Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass in piglets

Abstract

BackgroundSurgery under cardiopulmonary bypass (CPB) is still associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully understood. Abnormalities in coronary flow and function have been suggested to play an important role. Prior studies suggest protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A before CPB.MethodsBarrier-bred piglets (10–12 kg, n=20) underwent CPB for 45 min, with or without antegrade administration of cardioplegic solution. Prior to CPB, half of the animals in each group received an i.v. infusion of 100 mg/kg cyclosporine A. The left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, before and 8 hours after surgery. Plasma C-reactive protein (CRP) and fibrinogen were measured at both time-points.ResultsCyclosporine infusion did not influence any of the studied variables (p>0.4). Coronary peak flow velocity (cPFV) rose significantly after surgery especially in the cardioplegia group (p<0.01 vs. non-cardioplegia group and pre-surgery). cPFV responses to adenosine, but not to serotonin, tended to decrease (p=0.06) after surgery only in cardioplegia group (p=0.06; p=0.8 in non-cardioplegia group vs pre-surgery). Also, cPFV response to atrial pacing was lower in the cardioplegia than in the non-cardioplegia group (p=0.02). Neither vulnerability nor duration of induced Afib after CPB differed between groups (Chi-square p=0.4). Cyclosporine had no significant effect on coronary indexes or arrhythmia vulnerability (p>0.4). There was no difference in systolic myocardial function between groups at any time point.ConclusionIn piglets, CPB with cardioplegia was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, preconditioning with cyclosporine had no detectable protective effect on coronary circulation or arrhythmia vulnerability after CPB.

Review findings included diminished coronary flow reserve after surgery in children with congenital heart disease and inflammation

“…In an experimental study with piglets, coronary peak flow velocity rose significantly after surgery in the cardioplegia group (p < 0.01) vs presurgery and the noncardioplegia group. Coronary peak flow responses to adenosine, but not to serotonin, tended to decrease in the cardioplegia group (p = 0.06) . Another study reported that coronary blood flow increased immediately after cardiopulmonary bypass surgery .…”

The inflammatory state provokes sexual dimorphism in left ventricular and electrocardiographic effects of chronic cyclosporine in rats

“…Previous reports showed that CSA administration over 7 weeks produced signs of cardiac ischemia such as QTc prolongation and increases in T wave amplitude 4 . Nevertheless, the ischemic and arrhythmogenic effects of CSA vary widely and depend on the dose employed and animal species to which it is administered 22 . The ECG recordings collected from the current study provide several observations that reinforce the male specificity of the cardiotoxic effect of CSA.…”

Relevance and Recommendations for the Application of Cardioplegic Solutions in Cardiopulmonary Bypass Surgery in Pigs

“…The neutrophil elastase inhibitor sivelestat reduced neutrophilic activation in the lungs and improved oxygenation after CPB in 7 to 14-week-old pigs [ 53 ]. The pediatric pig models investigated short-lasting ischemic periods of 10–45 min [ 54 , 55 ] as well as longer ischemic periods of 60–120 min ( Supplementary Table S2 ). The on-pump and off-pump reperfusion periods ranged from 10 to 120 min and 30 min to 48 h, respectively.…”