Elsevier

The Annals of Thoracic Surgery

Volume 75, Issue 2, February 2003, Pages S661-S666
The Annals of Thoracic Surgery

Pathophysiology of ischemic reperfusion injury
Mechanisms and alternative methods of achieving cardiac arrest

Presented at the 3rd International Symposium on Myocardial Protection From Surgical Ischemic-Reperfusion Injury, Asheville, NC, June 2–6, 2002.
https://doi.org/10.1016/S0003-4975(02)04688-XGet rights and content

Abstract

Elective cardiac arrest during surgery can be achieved by inducing depolarization, polarization, or influencing calcium mechanisms. Depolarized arrest, induced by elevating the extracellular potassium concentration, is currently the most commonly used technique. However, injury associated with ionic imbalance involving sodium and calcium overload, together with maintained metabolic processes aimed at correcting these imbalances, have lead to alternatives being sought. “Polarized” arrest, induced by sodium-channel blockers or by agents that activate potassium channels, has been shown to exert equal or superior protection. Similarly, agents that induce calcium desensitization may also prove to enhance protection. These alternative techniques, however, require extensive characterization before introduction into routine clinical use can be recommended.

Section snippets

Hyperkalemia

The most commonly used method for inducing rapid diastolic arrest during cardiac surgery is moderate elevation of the extracellular potassium (K+) concentration (usually within the range of 15 to 40 mmol/L). As the extracellular K+ concentration increases, the resting membrane potential (Em) becomes progressively more depolarized [1] and, at each K+ concentration, a new resting Em is established. As the resting Em depolarizes to approximately −65 mV (at K+ concentrations around 10 mmol/L) the

Polarized arrest

An alternative to inducing arrest by depolarization (with elevated K+ concentrations) is to maintain polarization of the Em, close to the resting Em. Polarized arrest should have a number of advantages; ionic movement (particularly Na+ and Ca2+ ions) should be reduced, because the threshold potential for activation of the ion channels will not be reached and window currents will not be activated. This reduction in ionic imbalance should, in turn, reduce myocardial energy utilization for ion

Hypocalcemia

The absence of extracellular Ca2+ induces cardiac arrest in diastole by inhibiting excitation-contraction coupling [40]. This characteristic was used in early cardioplegic solutions (predominantly from Germany), although accompanying low extracellular Na+ also attenuated the Na+-channel current, thereby maintaining Em close to the resting Em. However, the absence of Ca2+ increased the risk of inducing a “calcium paradox” [41], although traces of contaminant Ca2+, hypothermia and low Na+, or

Comment

The induction of rapid depolarized arrest of the heart in diastole by moderately elevated concentrations of K+ is by far the most widely used technique (possibly because it is the simplest to apply and to remove) for cardiac arrest during cardiac surgery; however, it cannot be used haphazardly, has a number of disadvantages, and is not necessarily the best and most optimally protective. The concept of maintaining arrest by induction of polarization (or hyperpolarization) compared with

Acknowledgements

Some of the studies conducted in the author’s laboratory were funded by the British Heart Foundation.

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