Effects of isoproterenol on diaphragmatic contractility in septic peritonitis

We investigated the effects, and the mechanism of the effects, of isoproter enol on diaphragmatic contractility and fatigue in septic peritonitis in vi tro. Ninety-six rats were: divided into two groups of 48. One group (CLP gr oup) was treated with cecal ligation and perforation (CLP) and the other (s ham 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 fati gue was induced by rhythmically stimulating strips to contract at 60/min (2 0 Hz, 0.33-s trains, 1 train/s) over a rf-min period. Force-frequency curve s were determined before and after fatigue. Isoproterenol (10(-9), 10(-8) a nd 10(-7) M), a beta-adrenoceptor agonist, was cumulatively administered to the organ bath. Isoproterenol significantly increased diaphragmatic contra ctility. There were no significant changes in diaphragmatic contractility i n the sham group. Isoproterenol (10(-7) M) significantly accelerated diaphr agmatic recovery of fatigue and increased cAMP levels both in the sham grou p and the CLP group. Propranolol (10(-7) M), a general beta-adrenoceptor bl ocker, 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 diaphrag matic contractility and accelerates diaphragmatic recovery of fatigue in; s eptic peritonitis by activating the adenylate cyclase system.