Cardiotoxic effects of the Vipera ammodytes ammodytes venom fractions in the isolated perfused rat heart.
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 A2among which the venom component acting on the heart is most probably to be looked for.
Clinical Department of Infectious Diseases, University Hospital Centre Split, Šoltanska 1, Split, Croatia. Electronic address: svjetlana.karabuva@gmail.com.
Svjetlana
S
Karabuva
Department of Pharmacology, Mostar University School of Medicine, Bijeli brijeg bb, Mostar, Bosnia and Herzegovina. Electronic address: ivicabrizic@net.hr.
Ivica
I
Brizić
Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova cesta 39, Ljubljana, Slovenia; Jožef Stefan International Postgraduate School, Jamova cesta 39, Ljubljana, Slovenia. Electronic address: zorica.latinovic@ijs.si.
Zorica
Z
Latinović
Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova cesta 39, Ljubljana, Slovenia. Electronic address: Adrijana.Leonardi@ijs.si.
Adrijana
A
Leonardi
Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova cesta 39, Ljubljana, Slovenia; Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva cesta 5, Ljubljana, Slovenia. Electronic address: igor.krizaj@ijs.si.
Igor
I
Križaj
Clinical Department of Infectious Diseases, University Hospital Centre Split, Šoltanska 1, Split, Croatia; University of Split School of Medicine, Šoltanska 2, Split, Croatia. Electronic address: boris.luksic1@st.t-com.hr.
Boris
B
Lukšić
D000818:Animals; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D051381:Rats; D014757:Viper Venoms / Q000633:toxicity*; D017819:Viperidae
D014757:Viper Venoms
Cardiotoxicity; Isolated rat heart; Phospholipase A(2); Snake venom; Vipera ammodytes ammodytes