CONTRACTILE DYSFUNCTION OF VENTRICULAR MYOCYTES ISOLATED FROM ENDOTOXEMIC GUINEA-PIGS

Mechanisms responsible for the decline in cardiac function following s epsis or endotoxemia are unclear but may result from indirect effects of cardiodynamic readjustments to diminishing venous return or to dire ct effects of endogenous factors on myocardial function. We examined c ontractile properties of ventricular myocytes isolated from endotoxemi c guinea pig hearts to 1) verify and characterize inotropic dysfunctio n in the absence of immediate influences from extrinsic neurohumoral a gents, and 2) assess the ability of beta-adrenergic receptor activatio n to modulate contractility. Myocytes were isolated by enzymatic dispe rsion from hearts 4 h following an intraperitoneal injection of Escher ichia coli endotoxin. Contractility was assessed using a computer-driv en image analysis system. Inotropic responsiveness of endotoxemic myoc ytes to changes in frequency of stimulation (.2-2.0 Hz) or increases i n extracellular calcium ([Ca2+](o), 1.8-8.0 mM) was significantly less than control myocytes, even with maximally effective frequencies or [ Ca2+](o). These data demonstrate that the endotoxin-induced dysfunctio n is intrinsic to ex vivo cardiac myocytes and independent of immediat e influence from extracardiac factors by 4 h in vivo exposure to endot oxemia. Inotropic responsiveness to beta-adrenergic receptor activatio n remained intact in endotoxemic myocytes; maximally effective concent rations (>10 nM) reversed the endotoxin-induced contractile dysfunctio n. These data confirm that E. coil endotoxemia incorporates intrinsic contractile dysfunction of myocardial cells, while sparing their abili ty to respond to inotropic mechanisms activated by beta-adrenoceptor a gonists.