Treatment with dipyridamole improves cardiac function and prevent injury in a rat model of hemorrhage

Hemorrhagic shock is a leading cause of death despite the improvement in emergency services. One reason is that the resuscitation policies are designed to reestablish tissue perfusion, but not to prevent the inflammatory response to shock that cause myocardial dysfunction and injury. Dipyridamole is a platelet inhibitor that promotes anti-inflammatory effects. The present study investigated the therapeutic value of treatment with dipyridamole before resuscitation from hemorrhagic shock on myocardial injury and protection. Male Sprague-Dawley rats were assigned to 3 experimental groups (n = 6 per group): 1) hemorrhage, 2) hemorrhage treated with dipyridamole, and 3) sham hemorrhage. Rats were hemorrhaged over 60 min to reach a mean arterial blood pressure of 40 mm Hg. After 60 min hemorrhagic shock, rats were treated or not by injection of 1 mL of (20 μg/L) dipyridamole intra-arterially. Resuscitation was made in vivo by reinfusion of the shed blood to restore norm tension for 30 min. Arterial blood samples were collected for measurements of TNF-α. Left ventricular generated pressure and + dP/dtmax was significantly higher in dipyridamole treated rats compared to the untreated group. Myocardial biopsy samples were taken for light and electron microscopy. Dipyridamole decreased the number of inflammatory cells and mitochondrial swollen. Dipyridamole also decreased the plasma levels of TNF-α. Our results demonstrate that treatment with dipyridamole before in vivo resuscitation of hemorrhagic shock protect the myocardium against post-resuscitation myocardial dysfunction by decreasing the inflammatory response to shock.