The protective effects of a phosphodiesterase 5 inhibitor, sildenafil, on postresuscitation cardiac dysfunction of cardiac arrest: metabolic evidence from microdialysis

Qian Zhang, Wei Yuan, Guoxing Wang, Junyuan Wu, Miaomiao Wang, ChunSheng Li

IntroductionRecent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. The aim of the study was to determine if sildenafil will reduce the severity of post-resuscitation myocardial dysfunction and lead to cardioprotection through the beneficial effects on energy metabolism by obtaining metabolic evidence from microdialysis.MethodsTwenty-four male pigets were randomly divided into three groups, sildenafil (n =8), saline (SA; n =8); and sham operation (SHAM; n =8). Sildenafil pretreatment consisted of 0.5 mg/kg sildenafil, administered once intraperitoneally 30 minutes prior to ventricular fibrillation (VF). The myocardial interstitial fluid (ISF) concentrations of glucose, lactate, pyruvate, glutamate and glycerol were determined by microdialysis before VF. Afterward, the piglets were subjected to 8 minutes of untreated VF followed by 15 minutes of open-chest cardiopulmonary resuscitation. ISF was collected continuously and the experiment was terminated 24 hours after resuscitation.ResultsAfter 8 min of untreated VF, the sidenafil group exhibited higher glucose and pyruvate concentrations of ISF and lower lactate and glutamate levels in comparison with the SA group, and reached statistical significance (P <0.05, respectively). Advanced cardiac life support was delivered to both groups, where 24-hour survival rate expressed a promising trend in the sildenafil group (7/8 versus 3/8 survivors, P <0.05). Compared with the SA group, the sildenafil group had a better outcome in hemodynamic and oxygen metabolism parameters (P <0.05, respectively). Myocardial tissue analysis revealed a dramatic increase in the contents of ATP, ADP and phosphocreatine in the sildenafil group versus the SA group at 24 hours after return of spontaneous circulation (ROSC; P =0.03, P =0.02, P =0.02, respectively). Furthermore, after 24 hours of ROSC, the sildenafil group presented marked elevations of the activities of left ventricle Na+-K+-ATPase and Ca2+-ATPase than in the SA group (P =0.03, P =0.04, respectively).ConclusionsSildenafil could reduce the severity of post-resuscitation myocardial dysfunction and had better clearance of metabolic waste in the ISF. This work might provide insights into the development of a novel strategy to treat post-resuscitation myocardial dysfunction.