title: The protective effects of a phosphodiesterase 5 inhibitor, sildenafil, on postresuscitation cardiac dysfunction of cardiac arrest: metabolic evidence from microdialysis.
abstract: BACKGROUND
  Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion injury. The aim of this study was to determine, by obtaining metabolic evidence from microdialysis, if sildenafil could reduce the severity of postresuscitation myocardial dysfunction and lead to cardioprotection through beneficial effects on energy metabolism.
  
  
  METHODS
  Twenty-four male piglets were randomly divided into three groups: sildenafil (n = 8), saline (SA; n = 8) and sham operation (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.
  
  
  RESULTS
  After 8 minutes of untreated VF, the sildenafil group exhibited higher glucose and pyruvate concentrations of ISF and lower lactate and glutamate levels in comparison with the SA group, and these data reached statistical significance (P < 0.05). Advanced cardiac life support was delivered to both groups, with a 24-hour survival rate showing a promising trend in the sildenafil group (7 of 8 versus 3 of 8 survivors, P < 0.05). Compared with the SA group, the sildenafil group had a better outcome in terms of hemodynamic and oxygen metabolism parameters (P < 0.05). 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 and P = 0.02, respectively). Furthermore, 24 hours after ROSC, the sildenafil group had marked elevations in activity of left ventricular Na(+)-K(+)-ATPase and Ca(2+)-ATPase compared with the SA group (P = 0.03, P = 0.04, respectively).
  
  
  CONCLUSIONS
  Sildenafil could reduce the severity of postresuscitation myocardial dysfunction, and it produced better clearance of metabolic waste in the ISF. This work might provide insights into the development of a novel strategy to treat postresuscitation myocardial dysfunction.
authors.affiliation: Department of Emergency Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Chao-yang District, Beijing, 100020, China. zqian604@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Emergency Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Chao-yang District, Beijing, 100020, China. 2000ywei@sina.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Emergency Medicine, Beijing You-yi Hospital, Capital Medical University, 95# Yong-an Road, Xuan-wu District, Beijing, 100050, China. 13520240749@163.com.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Chao-yang District, Beijing, 100020, China. wu007838@sina.com.
authors.forename: Junyuan
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Emergency Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Chao-yang District, Beijing, 100020, China. wmm0327@126.com.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Chao-yang District, Beijing, 100020, China. lcscyyy@163.com.
authors.forename: ChunSheng
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016887:Cardiopulmonary Resuscitation / Q000639:trends*; D006323:Heart Arrest / Q000378:metabolism* / Q000517:prevention & control* / Q000628:therapy; D008297:Male; D008660:Metabolism / Q000187:drug effects / Q000502:physiology; D017551:Microdialysis / Q000639:trends*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013552:Swine
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D000068677:Sildenafil Citrate