Fujimura N, Sumita S, Narimatsu E, Nakayama Y, Shitinohe Y, Namiki A
Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):440-6. doi: 10.1164/ajrccm.161.2.9904044.
We investigated the effects, and the mechanism of the effects, of isoproterenol on diaphragmatic contractility and fatigue in septic peritonitis in vitro. Ninety-six rats were divided into two groups of 48. One group (CLP group) was treated with cecal ligation and perforation (CLP) and the other (sham group) was treated with laparotomy. The left hemidiaphragm was removed at 16 h after the operation. We assessed the diaphragmatic contractility by twitch characteristics and force-frequency curves in vitro. Diaphragm fatigue was induced by rhythmically stimulating strips to contract at 60/ min (20 Hz, 0.33-s trains, 1 train/s) over a 4-min period. Force-frequency curves were determined before and after fatigue. Isoproterenol (10(-9), 10(-8), and 10(-7) M), a beta-adrenoceptor agonist, was cumulatively administered to the organ bath. Isoproterenol significantly increased diaphragmatic contractility. There were no significant changes in diaphragmatic contractility in the sham group. Isoproterenol (10(-7) M) significantly accelerated diaphragmatic recovery of fatigue and increased cAMP levels both in the sham group and the CLP group. Propranolol (10(-7) M), a general beta-adrenoceptor blocker, completely abolished the positive inotropic effect of isoproterenol (10(-7) M) and increased cAMP levels in the CLP group. Dibutyryl cAMP (10(-3) M), a derivative of cyclic AMP, mimicked the effects of isoproterenol in the CLP group. These results suggest that isoproterenol increases diaphragmatic contractility and accelerates diaphragmatic recovery of fatigue in septic peritonitis by activating the adenylate cyclase system.
我们在体外研究了异丙肾上腺素对脓毒症性腹膜炎膈肌收缩力及疲劳的影响及其作用机制。96只大鼠被分为两组，每组48只。一组（CLP组）行盲肠结扎穿孔术（CLP），另一组（假手术组）行剖腹术。术后16小时切除左半膈肌。我们通过体外抽搐特征和力-频率曲线评估膈肌收缩力。通过在4分钟内以60次/分钟（20赫兹，0.33秒的串刺激，每秒1串）有节奏地刺激肌条收缩来诱导膈肌疲劳。在疲劳前后测定力-频率曲线。向器官浴槽中累积给予β-肾上腺素能受体激动剂异丙肾上腺素（10^(-9)、10^(-8)和10^(-7)摩尔/升）。异丙肾上腺素显著增加膈肌收缩力。假手术组膈肌收缩力无显著变化。异丙肾上腺素（10^(-7)摩尔/升）在假手术组和CLP组中均显著加速膈肌疲劳恢复并增加环磷酸腺苷（cAMP）水平。普萘洛尔（10^(-7)摩尔/升），一种通用的β-肾上腺素能受体阻滞剂，完全消除了异丙肾上腺素（10^(-7)摩尔/升）的正性肌力作用，并增加了CLP组中的cAMP水平。环磷腺苷衍生物二丁酰环磷腺苷（10^(-3)摩尔/升）在CLP组中模拟了异丙肾上腺素的作用。这些结果表明，异丙肾上腺素通过激活腺苷酸环化酶系统增加脓毒症性腹膜炎时的膈肌收缩力并加速膈肌疲劳恢复。
