction and production values of lactate and the adenosine triphosphate (ATP) catabolites inosine and hypoxanthine. Coronary venous and arterial blood was sampled at rest, during pacing-induced angina and 4--6 min after nitroglycerin at identical paced heart rates for enzymatic assay of inosine and hypoxanthine after separation by column chromatography and for determination of lactate. Sublingual nitroglycerin given to 10 patients with coronary artery disease decreased coronary venous lactate values from 1175 +/- 320 mumol/l during pacing-induced angina to 950 +/- 240 mumol/l (p less than 0.05). The calculated myocardial lactate production during angina (-31 +/- 19%) diminished after nitroglycerin (-1.7 +/- 22%) (p less than 0.0025). Coronary venous inosine values during angina (1275 +/- 865 nmol/l) decreased after nitroglycerin (795 +/- 555 nmol/l) (p = n.s.), the arterial values (885 +/- 610 nmol/l) increased (960 +/- 580 nmol/l) (p = n.s.), the myocardial inosine release (-26 +/- 20%) changed to extraction values (19 +/- 19%) (p less than 0.0005). Coronary venous hypoxanthine values during angina (1540 +/- 1035 nmol/l) were reduced (1110 +/- 675 nmol/l) (p = n.s.); the arterial values (1625 +/- 1050 nmol/l) decreased (1510 +/- 935 nmol/l) (p = n.s.), the myocardial hypoxanthine extraction (0.3 +/- 29%) with a wide individual variability increased after nitroglycerin (24 +/- 13%) (p less than 0.025). The myocardial release of inosine and lactate during severe angina with significant positive correlation (r = 0.66, p less than 0.0025) demonstrates that anaerobic glycolysis is accompanied by ATP breakdown. The unchanged myocardial inosine and hypoxanthine extraction after nitroglycerin indicates that nitroglycerin is capable of attenuating this effect. In spite of reduced mean myocardial lactate production after nitroglycerin ischemic myocardial energy deficiency may be less marked. Thus, the enhanced myocardial inosine uptake may be one factor contributing the beneficial effects of nitroglycerin including the improvement of myocardial oxygen balance.