The pathophysiology of septic shock: changes in hemodynamics in rats following live E coli injection. An application of the thermodilution method for measurement of cardiac output.

Abstract

Fifteen anesthetized rats, 273 +/- 9 gm (SEM), were monitored hemodynamically for six hours following an IV injection of a sublethal (4--5) X 10(8) organisms/100 gm body wt, n = 5) or lethal 12--15 X 10(8) organisms/100 gm body wt, n = 5) dose of live Escherichia coli or saline (control, n = 5). A transpulmonary thermodilution method was used for measurement of cardiac output. Changes in the arterial blood temperature and pressure were recorded on a polygraph. In a simulated hydraulic model system, the measured flow rate was well correlated ( r = 0.993, P less than 0.001) with various actual flow readings (30--130 ml/minute). A sublethal dose resulted in a transient hyperdynamic state in the early stage; the cardiac index was increased from the initial rate of 258.2 +/- 9.4 to 312.3 +/- 10.7 ml/minute/kg with a concomitant decrease in the total peripheral resistance from 0.497 +/- 0.019 to 0.367 +/- 0.022 mm Hg/ml/minute/kg which was sustained for 120 minutes after treatment. In contrast, a lethal dose caused a prolonged hyperdynamic state in the early stage followed by a hypodynamic state in the late stage. The cardiac index was increased from 2.54 +/- 4.5 to 306.0 +/- 10.8 ml/minute/kg and the total peripheral resistance was decreased from 0.513 +/- 0.024 to 0.337 +/- 0.015 mm Hg/ml/minute/kg in the early stage, while, in the late stage, the former decreased to 195.0 +/- 13.3 ml/minute/Kg and the latter increased to 0.615 +/0 0.054 m Hg/ml/minute/kg. The mean arterial blood pressure was decreased in both groups in the early stage but maintained above 100 mm Hg. Essentially, no hemodynamic changes were noted in the control group. These results confirm our hypothesis that an injection of live E coli can produce a hyperdynamic state in the early stage as well as hypodynamic state in the late stage, and that serial hemodynamic studies on bacteremia in rats can be done successfully using the thermodilution method.