Splanchnic perfusion in ovine sepsis: Effect of modified hemoglobin and L-arginine

Introduction: Modified hemoglobin solutions like pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) are able to reverse the hyperdynanuc circulatory state seen during sepsis. Hemoglobin binds nitric oxide (NO) which is produced in large amounts during sepsis. Splanchnic perfusion is often compromized in sepsis. We investigated the effect of sepsis. PHP and the NO precursor L-arginine on blood How to selected splanchnic organs. Methods: Six sheep were instrumented with arterial, venous, left aerial and pulmonary artery catheters. After 5 days they received an infusion of 6-10⁶ colonyforming units/kg/h Pseudomoneu aeruginosa. After 24 h an infusion with 20 mg/kg/h PHP was begun and continued for the rest of the experiment Four h later. L-arginine was given as a 100 mg/kg bolus followed by a 500 mg/kg/h infusion for 1 h. Fluorencem microspneres for Mood flow détermination were injected at 0, 24, 28, and 29 h. Statistical analysis by ANOVA; p<0.05 was considered significant. Results: shown in the table. Dan are presented as means ±SEM; CI: cardiac index in I/min/m², SVRI: systemic vascular resistance index in dyne sec/cm⁵ m², blood flow in ml/min/g tissue. * p<0.05 vs. Oh, † p<0.05vj.24h, ‡ p<0.05vs. 28h. variable 0 hr 24 hr - sepsis 28 hr - PHP 29 or- arginine CI 5.4±0.2 7.8±0.5* 6.9±0.6 9.310.7‡ SVRI 1588±33 944±102* 1221±104† 865±79‡ pencreas 2.71±0.37 2.35±0.34 1.78±0.33* 2.6910.42‡ ileum 0.76±0.19 0.47±0.09 0.51±0.09 0.67±0.09 colon 0.24±0.03 0.26±0.05 0.25±0.06 0.26±0.03 spleen 1.45±0.36 1.90±0.37 1.72±0.53 2.54±0.73 Discussion: PHP caused vasoconstriction and thus improves hypotension during sepsis. L-arginioe reversed the hemodynamic effect of PHP. Blood flow to the pancreas tended to decrease during sepsis and decreased after PHP. Previous data snowed a reduced pancreatic blood flow already at 24h (Am J Respir Cm Care Med 155. A929, 1997). Blood flow to the ileum tended to decreas during sepsis. Blood flow returned to baseline levels by L-arginine indicating that NO plays a role in regulating blood flow to these organs.