Cardiac electrophysiological effects of platelet-derived substances

Flores, Nicholas A.; Botchway, Alfred; Stavrou, Brigitte M.; Sheridan, Desmond J.

doi:10.1017/s095806709901773x

Cited by 6 publications

(5 citation statements)

References 66 publications

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“…Platelet activation results in the release of platelet products, the so-called secretome, which includes organic substances [e.g., adenosine-5′-triphosphate (ATP), serotonin, and histamine] and more than 2000 proteins (Coppinger et al, 2004). Many of these substances can alter electrophysiological properties of the heart in various animal species, supporting the notion that activated platelets exert pro-arrhythmic effects (Figure 1; Hoffman et al, 1996, 1997; Flores et al, 1999). Conversely, platelet antagonists counteract ischemia-induced arrhythmias in animal studies (Wainwright et al, 1989; Ahn et al, 1999).…”

Section: Cardiac Arrhythmiassupporting

confidence: 54%

“…Many of the substances released by platelets can alter the electrophysiological properties of the heart in various animal species (Flores et al, 1999). …”

Section: Platelet Adhesion and Activationmentioning

confidence: 99%

“…Normal extracellular ATP concentration is about 2 μM (Born and Kratzer, 1984) and may increase to 100 μM under pathological conditions (Coade and Pearson, 1989). Under normal conditions, ATP is rapidly converted to adenosine (Flores et al, 1999). …”

Section: Platelet Adhesion and Activationmentioning

confidence: 99%

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Platelets and Cardiac Arrhythmia

Jong

Dekker

2010

Front. Physio.

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Sudden cardiac death (SCD) remains one of the most prevalent modes of death in industrialized countries, and myocardial ischemia due to thrombotic coronary occlusion is its primary cause. The role of platelets in the occurrence of SCD extends beyond coronary flow impairment by clot formation. Here we review the substances released by platelets during clot formation and their arrhythmic properties. Platelet products are released from three types of platelet granules: dense core granules, alpha-granules, and platelet lysosomes. The physiologic properties of dense granule products are of special interest as a potential source of arrhythmic substances. They are released readily upon activation and contain high concentrations of serotonin, histamine, purines, pyrimidines, and ions such as calcium and magnesium. Potential arrhythmic mechanisms of these substances, e.g., serotonin and high energy phosphates, include induction of coronary constriction, calcium overloading, and induction of delayed after-depolarizations. Alpha-granules produce thromboxanes and other arachidonic-acid products with many potential arrhythmic effects mediated by interference with cardiac sodium, calcium, and potassium channels. Alpha-granules also contain hundreds of proteins that could potentially serve as ligands to receptors on cardiomyocytes. Lysosomal products probably do not have an important arrhythmic effect. Platelet products and ischemia can induce coronary permeability, thereby enhancing interaction with surrounding cardiomyocytes. Antiplatelet therapy is known to improve survival after myocardial infarction. Although an important part of this effect results from prevention of coronary clot formation, there is evidence to suggest that antiplatelet therapy also induces anti-arrhythmic effects during ischemia by preventing the release of platelet activation products.

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Section: Cardiac Arrhythmiassupporting

confidence: 54%

“…Many of the substances released by platelets can alter the electrophysiological properties of the heart in various animal species (Flores et al, 1999). …”

Section: Platelet Adhesion and Activationmentioning

confidence: 99%

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Platelets and Cardiac Arrhythmia

Jong

Dekker

2010

Front. Physio.

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“…Another possibility is that products of the platelet release reaction cause the adverse effects on ischemicreperfused cardiomyocytes. The contribution of serotonin, thromboxane A 2 , thrombin, and platelet-activating factor to arrythmogenesis and vasoconstriction has been described and recently reviewed (10). It has also been demonstrated that substances released by platelets are able to mimic the electrophysiological effects produced by the presence of platelets during ischemia in isolated hearts (11).…”

Section: Discussionmentioning

confidence: 99%

Platelets activated by transient coronary occlusion exacerbate ischemia-reperfusion injury in rat hearts

Mirabet

Garcı́a-Dorado

Inserte

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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Platelets (Plt) accumulate in reperfused myocardium but their effect on myocardial necrosis has not been established. We tested the hypothesis that the effect of Plt depends on their activation status. Pig Plt were obtained before 48 min of coronary occlusion (pre-CO-Plt), 10 min after reperfusion (R-Plt), or after a 60-min sham operation (sham-Plt). Plt were infused into isolated rat hearts (n = 124) and subsequently submitted to 60 min of ischemia and 60 min of reperfusion. P-selectin expression was higher (P = 0.02) in R-Plt than in pre-CO-Plt or sham-Plt. Lactate dehydrogenase (LDH) release during reperfusion was similar in hearts receiving pre-CO-Plt, sham-Plt, or no Plt, but R-Plt increased LDH release by 60% (P = 0.004). Activation of pre-CO-Plt with thrombin increased P-selectin expression and LDH release (P < 0.001), and these results were unaffected by tirofiban. There was a close correlation between P-selectin expression and LDH release (r = 0.84; P < 0.001), and myocardial Plt accumulation (r = 0.85; P < 0.001). We conclude that the deleterious effect of Plt on reperfused myocardium depends on their activation status as represented by P-selectin expression, which is enhanced by ischemia-reperfusion.

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“…Attempts to reduce the mortality associated with ischaemic heart disease have considered the importance of platelet activation in acute coronary syndromes due to the ability of platelet-derived compounds to alter myocardial perfusion and the electrophysiological properties of the heart (Flores, 1996;Flores et al, 1999a). A clear understanding of the underlying mechanisms and the ways through which the heart may become vulnerable to arrhythmogenesis following platelet activation remains a primary objective.…”

Section: Introductionmentioning

confidence: 99%

Changes in extracellular pH and myocardial ischaemia alter the cardiac effects of diadenosine tetraphosphate and pentaphosphate

Stavrou

Beck

Flores

2001

British J Pharmacology

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1 The structural conformation of diadenosine tetraphosphate (Ap 4 A) and pentaphosphate (Ap 5 A) has been reported to alter as pH is reduced. As such, it is possible that the cardiac eects of Ap 4 A and Ap 5 A vary during acidosis and myocardial ischaemia due to changes in ligand structure, receptor proteins or intracellular signalling. 2 We investigated whether the cardiac electrophysiological and coronary vasomotor eects of Ap 4 A and Ap 5 A are preserved under conditions of extracellular acidosis (pH 6.5) and alkalosis (pH 8.5) and whether Ap 4 A has any electrophysiological or antiarrhythmic eects during ischaemia. 3 Transmembrane right ventricular action potentials, refractory periods and coronary perfusion pressure were recorded from isolated, Langendor-perfused guinea-pig hearts under constant¯ow conditions. The eects of 1 nM and 1 mM Ap 4 A and Ap 5 A were studied at pH 7.4, 6.5 and 8.5. The eects of 1 mM Ap 4 A were studied during global low-¯ow ischaemia and reperfusion. 4 At pH 7.4, Ap 4 A and Ap 5 A increased action potential duration (APD 95 ) and refractory period (RP) and reduced coronary perfusion pressure. The electrophysiological eects were absent at pH 6.5 while the reductions in perfusion pressure were attenuated. At pH 8.5, Ap 4 A increased RP but the eects of Ap 4 A and Ap 5 A on perfusion pressure were attenuated. During ischaemia, Ap 4 A had no antiarrhythmic or electrophysiological eects. 5 These data demonstrate the importance of extracellular pH in in¯uencing the eects of Ap 4 A and Ap 5 A on the heart and indicate that any potentially cardioprotective eects of these compounds during normal perfusion at physiological pH are absent during ischaemia.

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Cardiac electrophysiological effects of platelet-derived substances

Cited by 6 publications

References 66 publications

Platelets and Cardiac Arrhythmia

Platelets and Cardiac Arrhythmia

Platelets activated by transient coronary occlusion exacerbate ischemia-reperfusion injury in rat hearts

Changes in extracellular pH and myocardial ischaemia alter the cardiac effects of diadenosine tetraphosphate and pentaphosphate

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