Abstract 19945: Acute Alcohol Intoxication and Hemorrhagic Shock Lead to Microvascular Hyperpermeability and Cardiovascular Arrhythmias

Abstract

Background: Binge drinking combined with trauma is a major cause of mortality in US. It is known that acute alcohol intoxication (AAI) causes deleterious electrical changes in the heart, including involving QTc dispersion. We also recently demonstrated that acute alcohol intoxication (AAI) increases microvascular permeability. In the current study we investigated the consequences of combined hemorrhagic shock and resuscitation (HSR) and AAI on both microvascular permeability and cardiac electrical activity. Hypothesis and Methods: We hypothesized that AAI combined with HSR causes microvascular leakage and electrical dysfunction in the heart. We used an established rat model of AAI/HSR to test the microvascular and cardiac effects. Results: We identified that combined AAI/HSR significantly (p<0.0007) prolongs the QTc interval (ms) compared to control water fed, sham rats (190.8±7.1 vs. 138.4±4.4, p<0.05). Ex vivo acquired left ventricular monophasic action potential (AP) data revealed increased AP duration in the AAI/HSR group at 20 (9.7±0.6 vs. 5.5±0.2; p<0.0004 ), 50 (16±1.1 vs. 8.8±0.6; p<0.001), and 70% (24.7±2.4 vs. 19.5±0.5; p<0.03) repolarization level relative to water/sham controls. Microvascular hyperpermeability was apparent in the mesenteric microcirculation in the AAI/HSR group compared to AAI/sham, water/HSR, and water/sham controls (IOI of 1061.7±208 HSR-alcohol vs. 698.4±311 HSR-water, p<0.05; vs. 209.5±42 sham-alcohol, p<0.001; and vs. 62.3±9 sham-water, p<0.001). Conclusions: We report for the first time the cardiovascular hallmarks of AAI/HSR associated injury, which include prolonged QTc and AP durations and elevated microvascular permeability.