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

^a Department of Surgical Sciences, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway
^b Institute of Medicine, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway
^c Section of Cardiothoracic Surgery, Department of Heart Disease, Haukeland University Hospital, N-5021 Bergen, Norway

Received 5 June 2007; received in revised form 13 October 2007; accepted 16 October 2007.

^_* Corresponding author. Address: Department of Surgical Sciences, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway. Tel.: +47 55976718; fax: +47 55972120. (Email: tfan{at}online.no).

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 β-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^–1 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 ± 12.7 mmHg (SD) in controls and 72.7 ± 11.1 mmHg in esmolol-treated animals. In controls PRSW_slope decreased to 62.1 ± 11.0 and 58.4 ± 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 ± 11.4 and 73.7 ± 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 ± 0.86 and 2.51 ± 0.96 mmHg ml^–1 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.

Key Words: Animal model • Cardiac function • Cardioplegia • Cardiopulmonary bypass • Esmolol