Left ventricular performance during continuous endotoxin-induced hyperdynamic endotoxemia in sheep

Abstract

Cardiac function was studied in an unanesthetized ovine model of hyperdynamic endotoxemia. Sixteen sheep were instrumented with ultrasonic crystals on the left ventricle to measure changes in its external diameter, a pressure transducer in the left ventricle, and aortic and Swan-Ganz catheters. The animals received either Escherichia coli endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1; LPS group, n = 10] or an equivalent amount of 0.9% NaCl (sham group, n = 6). Between 1 and 8 h after LPS, a hypodynamic state with low cardiac output ensued (LPS 5.0 +/- 0.2 vs. sham 6.3 +/- 0.4 l.min-1.m-2). During this period, the end-systolic pressure-diameter relationship, a sensitive index of myocardial contractility, was reduced (LPS 10.4 +/- 1.2 vs. sham 17.2 +/- 0.8 mmHg/mm). After this first phase, the sheep developed a persistent hyperdynamic state characterized by a significant increase in cardiac output. By 24 h after LPS administration, the cardiac output was 10.1 +/- 0.5 l.min-1.m-2 (sham 6.3 +/- 0.3). Despite the marked elevation of cardiac output, the end-systolic pressure-diameter relationship had fallen to 8.5 +/- 0.9 mmHg/mm (sham 16.0 +/- 1.2). In a model of hyperdynamic state, an increased cardiac output occurs despite a significant depression in myocardial contractility.

Cardiac and regional haemodynamics, inducible nitric oxide synthase (NOS) activity, and the effects of NOS inhibitors in conscious, endotoxaemic rats

“…Central venous pressure was reduced, consistent with venodilatation (Vallance et al, 1992), and the marked renal hyperaemic vasodilatation was maintained. This picture is of a hyperdynamic circulation, as described recently in LPStreated conscious sheep (Traber et al, 1988;Sugi et al, 1991;Meyer et al, 1992;Weber et al, 1992;Noshima et al, 1993). In those studies, estimates of cardiac function indicated that, in spite of an elevation in cardiac output, there was myocardial depression.…”

“…This approach has been employed successfully in recent studies on the effects of LPS on cardiac haemodynamics in conscious sheep (Traber et al, 1988;Sugi et aL, 1991;Meyer et al, 1992;Weber et al, 1992;Noshima et al, 1993).…”

Cardiac Failure in Transgenic Mice With Myocardial Expression of Tumor Necrosis Factor-α

“…Parillo et al 35 and Reilly et al 36 first identified myocardial depressant substances in the serum of patients with septic shock. Cardiac dysfunction has since been documented in human volunteers given small doses of bacterial endotoxin 37 and in a variety of animal models, including administration of endotoxin to numerous species [38][39][40][41][42][43][44][45][46] ; intravenous administration of TNF to guinea pigs and dogs 20 -23 ; and implantation of intraperitoneal fibrin clots impregnated with Gram-positive or Gram-negative bacteria, endotoxin, or TNF in dogs. [47][48][49] Blockade of TNF activity prevents cardiac dysfunction after LPS challenge or cutane- …”

Systemic pressure-flow reactivity to norepinephrine in rabbits: impact of endotoxin and fluid loading

“…Using the same model, we have shown that, in the absence of fluid resuscitation, nitric oxide donors can induce similar hemodynamic patterns to fluid loading [11,12]. Several studies have shown a low systemic blood flow [11,15,21,22], rather than a high systemic blood flow [1,4,5,16], in septic shock, that might be related to fluid resuscitation [1,22,27]. Considering the pathophysiology of endotoxic shock, it is admitted that endotoxin induces a peripheral vascular hypocontractility [7][8][9][10]18], considerable vasodilation [4,5,7], an altered cardiac function [2][3][4], relative hypovolemia resulting from capillary leak [28,29] and increased resistance to venous return [17].…”

“…Both factors have been shown to be altered during sepsis. Cardiac function [16] and contractility [3] are impaired, together with a reduced venous return in the absence of fluid resuscitation [17]. As a result, in the absence of resuscitation, a decreased systemic flow can be expected after a septic injury.…”