Abstract 2463: Hypercapnic Resuscitation Mitigates Post-resuscitation Left Ventricular Systolic and Diastolic Dysfunction by Ameliorating Myocardial Necrosis and Apoptosis
Background: Myocardial dysfunction is usually encountered in the early post-resuscitation phase and can lead to circulatory failure and early mortality. Hypercapnic reperfusion has been shown to reduce reactive oxygen species (ROS) and improve survival of the ischemic cardiomyocytes. We therefore investigate whether hypercapnic resuscitation mitigates post-resuscitation myocardial dysfunction and improves prognosis.
Methods: Using a rat model of asphyxia cardiac arrest (6 min) and CPR, we employed hypercapnic ventilation (5% CO2, 95% O2) during CPR and the first 2 h post-resuscitation, and compared the cardiac function with that of normocapnia control (5% N2, 95% O2). The arterial blood was sampled regularly for gas analysis and measurement of ROS (chemiluminescence method). The left ventricular (LV) systolic and diastolic functions were assessed by dP/dt max and −dP/dt max using a catheter inserted into LV. Bax, Bcl-2 and cleaved caspase 3 (Asp175) were measured 2 h after CPR. In a subgroup the survival and neurological scores were monitored up to 3 days. Pathological examination of the heart was done on day 3.
Results: In the first 2 h post-CPR, the PaCO2 was significantly higher (P<0.001) and pH lower (P<0.01) in the hypercapnia group. In normocapnia control, the dP/dt max and −dP/dt max were significantly compromised in the first few hours post-resuscitation. Hypercapnic resuscitation significantly improved dP/dt max and −dP/dt max from the beginning of return of spontaneous circulation (P<0.05 and 0.01, respectively). The systemic ROS generation was also lower (P<0.05). On pathological examination, the myocardial necrosis and fibrosis were much less in the hypercapnia group on day 3. Apoptosis was also decreased as suggested by reduced Bax/Bcl-2 ratio and cleaved caspase 3 at 2 h. For prognosis, both survival and neurological outcomes were significantly improved by hypercapnic resuscitation (log-rank P<0.001 and P<0.05, respectively).
Conclusion: Hypercapnic resuscitation during CPR and early post-resuscitation phase mitigates LV systolic and diastolic dysfunctions by decreasing both necrotic and apoptotic cell death. This enhances organ perfusion and reduces ROS generation, which in turn improves survival and neurological outcomes.