Cardioplegia and cardiac surgery: Pharmacological arrest and cardioprotection during global ischemia and reperfusion

Abstract

Since the start of cardiac surgery in the 1950s, multiple techniques have been used to protect the heart during the surgical requirement for elective global ischemia (and the still, relaxed, bloodless field that this provides the surgeon for repair of the lesion). Most of these techniques have been discarded. The current gold standard, established over 30 years ago, is hyperkalemic (moderately increased extracellular potassium) cardioplegia; this technique revolutionized cardiac surgery, allowing significant surgical advancement with relative safety. Hyperkalemic cardioplegia induces a rapid depolarized arrest that is readily reversible. Recent patient demographic changes, with surgeons operating on older, sicker patients who have more severe and diffuse disease, potentially requires a more prolonged elective ischemia; hence, an improved myocardial protection would be of benefit. Several areas of study have demonstrated that a new concept of myocardial protection—‘polarized’ arrest—may provide this additional protection. Many pharmacological agents have been shown (in experimental studies), to have the ability to induce a polarized arrest and to provide improved protection. However, the often-overlooked requirements of effect reversibility and systemic safety have meant that these agents usually remain experimental in nature. This review attempts to highlight the cellular components that can be targeted, within the excitation–contraction coupling cascade, to induce cardiac arrest, and to provide an explanation for the mechanism of action of these agents. In this context, the agents are discussed in terms of their clinical potential for use during cardiac surgery, with particular reference to the safety aspects of the agents.

Introduction

During cardiac surgery, the majority of surgeons prefer a relaxed, still (non-beating) heart with a blood-free operating field. The easiest way to achieve this is to induce a global ischemia to the heart by cross-clamping the aorta (and thereby preventing coronary artery perfusion), with systemic blood circulation transferred to a heart–lung machine. Although convenient for the surgeon, global ischemia of the heart is detrimental; considerable research has been conducted in exploring ways to reduce the damaging effects of surgically-induced ischemia. It is important to realise that ischemia is a progressive process; as the ischemic duration increases, the cellular and molecular changes become more severe such that, without timely reperfusion, they will eventually lead to cell death. Reversible changes occur over short periods (seconds to a few minutes) of ischemia, with reperfusion resulting in full recovery (albeit potentially prolonged). However, at some unknown point after a longer ischemic duration, the changes lead to an irreversible injury that will not benefit from reperfusion. In fact, ‘reperfusion injury’ can occur that may exacerbate the ischemic injury. Hence, it is important during cardiac surgery to initiate cardioprotective procedures so that any ischemic injury is minimized by extending the period of reversible injury, and delaying the onset of irreversible injury for as long as possible.