Muller C A, Opie L H, Peisach M, Pineda C A
MRC Ischaemic Heart Disease Research Unit, Groote Schuur Hospital, Cape Town, South Africa.
J Cardiovasc Pharmacol. 1992 May;19(5):748-54.
Previous studies on the possible antiarrhythmic effects of angiotensin converting enzyme (ACE) inhibitors during early ischemia in pigs have been inconclusive or negative; however, proof of adequate ACE inhibition was not provided. Perindoprilat, 0.06 mg/kg, i.v., was administered 30 min prior to ligation of the anterior descending coronary artery (CAL) in anesthetised open-chest pigs. Plasma ACE activity was decreased by 95.0 +/- 1.9% when measured 5 min before CAL. Within 5 min of CAL, the ventricular fibrillation threshold (VFT) in the control group was decreased from 11.8 +/- 1.9 to 7.2 +/- 1.2 mA (p less than 0.01). Perindoprilat prevented the fall in the VFT and the increase in left ventricular end-diastolic pressure caused by CAL. Perindoprilat decreased arterial pressure. Cardiac output (thermodilution) was decreased by 23 +/- 3% after CAL in the control group and by only 10 +/- 5% (p less than 0.05) in the perindoprilat group (both versus pre-CAL values). In the control group cyclic AMP was increased from 0.97 +/- 0.04 (pre-CAL) to 1.16 +/- 0.04 nmol/g (p less than 0.05) in the central ischemic zone 20 min after CAL. Perindoprilat prevented this increase in cyclic AMP. Twenty minutes after CAL blood flow (microsphere method) in the nonischemic zone of the perindoprilat group was increased, whereas blood flow in the central ischemic zone was decreased compared to the control group. However, levels of tissue metabolites (ATP, phosphocreatine, lactate) measured in drill biopsies in the same zones of the two groups were similar.(ABSTRACT TRUNCATED AT 250 WORDS)
先前关于血管紧张素转换酶（ACE）抑制剂在猪早期缺血时可能具有的抗心律失常作用的研究结果尚无定论或呈阴性；然而，并未提供充分抑制ACE的证据。在麻醉开胸猪中，于结扎冠状动脉前降支（CAL）前30分钟静脉注射0.06mg/kg培哚普利拉。在CAL前5分钟测量时，血浆ACE活性降低了95.0±1.9%。CAL后5分钟内，对照组的心室颤动阈值（VFT）从11.8±1.9 mA降至7.2±1.2 mA（p<0.01）。培哚普利拉可防止CAL引起的VFT下降以及左心室舒张末期压力升高。培哚普利拉可降低动脉压。对照组CAL后心输出量（热稀释法）降低了23±3%，而培哚普利拉组仅降低了10±5%（p<0.05）（两者均与CAL前值相比）。对照组中，CAL后20分钟，中央缺血区的环磷酸腺苷（cAMP）从0.97±0.04（CAL前）升高至1.16±0.04 nmol/g（p<0.05）。培哚普利拉可防止cAMP的这种升高。CAL后20分钟，培哚普利拉组非缺血区的血流量（微球法）增加，而与对照组相比，中央缺血区的血流量减少。然而，两组相同区域钻孔活检中测得的组织代谢物（三磷酸腺苷、磷酸肌酸、乳酸）水平相似。（摘要截断于250字）
