Shen 2013

Reduction of Myocyte Hydrogen Peroxide and Mitochondrial Damage in Rats Following Hemorrhagic Shock and Fluid Resuscitation with Ubiquinol

Qiuhua Shen, PhD, RN, John Hiebert, MD, Thomas Pierce, PhD, Richard L. Clancy, PhD and Janet D. Pierce, DSN, APRN, CCRN, FAAN

School of Nursing, University of Kansas Medical Center, Kansas City, KS

Introduction: Hypoperfusion in hemorrhagic shock induces significant formation of reactive oxygen species (ROS). Traditional fluid resuscitation following hemorrhagic shock contributes to reperfusion injury, causing mitochondrial damage. This study investigated the effects of ubiquinol, a potent antioxidant, on hydrogen peroxide production and mitochondrial damage following hemorrhagic shock and fluid resuscitation.

Hypothesis: Administration of ubiquinol intravenously with fluid resuscitation following hemorrhagic shock decreases hydrogen peroxide production and mitochondrial damage in the heart and diaphragm.

Methods: Hemorrhagic shock in anesthetized male Sprague-Dawley rats was produced by manually withdrawing 40% of the blood volume, resulting in a mean arterial pressure < 50 mmHg for one hour. Following hemorrhagic shock, fluid resuscitation was initiated (the blood removed and lactated Ringer’s, twice volume of blood removed, with or without ubiquinol (1 mg per 100 g of body weight)). Hemodynamics, respiration rate, and body temperature were recorded every 10 minutes for 180 minutes. Hematocrit and hemoglobin were measured at baseline, following hemorrhagic shock, and fluid resuscitation. At the end of the experiments, the rats were euthanized and the diaphragm and heart were removed and processed for analysis. Hydrogen peroxide in the diaphragm was measured by dihydrofluorescein-DA using confocal microscopy. The mitochondrial damage in the diaphragm and heart was assessed by transmission electron microscopy.

Results: No significant differences in blood loss, hemodynamics, hematocrit, and hemoglobin between the animals treated with or without ubiquinol were found. However, hydrogen peroxide production in the diaphragm was significantly less with administration of ubiquinol. The electron microscopy images demonstrated substantial reduction of myocyte mitochondrial damage in the heart and diaphragm from the rats resuscitated with ubiquinol.

Conclusions: Ubiquinol can reduce production of hydrogen peroxide and mitochondrial damage in the heart and diaphragm following hemorrhagic shock and fluid resuscitation.