d-Limonene Ameliorates Myocardial Infarction Injury by Reducing Reactive Oxygen Species and Cell Apoptosis in a Murine Model.

Myocardial infarction (MI) leads to high mortality, and pharmacological or percutaneous primary interventions do not significantly inhibit ischemia/reperfusion injuries, particularly those caused by oxidative stress. Recently, research groups have evaluated several naturally occurring antioxidant compounds for possible use as therapeutic alternatives to traditional treatments. Studies have demonstrated that d-limonene (DL), a monoterpene of citrus fruits, possesses antioxidant and cardiovascular properties. Thus, this work sought to elucidate the mechanisms of protection of DL in an isoproterenol-induced murine MI model. It was observed that DL (10 µmol) attenuated 40% of the ST elevation, reduced the infarct area, prevented histological alterations, abolished completely oxidative stress damage, restored superoxide dismutase activity, and suppressed pro-apoptotic enzymes. In conclusion, the present study demonstrated that DL produces cardioprotective effects from isoproterenol-induced myocardial infarction in Swiss mice through suppression of apoptosis.

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.

Bradycardic and Antiarrhythmic Effects of the D-Limonene in Rats.

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.

The positive inotropic effect of the ethyl acetate fraction from Erythrina velutina leaves on the mammalian myocardium: the role of adrenergic receptors.

OBJECTIVES: We studied the effects of ethyl acetate fraction (EAcF) obtained from Erythrina velutina leaves on mammalian myocardium. METHODS: The effect of EAcF on the contractility was studied using guinea-pig left atria mounted in a tissue bath (Tyrode's solution, 29°C, 95% CO2 , 5% O2 ) and electrically stimulated (1 Hz). Concentration-response curves of EAcF were obtained in the presence of propranolol (1 µm), nifedipine (1 µm) and in reserpinized animals (5 mg/kg). The involvement of l-type calcium current (ICa,L ) on the EAcF effect was observed in cardiomyocytes of mice assessed using patch-clamp technique. KEY FINDINGS: EAcF (550 µg/ml) had a positive inotropic effect, increasing the atrial force by 164% (EC50 = 157 ± 44 µg/ml, n = 6), but it was less potent than isoproterenol (EC50 = 0.0036 ± 0.0019 µg/ml, n = 8). The response evoked by EAcF was abolished by propranolol or nifedipine. Reserpine did not alter the inotropic response of EAcF. Furthermore, an enhancement of the ICa,L peak (31.2%) with EAcF was observed. Chemical analysis of EAcF revealed the presence of at least 10 different flavonoid glycoside derivatives. Two were identified as vicenin II and isorhoifolin. CONCLUSIONS: We conclude that EAcF increases the cardiac contractile force by increasing the l-type calcium current and activating the adrenergic receptor pathway.

Extract from leaf of Psidium guajava L depresses the guinea pig atrial contractility by interfering with potassium and calcium channels / Extrato de folha de Psidium guajava L deprime a contratilidade atrial de cobaia, interferindo com os canais de potássio e cálcio

The negative inotropic effect of aqueous fraction (AqF) obtained from the acetic extract of Psidium guajava L leaf was investigated on the guinea pig left atrium. Myocardial force was measured isometrically (27 ± 0.1 ºC, 2 Hz). AqF (100 μg/ml) reduced contractility of about 85 ± 9.4 percent (n = 4, p < 0.001, Fcalc = 51.70, F(0.01; 4; 21) = 5.09, EC50 = 14.28 ± 3 μg/mL) in a concentration-dependent fashion. This effect was reduced by 20 mM of tetraethylammonium (TEA), increasing EC50 to 50 ± 7 μg/ml (n = 4, p < 0.001, Fcalc = 282.13; F(0.01; 21; 66) = 2.36). AqF (100 μg/ml) shifted to the right the CaCl2 concentration-effect curve, increasing the EC50 from 2170 ± 112 to 2690 ± 132 μM (n = 3, p < 0.001, Fcalc = 220.80 ; F(0.01; 29; 60) = 2.19). L-NAME (100 μM) did not modify the AqF inotropic effect (n = 3, p > 0.05) sugesting that the oxide nitric pathway did not participate of the action mechanism of AqF. We can conclude that AqF depresses the atrial contractile by reducing the calcium entry in myocardial cells and also by openenig potassium channels of cardiac tissue.

O efeito inotrópico da fração aquosa (AqF) do extrato acético das folhas de Psidium guajava L. foi investigado em átrio esquerdo de cobaia. A força miocárdica foi medida isometricamente (27 ± 0,1 ºC; 2 Hz). A AqF (100 μg/mL) reduziu a contratilidade em até 85 ± 9,4 por cento (n = 4; p < 0,001; Fcalc = 51,70; F(0,01; 4; 21) = 5,09; CE50 = 14,28 ± 3 μg/mL) de forma dependente da concentração. Este efeito foi reduzido pelo tetraetilamônio (TEA, 20 mM) que também aumentou a CE50 de 14,28 ± 3 μg/mL para 50 ± 7 μg/mL (n = 4; p < 0,001; Fcalc = 282,13; F(0,01; 21; 66) = 2,36). A AqF (100 μg/mL) deslocou para a direita a curva concentração-efeito do CaCl2, aumentando a CE50 de 2170 ± 112 para 2690 ± 132 μM (n = 3; p < 0,001; Fcalc = 220,80 ; F(0,01; 29; 60) = 2,19). Por outro lado, o L-NAME (100 μM) não alterou o efeito inotrópico da AqF (n = 3; p > 0,05), sugerindo que a via do óxido nítrico não participa do mecanismo de ação da AqF. Conclui-se que a AqF deprime a contratilidade atrial por reduzir a entrada de cálcio nas células miocárdicas e por abrir canais de potássio deste tecido.