Esmolol before 80min of cardiac arrest with oxygenated cold blood cardioplegia alleviates systolic dysfunction. An experimental study in pigs☆

Abstract

Objective: Myocardial dysfunction after reperfusion can be a clinical problem in the early postoperative phase after on-pump cardiac surgery. The aim was, in an experimental setting, to investigate if administration of the b-adrenergic receptor blocker esmolol prior to cross-clamping for 80 min with cold oxygenated blood cardioplegia would improve myocardial protection and early postoperative function. Methods: Twenty-four anaesthetised pigs were randomly allocated into one of two equally sized groups and put on mild hypothermic cardiopulmonary bypass. Esmolol 1 mg kg À1 or saline was administered into the arterial line 4 min prior to aortic cross-clamp. Cardiac arrest during 80 min of cross-clamp was obtained with repeated antegrade cold oxygenated blood cardioplegia; the pigs were weaned from bypass following a standardised protocol. Left ventricular global and regional myocardial function and tissue blood flow were evaluated with conductance catheter, echocardiography and coloured microspheres at baseline and at 1, 2 and 3 h after declamping. Four animals did not fulfil the protocol and were excluded. Results: No significant differences between groups could be demonstrated for left ventricular global and local function and tissue blood flow at baseline. At 1 h after declamping the slope of preload recruitable stroke work (PRSW slope ) averaged 73.7 AE 12.7 mmHg (SD) in controls and 72.7 AE 11.1 mmHg in esmolol-treated animals. In controls PRSW slope decreased to 62.1 AE 11.0 and 58.4 AE 12.7 mmHg after 2 and 3 h, respectively ( p < 0.005 vs 1 h for both). In the esmolol-treated animals PRSW slope remained unchanged at 72.0 AE 11.4 and 73.7 AE 12.9 mmHg at 2 and 3 h after declamp and were significantly higher ( p < 0.025 and <0.001) than the corresponding values in the control group. The slope of the end systolic pressure volume relationship did not differ between groups at 1 and 2 h after declamp, but were 1.85 AE 0.86 and 2.51 AE 0.96 mmHg ml À1 in controls and in esmolol-treated animals, respectively, after 3 h ( p < 0.025). Conclusions: Esmolol administered prior to cold oxygenated cardioplegic arrest alleviates left ventricular dysfunction in the early hours after cardiopulmonary bypass. #

Myocardial protection with prophylactic oral metoprolol during coronary artery bypass grafting surgery: evaluation by troponin I

“…The mechanisms of myocardial protection of beta-blockers in CABG are not yet fully understood. Animal experiments suggest that beta-blockade is cardioprotective during reperfusion, either by reduction in infarct size, improvement of ventricular function, reduction in apoptosis or decrease of myocardial edema [ 9 , 10 ] . The possible mechanisms involved in this protection include reducing the release of oxygen free radicals and adhesion to endothelium nuclear polymorphs (major source of inflammatory response) [ 11 ] .…”

Novel cardioprotection strategies for the aged heart: evidence from pre‐clinical studies

“…Others have investigated the potential for beta‐blockers to enhance the efficacy of cardioplegia, based on evidence that these agents are beneficial in ischaemic heart disease . There has been particular interest in the beta‐blocker esmolol, as its short elimination half‐life (9 mins) would minimize prolonged negative inotropic effects expected with conventional beta‐blockers . Indeed, arrest with esmolol alone has been shown experimentally to protect from damage induced by cardioplegia and esmolol pre‐treatment improves outcomes in the pig cardiopulmonary bypass model .…”

“…53 Indeed, arrest with esmolol alone has been shown experimentally to protect from damage induced by cardioplegia 54,55 and esmolol pre-treatment improves outcomes in the pig cardiopulmonary bypass model. 53 A more recent study has shown that use of a blood-based cardioplegic solution supplemented with esmolol improves both pre-load recruitable stroke work and the cardiac index in a pig bypass model compared to cardioplegia alone (Table 3). 56 Thus, beta-blockers appear to enhance recovery of function following cardioplegia.…”

Effect of short-acting beta blocker on the cardiac recovery after cardiopulmonary bypass

“…Also, cardioplegia contained esmolol, an ultra-short acting (9-minute half-life) cardioselective beta blocker [3], has cardioprotection in animal model and clinical patients [4-7]. However few studies have investigated beta-adrenergic antagonist on the details of the cardiac recovery and rhythm during CPB.…”