Beyond hyperkalemia: β-blocker-induced cardiac arrest for normothermic cardiac operations

Background. Four experimental protocols were carried out to assess the ability of esmolol to induce and maintain reversible cardiac arrest under continuous normothermic (37°C) perfusion. Methods and results. In the first protocol, 8 perfused rat hearts were subjected to 20, 60, 90, and 120 minutes of esmolol arrest, after which positive and negative first derivative of pressure, heart rate, left ventricular developed pressure, and left ventricular end-diastolic pressure were evaluated. Arrest was achieved 45 to 60 seconds after beginning the infusion of esmolol. Mechanical arrest was achieved before electrical arrest. In the second protocol, dose-response curves were obtained using isolated (Langendorff) rat and rabbit (n = 6) hearts. The concentrations of esmolol varied from 0.084 to 6.7 mmol/L and from 0.12 to 1.45 mmol/L in the rat and rabbit heart experiments, respectively. In the third protocol, the effects of 20 minutes of normothermic (37°C) ischemia on the function of isolated rat hearts perfused with esmolol-containing Krebs solution were compared with those using high-potassium (25 mmol/L) Krebs solution. Group A subjects (n = 9) received the ischemic injury after being perfused (and arrested) for 20 minutes with either esmolol or potassium (KCl, 25 mmol/L). Group B subjects (n = 10) received the same ischemic insult before being perfused with either esmolol or potassium. Esmolol-treated hearts showed better recovery than those receiving potassium, in terms of ±dP/dt (p < 0.01), left ventricular systolic pressure (p < 0.01), and left ventricular developed pressure (p < 0.009). Finally, the fourth protocol was done to evaluate the effects of esmolol in a clinically relevant experimental model. Pigs were divided into esmolol (n = 6) and potassium (n = 5) groups and subjected to normothermic cardiopulmonary bypass and a 1-hour period of cardiac arrest. Twenty minutes after stopping infusion of the cardioplegic agents, all animals were weaned off bypass. There were no statistically significant differences between the groups. Conclusions. Esmolol hydrochloride can be used as effectively as potassium for inducing and maintaining predictable and reversible cardiac arrest during normothermic cardiac operations.