Cardiotoxic effects of the Vipera ammodytes ammodytes venom fractions in the isolated perfused rat heart. (October 2016)

• Record Type: Journal Article
• Authors: Karabuva, Svjetlana; Brizić, Ivica; Latinović, Zorica; Leonardi, Adrijana; Križaj, Igor; Lukšić, Boris
• Is Part Of: Toxicon. Volume 121(2016)
• Page Start: 98
• Page End: 104
• Publication Date: 2016-10
• Subjects: Snake venom -- Vipera ammodytes ammodytes -- Cardiotoxicity -- Isolated rat heart -- Phospholipase A2; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2016.09.001
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: The nose-horned viper ( Vipera ammodytes ammodytes ) is the most venomous European snake. Its venom is known as haematotoxic, myotoxic and neurotoxic but it exerts also cardiotoxic effects. To further explore the cardiotoxicity of the venom we separated it into four fractions by gel filtration chromatography. Three fractions that contain polypeptides (A, B, and C) were tested for their effects on isolated rat heart. Heart rate (HR), incidence of arrhythmias (atrioventricular (AV) blocks, ventricular tachycardia, ventricular fibrillation, and asystolia), coronary flow (CF), systolic, developed and diastolic left ventricular pressure (LVP) were measured before, during, and after the application of venom fractions in three different concentrations. Fraction A, containing proteins of 60–100 kDa, displayed no effect on the rat heart. Fractions B and C disturbed heart functioning in similar way, but with different potency that was higher by the latter. This was manifested by significant decrease of HR and CF, the increase of diastolic, and the decrease of systolic and developed LVPs. All hearts treated with fraction C in the final CF concentrations 22.5 and 37.5 μg/mL suffered rapid and irreversible asystolia without AV blockade. They underwent also ventricular fibrillation and ventricular tachycardia. Fraction B affected hearts only at the highest dose inducing asystolia in all hearts, ventricular fibrillation in 80% and ventricular tachycardia in 70% of the hearts. Venom fraction C induced 71% of all recorded heart rhythm disturbances, significantly more than fraction B, which induced 29%. Most abundant proteins in fraction C were secreted phospholipases A2 among which the venom component acting on the heart is most probably to be looked for. Highlights: Cardiotoxic effects of the Vipera a. ammodytes venom were mainly associated with fraction harboring proteins of ∼14 kDa. The main cardiotoxic fraction of the venom induced rapid and irreversible asystolia in isolated rat heart. This fraction generated also ventricular fibrillation and tachycardia of the isolated rat heart. Cardiotoxicity of the venom is likely associated with the venom secreted phospholipases A2 .