Masando Takahashi

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

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 μmol/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 μmol/g in groups 2, 4, and 5, respectively) compared with those in group 1 (2.09 ± 0.45 μmol/g in ATP and 8.77 ± 2.34 μmol/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.

Electrophysiologic and myocardial metabolic changes in the acute phase of partial coronary occlusion

The acute effects of the partial reduction of coronary blood flow (CBF) on electrical and metabolic changes in myocardium were studied in 59 dogs. In seven dogs with a CBF reduction of 20% to 49%, the adenosine triphosphate (ATP) content (3.59 +/- 0.45 mumol/gm) and the width of the composite electrogram (54 +/- 5 msec) were not significantly different from those of 14 control dogs. In 14 dogs with a CBF reduction of 50% to 74%, ATP decreased significantly (3.09 +/- 0.30 mumol/gm, p less than 0.01); however, widening of the composite electrogram was not noted. Malignant ventricular arrhythmias developed in 5 of 10 dogs with a CBF reduction of 75% to 90% and 6 of 14 dogs with a 100% occlusion, but in none of the dogs with a CBF reduction of less than 75%. Marked widening of the composite electrogram (94 +/- 42 msec, p less than 0.05; and 115 +/- 54 msec, p less than 0.001) and further decrease in ATP (2.49 +/- 0.28 mumol/gm, p less than 0.001; and 2.66 +/- 0.45 mumol/gm, p less than 0.05) were noted in these two groups with a CBF reduction of greater than or equal to 75%. In conclusion, more advanced ischemia was mandatory for electrical derangements than for metabolic deterioration.

Comparative effects of intracoronary administration of propranolol with systemic administration on hypoxic canine myocardium

Myocardial protective effects of intracoronary administration of relatively small doses of propranolol were examined and compared with systemic administration in 20 open-chest dogs. In group 1 (n = 6) rate-pressure-product (R X P) did not change during 5-minute left anterior descending artery (LAD) perfusion with deoxygenated Krebs-Henseleit solutions (KHS). However, R X P decreased by the same degree in group 2 (n = 7), which received perfusion with KHS containing 0.4 or 0.8 mg/dl of propranolol, and in group 3 (n = 7) given LAD perfusion with original KHS and systemic administration of 0.02 to 0.04 mg/kg of propranolol. Total administered doses of propranolol were the same for groups 2 and 3. Transmural biopsy after 5 minutes of perfusion revealed less severe metabolic deterioration of hypoxic myocardium in group 2 when compared with that in group 1, as evidenced by higher ATP (adenosine triphosphate) (2.81 +/- 0.35 versus 2.23 +/- 0.45 mumol/g, p less than 0.05) and lower lactate content (5.62 +/- 1.44 versus 9.01 +/- 2.62 mumol/g, p less than 0.05). On the other hand, significant metabolic preservation was not noted in group 3. Sequential changes in regional myocardial contraction did not differ among the three groups. In conclusion, intracoronary administration of propranolol showed myocardial protective effects that were not mediated by the changes in hemodynamics and myocardial contraction.