Experimental study on fasudil for increasing preserving effect on porcine DCD heart induced by ischemia / 重庆医学

ABSTRACT

Objective To evaluate the effects of fasudil on DCD hearts .Methods Sixteen domestic ,mixed‐breed male porcine [mean body weight (28 ± 3)kg] were randomly divide into experiment group and control group (n= 8 in each) .Experiment group :animals were sedated ,anesthetized and paralyzed .Mechanical ventilation with room air was provided .After thoroctomy ,cardiac arrest was established by bloodletting ,and then keeps at room temperature for additional 25 minutes (warm ischemia) .Hearts were perfused via the aortic root with fasudil (0 .1 mg/kg) enriched cold Stanford solution for coronary artery flushing ,rapidly excised and the aorta was cannulated .Hearts were subjected to isolated Langendorff perfusion (retrograde perfused with warm oxygenated autologous blood) afterwards ,and then underwent 20 minutes of equilibrium ,immersed in fasudil (0 .5 mg/kg) enriched cold Stan‐ford solution for 2 hours in situ cold preservation .Finally ,all the hearts were resuscitated with the warm oxygenated autologous blood perfusion .Control group :hearts from the animals experienced the same except for fasudil supplement .Left ventricular per‐formances were evaluated .Coronary blood flow ,myocardial infarction volume ,myocardial water content ,and myocardial enzyme were measured .Myocardial electron microscopic examinations were carried out as well .Results All the hearts from both groups were successfully resuscitated ,fasudil significantly decreased water content ,enzyme leakage (P< 0 .01 each versus control group) , and increased coronary blood flow (P< 0 .01 versus control group) .Left ventricular function were better preserved (P< 0 .01 each versus control group) .All hearts lacked severe necrosis as determined by tetrazolium staining ,myocardial infarction volume were decresed in experiment group (P< 0 .01 each versus control group) .Intracellular components retained various types of organelle in both group ,but still ultrastructural alterations in control group were more distinctive than in experiment group .Conclusion (1) Donor heart arrested by exsanguinations and plus 25 minutes warm ischemia ,could still be resuscitated with satisfactory result ;(2) The addition of fasudil to Stanford solution (before excise of graft ,during the cold preservation) ,might alleviate DCD heart I‐R in‐jury ,improving the effect of DCD heart preservation ,and hopefully ,might be a novel arsenal in clinical DCD heart transplantation in the future .