Augmentation of cyclic AMP content induced by lysophosphatidyl choline in rabbit hearts

Ahumada, Gail G.; Bergmann, Steven R.; Carlson, Erin E.; Corr, Peter B.; Sobel, Burton E.

doi:10.1093/cvr/13.7.377

Cited by 40 publications

(27 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ethanol was evaporated under nitrogen at 40°C. As reported previously and as confirmed in this study, vehicle alone prepared in this manner induced no electrophysiological alterations on isolated Purkinje fibers (Corr et al, 1979).…”

Section: Supervision Mediasupporting

confidence: 91%

“…Hearts were removed rapidly and placed in oxygenated Krebs solution at 21 C C. Purkinje fiber strands with attached endocardial tissue were dissected from the right and left ventricles, pinned to the bottom of a 7.5-ml tissue bath lined with wax, and continuously superfused with a modified Krebs solution at 37°C, pH 7.4, gassed with 95% O 2 and 5% CO 2 and containing the following (in mM): sodium = 150, potassium = 4.0, magnesium = 1.0, calcium = 1.2, chloride = 136, phosphate = 0.9, HCO 3 " = 22.0, and glucose = 5.0. Transmembrane potentials were recorded by standard microelectrode techniques as described previously (Witkowksi and Corr, 1978;Corr et al, 1979). Briefly, the attached endocardial tissue was stimulated with 2-msec duration pulses from a photon-isolated stimulator via a Teflon-coated stainless steel bipolar electrode, usually at a cycle length of 800 msec.…”

Section: Tissue Preparationsmentioning

confidence: 99%

“…Recently, amphiphilic compounds such as acyl carnitine (Liedtke et al, 1978) and lysophosphoglycerides (Sobel et al, 1978) have been found to accumulate in ischemic myocardium and in effluents from ischemic isolated perfused rabbit hearts. Furthermore, lysophosphatidyl choline (LPC) bound to albumin induced marked electrophysiological alterations in normoxic Purkinje fi-bers in vitro analogous to changes in ischemic tissue in vivo, implicating this amphiphilic compound as a potential biochemical mediator of dysrhythmia (Corr et al, 1979).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Electrophysiological effects of amphiphiles on canine purkinje fibers. Implications for dysrhythmia secondary to ischemia.

Corr¹,

Snyder²,

Cain³

et al. 1981

Circulation Research

128

View full text Add to dashboard Cite

SUMMARY Lysophosphogiycerides and long-chain acyl carnitines accumulate in igchemic myocardium soon after coronary occlusion. Since both are amphiphi.cs and have some structural similarities, we studied their clectrophysiological effects on transmembrane action potentials (AP) of isolated canine Purkinje fibers. Lysophosphatidyl choline (LPC) in the absence of albumin induced concentration-dependent (75-300 /IM) and reversible decreases in maximum diastolic potential (MDP), AP amplitude, maximum upstroke velocity of phase 0 (V,,,.,) and action potential duration (APD). These responses were identical to those elicited by LPC in the presence of albumin at 10-fold higher concentrations (750-3000 /m). Palmitoyl carnitine induced similar concentration-dependent (75-300 JIM) decreases in MDP, V m u , AP amplitude, and APD. In addition, at concentrations >100 /IM, both compounds induced additional alteration!) characteristic of ischemic tissue in vivo: triangularization of the AP configuration, increased threshold for extracellular stimulation, conduction delay, non-uniform phase 0 depolarization and electrical alternans. Neither FFA, glycerophosphoryl choline, nor carnitine, all possible catabolites of LPC or acyl carnitine, induced any significant electrophysiological alterations analogous to those caused by LPC. The derangements induced by LPC and palmitoyl carnitine were additive. Acidosis comparable to that seen during early ischemia in vivo (pH «= 6.7) led to a 2-to 3-fold leftward shift in the concentration-response curve for LPC and palmitoyl carnitine. Acidosis alone without the amphiphile during the 10-minute superrusion period failed to alter MDP or AP amplitude, although Vm,, was reduced (517 to 429 V/sec) and APO was prolonged rather than shortened. Thus, both lysophosphoglycerides and long-chain acyl carnitines increase in ischemic tissue and induce profound electrophysiological derangements closely analogous to those seen in ischemic myocardium In vivo, implicating both metabolites as potential progenitors of dysrhythmias during ischemia.

show abstract

Section: Supervision Mediasupporting

confidence: 91%

Section: Tissue Preparationsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Electrophysiological effects of amphiphiles on canine purkinje fibers. Implications for dysrhythmia secondary to ischemia.

Corr¹,

Snyder²,

Cain³

et al. 1981

Circulation Research

128

View full text Add to dashboard Cite

show abstract

“…Two prominent electrophysiological effects of LPC have been suggested. (1) LPC increases the cellular level of cAMP, which may potentiate Ca influx via Ca channels (AHUMADA et al, 1979). (2) LPC reduces transmembrane resting potential of cardiac tissues .…”

mentioning

confidence: 99%

Lysophosphatidylcholine decreases single channel conductance of inward rectifier K channel in mammalian ventricular myocytes.

1984

View full text Add to dashboard Cite

Summary Effect of lysophosphatidylcholine (LPC) on the inward rectifier K channel of the isolated guinea pig ventricular cell was studied using patch clamp technique. In that LPC (100 ,uM) decreased the magnitude of the single channel conductance from 48±5 pS (mean and S.D., n=5) to 12±9 pS (n=8), this event may be the prime factor related to the alleged LPC-induced depolarization of cardiac tissues.

show abstract

“…It has been shown that LPC produces Ca"-overload in rabbit cardiac myocytes (15) and potentiates Ca" accumulation in rat cardiac myocytes (16). Although the exact mechanism by which LPC induces intracellular Ca"-overload remains speculative, several mechanisms have been proposed: 1) LPC has a direct effect to increase the sarcolemmal permeability to Ca" (17), 2) LPC increases the level of myocardial cyclic AMP (18), which may cause Ca2+-influx via slow Ca 21 channel (19), 3) LPC activates protein kinase C directly (20,21) or indirectly (22) leading to Ca 21 -overload, 4) LPC inhibits myocardial Na+-K+ ATPase and therefore may increase the intracellular Na+ concentration with consequent acceleration of Na+-/Ca 2+ exchange (23,24) leading to Ca 2+-overload, 5) LPC produces long-lasting bursts of Na+ channel openings (25) leading to Ca 2+-overload. If there is Ca 2+-overload, mitochondrial damage would also occur.…”

Section: Discussionmentioning

confidence: 99%

A Study on Dilazep: II. Dilazep Attenuates Lysophosphatidylcholine-Induced Mechanical and Metabolic Derangements in the Isolated, Working Rat Heart

Hoque

Hashizume

et al. 1995

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-The effects of dilazep, d-propranolol and lidocaine on the mechanical and metabolic changes induced by lysophosphatidylcholine (LPC) were studied in isolated, perfused working rat heart. After a stabilization period, the heart was perfused for 5 min with LPC (10 €M) alone, LPC plus dilazep (5, 10 or 20 pM), LPC plus d-propranolol (30 or 50 pM) or LPC plus lidocaine (30 or 100 pM) and then perfused with normal Krebs-Henseleit bicarbonate (KHB) buffer for a further 20 min. Perfusion with LPC for 5 min followed by KHB for 20 min irreversibly decreased cardiac mechanical function, decreased the tissue levels of adenosine triphosphate and creatine phosphate significantly, and increased the tissue levels of lactate and free fatty acids including arachidonic acid. Dilazep or d-propranolol significantly attenuated the mechanical and metabolic changes induced by LPC, but lidocaine did not. These results indicate that the exogenous LPC causes ischemia-like changes, suggesting that LPC is one of the important factors in producing ischemia-reperfusion derangements in terms of mechanical and metabolic functions, and that both dilazep and d-propranolol can prevent the LPC-induced myocardial damage.

show abstract

Augmentation of cyclic AMP content induced by lysophosphatidyl choline in rabbit hearts

Cited by 40 publications

References 0 publications

Electrophysiological effects of amphiphiles on canine purkinje fibers. Implications for dysrhythmia secondary to ischemia.

Electrophysiological effects of amphiphiles on canine purkinje fibers. Implications for dysrhythmia secondary to ischemia.

Lysophosphatidylcholine decreases single channel conductance of inward rectifier K channel in mammalian ventricular myocytes.

A Study on Dilazep: II. Dilazep Attenuates Lysophosphatidylcholine-Induced Mechanical and Metabolic Derangements in the Isolated, Working Rat Heart

Contact Info

Product

Resources

About