Hemorrhagic‐Shock/Resuscitation‐Induced Microvascular Permeability in the Rat Mesentery is Exacerbated by Acute Alcohol Intoxication

Abstract

Traumatic injury and acute alcohol intoxication (AAI) often are associated, yet little is known about how this combination affects the microcirculation. We tested the hypothesis that AAI exacerbates hemorrhagic shock and resuscitation (HS-R)-induced microvascular leakage. Carotid artery, jugular vein, and indwelling gastric catheters were placed in anesthetized Sprague Dawley rats. Following 2-3 days recovery, conscious, unrestrained rats received 2.5 g/kg alcohol i.g., followed by HS-R (fixed pressure of 40 mm Hg for 1 h, followed by Lactated Ringers (LR), 40% i.v. bolus + 2x total blood removed (TBR) infusion over 1 h). Following HS-R, the rats were anesthetized for intravital microscopy of the mesenteric microcirculation. FITC-Albumin served as a tracer to determine extravasation, quantified by measuring integrated optical intensity (IOI) of the extravascular areas adjacent to postcapillary venules. Alcohol antagonizes the restoration of normal blood pressure during fluid resuscitation. Alcohol increases extravasation of FITC-Albumin compared to sham-water rats (209.5 ± 42 sham-alcohol vs. 62.3 ± 9 sham-water, p<0.001). HS-R also increases hyperpermeability compared to respective shams (698.4 ± 311 HS-R-water vs. 62.3 ± 9 sham-water, p<0.01; and 1061.7 ± 208 HS-R-alcohol vs. 209.5 ± 42 sham-alcohol, p<0.001). HS-R-induced hyperpermeability was significantly higher in alcohol animals compared to water (1061.7 ± 208 HS-R-alcohol vs 698.4 ± 311 HS-R-water, p<0.05). These data show that AAI worsens trauma-induced microvascular hypermeability. Supported by NIH grants R01HL098215 and R21AA020049, and the ABMRF/Foundation for Alcohol Research.