Hemodynamic and Histopathologic Effects of Hydroxyethyl Starch and Superoxide Dismutase Following Splanchnic Arterial Occlusion in a Murine Model

The purpose of this study was to examine biophysical and biochemical approaches that would reduce circulatory collapse produced in a splanchnic artery occlusion (SAO) shock rat model. Sprague-Dawley rats were divided into six groups: (1) control (Ctl) rats-no infusions, n=5; (2) control rats receiving 10 mg/kg superoxide dismutase (SOD), n=7; (3) SAO shock rats-no infusion, n=7; (4) SAO shock rats receiving 1.75 mL of normal saline (Sal), n=7; (5) SAO shock rats receiving 1.75 mL of hydroxyethyl starch (HES), n=7; (6) SAO shock rats receiving SOD, n=7. All animals, except controls, underwent clamping of the celiac and superior mesenteric arteries for fifty minutes. Intravenous heparin (500 units/kg) was administered twenty minutes prior to clamping. Following release of the clamps mean arterial blood pressure (MABP) was monitored for an additional one hundred minutes. Animals whose MABP could not be maintained above 50 mmHg at one hundred minutes after reperfusion was initiated were considered nonsurvivors. Blood chemistries and serum osmolarity were measured at the end of each experiment. HES was conjugated to 10 nm gold particles prior to infusion to allow HES location in electron micrographic (EM) studies. The following results were obtained: Tab Group 1 (Ctl) Group 2 (SAO) Group 3 (Sal) Group 4 (HES) Group 5 (SOD) Final MABP (mmHg) 120±6.14 43.5±3.5 53.3±4.8 79±8.9 51.2±5.0 Osmolarity (mOsm/kg) 304±6.3 309±10.1 306±7.1 311±9.3 306±8.0. The group 4 (HES) MABP was significantly higher than that in groups 2, 3, and 5 (P<.05), but not when compared with that in group 1 (controls). No significant differences were found in serum osmolarity. EM studies showed the HES-gold conjugate localized to the intravascular and interendothelial spaces of capillaries and postcapillary venules as compared with interstitial sites. The authors conclude that HES can maintain MABP at significantly higher levels in an SAO shock rat model, unlike the results following infusions of normal saline or SOD. HES may act as both a capillary sealant and source of oncotic pressure. The lack of efficacy of SOD in this investigation may be due to the severity of the shock model and an inadequate dosing regimen. Further studies are needed to evaluate the rode of pharmacologic agents along with fluid resuscitation and capillary sealants. Their combined use may in fact ultimately prove to be the optimal means to treat SAO shock.