Health: Understanding how fever affects heart function

A key regulator of heart cell electrical signals that protects against irregular heart rhythm arising in fever, is described in in a mouse study published in Nature Communications this week. The paper suggests that, in the future, therapies developed to target the protein could be used to help control heart rhythm when body temperature increases.

Fever commonly develops as part of body’s defense system against infection. Although providing a survival benefit, fever may also adversely affect the function of excitable tissues, such as the brain and heart causing seizures or life-threatening changes in heart rhythm (arrhythmia).

Glenn Fishman and colleagues genetically modified mice to lack a specific protein - fibroblast growth factor homologous factor 2 (FHF2) - that is known to modulate the response of excitable cells, such as cardiac muscle, to electrical signals. They find the mutant mice show normal heart rhythm at 37°C, but that increasing their core body temperature by as little as 3°C causes progressive and life-threatening deceleration of heart beats, due to failure of the heart’s electrical conduction system. They show this condition is fully reversible upon return to normal body temperature, or normothermia. The authors identify altered sodium channel inactivation as the mechanism behind this temperature-sensitive block of cardiomyocyte excitation.

They suggest that their data may also provide potential mechanistic connections between fever-induced arrhythmia and fever-induced epilepsy.