Antiarrhythmic peptide has no direct cardiac actions

Abstract

The electrophysiologic, inotropic, and muscarinic effects of antiarrhythmic peptide (AAP) were examined in canine cardiac Purkinje fibers, ferret papillary muscle, and canine cardiac membranes, respectively. Aside from a prolongation of time to peak force in papillary muscle, no biologically significant effects of AAP could be determined in any preparation, suggesting that its antiarrhythmic effects are not mediated by direct membrane actions.

Pharmacological Characterization of the New Stable Antiarrhythmic Peptide Analog Ac-d-Tyr-d-Pro-d-Hyp-Gly-d-Ala-Gly-NH2 (ZP123): In Vivo and in Vitro Studies

“…These observations are in accordance with previous findings for these compounds and for the endogenous antiarrhythmic peptide AAP and the synthetic derivative HP-5 (Argentieri et al, 1989;Dhein et al, 1994;Kjølbye et al, 2002;Xing et al, 2003). In isolated rabbit hearts subjected to hypokalemic ischemia-reperfusion, 0.1 nM HP-5 significantly reduced dispersion of APD 90 without affecting average APD, heart rate, contractility, or coronary flow (Kjølbye et al, 2002).…”

“…In isolated rabbit hearts subjected to hypokalemic ischemia-reperfusion, 0.1 nM HP-5 significantly reduced dispersion of APD 90 without affecting average APD, heart rate, contractility, or coronary flow (Kjølbye et al, 2002). In isolated canine Purkinje fibers, it was shown that AAP did not affect inotropy or any of the electrophysiological parameters measured (maximum diastolic potential, action potential amplitude, maximum rate of depolarization, and action potential duration at 50 and 95% repolarization) (Argentieri et al, 1989). In the isolated rabbit heart, AAP10 had no effect on mean action potential duration, left ventricular end-diastolic pressure, coronary flow, QRS duration, or on the PQ interval (Dhein et al, 1994).…”

ZP123 Increases Gap Junctional Conductance and Prevents Reentrant Ventricular Tachycardia During Myocardial Ischemia in Open Chest Dogs

“…In isolated rabbit hearts subjected to regional ischemia, HP‐5 specifically reduced dispersion of monophasic action potential onset and duration without affecting action potential duration, heart rate, maximum developed left ventricular pressure, or mean coronary flow 17 . It was shown in isolated canine Purkinje fibers that naturally occurring AAP did not affect inotropy or any of the electrophysiologic parameters measured 26 . Similarly, no effects were seen in the isolated rabbit or guinea pig hearts with AAP10 in concentrations up to 1 μM 18 .…”

Pharmacological modulation and differential regulation of the cardiac gap junction proteins connexin 43 and connexin 40

“…Regarding the mechanism of action of AAPnat, electrophysiological experiments on canine Purkinje fibers showed that the transmembrane action potential was not altered (Argentieri et al, 1989), thus indicating that transmembrane ionic currents are not involved. Dhein and coworkers (Dhein et al, 1994;Müller et al, 1997a, b;Dhein et al, 2001a) demonstrated that the effect of AAPnat and related peptides consists of an improvement of cellular coupling and an increase in gap junctional conductance.…”