Sawada Tadashi, Kitagawa Hirotoshi, Nosaka Shuich
Department of Anesthesiology, Shiga University of Medical Science, Otsu 520-2192.
Masui. 2013 Nov;62(11):1351-9.
Although propranolol is well known to induce the preventive effect against ischemic disease, its effect on ischemia/reperfusion injuries remains unknown. We examined whether propranolol provides cardioprotection against ischemia/reperfusion injuries.
Microdialysis and 30 min of coronary artery occlusion followed by 60 min of reperfusion were applied in anesthetized rats. The dialysate myoglobin levels served as indices of myocardial injury, and were measured in the following groups: without propranolol administration (vehicle); with propranolol (2 mg x kg(-1), pro(2)-pre), (5 mg x kg(-1), pro (5) -pre) administration; zatebradine (0.5 mg x kg(-1), zat-pre) administration. Drugs were administered before coronary occlusion.
In the pro(2)-pre, pro(5)-pre and zat-pre groups the heart rate was suppressed during the entire period. Ischemia-induced increase in dialysate myoglobin level was suppressed in the pro(2)-pre, pro(5)-pre and zat-pre groups in comparison with vehicle group. Reperfusion-induced increase in dialysate myoglobin level was suppressed in the pro(2)-pre, pro(5)-pre and zat-pre groups in comparison with vehicle group. The ratios of reperfusion/ischemia myoglobin level in pro (2)-pre and pro(5)-pre were lower than those in vehicle and zat-pre. Reperfusion-induced increase in myoglobin level was suppressed by administration of propranolol immediately before reperfusion.
The results suggest that propranolol provides myocardial protection against ischemia/reperfusion injury. The protective effect of propranolol on reperfusion might be independent of its effect on ischemia.
虽然普萘洛尔对缺血性疾病具有预防作用已广为人知,但其对缺血/再灌注损伤的影响仍不清楚。我们研究了普萘洛尔是否能对缺血/再灌注损伤提供心脏保护作用。
对麻醉大鼠进行微透析,并使其冠状动脉闭塞30分钟,随后再灌注60分钟。透析液中肌红蛋白水平作为心肌损伤指标,在以下几组中进行测量:未给予普萘洛尔(溶剂对照组);给予普萘洛尔(2mg·kg⁻¹,pro(2)-pre)、(5mg·kg⁻¹,pro(5)-pre);给予扎替丁(0.5mg·kg⁻¹,zat-pre)。药物在冠状动脉闭塞前给药。
在pro(2)-pre、pro(5)-pre和zat-pre组中,整个期间心率均受到抑制。与溶剂对照组相比,pro(2)-pre、pro(5)-pre和zat-pre组中缺血诱导的透析液肌红蛋白水平升高受到抑制。与溶剂对照组相比,pro(2)-pre、pro(5)-pre和zat-pre组中再灌注诱导的透析液肌红蛋白水平升高受到抑制。pro(2)-pre和pro(5)-pre组中再灌注/缺血肌红蛋白水平的比值低于溶剂对照组和zat-pre组。在再灌注前立即给予普萘洛尔可抑制再灌注诱导的肌红蛋白水平升高。
结果表明普萘洛尔能对缺血/再灌注损伤提供心肌保护作用。普萘洛尔对再灌注的保护作用可能与其对缺血的作用无关。