Left ventricular function during lethal and sublethal endotoxemia in swine.

Our previous studies suggested that after a median lethal dose (LD50) of endotoxin, cardiac contractility was depressed in nonsurviving dogs. The canine cardiovascular system is unlike humans in that dogs have a hepatic vein sphincter that is susceptible to adrenergic stimulation capable of raising hepatic and splanchnic venous pressures. We retested the hypothesis that lethality after endotoxin administration is associated with cardiac contractile depression in pigs, because the hepatic circulation in this species is similar to that of humans. We compared cardiac mechanical function of pigs administered a high dose (250 micrograms/kg) or a low dose (100 micrograms/kg) endotoxin by use of the slope of the end-systolic pressure-diameter relationship (ESPDR) as well as other measurements of cardiac performance. In all the pigs administered a high dose, ESPDR demonstrated a marked, time-dependent depression, whereas we observed no significant ESPDR changes after low endotoxin doses. The other cardiodynamic variables were uninterpretable, due to the significant changes in heart rate, end-diastolic diameter (preload), and aortic diastolic pressure (afterload). Plasma myocardial depressant factor activity accumulated in all endotoxin-administered animals, tending to be greater in the high-dose group. In this group, both subendocardial blood flow and global function were depressed, whereas pigs administered the low dose of endotoxin demonstrated slight, but nonsignificant, increases in flow and function. These observations indicate that myocardial contractile depression is associated with a lethal outcome to high doses of endotoxin. One possible mechanism for this loss of contractile function may be a relative hypoperfusion of the subendocardium.

Depression of left ventricular performance during canine splanchnic artery occlusion shock.

We studied canine left ventricular contractile performance following splanchnic artery occlusion (SAO) shock. We evaluated contractile performance by analyzing the left ventricular end systolic pressure-diameter relationship (sigma ES) because we have previously shown that sigma ES is independent of large changes in preload, afterload, and heart rate but sensitive to changes in ventricular contractility. Following release from 2 hours of SAO, seven dogs survived, five expired immediately, and ten expired between 0.5 and 3.5 hours (termed nonsurvivors, [NS]). The NS dogs exhibited slight tachycardia, slight increase in total peripheral resistance, marked decreases in +dP/dt, cardiac output, arterial blood pressure, stroke volume, and stroke work. Ventricular performance (sigma ES) declined with time following SAO release in the nonsurviving dogs; in contrast, surviving animals exhibited an augmentation of sigma ES during SAO and following SAO release. Sham dogs exhibited no time-dependent changes in sigma ES. The dogs that expired immediately following SAO release exhibited a precipitous decline in sigma ES from 43.0 +/- 9.0 to 23.0 +/- 4.8 mm Hg/mm within minutes of SAO release. We analyzed these data by Cox multiple regression analysis to determine the major covariates of survivability. The analysis revealed that sigma ES at the midpoint in time between SAO release and death was best correlated with the survival function. These results suggest that cardiovascular collapse of SAO shock is associated with an early and sustained loss of ventricular contractility.