CARDIOVASCULAR-RESPONSE TO ACUTE AND CHRONIC ENDOTOXEMIA IN AN AWAKE,VOLUME-RESUSCITATED, CANINE MODEL

The cardiovascular response to endotoxemia was evaluated in an awake, intravascular volume-resuscitated canine model. The animals were chron ically instrumented for ultrasonic crystal dimension analysis and pres sure measurements of the left ventricle (LV), aorta, right atrium (RA) , and pulmonary artery (PA) and for cardiac output (GO) measurement. L ipopolysaccharide (Escherichia coil 011:B4) (LPS) was administered int ravenously either as an acute, high dose bolus (5 mg/kg; n = 5), a hig h dose bolus after complete beta-blockade with propranolol (n = 3), or a chronic, low dose infusion (5 mu g/kg/h; n = 7). Relative to baseli ne values, cardiac contractility was increased after acute high dose L PS bolus, however this effect was negated by beta-blockade. Chronic, l ow dose LPS infusion produced an increase in cardiac contractility at 1 h, a return to baseline by 4 h, and maximal contractile depression b y 24 h. No change was seen in LV compliance after the high dose LPS bo lus. The LV end diastolic volume was decreased by the high dose LPS bo lus. This change was blocked by propranolol administration. Chronic LP S administration was accompanied by a decrease in LV compliance and an increase in LV end diastolic volume. Other cardiovascular indices (he art rate, CO, systemic vascular resistance) changed in a fashion simil ar to human sepsis. These findings confirm that endotoxemia in conscio us canine subjects causes changes in cardiovascular function similar t o that seen in human and animal models of sepsis. This study also allo ws us to explain some of the discrepancies between earlier studies of human sepsis and animal models in which the appropriate clinical condi tions and an intact neuro-endocrine axis were not maintained.