ESCHERICHIA-COLI ENDOTOXIN DEPRESSES LEFT-VENTRICULAR CONTRACTILITY IN NEONATAL LAMBS

We evaluated the effects of Escherichia coli endotoxin on the peripher al vascular hemodynamics and myocardial function of the newborn lamb t o understand how gram-negative endotoxemia can lead to cardiovascular collapse in newborn infants. Fifteen lambs, 0-3 d old, were acutely in strumented with a micromanometer-tipped catheter and two pairs of ultr asonic crystals to measure left ventricular (LV) pressure and LV anter ior-posterior and septal-free wall dimensions, a fluid-filled catheter for monitoring aortic pressure, and an electromagnetic flow probe to measure systemic blood flow. Cardiovascular performance was evaluated by measuring or deriving the following variables: mean arterial blood pressure (MABP), LV pressure, heart rate, stroke volume, systemic vasc ular resistance, LV dp/dt, end-diastolic area, arterial elastance, and end-systolic elastance (the slope of the end-systolic pressure-area r elationship) as an index of contractility independent of loading condi tions and heart rate. Once instrumented, nine lambs received endotoxin , 0.5 mg/kg i.v, and six animals, serving as controls, received a sali ne infusion. Of the endotoxin-treated lambs, five survived the duratio n of the study (I 20 min from the beginning of the endotoxin infusion) , and four died by 90 min from the beginning of the endotoxin infusion . No significant changes in any of the cardiovascular variables occurr ed in the control group. A significant decrease in MABP was seen in al l endotoxin-treated animals by 45 min after the beginning of the endot oxin infusion. MABP decreased by 52% from baseline in the survivors an d 38% in the nonsurvivors. In the survivors, the MABP stabilized with saline boluses, whereas in the nonsurvivors MABP continued to decrease until death. In the survivors, end-systolic elastance remained stable , and, despite changes in afterload, LV dp/dt also remained stable thr oughout the study. In the nonsurvivors, the end-systolic elastance and LV dp/dt exhibited a progressive decline until death, with the change s in the end-systolic elastance preceding the changes in LV dp/dt. End -diastolic area and stroke volume remained stable during the study in both groups of endotoxin-treated animals, decreasing in the nonsurvivo rs just before death. Because the changes in end-systolic elastance an d LV dp/dt clearly preceded the decreases in end-diastolic area and st roke volume in the nonsurvivors, we conclude that the myocardial depre ssion in the nonsurvivors was primarily due to depressed myocardial co ntractility, not decreased preload.