Cardiogenic endotoxin shock: coronary flow and contractile protein dysfunction as determinants of depressed cardiac contractility.

Cardiogenic endotoxin shock (ES) refers to the intermediate and latter stages of ES characterized by a progressive myocardial dysfunction. This laboratory has been developing the hypothesis that a major etiology of this observed myocardial failure is a progressive state of global ischemia. In order to further test this hypothesis, ES (E coli, Difco Labs, 026:B6, 4 mg/kg) was induced in the canine model (n = 6) and coronary flow, myocardial contractility (dP/dtmax), and systemic hemodynamics were continuously monitored for five hours, following which the cardiac contractile proteins were isolated and characterized. In the ES group, control coronary flow (CF) = 90.5 +/- 3.6 ml/min/100 gm LV, coronary vascular resistance (CVR) = 61.82 X 10(3) +/- 2.28 X 10(3) dyne . sec. cm--5 and dP/dtmax 2,200 +/- 160 mm Hg/sec. Between four and five hours, CF decreased to 58.6 +/- 16 ml/min/100 gm LV, CVR increased to 128.6 X 10(3) +/- 18 X 10(3) dyne . sec. cm--5, and dP/dtmax decreased to 968 +/- 62 mm Hg/sec. Sham animals (n = 7) demonstrated no significant difference in CF, CVR, or dP/dtmax. Control myofibrillar ATPase activity demonstrated 50% activation (specific activity = 0.072 +/- 0.002 mumoles Pi/mg protein . min) at p Ca++ = 6.4, with no significant difference between endocardium and epicardium. ES myofibrils demonstrated 50% activation (specific activity = 0.060 +/- 0.002 mumoles Pi/mg protein . min endocardial, and 0.068 +/- 0.005 mumoles Pi/mg protein . min epicardial at pCa++ = 6.48 and 6.45, respectively, incriminating a change in affinity for Ca++ binding to the regulatory proteins. Thus, it would appear that the documented decrease in myocardial contractility is due in part to a depression of myofibrillar ATPase activity, which is related to a decrease in coronary flow, an increase in coronary vascular resistance, and a state of global myocardial ischemia.