Bradycardic and Antiarrhythmic Effects of the D-Limonene in Rats / Efeitos Bradicárdicos e Antiarrítmicos do D-Limoneno em Ratos

Abstract Background: D-limonene (DL) is a monoterpene and is the major component in the essential oil of citrus fruit. It presents antihyperglycemic and vasodilatation activities. Objectives: This study evaluated the cardiovascular effects and potential antiarrhythmic of DL in rats. Methods: Hemodynamic and electrocardiographic (ECG) parameters were measured in male Wistar rats, which under anesthesia had been cannulated in the abdominal aorta and lower vena cava and had electrodes subcutaneously implanted. In the in vitro approach, the heart was removed and perfused using the Langendorff technique. The significance level adopted was 5% (p < 0.05). Results: DL, in doses of 10, 20, and 40 mg/kg (i.v), produced intense and persistent bradycardia associated with hypotension. Bradycardia with prolonged QTc was observed in the ECG in vivo recording. In the in vivo model of arrhythmia induced by Bay K8644, DL (10 mg/kg) decreased the arrhythmia score from 15.33 ± 3.52 to 4.0 ± 2.64 u.a (p < 0.05, n = 4). In isolated perfused hearts, DL (10-3 M) promoted significant reductions in heart rate (from 228.6 ± 8.5 ms to 196.0 ± 9.3 bpm; p < 0.05) and left ventricular development pressure (from 25.2 ± 3.4 to 5.9 ± 1.8 mmHg; n = 5, p < 0.05). Conclusions: DL produces bradycardia and antiarrhythmic activity in rat heart.

Resumo Fundamento: O D-limoneno (DL) é um monoterpeno e o principal componente do óleo essencial de frutas cítricas. Ele apresenta atividades anti-hiperglicêmicas e vasodilatadoras. Objetivos: Este estudo avaliou os efeitos cardiovasculares e antiarrítmicos potenciais do DL em ratos. Métodos: Os parâmetros hemodinâmicos e eletrocardiográficos (ECG) foram mensurados em ratos Wistar machos que, sob anestesia, tiveram a aorta abdominal e a veia cava inferior canuladas e receberam eletrodos implantados subcutaneamente. Na abordagem in vitro, o coração foi removido e perfundido utilizando a técnica de Langendorff. O nível de significância adotado foi de 5% (p < 0,05). Resultados: DL, nas doses de 10, 20 e 40 mg/kg (i.v), produziu bradicardia intensa e persistente associada à hipotensão. A bradicardia com QTc prolongado foi observada no registro in vivo do ECG. No modelo in vivo de arritmia induzida por Bay K8644, DL (10 mg / kg) houve diminuição do escore da arritmia de 15,33 ± 3,52 para 4,0 ± 2,64 u.a (p < 0,05, n = 4). Em corações perfundidos isolados, o DL (10-3 M) promoveu reduções significativas na frequência cardíaca (de 228,6 ± 8,5 ms para 196,0 ± 9,3 bpm; p < 0,05) e na pressão desenvolvida do ventrículo esquerdo (de 25,2 ± 3,4 para 5,9 ± 1,8 mmHg; n = 5, p < 0,05). Conclusões: O DL produz bradicardia e atividade antiarrítmica no coração de ratos.

[Investigation of the effect of the aqueous extract of the root of Prosopis farcta plant on the function of the isolated hearts of rats under ischemia - reperfusion condition]

Prosopis farcta plant is used traditionally in several parts of the country. Due to lack of scientific information on the cardiovascular effects of this plant, especially during ischemia - reperfusion and the importance of the issue, the present study was designed to investigate the effect of Prosopis farcta root extract on the isolated hearts of rats under ischemia-reperfusion condition. This experimental study included 58 rats which were divided into perfusion and ischemia-reperfusion groups. The hearts of the animals were isolated and then subjected to ischemia and reperfusion in Iangendorff setup, after baseline step. Parameters of cardiac function, including heart rate, left ventricular developed pressure [LVDP], rate pressure product [RPP] and coronary flow [CF] were assessed. The results showed that administration of aqueous extract of Prosopis farcta plant significantly reduced cardiac parameters including RPP [p=0.0242] and CF [p=0.01113] in perfusion group, and also exacerbated cardiac damage [RPP] induced by ischemia in the ischemic group compared to the control group [p= 0.0126]. Considering the inhibitory effect of Prosopis farcta root extract on cardiac function, this plant may have useful effect on lowering blood pressure, but owing to its undesirable effects following myocardial ischernia, its administration is not recommended in these cases. The present results were not consistent with previous reports on nitric oxide dependent vasodilatory effect of this plant, and investigation of the compounds of this plant in different regions of the country is recommended in the future studies

Efectos del danazol y hemisuccinato de danazol sobre la presión de perfusión y resistencia vascular / Effects of danazol and danazol hemisuccinate on perfusión pressure and vascular resistance

Estudios clínicos y epidemiológicos sugieren que el danazol ha sido considerado como un factor de riesgo para desarrollar hipertensión. Para proporcionar información adicional acerca de este fenómeno, en este trabajo fue caracterizado el efecto inducido por el danazol y el hemisuccinato de danazol sobre la presión de perfusión y la resistencia vascular en corazón aislado de rata a flujo constante (modelo de Langendorff). Los resultados, mostraron que; 1) el hemisuccinato de danazol [10-9 M] incrementa la presión de perfusión en comparación con el danazol [10-9 M]; 2) los efectos del derivado de danazol [10-9 M - 10-4 M] sobre la presión de perfusión fueron inhibidos por flutamida [10-6 M]; 3) la nifedipina [10-6 M], bloqueó los efectos ejercidos por el hemisuccinato de danazol [10-9 M -10-4 M] sobre la presión de perfusión y 4) el efecto del derivado de danazol [10-9 M - 10-4 M] sobre la presión de perfusión en presencia del montelukast [10-6 M] fue inhibido significativamente (p=0,008). En conclusión, los efectos inducidos por el danazol y hemisuccinato de danazol sobre la presión de perfusión y la resistencia vascular podrían depender de su estructura química. Este fenómeno podría involucrar la interacción del receptor de andrógenos e indirectamente la activación de la síntesis de leucotrienos D4 (LTD4) y consecuentemente inducir variaciones en la presión de perfusión.

Epidemiological and clinical studies suggest that danazol has been considered a risk factor for hypertension development. In order to provide additional information about this phenomenon, the effect induced by both danazol and hemisuccinate of danazol on perfusion pressure and vascular resistance was characterized in isolated rat heart at constant flow (Langendorff model) and it was evaluated in this work.The results showed that; 1) hemisuccinate of danazol [10-9 M] increases perfusion pressure and vascular resistance in comparison with danazol [10-9 M]; 2) the effects of danazol-derivative [10-9 M - 10-4 M] on perfusion pressure were inhibited by flutamide [10-6 M]; 3) nifedipine [10-6 M] blockaded the effects exerted by hemisuccinate of danazol [10-9 M -10-4 M] on perfusion pressure; and 4) the effect of danazol-derivative [10-9 M - 10-4 M] on perfusion pressure in presence of montelukast [10-6 M] was significantly inhibited (p=0.008). In conclusion, the effects induced by both danazol and hemisuccinate of danazol on perfusion pressure and vascular resistance could depend on their chemical structure. This phenomenon could involve the interaction of androgene steroid-receptor and indirect activation of leukotriene D4 (LTD4) synthesis and consequently, induce variations in the perfusion pressure.

Cardiac field potentials and activation sequence in Langendorff perfused heart, cardiac tissue slices and cultured ventricular myocytes recorded by microelectrode arrays system / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe field potentials (FPs) and activation sequence at Langendorff perfused guinea pigs heart, SD rat cardiac tissue strips perfused by Tyrode's solution and cultured ventricular cardiomyocytes of suckling mice by microeletrode arrays (MEA) technique.</p><p><b>METHOD</b>FPs and activation sequence were recorded from perfused heart, cardiac tissue strips (5 mm x 5 mm) and cultured ventricular cardiomyocytes by MEA.</p><p><b>RESULTS</b>(1) FPs could be recorded in hearts perfused for 30 to 90 min with a heart rate 90 - 120 beats/min. FP durations of both ventricular and atrial tissue were (210 +/- 78) ms and (164 +/- 58) ms, respectively and atrial ventricular conduction time was (320 +/- 150) ms. (2) The excitability of Tyrode's solution perfused tissue strips was visible for more than 2 h, and FP durations of ventricular and atrial tissue strips were (115.80 +/- 11.61) ms and (83.71 +/- 6.48) ms, respectively. (3) Spontaneous beating frequency (150 +/- 100) beats/min and FPs could be readily recorded in cardiomyocytes cultured between 2 to 72 hours.</p><p><b>CONCLUSION</b>MEAs is a sensitive, low noise and stable technique for observing local tissue action potential and activation sequence of whole heart, cardiac tissue strips and cultured cardiomyocytes.</p>