Acute hemorrhage is associated with a decrease in cardiac function and contractility, increase in heart rate and fall in blood pressure. Decreased myocardial function and contractility have been shown to be caused by generation of free radicals in the ischemic myocardium. These toxic effects can be significantly attenuated by pretreatment of animals with superoxide dismutase and catalase, suggesting the involvement of free radicals in the depression of cardiovascular function. In the present study, the role of ascorbic acid as a free radical scavenger in protection from the deleterious effects of excess blood loss was examined. The study was conducted on healthy mongrel dogs anesthetized with _-chloralose (80mg / kg, intravenous) maintained on artificial ventilation using a respiratory pump. Catheterisation was done to measure arterial blood pressure, left ventricular pressure, cardiac output, cardiac contractility, right atrial pressure and heart rate. All parameters were recorded on a polygraph. Cardiac output was measured by the thermodilution technique. Hemorrhage was induced by withdrawing 40% of estimated total blood volume in steps of 10% each at 10 min intervals. Arterial blood samples were withdrawn at each step for malondialdehyde (MDA) estimation. After inducing 40% hemorrhage, ascorbic acid was given as a bolus injection (70 mg / kg) in one group whereas, the other group received a continuous slow infusion of ascorbic acid (15 mg / min for an hour). After treatment, all the above-mentioned cardiovascular parameters were recorded and MDA estimation was done at 1, 15, 30, 45 and 60 min in both the groups. A fall in all the cardiovascular parameters was observed on hemorrhage. MDA rose from the basal level of 2.56 ± 0.7 nmol / dl to 3.3 ± 1.0 nmol / dl (p<0.05). Immediately after treatment, MDA level fell to 0.76 ± 0.03 nmol / min. This transient rise in MDA level observed at 40% blood loss suggests involvement of free radicals in the pathogenesis of the consequences of hemorrhage. Administration of ascorbic acid resulted in the recovery of hemodynamic parameters, which were adversely influenced by the induction of hemorrhage. Our results demonstrate the involvement of oxidants in hemorrhage-induced cardiovascular depression and cardioprotection by ascorbic acid, an antioxidant. The restoration of cardiovascular parameters towards normalcy by ascorbic acid was largely due to its antioxidant activity with a smaller contribution by the auto regulatory compensatory mechanisms.
Department of Physiology Vallabhbhai Patel Chest Institute, University of Delhi, Delhi-110 007, India.
Publication date: March 1, 2004
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