How does body temperature affect normal action potential duration (APD) in cardiac cells?

Effect of Temperature on Cardiac Action Potential Duration

Body temperature significantly affects cardiac action potential duration (APD), with lower temperatures prolonging APD and higher temperatures shortening it. This relationship has important clinical implications, particularly in the context of targeted temperature management (TTM) for post-cardiac arrest care.

Physiological Effects of Temperature on Cardiac Electrophysiology

• Temperature directly influences cardiac cellular electrophysiology through control over ion channel gating mechanisms, with lower temperatures prolonging action potential duration 1
• For each degree Celsius decrease in body temperature, cerebral metabolism decreases by approximately 7%, which has protective effects on neurological function during cardiac events 2
• As temperature decreases, there is a significant prolongation of cardiac action potential duration and refractory period due to delayed repolarization 3
• Hypothermia causes a reduction in resting membrane potential and slows myocardial conduction, reflected by widening of the QRS complex on ECG 3
• The QT interval on ECG increases during hypothermia, reflecting the prolonged action potential duration 3

Temperature-Specific Effects on APD

• Even small temperature changes of 1-2°C can cause significant changes in action potential duration, creating potential for arrhythmogenic dispersion of repolarization 3
• At 37°C (normal body temperature), action potential duration is shorter compared to lower temperatures 4
• At 27°C, the magnitude of APD prolongation is significantly greater than at 37°C, with studies showing a difference of 143±21 ms versus 18±6 ms when comparing different pacing cycle lengths 4
• Moderate hypothermia (33°C) produces less spatially discordant alternans compared to severe hypothermia (30°C), making it safer for therapeutic use 5

Clinical Applications in Targeted Temperature Management (TTM)

• Current guidelines recommend maintaining a constant target temperature between 32°C and 36°C for comatose patients after cardiac arrest 6
• The 2024 American Heart Association guidelines state that there is no benefit in selecting a higher versus lower temperature target within the recommended range 6
• TTM is strongly recommended for adults after out-of-hospital cardiac arrest with initial shockable rhythm who remain unresponsive after return of spontaneous circulation (ROSC) 6
• For non-shockable rhythms and in-hospital cardiac arrests, TTM is suggested but with a weaker recommendation 6
• If TTM is used, duration should be at least 24 hours, as done in the largest clinical trials 6

Mechanisms of Temperature Effects on APD

• Hypothermia slows the rate of depolarization of the action potential, contributing to reduced conduction velocity 3
• Cold temperatures affect the kinetics of multiple ion channels, with particularly pronounced effects on repolarization currents 1
• Different regions of the heart respond heterogeneously to temperature changes, which can create a substrate for arrhythmias during non-uniform cooling or rewarming 1
• Mathematical modeling has demonstrated that coupling bioheat equations with cardiac electrophysiology models can predict the effects of temperature on cardiac action potential 7

Clinical Implications and Considerations

• Nonuniform cooling or rewarming of the heart may cause significant dispersion of conduction, action potential duration, and refractoriness in the myocardium, potentially creating a substrate for reentry arrhythmias 3
• Moderate hypothermia (33°C) decreases susceptibility to pacing-induced ventricular fibrillation compared to severe hypothermia (30°C) by attenuating spatially discordant alternans 5
• For patients with cardiomyopathy, extreme cold exposure initially increases sympathetic tone, followed by depression of cardiac activity as temperature decreases further 8
• Temperature affects respiratory rate, which in turn influences CO2 levels and acid-base balance, potentially impacting cardiac function 9

In conclusion, understanding the relationship between temperature and cardiac action potential duration is crucial for optimizing therapeutic approaches in cardiac care, particularly in post-arrest management where targeted temperature management has become standard practice.