In vivo en in vitro kardiovaskulere effekte van choliensuur met die wistarrot as proefdier

[摘要] English: 4.1 THE CARDIOVASCULAR EFFECTS OF CHOLIC ACID IN THEWISTAR RAT:4.1.1. Bradycardia associated with obstructivejaundice is a well recognised clinical observation. Althoughthis phenomenon is usually attributed to increased concentrationsof circulating bile salts, the literature on thecardiovascular effects of bile salts is sparse, contradictoryand confusing.The object of this investigation was therefore to studythe effects of a specific bile acid (cholic acid) on thecardiovascular system of a specific species (the Wistar rat) .Three aspects received particular attention, namelyi) to ascertain whether cholic acid does in factelicit negative chronotropism,ii) to ascertain whether negative chronitropism is dosedependent,iii) to study the possible mechanism or mecpanismsresponsible for negative chronotropism.4.1.2. Experimentally produced obstructive jaundicecauses a statistically significant decrease in restingheart rate in thê Wistar rat.4.1.3. Cholic acid administration in vivo elicitsa dose-dependent negative chronotropic effect, which at lowerdoses is the result of an uncomplicated sinus bradycardia. Progressive impairment of conduction occurs with higher dosesand extreme toxicity is manifested as cessation of electrical activity In the heart. A dose-dependent hypotensive effect,which probably results from a decreased cardiac output, alsooccurs.4.1.4. An investigation into the role of the autonomicnervous system, revealed that cholic acid causes bradycardiaby a direct, as well as by a vagotonic mechanism.This results in a moderate degree of reflex sympathetic compensation.The vagotonic effect of cholic acid probably resultsfrom an effect on afferent vagal nerve endings in the aorticarch.4.1.5. A clearcut negative chronotropic effect waselicited in response to cholic acid in vitro, utilizing isolatedrat atrium preparations. A concomitant positive inotropismwas observed which was r.elated to the decrease in heart rateand which could be eliminated by electrical pacing at a constantrate.4.1.6. In vitro negative chronotropism is not directlyrelated to the decrease in surface tension and is not substantiallyinfluenced by changes in potassium or sodium concentrations.Atropine does not significantly influence in vitro negativechronotropism, but cholic acid shows physiological antagonismof the positive chronotropic effect of isoprenaline. 4.1.7. The in vitro pharmacological effect ofcholic acid (i.e. negative chronotropism) can not be attributedto any histochemical or electron microscipical changes.The effect of higher concentrations of cholic acid may howeverbe related to mitochondrial swelling and a decrease in glycogencontent of the cells. 4.1.8. Although haemolysis occurs in vivo, itdoes not contribute to negative chronotropism. Haemolysisprobably occurs because of a mechanical monolayer effecton the cell membrane. Although this effect is concentrationdependent,the number of red cells in suspension is also acritical factor. This mechanical effect probably alsooccurs in cardiac pacemaker and conducting tissues inhibitingionic flow in a non-specific way.4.1.9. Observations during some of the experimentsand the results of a short study, suggest the cholic acidhas anti-arrhythmic properties.

[发布机构] University of the Free State