Diaspirin cross-linked hemoglobin improves mucosal perfusion in the ileum of septic rats

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Abstract
To determine the effect of a bolus infusion of diaspirin cross-linked hemoglobin (DCLHb or hemoglobin crosfumaril) on the ileal mucosal microcirculation in septic rats. Prospective, randomized, single-blinded study. University-affiliated animal research laboratory. Twenty-four male Sprague-Dawley rats, weighing 320-380 g. Under inhalational anesthesia, arterial and venous catheters were inserted and sepsis was created by cecal ligation and perforation (CLP). Twenty-four hours later, animals were reanesthetized and ventilated. Via midline abdominal incision, the ileum was mobilized and prepared for intravital microscopy. Post-CLP hemodynamic values were obtained, and videomicroscopy was performed on four to ten villi. Animals were then randomized to receive 2 mL of DCLHb solution (100 mg/mL; n = 12) or pentastarch (n = 12) intravenously, and measurements were repeated after 20 mins. Rats treated with DCLHb then received nitroprusside to restore mean arterial pressure to post-CLP levels, and final measurements were obtained 15 mins later. Cardiac index increased with both treatments (p < .001), whereas systemic vascular resistance index and mean arterial blood pressure were augmented only with DCLHb (p < .0001 compared with pentastarch). Intercapillary areas (ICA; inversely related to capillary density) were determined using computerized image analysis. ICA size decreased after treatment, from 974 +/- 79 to 791 +/- 106 microm2 with DCLHb and from 1044 +/- 90 to 840 +/- 82 microm2 with pentastarch (both p < .05). Red blood cell velocity in terminal arterioles, as assessed by velocimetry from the recorded images, increased by 15% with both treatments (p < .05). Restoration of mean arterial pressure to post-CLP levels in DCLHb animals by nitroprusside infusion abolished the effects of the hemoglobin solution on ICA size and red blood cell velocity. Both DCLHb and pentastarch infusion improved microcirculatory perfusion in the ileum of septic rats. In addition, DCLHb also exhibited vasopressor properties, which in combination with improved perfusion may be particularly useful in the treatment of sepsis.