Examination of the Direct Effects of Nicorandil, Verapamil, Propranolol, and Nitroglycerin on the Hypoxic Canine Myocardium

Abstract

Effects of intracoronary administration of verapamil (VER), nitroglycerin (TNG), propranolol (PRO), and nicorandil (NIC) on regional hypoxia were examined in 39 open-chest dogs. Distal left anterior descending coronary artery was perfused for 5 min with deoxygenated Krebs-Henseleit solution (KHS) in group 1 (n = 9), VER-containing (1.3 mg/dl) KHS in group 2 (n = 9), TNG-containing (0.5 mg/dl) KHS in group 3 (n = 7), PRO-containing (0.4 or 0.8 mg/dl) KHS in group 4 (n = 7), and NIC-containing (0.5 or 2.5 mg/dl) KHS in group 5 (n = 7). Transmural biopsy at 5 min revealed a less severe metabolic deterioration in the hypoxic myocardium in groups 2, 4, and 5, as evidenced by higher ATP content (2.99 +/- 0.73, 2.81 +/- 0.35, and 3.14 +/- 1.20 mumol/g in groups 2, 4, and 5, respectively) and lower lactate accumulation (5.16 +/- 0.59, 5.62 +/- 1.44, and 5.05 +/- 1.12 mumol/g in groups 2, 4, and 5, respectively) compared with those in group 1 (2.09 +/- 0.45 mumol/g in ATP and 8.77 +/- 2.34 mumol/g in lactate). Metabolic preservation by VER, PRO, and NIC were not mediated by changes in hemodynamics and regional myocardial contraction. On the other hand, any significant protective effects were not noted in group 3, despite a significant reduction in rate-pressure products. Under an aerobic condition these agents affected regional myocardial contraction in a different manner from each other.