Myocardial protection: The efficacy of an ultra-short-acting β-blocker, esmolol, as a cardioplegic agent

Abstract

Objective: During myocardial revascularization, some surgeons (particularly in the United Kingdom) use intermittent crossclamping with fibrillation as an alternative to cardioplegia. We recently showed that intermittent crossclamping with fibrillation has an intrinsic protection equivalent to that of cardioplegia. In this study we hypothesized that arrest, rather than fibrillation, during intermittent crossclamping may be beneficial. Because esmolol, an ultra-short-acting β-blocker, is known to attenuate myocardial ischemia-reperfusion injury, we compared the protective effect of esmolol arrest with that of intermittent crossclamping with fibrillation and conventional cardioplegia (St Thomas' Hospital solution). Methods: Isolated rat hearts were Langendorff perfused at either constant flow (14 mL/min) or constant pressure (75 mm Hg) with oxygenated Krebs-Henseleit bicarbonate buffer (37°C), and left ventricular developed pressure was assessed. In study 1 (constant flow perfusion) 8 groups (n = 6 hearts per group) were studied: (1) 40 minutes of global ischemia; (2) 2 minutes of St Thomas' Hospital infusion and 40 minutes of ischemia; (3) multidose (every 10 minutes) infusions of St Thomas' Hospital solution during 40 minutes of ischemia; (4) 2 minutes of esmolol infusion and 40 minutes of ischemia; (5) multidose (every 10 minutes) esmolol infusions during 40 minutes of ischemia; (6) continuous infusion of esmolol for 40 minutes during coronary perfusion; (7) intermittent (4 × 10 minutes) ischemia with ventricular fibrillation; and (8) intermittent (4 × 10 minutes) ischemia preceded by intermittent esmolol administration. All protocols were followed by 60 minutes of reperfusion. Further experiments (study 2) examined the esmolol administration method in hearts perfused by constant pressure. Results: An optimal arresting dose of 1.0 mmol/L esmolol was established. In study 1 recovery of left ventricular developed pressure (expressed as percentage of preischemic value) was 7% ± 4%, 28% ± 8%, 70% ± 5%, 8% ± 1%, 90% ± 4%, 65% ± 3%, 71% ± 5%, and 76% ± 5% in groups 1 to 8, respectively. Intermittent esmolol arrest with global ischemia provided equivalent myocardial protection to intermittent crossclamping with fibrillation, continuous esmolol perfusion, and multidose St Thomas' Hospital solution. Surprisingly, multidose esmolol infusion was more protective than all other treatments. In further experiments (study 2) optimal recovery was obtained with multiple esmolol infusions (by constant flow or constant pressure), but continuous esmolol infusion (at constant flow) was less effective than constant pressure infusion. Conclusions: Intermittent arrest with esmolol did not enhance protection of intermittent crossclamping with fibrillation; however, multiple esmolol infusions during global ischemia provided improved protection. Administration (constant flow or constant pressure) of arresting solutions influenced outcome only during continuous infusion. Multidose esmolol arrest may be a beneficial alternative to intermittent crossclamping with fibrillation or conventional cardioplegia.