Positive inotropic effect of porcine left ventricular extract on canine ventricular muscle

Abstract

1 We previously isolated an extract from porcine left ventricle that possessed digitalis-like properties such as inhibition of cardiac and kidney Na+, K+-ATPase, displacement of [3H]-ouabain from its binding sites and cross reactivity with digoxin antibodies. The extract also had a positive inotropic effect on the guinea-pig heart. 2 In the present study the positive inotropic response of the extract was characterized in canine right ventricular trabeculae. Maximum inotropic response (501 + 20%) was produced by 300,1 and the half maximal increase occurred with 125 ,ul of the extract. 3 Ouabagenin produced aftercontractions in rapidly paced trabeculae. Equipotent and even greater amounts of the extract did not produce aftercontractions. 4 The extract increased the amplitude of the delayed component (P2) of biphasic contractions produced by replacing about 92-96% of the external Ca with Sr. A smaller increase in the size of the early component (P1) was also seen. 5 The extract decreased post-rest potentiation after rest for 30s and 2 min. After 8 min of rest, post-rest potentiation was converted to post-rest depression.6 The extract (20#u1) produced a decrease in the amplitude of the post-rest rapid cooling contracture (RCC) at all rest intervals. The steady state RCC, although greater than that in the control muscle, was increased to a lesser extent than the size of the steady state electrically driven contractions. 7 It is suggested that the extract from porcine left ventricle produces a positive inotropic response by increasing the trans-sarcolemmal influx of Ca. It also has additional effect(s) on the sarcoplasmic reticulum in that it may facilitate the loss of Ca from the sarcoplasmic reticulum and/or inhibit the uptake of Ca by the organelle.

Endogenous inotropic factor‐induced endothelium‐dependent relaxation of vascular smooth muscle

“…This factor was characterized pharmacologically as an endogenous inotropic factor (EIF). We have also demonstrated that EIF, in spite of its positive inotropic effect on cardiac preparations, lacks digitalis-like cardiac toxicity (Navaratnam et al, 1990) and only weakly cross-reacted with digitoxin anti-serum (Khatter et al, 1991). More recently, after several steps of purification of the crude fraction Navaratnam et al, 1990;Khatter et al, 1991), we demonstrated that one of the possible mechanisms of the EIF inotropic effect may be an increased transmembrane calcium influx (Chen et al, 1993).…”