Cardiopulmonary bypass alters vasomotor regulation of the skeletal muscle microcirculation.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with alterations in the regulation of organ perfusion and vascular permeability. The purpose of this study was to examine the effects of hypothermic CPB on the regulation of the skeletal muscle microcirculation and the modulating influence of the priming solution.
METHODS: Sheep were placed on hypothermic CPB with a prime of either Pentastarch hydroxylethyl starch (HS) solution (n = 7), a solution in which HS is conjugated with deferoxamine (n = 7), or Ringer's lactate solution (n = 7). Sheep were placed on hypothermic CPB (27 degrees C) for 90 minutes while the heart was protected with cold blood cardioplegia. Sheep were then separated from CPB and perfused for an additional 3 hours off CPB. Hemodynamics and total water content were measured.
RESULTS: In vitro relaxation responses of gracilis muscle arterioles (70 to 180 microns) to the endothelium-dependent agent acetylcholine, the endothelium-independent cyclic GMP-mediated vasodilator sodium nitroprusside, the beta-adrenergic agonist isoproterenol, and the adenylate cyclase activator forskolin were studied. No statistically significant hemodynamic differences were observed between groups. However, weight gain was significantly less when the priming solution was HS or HS-deferoxamine compared to when Ringer's lactate was used. Skeletal muscle arteriolar relaxations to the endothelium-dependent vasodilator acetylcholine and the beta-adrenergic agonist isoproterenol were impaired after CPB in the HS and Ringer's lactate groups. Acetylcholine response was preserved in the HS-deferoxamine group, whereas the response to isoproterenol remained impaired. The responses to sodium nitroprusside and forskolin were similar in all groups.
CONCLUSIONS: Skeletal muscle microvascular endothelium-dependent relaxation and beta-adrenergic relaxation are reduced after CPB using either a crystalloid or HS prime. Skeletal muscle microvascular endothelial dysfunction may be attributable to oxygen-derived free radical-mediated injury, whereas altered beta-adrenergic regulation is attributable to mechanisms other than the generation of oxygen-derived free radicals during CPB.