Acute exposure to Catha edulis depresses contractility and induces myocardial infarction in spontaneously contracting, isolated rabbit's heart

Abstract

Khat chewing is a recreational habit known to pose major socio-economic and medical problems in countries of Southern Arabia and the Horn of Africa. Among other adverse health effects, khat chewing has been associated with an increased risk of myocardial infarction (MI) in heavy consumers. This study was carried out to examine the direct effects of Catha edulis extract on contractility of spontaneously contracting, isolated rabbit heart and to investigate its mechanism of action. Isolated six rabbit's hearts attached to a Langendorff apparatus were perfused with extract at a constant flow rate and continuously bubbled with a 95% O2/5% CO2 gas mixture. Each heart served as its own control, as responses were recorded before and after administration of C. edulis extract. Varying concentrations of extract (50, 100 and 250 mg/ml) were loaded in the perfusate, their effects recorded and effluent fluid collected for assay of cardiac enzymes. Histological examination of the cardiac tissue was performed at the end of perfusion with 250 mg/ml extract. This study revealed that acute exposure to C. edulis extract exerted negative inotropic and chronotropic effects on isolated hearts. The extract also had a vasoconstrictor effect on coronary vessels, independent of α1 adrenergic receptor stimulation. Histological examination of hearts perfused with 250 mg/ml C. edulis extract revealed the presence of histological changes unique to myocardial infarction, a finding consistent with observed increased levels of cardiac enzymes in perfusates. Thus, we have demonstrated experimentally a direct cardiac depressant- and MI inducing effects of C. edulis extract. These results are consistent with the earlier reported deleterious effects of khat on cardiovascular function among khat chewers.

Keywords: Catha edulis; Contractility; Heart; Myocardial infarction; Rabbit.

Figure 1

Experimental procedure.

Figure 2

Effect of hydro-ethanol extract of Catha edulis on the heart rate of isolated rabbit’s heart. (A) 50 mg/ml, (B) 100 mg/ml and (C) 250 mg/ml. Results are mean ± SD, n = 6, ∗ significantly different from control at P < 0.05.

Figure 3

Effect of hydro-ethanol extract of Catha edulis on the force of myocardial contraction of isolated rabbit’s heart. (A) 50 mg/ml, (B) 100 mg/ml and (C) 250 mg/ml. Results are mean ± SD, n = 6, ∗ significantly different from control at P < 0.05.

Figure 4

Cardiotonic effect of Catha edulis hydro-ethanol crude extract on the isolated rabbit’s heart. (A) Control, (B) positive inotropic effect of excess calcium (0.24%), (C) adrenalin effect showing positive inotropic and chronotropic effects, (D) 50 mg/ml of the extract shows negative inotropic effect, (E) 100 mg/ml of the extract showing negative inotropic and potent negative chronotropic effects, (F) 250 mg/ml of the extract that shows potent negative inotropic and negative chronotropic effects, (G) negative inotropic and chronotropic effect of Catha edulis extract (250 mg/ml) with no effect of excess calcium (0.24% and 0.48%) on force of contraction, and (H) negative inotropic and chronotropic effects of the extract in the presence of α-adrenergic blocker.

Figure 5

Histopathology photomicrographs (100×): normal (A). Catha edulis treated rabbits (B–F). Photomicrographs from B–F shows features of myocardial infraction in which B represents contracting band (arrow), C shows wavy fibers (arrow) and karyolysis (arrow head), D shows increased hyalinization (arrow), E shows karyolysis (arrow) and F shows increased hyalinization and apoptosis.