cinobufagin and Heart-Failure

The effects of bufadienolides (bufalin, bufotalin, cinobufagin, cinobufotalin, gamabufotalin and resibufogenin) isolated from Toad Cake was compared to that of cardenolides (digitoxin and ouabain) on cardiac function in a guinea-pig working heart preparation. All the steroids showed the cardiotonic effect in a concentration-dependent manner, and the minimum threshold concentration was 10(-8) M for bufalin, cinobufagin, gamabufotalin and digitoxin and 10(-7) M for bufotalin, cinobufotalin and ouabain. In addition, the order of maximum efficacy of cardiotonic action was as follows: cinobufagin (3 X 10(-7) M) = ouabain (3 X 10(-7) M) greater than digitoxin (1 X 10(-7) M) = gamabufotalin (3 X 10(-7) M) greater than cinobufotalin (3 X 10(-7) M) greater than bufotalin (1 X 10(-7) M). The effect of cinobufagin was examined on experimentally induced heart failure caused by acute local ischemia through ligation of the left anterior descending coronary artery in perfused guinea-pig heart. Cinobufagin (3 X 10(-7) M) and digitoxin (1 X 10(-7) M) reestablished the coronary flow of perfused guinea-pig heart to 90% and 98% of the level prior to the coronary artery ligation. The cardiac output and left ventricular pressure of perfused heart were increased to the level prior to the acute local ischemia, and the left ventricular work was increased by cinobufagin (3 X 10(-7) M) and digitoxin (1 X 10(-7) M) to 108% and 106%, respectively, of the pre-ligation level. These results indicate that cinobufagin possesses strong cardiotonic action, similar, to digitoxin, in experimentally induced heart failure due to acute local ischemia.

Topics: Animals; Bufanolides; Cardiotonic Agents; Coronary Circulation; Coronary Disease; Guinea Pigs; Heart; Heart Failure; In Vitro Techniques; Male; Myocardial Contraction; Perfusion

The dog heart-lung preparations were prepared. The "equilibrium point", which could be defined as the point at which the cardiac output (CO)-curve and the venous return (VR)-curve crossed, when the CO and VR were plotted against the right atrial pressure, was recorded directly by utilizing an X-Y recorder. The CO-curve was obtained, as a locus of the equilibrium point, by raising and lowering the level of blood in the venous reservoir (competence test). The meaning of the procedure was shown to increase or decrease the mean systemic pressure, and to cause the corresponding parallel shift in the VR-curve. The VR-curve was obtained by changing myocardial contractility. When heart failure was induced by pentobarbital or by chloroform, the equilibrium point shifted downwards to the right, depicting the VR-curve. During development of the failure, the slopes of CO-curves decreased gradually. Effects of cinobufagin and norepinephrine were also analyzed. Utilization of the X-Y recorder enabled us to settle the uniform experimental conditions more easily, and to follow the effects of drugs continuously on a diagram equating the CO- and VR-curves (Gyton's scheme).

Topics: Animals; Blood Pressure; Bufanolides; Cardiac Output; Chloroform; Dogs; Heart Failure; Male; Models, Biological; Norepinephrine; Pentobarbital; Postural Balance; Veins