Electrophysiological effects of acetyl glyceryl ether phosphorylcholine on cardiac tissues: comparison with lysophosphatidylcholine and long chain acyl carnitine

Abstract

1 Electrophysiological effects of synthetic platelet activating factor, acetyl glyceryl ether phosphorylcholine (AGEPC), were examined and compared with those of lysophosphatidylcholine (LPC) and long chain acyl carnitine (AC) in canine Purkinje fibres and guinea-pig papillary muscles, by use of standard microelectrode techniques.2 In canine Purkinje fibres, AGEPC at concentrations higher than 3 x 10-5 M, decreased maximum diastolic potential, action potential amplitude and the maximum upstroke velocity ofphase 0. AGEPC also induced abnormal automaticity arising from depolarized membrane potentials.3 LPC and AC in concentrations higher than 3 x 1O-5M also produced virtually identical electrophysiological alterations in Purkinje fibres. 4 Although twitch tension was slightly decreased by low concentrations (10-6_1l-0M) of these amphiphilic lipids, a transient positive inotropic response appeared at the beginning of a progressive depolarization after exposure to higher concentrations of the amphiphiles. 5 In guinea-pig papillary muscles, AGEPC in concentrations higher than 3 x 10I-5 M produced slight decreases in resting membrane potential, action potential amplitude and action potential durations, concomitantly with a positive inotropic response. These electrophysiological and mechanical changes were also induced by LPC and AC at comparable concentrations.6 In guinea-pig papillary muscles depolarized with 25 mM [K']0, AGEPC, LPC and AC all evoked slow action potentials at a concentration of 10-'M. 7 It is concluded that in isolated cardiac tissues AGEPC exerts electrophysiological effects similar to those of LPC and AC only at high concentrations, and that the non-specific interaction of amphiphiles with sarcolemmal membrane may be responsible for the electrophysiological and mechanical effects.

Platelet-Activating Factor in Cardiovascular Stress Situations

“…PAF was found to interfere with the cardiac conducting system, and to produce lethal arrhythmias (24). More over, purkinje fibers of guinea pigs demonstrated PAFinduced electrophysiological changes such as abnormal automaticity and decreased action potential amplitude (61). Interestingly, similar effects were found in the papillary muscle as well.…”

Long-Chain Acylcarnitines and Cardiac Excitation-Contraction Coupling: Links to Arrhythmias

“…These findings have been replicated by many groups in canine, guinea pig, and rabbit isolated cardiomyocyte and multicellular preparations exposed to similarly high LCAC doses and to lower LCAC doses (0.1-50 µM). Moreover, as with endogenous LCAC upregulation, exogenous LCAC delivery also induces spontaneous electrical arrhythmias, inhibits gap junction conductance, and promotes in vivo ventricular extra-systoles (see Figure 2B; Hayashi et al, 1982;Nakaya and Tohse, 1986;Aomine et al, 1988;Sakata et al, 1989;Meszaros and Pappano, 1990;Mèszàros, 1991;Wu and Corr, 1992Sato et al, 1993; Roussel et al (2015), with permission from Elsevier. Shen and Pappano, 1995;Roussel et al, 2015).…”

“…More recent work has found that LCAC-mediated APD retardation can be modeled in silico based on results in recombinant HEK-293 cells ( Ferro et al, 2012 ). These electrical derangements associated with exogenous LCACs also exhibit reversibility; however, this is more common at lower doses, presumably due to detergent-like effects evident at high LCAC doses ( Nakaya and Tohse, 1986 ; Busselen et al, 1988 ; Sakata et al, 1989 ). Others have reported less straight-forward LCAC effects.…”

“…The latency of these positive contractility effects is inversely related to LCAC concentration. Inotropic modulations of multicellular preparations typically manifest within 10–20 min at higher exogenous doses (100–300 μM), while lower doses (1–30 μM) require relatively longer exposure durations ranging from 30 to 120 min ( Inoue and Pappano, 1983 ; Nakaya and Tohse, 1986 ; Aomine et al, 1988 ; Sakata et al, 1989 ; Clarke et al, 1996 ). At equivalent lower doses, inotropic latency is reduced in isolated myocytes and myocyte aggregates ( Patmore et al, 1989 ; Shen and Pappano, 1995 ), most likely due to a greater LCAC to membrane phospholipid mole ratio (discussed later).…”

The effects of novel vasodilator long chain acyl carnitine esters in the isolated perfused heart of the rat

“…Accumulation of long chain acyl carnitines occurs in the ischaemic myocardium (Liedtke et al, 1978;Corr et al, 1984) and these fatty acid metabolites exert detrimental electrophysiological, biochemical and mechanical effects on the heart (Adams et al, 1979;Knabb et al, 1988;Nakaya & Tohse, 1986). They have also been reported to be calcium channel activators (Spedding & Mir, 1987) and are thought to be the mediators of the increase in a-adrenoceptor numbers seen in the ischaemic myocardium (Corr et al, 1981;Heathers et al, 1987;Allely & Brown, 1988).…”