Related Experiment Videos
Inhibition of the pacemaker current: a bradycardic therapy for off-pump coronary operations
1Department of Cardiovascular Surgery and INSERM U-127, Hôpital Lariboisière, Paris, France.
Insights
Pharmacological myocardial immobilization via pacemaker current inhibition effectively induces bradycardia for coronary anastomosis without compromising cardiac function or flow. This method offers superior results compared to potassium arrest, beta-blockade, or adenosine triphosphate-dependent potassium channel activation.
Area of Science:
- Cardiovascular Surgery
- Pharmacology
- Cardiac Electrophysiology
Background:
- Myocardial immobilization is crucial for accurate coronary anastomosis on a beating heart.
- Pharmacological agents are used to induce bradycardia, but optimal choices for off-pump surgery remain unclear.
Purpose of the Study:
- To determine the most effective pharmacological approach for inducing bradycardia during off-pump coronary artery bypass surgery.
- To compare the efficacy and safety of different drug classes in immobilizing the myocardium.
Main Methods:
- Fifty-six rabbit hearts underwent perfusion and were divided into seven groups.
- Tested interventions included potassium arrest, esmolol (beta-blockade), nicorandil (KATP channel opener), and S 16257-2 (pacemaker current inhibitor).
- Hemodynamic parameters and coronary flow were assessed during and after drug infusion.
Main Results:
- Potassium arrest resulted in the poorest functional recovery.
- Esmolol and nicorandil failed to induce significant bradycardia; esmolol impaired cardiac function.
- Pacemaker current inhibition (S 16257-2) achieved significant bradycardia with excellent preservation of cardiac function and coronary flow.
Conclusions:
- Inhibition of the pacemaker current is a highly effective strategy for intraoperative bradycardia.
- This approach successfully immobilizes the myocardium without adverse effects on left ventricular function or coronary blood flow.
Background:
The accurate performance of coronary anastomoses on the beating heart requires some form of myocardial immobilization that can be achieved pharmacologically. Different classes of drugs can be used to induce bradycardia, but the most effective in this setting of off-pump operation has not yet been determined.
Methods:
Fifty-six isolated buffer-perfused rabbit hearts were divided into seven equal groups. Control hearts were continuously perfused throughout the experimental time course. A second group of hearts underwent 60 minutes of potassium arrest (at 37 degrees C) followed by 1 hour of reperfusion. The following pharmacologic approaches were tested in the remaining five groups: short-acting beta-blockade (esmolol, 6 x 10(-3) mol/L and 3 x 10(-4) mol/L), opening of adenosine triphosphate-dependent potassium channels (nicorandil, 10(-3) mol/L and 10(-5) mol/L), and inhibition of the pacemaker current, which largely accounts for the diastolic depolarization of sinoatrial node cells (S 16257-2, 3 x 10(-6) mol/L). Each drug was infused at a constant rate for 60 minutes, after which hearts were perfused for 1 additional hour with drug-free buffer. Heart rate and isovolumic measurements of function and coronary flow were serially taken during and after drug infusion.
Results:
The worst recovery of systolic and, moreover, diastolic function was yielded by potassium arrest. Neither esmolol nor nicorandil was able to induce a significant bradycardia. However, nicorandil did not impair function which, conversely, was markedly depressed after esmolol therapy. Significant bradycardia (p < 0.0001 versus corresponding baseline values and versus all other groups) was only achieved with pacemaker current inhibition, which was otherwise associated with an excellent preservation of contractility, diastolic function, and coronary flow.
Conclusions:
Inhibition of the pacemaker current seems to be an effective approach for inducing intraoperative bradycardia without compromising left ventricular function or flow.