CHOLIC ACID AND THE HEART: IN VITRO STUDIES OF THE EFFECT ON HEART RATE AND MYOCARDIAL CONTRACTILITY IN THE RAT

Abstract

1. Cholic acid has a dose-dependent negative chronotropic effect on isolated atria of Wistar rats. 2. The positive inotropic effect of cholic acid is the result of a negative chronotropic effect and can be eliminated by electrical pacing. 3. Cholic acid does not appear to exert its negative chronotropic effect through cholinoceptors and alterations in bath concentrations of calcium and potassium does not influence this effect significantly. 4. Cholic acid is a functional antagonist of isoprenaline. 5. It is suggested that cholic acid exerts its negative chronotropic effect by forming a monolayer on the surface of the cell membrane, thereby mechanically interfering with membrane function.

Bile acids induce arrhythmias in human atrial myocardium—implications for altered serum bile acid composition in patients with atrial fibrillation

“…A possible mechanism for bile acid-induced arrhythmogenesis is interaction of bile acids with the cell membrane and cell membrane ion channels or transporters 21 25 26. Bile acids are amphiphilic molecules and are negatively charged at physiologic conditions 27.…”

Effect of bile acid on electrophysiological properties of rabbit sino‐atrial node in vitro

“…Bile acids have been shown to exert a direct depressant effect on cardiac function (Wakim et al, 1940;Joubert, 1978;Bogin et al, 1983;Green et al, 1984). Furthermore, Song et al (1983) demonstrated that sinus bradycardia is induced by obstructive jaundice.…”

Reduced susceptibility to epinephrine-induced arrhythmias in cirrhotic rats: The roles of nitric oxide and endogenous opioid peptides

“…This contrast was also observed in isolated papillary muscle contractility studies [13,27]. The existence of other cardiodepressant substances, e.g., bile acids [28,29], which are in their maximum serum concentration approximately toward the end of the first week and gradually decline with time [30], alongside with NO and endogenous opioid peptides, might be the reason why L-NAME treatment restores baseline hemodynamic parameters as well as the attenuated inotropic responses to isoproterenol in the cirrhotic rats, whereas such responses were not observed in the acute cholestatic animals. The failure of acute L-NAME administration to either correct QT c interval or restore the susceptibility to arrhythmias suggests these changes are the results of long-term overproduction of NO which cannot be reversed by acute inhibition of NO production.…”