Clinical & Experimental Cardiology
Open Access

Abstract

Sildenafil Postconditioning in a Rat Model of Ventricular Fibrillation/ Resuscitation

Ward Y Vanagt, Hesam Amin, Arno Brouwers, Chantal C H Pöttgens, Tim G A M Wolfs, Jack P M Cleutjens, Quirine Swennen, Tammo Delhaas and Frits W Prinzen

Objective: To evaluate the multi-organ postconditioning potential of sildenafil during resuscitation. Circulatory arrest/resuscitation induces ischemia/reperfusion (I/R) injury in all organs. I/R injury can be reduced using postconditioning during reperfusion. Sildenafil has proven strong single-organ postconditioning properties.
Methods: Ventricular fibrillation (VF) was induced and left untreated for 6 min in anesthetized adult male Wistar rats. During resuscitation, placebo (n=10) or intravenous sildenafil 0.2 mg/kg (n=10) was administered. Troponin-i release, lactate release, blood gases and hemodynamic parameters were assessed. After 3 h of reperfusion, rats were euthanized; brain and heart were removed for infarct staining with triphenyltetrazolium chloride. Urinary kidney injury molecule (KIM-1) was assessed. Data expressed as median (interquartile range), p<0.05 significant.
Results: Resuscitation/defibrillation resulted in return of spontaneous circulation in all rats. Compared with the sildenafil group, the control group showed higher overall troponin release (Control 50 (32-60) versus Sildenafil 16 (12-42) h·microg/L, p=0.032) and higher left ventricular infarct percentage (Control 19 (16-24) versus Sildenafil 16 (12-18)%, p=0.039). There was no significant difference between the groups with respect to mortality, hemodynamic recovery, cerebral cortex infarct percentage, lactate release, blood gas values and urinary KIM-1 release. Three rats in the sildenafil group developed pulmonary edema versus none in the control group.
Conclusions: Sildenafil postconditioning during resuscitation significantly reduces cardiac injury but does not affect mortality, cerebral and renal injury after resuscitation.