Electrocardiographic profile of guinea pig heart submitted to Ginkgo biloba extract and its terpenoids / Perfil eletrocardiográfico do coração de cobaia submetido ao extrato de Ginkgo biloba e seus terpenóides

Electrocardiographic effects produced by Ginkgo biloba extract (EGb) and by ginkgolides A (GA) and B (GB), and bilobalide (BB) were investigated in guinea pig heart mounted in Langendorff apparatus (Tyrode, 34 ± 0.1 ºC, 95% O2, 5% CO2). Electrocardiographic parameters were evaluated in the conditions: 1) control with Tyrode and DMSO, 2) EGb (n=4), GA (n=5), GB (n=5) or BB (n=6), and 3) washout. The results showed that 0.1 and 1.0 mg/ml of EGb do not change the electrocardiographic parameters. However, 10 mg/ml of EGb increased the PR interval (PRi) at 21% (p<0.001). This increase was also observed for 50 mM GA (20%, p<0.001) and 70 mM BB (13%, p<0.001), which indicates Ca2+ channel block. However, the 50 mM GB reduced the PRi at 11 % (p<0.001). The GA (23%, p<0.001), GB (16%, p<0.001), and BB (40%, p<0.001) reduced the QT interval (QTi), which suggests the activation of the potassium channel. However, EGb increased QTi (6%, p<0.001). The EGb (28%, p<0.05) and GB (13%, p<0.05) reduced the heart rate. Atrioventricular (AV) block was observed with EGb, GA, and BB. We can conclude that EGb and its terpenoids alter the ECG parameters inducing AV block, which indicates possible arrhythmogenic potential.

Os efeitos eletrocardiográficos produzidos pelo extrato de Ginkgo biloba (EGb) e gingkolídeos A (GA) e B (GB), e bilobalide (BB) foram investigados em coração de cobaia montado sistema de Langendorff (Tyrode, 34 ± 0.1 ºC, 95% O2, 5% CO2). Os parâmetros do ECG foram avaliados nas condições: 1) Tyrode e DMSO, 2) EGb (n=4), GA (n=5), GB (n=5) ou BB (n=6) diluídos em DMSO e 3) washout. Os resultados demonstram que 0,1 e 1,0 mg/mL de EGb não alteraram os parâmetros eletrocardiográficos. Entretanto, 10 mg/ml de EGb aumentaram o intervalo PR (PRi) em 21% (p<0.001). Esse aumento também foi observado com GA a 50µM (20%, p<0,001) e BB a 70 mM (13%, p<0,001) indicando bloqueio de canais de cálcio. Por outro lado, GB reduziu o PRi (11%, p<0,001). O intervalo QT (QTi) foi reduzido por GA (23%, p<0,001), GB (16%, p<0,001) e BB (40%, p < 0.001) sugerindo uma ativação de canais de potássio. Entretanto, EGb aumentou o QTi (6%, p<0.001). A frequência cardíaca foi reduzida por EGb (28%, p<0.05) e GB (13%, p<0.05). Bloqueios átrio-ventriculares (BAV) foram observados com EGb, GA e BB. Podemos concluir que EGb e os terpenos alteram parâmetros eletrocardiográficos induzindo BAV e demonstrando possível potencial arritmogênico.

Electrophysiological effects of the aqueous extract of Averrhoa carambola L. leaves on the guinea pig heart.

This work aims to describe some electrophysiological changes promoted by the aqueous extract (AEx) from Averrhoa carambola leaves in guinea pig heart. The experiments were carried out on isolated heart or on right atrium-ventricle preparations. In 6 hearts, the extract induced many kinds of atrioventricular blocks (1st, 2nd, and 3rd degrees); increased the QT interval from 229+/-23 to 264+/-19 ms; increased the QRS complex duration from 27+/-3.1 to 59+/-11 ms, and depressed the cardiac rate from 136+/-17 to 89+/-14b pm. Furthermore, it decreased the conduction velocity of atrial impulse (17+/-3%); reduced the intraventricular pressure (86+/-6%), and increased the conduction time between the right atrium and the His bundle (27+/-6.5%). The conduction time from the His bundle to the right ventricle was not altered. Atropine sulfate did not change either the electrocardiographic parameters or the intraventricular pressure effects promoted by the A. carambola AEx. Based on these results, the popular use of such extracts should be avoided because it can promote electrical and mechanical changes in the normal heart.

Negative inotropic and chronotropic effects on the guinea pig atrium of extracts obtained from Averrhoa carambola L. leaves.

It has been reported that star fruit can lead to a fatal outcome in uremic patients. The intoxication syndrome consists of hiccups, mental confusion, dizziness, and vomiting. On the other hand, folk medicine uses teas and infusions of carambola leaves to treat headache, vomiting, cough, insomnia, and diabetes. This motivated us to determine if Averrhoa carambola can act on the contractility and automaticity of the guinea pig heart. We measured the atrial isometric force in stimulated left atria and determined the chronotropic changes in spontaneously beating right atria. The carambola leaf extracts (1.5 mg/ml) abolished the contractile force in a concentration-dependent manner. Among the crude, methanolic, ethanolic, aqueous, and acetic extracts, the aqueous one was the most potent (EC50 = 520 +/- 94 microg/ml; flavonoids and tannins are the main constituents; Na+ and K+ contents in 1.0 mg/ml of aqueous extract were 0.12 +/- 0.016 and 1.19 +/- 0.15 mM, respectively). The aqueous extract abolished the positive Bowditch staircase phenomenon and reduced the inotropic response to CaCl2 (0.17-8.22 mM), events that are dependent on the cellular Ca2+ inward current. The adrenergic, muscarinic or opioid membrane receptors do not seem to participate in the mechanism of action of the cardioactive substance(s). In spontaneously beating atria, the aqueous extract promoted a negative chronotropic effect that was antagonized by 0.1 microM isoproterenol bitartrate. With this agonist, the EC50 of the aqueous extract increased from 133 +/- 58 to 650 +/- 100 microg/ml. These data regarding the effect of A. carambola on guinea pig atrial contractility and automaticity indicate an L-type Ca2+ channel blockade.

Negative inotropic and chronotropic effects on the guinea pig atrium of extracts obtained from Averrhoa carambola L. leaves

It has been reported that star fruit can lead to a fatal outcome in uremic patients. The intoxication syndrome consists of hiccups, mental confusion, dizziness, and vomiting. On the other hand, folk medicine uses teas and infusions of carambola leaves to treat headache, vomiting, cough, insomnia, and diabetes. This motivated us to determine if Averrhoa carambola can act on the contractility and automaticity of the guinea pig heart. We measured the atrial isometric force in stimulated left atria and determined the chronotropic changes in spontaneously beating right atria. The carambola leaf extracts (1.5 mg/ml) abolished the contractile force in a concentration-dependent manner. Among the crude, methanolic, ethanolic, aqueous, and acetic extracts, the aqueous one was the most potent (EC50 = 520 ± 94 æg/ml; flavonoids and tannins are the main constituents; Na+ and K+ contents in 1.0 mg/ml of aqueous extract were 0.12 ± 0.016 and 1.19 ± 0.15 mM, respectively). The aqueous extract abolished the positive Bowditch staircase phenomenon and reduced the inotropic response to CaCl2 (0.17-8.22 mM), events that are dependent on the cellular Ca2+ inward current. The adrenergic, muscarinic or opioid membrane receptors do not seem to participate in the mechanism of action of the cardioactive substance(s). In spontaneously beating atria, the aqueous extract promoted a negative chronotropic effect that was antagonized by 0.1 æM isoproterenol bitartrate. With this agonist, the EC50 of the aqueous extract increased from 133 ± 58 to 650 ± 100 æg/ml. These data regarding the effect of A. carambola on guinea pig atrial contractility and automaticity indicate an L-type Ca2+ channel blockade.