Kojima S, Nakamura Y, Mori H, Abe S, Miyamori R, Miyazaki T, Sakurai K, Hattori S, Takahashi M
Am Heart J. 1986 Nov;112(5):1011-6. doi: 10.1016/0002-8703(86)90314-5.
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.
在20只开胸犬中,研究并比较了冠状动脉内注射相对小剂量普萘洛尔与全身给药的心肌保护作用。在第1组(n = 6)中,用脱氧的克雷布斯 - 亨塞尔特溶液(KHS)对左前降支动脉(LAD)进行5分钟灌注期间,心率 - 血压乘积(R×P)未发生变化。然而,在第2组(n = 7)中,R×P下降程度相同,该组接受含0.4或0.8mg/dl普萘洛尔的KHS灌注;在第3组(n = 7)中,给予LAD灌注原始KHS并全身给予0.02至0.04mg/kg普萘洛尔。第2组和第3组普萘洛尔的总给药剂量相同。灌注5分钟后的透壁活检显示,与第1组相比,第2组缺氧心肌的代谢恶化较轻,表现为较高的三磷酸腺苷(ATP)(2.81±0.35对2.23±0.45μmol/g,p<0.05)和较低的乳酸含量(5.62±1.44对9.01±2.62μmol/g,p<0.05)。另一方面,第3组未观察到明显的代谢保护作用。三组之间局部心肌收缩的顺序变化无差异。总之,冠状动脉内注射普萘洛尔显示出心肌保护作用,这种作用不是由血流动力学和心肌收缩的变化介导的。