Dose‐related effects of isoflurane on superior mesenteric vasoconstriction induced by endotoxemia in the rat

Abstract

To investigate the interplay between endotoxin-induced circulatory shock and the cardiovascular effects of different doses of isoflurane, mean aortic pressure (MAP), central venous pressure (CVP), mean pulmonary arterial pressure (MPAP), heart rate (HR), cardiac output and superior mesenteric artery flow (SMAF), were monitored in rats anesthetized with either 1.4% or 2.0% isoflurane in oxygen. Cardiac index (Cl), total peripheral vascular resistance (TPR) and superior mesenteric vascular resistance (SMVR) were derived. During continuous administration of isoflurane, endotoxin (LD90, 40 mg X kg-1 iv) was given after a 30-min baseline period, and data were collected for an additional 2-h period. Sham-challenged (saline) animals served as controls. The response to endotoxin in the systemic circulation showed a decrease in Cl and MAP, while HR and TPR increased. MPAP and CVP were essentially unchanged. There were no significant differences in the systemic circulation variables between endotoxin groups, apart from a more pronounced HR increase during 1.4% isoflurane. Regionally, however, SMAF was lower and SMVR was higher in the 2.0% versus the 1.4% isoflurane group following endotoxin. To conclude, the degree of mesenteric vasoconstriction during endotoxemia was dependent on the dose of isoflurane. This dose-related effect seems to be mediated through interaction with intrinsic vascular control, a higher dose allowing a more pronounced local blood flow reduction.

A synthetic lipopolysaccharide-binding peptide based on the neutrophil-derived protein CAP37 prevents endotoxin-induced responses in conscious rats

“…This particular model of endotoxemia was developed to manifest a hyperdynamic response (increased cardiac output and decreased systemic vascular resistance) similar to the initial stage of shock found in human sepsis and has been the model chosen for other studies of sepsis hemodynamics (1,22). However, we believe that this is the first study to exploit the characteristics of this nonlethal sepsis model in the conscious animal, eliminating depression or alteration of cardiovascular and metabolic function and compensatory responses associated with the use of anesthesia (5,55,56). The hyperdynamic response in this particular conscious-rat model of sepsis is transient, occurring during the first hour, and is immediately followed by a hypodynamic response characterized by decreased cardiac output and stroke volume and increased systemic vascular resistance.…”

“…An effect or the lack of an effect on blood pressure alone is insufficient to make definitive conclusions regarding the cardiovascular system since normal blood pressures can occur in the presence of either high or low cardiac output depending on the status of the vascular system. Other studies using a similar model (1,22) have reported changes in these parameters which may have been due to the influence of anesthesia on the cardiovascular system and the effectiveness of compensatory responses during cardiovascular challenge (5,55,56).…”