Sepsis depresses the metabolic oxygen reserve of the coronary circulation in mature sheep.

Abstract

This study was undertaken to describe the metabolic O2 reserve of the coronary circulation in an awake sheep model of hyperdynamic sepsis. Forty-eight hours after sheep were randomized to either a SHAM group (n = 8) or a cecal ligation and perforation (CLP) group (n = 8), we measured hemodynamics, organ blood flows, and systemic and myocardial O2 metabolism variables at baseline and through four stages of progressive hypoxia. A significant elevation in arterial lactate levels occurred at a higher O2 delivery in the CLP group (527 +/- 55 ml/min/m2) than in the SHAM group (357 +/- 29 ml/min/m2, p < 0.05). The heart's metabolic O2 reserve (difference in circulatory determinants of O2 availability between baseline and where O2 uptake could not be sustained) was exhausted at an O2 content of 56.9 +/- 4.2 ml O2/L in SHAM sheep and 79.6 +/- 7.2 ml O2/L (p < 0.05) in CLP sheep. An increase in coronary blood flow was three times greater in SHAM than in CLP animals. Myocardial O2 extraction increased in hypoxia in SHAM sheep (0.78 +/- 0.03 to 0.88 +/- 0.02, p < 0.05), but not in CLP sheep (0.79 +/- 0.02 to 0.80 +/- 0.04). We conclude that the metabolic O2 reserve of the coronary circulation is depressed in this model of hyperdynamic sepsis as the ability to increase both coronary blood flows and myocardial O2 extraction was significantly limited.

Effect of a Novel Thromboxane A2 Inhibitor on Right Ventricular-Arterial Coupling in Endotoxic Shock

“…The precise mechanism by which homeometric regulation appears to be reduced during endotoxin infusion needs further investigation. There is, however, growing evidence that coronary circulation in sepsis is susceptible to maldistribution of regional blood flow (28) and that myocardial blood flow could be unable to augment in response to higher oxygen demands (29). These abnormalities in cardiac performance are largely attributed to TXA 2 formation (28).…”

Massive Transfusion and Its Influence on Oxygen Transport and Electrolyte Balance

“…Coronary ischemia [32] or the use of a cardiopulmonary bypass [33] diminish the capillary density of the myocardium. Endotoxin also reduces the metabolic oxygen reserve of the myocardium by the same mechanism [34]. This effect is also evident at the mucosa of the gut [35].…”

Staphylococcal α-toxin provokes neutrophil-dependent cardiac dysfunction: role of ICAM-1 and cys-leukotrienes

“…Because LTs apparently do not directly suppress heart muscle contractile function (37), the most reasonable explanation is a maldistribution of regional perfusion caused by the vasoconstrictor potency of the cys-LTs. Such a phenomenon, characterized by the coexistence of under-and overperfused capillaries in close vicinity, has long been considered as a pathogenetic mechanism in septic heart failure (7,12,22). Interestingly, similar abnormalities were also observed in rat hearts undergoing high-dose ␣-toxin challenge, with thromboxane being implicated as the predominantly responsible vasoconstrictor agent under these conditions.…”

“…Cardiodepressant effects of cytokines, predominantly tumor necrosis factor-␣ and interleukin-1␤, have been implicated in the development of cardiac depression in sepsis (26,27). In addition, experimental data suggest that-despite preserved coronary blood flow in sepsis (10)-impairment of coronary vasoregulation and myocardial regional perfusion may also depress cardiac performance (7,13,22,40). Moreover, there is recent experimental evidence that recruitment and activation of polymorphonuclear neutrophils (PMN) may also contribute to the development of septic myocardial failure.…”