title: Preoperative Sildenafil administration in children undergoing cardiac surgery: a randomized controlled preconditioning study.
abstract: OBJECTIVE
  Sildenafil has strong cardiac preconditioning properties in animal studies and has a safe side-effect profile in children. Therefore, we evaluated the application of Sildenafil preconditioning to reduce myocardial ischaemia/reperfusion injury in children undergoing surgical ventricular septal defect (VSD) closure.
  
  
  METHODS
  This is a randomized, double-blind study. Children (1-17 years) undergoing VSD closure were randomized into three groups: placebo (Control group), preconditioning with 0.06 mg/kg (Sild-L group) and 0.6 mg/kg Sildenafil (Sild-H group).
  
  
  METHODS
  troponin release. CK-MB, Troponin I, inflammatory response (IL-6 and TNF-α), bypass and ventilation weaning times, inotropy score and echocardiographic function were assessed. Data expressed as median (range), and a value of P < 0.05 was considered significant.
  
  
  RESULTS
  Thirty-nine patients were studied (13/group). Aortic cross-clamp time was similar [27 (18-85) and 27 (12-39) min] in the Control and Sild-L groups, respectively, but significantly longer [39 (20-96) min] in the Sild-H group when compared with the Control group. Area under the curve of CK-MB release was 1105 (620-1855) h ng/ml in the Control group, 1672 (564-2767) h ng/ml in the Sild-L group and was significantly higher in the Sild-H group [1695 (1252-3377) h ng/ml] when compared with the Control group. There were no significant differences in inflammatory response markers, cardiopulmonary bypass and ventilation weaning times, inotropy scores and echocardiographic function between the groups.
  
  
  CONCLUSIONS
  In this small study, Sildenafil failed to reduce myocardial injury in children undergoing cardiac surgery, nor does it alter cardiac function, inotropic needs or postoperative course. A subclinical increase in cardiac enzyme release after Sildenafil preconditioning cannot be excluded.
  
  
  BACKGROUND
  CTRI/2014/03/004468.
authors.affiliation: Department of Pediatric Cardiology, Narayana Institute of Cardiac Sciences, Bangalore, India.
authors.forename: Varsha
authors.initials: V
authors.lastname: Walavalkar
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, Maastricht, Netherlands.
authors.forename: Egmond
authors.initials: E
authors.lastname: Evers
authors.affiliation: Department of Pediatric Cardiology, Narayana Institute of Cardiac Sciences, Bangalore, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Pujar
authors.affiliation: Department of Pediatric Cardiology, Narayana Institute of Cardiac Sciences, Bangalore, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Viralam
authors.affiliation: Department of Pediatric Cardiology, Narayana Institute of Cardiac Sciences, Bangalore, India.
authors.forename: Shreesha
authors.initials: S
authors.lastname: Maiya
authors.affiliation: Department of Pediatric Cardiology, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, Maastricht, Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Frerich
authors.affiliation: Department of Pediatric Cardiac Surgery, Narayana Institute of Cardiac Sciences, Bangalore, India.
authors.forename: Colin
authors.initials: C
authors.lastname: John
authors.affiliation: Department of Pediatric Cardiac Surgery, Narayana Institute of Cardiac Sciences, Bangalore, India.
authors.forename: Shekhar
authors.initials: S
authors.lastname: Rao
authors.affiliation: Department of Pediatric Cardiac Surgery, Narayana Institute of Cardiac Sciences, Bangalore, India.
authors.forename: Chinnaswamy
authors.initials: C
authors.lastname: Reddy
authors.affiliation: Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, Maastricht, Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Spronck
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, Maastricht, Netherlands.
authors.forename: Frits W
authors.initials: FW
authors.lastname: Prinzen
authors.affiliation: Department of Pediatric Cardiology, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, Maastricht, Netherlands Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, Maastricht, Netherlands.
authors.forename: Tammo
authors.initials: T
authors.lastname: Delhaas
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, Maastricht, Netherlands Department of Pediatric Cardiology, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, Maastricht, Netherlands ward.vanagt@maastrichtuniversity.nl.
authors.forename: Ward Y
authors.initials: WY
authors.lastname: Vanagt
mesh_terms: D000293:Adolescent; D001794:Blood Pressure / Q000187:drug effects; D006348:Cardiac Surgical Procedures / Q000009:adverse effects* / Q000379:methods* / Q000401:mortality / Q000706:statistics & numerical data; D002648:Child; D002675:Child, Preschool; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006330:Heart Defects, Congenital / Q000601:surgery; D006801:Humans; D007223:Infant; D019157:Ischemic Preconditioning, Myocardial / Q000009:adverse effects* / Q000379:methods* / Q000401:mortality / Q000706:statistics & numerical data; D008297:Male; D000068677:Sildenafil Citrate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000068677:Sildenafil Citrate
keywords: Cardiac surgery; Cardioprotection; Congenital heart disease; Preconditioning