Isolated cardiac preparations: models of intrinsic myocardial dysfunction in circulatory shock

Isolated cardiac preparations have been adapted for modeling intrinsic myocardial responses to circulatory shock syndromes independently of immediate influence from depressive or supportive constraints operative in the intact host. Left atrial and left ventricular (LV) papillary muscles and coronary-perfused hearts were removed from guinea pigs during development of Escherichia coli endotoxin shock. Preparations were then subjected to a battery of functional analyses under conditions of constant perfusate pH, pO2, pCO2, electrolyte and substrate concentrations, osmolality, and temperature. Evidence for contractile depression intrinsic to the myocardium itself was a consistent and reproducible finding in all three tissue models. The LV mechanical disadvantage of shock hearts was not correlated with changes in cardiac cycle length (beating frequency), active state duration (contraction-relaxation intervals), or tissue water content; neither was it surmounted by maximally effective increments in coronary flow, [Ca2+]o, or diastolic fiber length. Taken in concert, studies to date suggest that gram-negative endotoxin leads in some way to a reduction of intrinsic contractile reserves of the myocardium, and we have postulated that this change underlies the circulatory shock phase of endotoxicosis. The experimental approach embodied in these models may yield unique cardiodynamic interpretations that will allow the formulation of testable hypotheses about the pathogenesis and prevention of intrinsic cardiac complications of endotoxin and related shock forms.