Salutary effects of ATP-MgCl2 on the depressed endothelium-dependent relaxation during hyperdynamic sepsis.

Abstract

Studies have shown that endothelium-dependent relaxation (mediated by endothelium-derived nitric oxide) is depressed during the early, hyperdynamic stage of sepsis. Although it is known that ATP-MgCl2 produces beneficial effects following various adverse circulatory conditions, it remains unknown whether this agent attenuates the depressed endothelium-dependent relaxation during early sepsis. The aim of this study, therefore, was to determine whether or not the administration of ATP-MgCl2 early after the onset of sepsis improves or maintains endothelium-dependent relaxation. Prospective, controlled animals study. A university research laboratory. Adult male Sprague-Dawley rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP), followed by administration of 3 mL/100 g body weight normal saline to these and sham-operated rats. At 1 hr after CLP, ATP-MgCl2 (50 micromol/kg body weight) or an equivalent volume of normal saline was infused intravenously over 90 mins. At 5 hrs or 10 hrs after CLP (i.e., the early, hyperdynamic stage of sepsis), the thoracic aorta was isolated, cut into rings, and placed in organ chambers. Norepinephrine was used to preconstrict vessel rings. Dose responses for an endothelium-dependent vasodilator, acetylcholine (ACh, via endothelium-dependent nitric oxide), and an endothelium-independent vasodilator, nitroglycerin, were determined. These results indicate that endothelium-dependent relaxation induced by ACh was significantly depressed at 5 and 10 hrs after CLP. Administration of ATP-MgCl2 after the onset of sepsis, however, maintained ACh-induced vascular relaxation. In contrast, no significant difference in nitroglycerin-induced vascular relaxation as well as norepinephrine-induced contraction was observed, irrespective of administration of ATP-MgCl2. Since administration of ATP-MgCl2 prevents the impaired vascular relaxation to the endothelium-dependent vasodilator ACh, this agent may be a useful adjunct for maintaining endothelial cell function during the hyperdynamic stage of sepsis.