Differential subendocardial perfusion and injury during the course of gram-negative endotoxemia.

This laboratory has been investigating the concept that a progressive state of global myocardial ischemia is a major precipitating factor in the etiology of the myocardial failure in endotoxin shock. To further test this hypothesis, endotoxin shock (E coli, B5, 4 mg/kg) was induced in the canine model, and coronary and systemic hemodynamics were monitored for five hours. Coronary flow decreased from 90.05 +/- 28 ml/min/100 gm left ventricle (n = 7) to 45 +/- 10 at five hours (n = 6), with two experimental deaths between four and five hours. Coronary vascular resistance increased from 61.82 +/- 2.5 X 10(3) dynes . sec . cm-5 to 128.6 X 10(3) +/- 18 X 10(3) dynes . sec . cm-5. Sham controls (n = 7) demonstrated no significant difference in either flow or resistance between zero to five hours. Gross examination of the shocked hearts demonstrated patchy to diffuse subendocardial hemorrhage not present in the sham preparations. Thioflavin S injection (4%, 1 ml/kg) demonstrated uniform perfusion under UV light (360 nm) in the sham preparations and marked nonuniform perfusion in the subendocardial surface of the shocked hearts. Histologic examination demonstrated diffuse intramyocardial hemorrhage, more marked in the subendocardium than the midmyocardium. Electron micrographs demonstrated swelling and distortion of the subendocardial sarcoplasmic reticulum and T-tubules and dehiscence of the myofibrils. It is concluded that the decrease in flow and concomitant increase in intramyocardial resistance progresses to a state of global ischemia and ischemic necrosis at the more vulnerable subendocardial surface.