The influence of sildenafil on myocardial catecholamine level in a swine model of ventricular fibrillation

Abstract

Objective To reveal the changes of catecholamine and lactate levels in myocardial interstitial fluid during cardiopulmonary resuscitation in order to prove the protective effects of sildenafil pretreatment on post-resuscitation myocardial function in swine model of ventricular fibrillation(VF). Methods Twenty-four swine were randomly(random number) divided into three groups: saline group, sildenafil group and shame operation group. Sildenafil in dose of 0.5 mg/kg dissolved in 40 mL of saline was given to swine once intraperitoneally 40 min prior to VF in sildenafil group.The equivalent volume of saline (0.9% NaCl) alone was administered instead in saline groups. There was no treatment in shame operation group. After ventricular fibrillation untreated for 8 min, open-chest cardiopulmonary resuscitation was initiated. The hemodynamic variables were recorded at baseline, 4 min, 1 h and 6 h after restoration of spontaneous circulation(ROSC). The interstitial fluid from the left ventricle wall was collected by using the microdialysis tubes at given intervals, in which the levels of dopamine, norepinephrine, epinephrine, and lactate were measured. The samples for pathological examination were taken at 24 hours after ROSC. Results The levels of catecholamine and lactate in the sildenafil group were lower than those in saline group at all different intervals(P<0.05 or P<0.01). The cumulative defibrillation energy was lower in the sildenafil group than that in the saline group(P<0.05). The hemodynamic changes and myocardial histological damage in sildenafil group were milder than those in saline group(P<0.05). The pathologic changes of myocardium and mitochondria in saline group were more severe than those in sildenafil group. Conclusions Sildenafil pretreatment prior to VF can effectively reduce endogenous catecholamine secretion and lactate levels in myocardial tissue, protecting the myocardium and improving post-resuscitation myocardial function. Key words: Sildenafil; Cardiopulmonary resuscitation; Microdialysis; Catecholamine; Lactate; Hemodynamics