Effects of isoproterenol on diaphragmatic contractility in septic peritonitis

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.