Effects of isoproterenol on myocardial structure and function in septic rats

In this study we sought to determine the effect of sepsis on two sequelae o f prolonged (24-h) beta-agonist administration, myocardial hypertrophy and catecholamine-induce cardiotoxicity. Sprague-Dawley rats were randomized to cecal ligation and perforation (C-LP) or sham study groups and then furthe r randomized to receive isoproterenol (2.4 mg kg(-1).day(-1). iv) or placeb o treatment. At 24 h, myocardial function was assessed by using the Langend orff isolated-heart technique or the heart processed for plain light micros copy. We found that 1) sepsis reduced contractile function, indicated by a rightward shift in the Starling curve (ANOVA with repeated measures, sepsis effect, P < 0.002); 2) sepsis-induced myocardial depression was reversed b y isoproterenol treatment (isoproterenol effect, P < 0.0001); 3) sepsis red uced, but did not block, isoproterenol-induced myocardial hypertrophy (isop roterenol effect, P < 0.0001); 4) sepsis did not protect the heart from cat echolamine-induced tissue injury; 5) the septic heart was protected against the effects of ischemia-reperfusion (decreased postreperfusion resting ten sion, ANOVA with repeated measures, P < 0.01), an effect attenuated by isop roterenol treatment (P < 0.005); and 6) sepsis reduced the incidence of sus tained asystole or ventricular fibrillation after ischemia-reperfusion (P < 0.05), an effect also attenuated by isoproterenol treatment (P < 0.01). We conclude that, in sepsis, beta-agonists induce changes in myocardial weigh t and function consistent with acute myocardial hypertrophy. These changes occur at the expense of significant tissue injury and increased sensitivity to ischemia-reperfusion-induced tissue injury.