Cardiac and coronary consequences of intracoronary platelet activating factor infusion in the domestic pig

Ezra, David; Laurindo, Francisco Rafael Martins; Czaja, J. F.; Snyder, Fred; Goldstein, Robert E.; Feuerstein, Giora

doi:10.1016/0090-6980(87)90261-9

Cited by 36 publications

(10 citation statements)

References 23 publications

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“…PAF has been detected in the effluent blood from the coronary sinus in patients with coronary artery disease undergoing atrial pacing (Montrucchio et al, 1986) and release of PAF from ischaemic-reperfused rabbit heart has been demonstrated (Montrucchio et al, 1989). The effects of PAF in the coronary circulation have been shown in a number of in vivo (Levi et al, 1984;Piper & Stewart, 1986;Man et al, 1990) and in vitro studies (Feuerstein et al, 1984;Jackson et al, 1986;Mehta et al, 1986;Ezra et al, 1987;Fiedler et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Interaction of vasoactive substances released by platelet‐activating factor in the rat perfused heart

Man

1991

British J Pharmacology

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1 The coronary vascular effects of platelet-activating factor (PAF) have been intensively studied and it has been proposed that they are mediated by the release of vasoactive substances. In this study, a cascade perfusion model using two rat perfused hearts was developed to investigate the properties of PAF-released vasoactive substances and the interplay of these substances. The properties of the vasoactive substances after an injection of PAF (100pmol) in the rat perfused heart were examined by collecting the effluent from the first heart for the perfusion of a second (recipient) heart. The presence of vasoconstrictor substances in the effluent was characterized by an increase in the perfusion pressure of the recipient heart. 2 Previous exposure of the recipient heart of PAF (100pmol) abolished the response of the heart to subsequent administration of PAF, but did not affect the response of the recipient heart to the effluent. This suggested that the coronary vasoconstrictor response of the recipient heart was not due to the presence of PAF in the effluent but to other vasoactive substances. 3 Pretreatment of the recipient heart with the leukotriene receptor antagonist, L-649,923 (5pM), partially reduced the vasoconstrictor effect of the effluent. Pretreatment of the first heart with indomethacin (2.8 pM) also partially reduced the vasoconstrictor effect of the effluent. The combination of indomethacin pretreatment of the first heart and L-649,923 pretreatment of the recipient heart completely abolished the vasoconstrictor effect of the effluent suggesting that both prostaglandins and leukotrienes are involved in the vasoconstrictor effect of the effluent. 4 Pretreatment of both hearts with L-649,923 or the first heart with the leukotriene synthesis inhibitor (MK-886, 10pUM) completely abolished the vasoconstrictor effect of the effluent. This suggested that the indomethacin sensitive vasoconstrictor component of the effluent might be regulated by leukotrienes in the first heart. However, infusion of leukotrienes (LTB4, LTC4 and LTD4) to the first heart did not reproduce this vasoconstrictor component of the effluent in the recipient heart. 5 In conclusion, our study demonstrated through the use of a leukotriene receptor antagonist, a leukotriene synthesis inhibitor and a cyclo-oxygenase inhibitor that the vasoconstrictor effect of the effluent of the rat perfused heart after an injection of PAF is mediated by leukotrienes and prostaglandins. The ability of leukotriene receptor blockade and inhibition of leukotriene synthesis to mimic the effect of indomethacin indicates that the production and/or release of cyclo-oxygenase products in the effluent by PAF can be modulated by leukotrienes. The inability of exogenously applied leukotrienes to modulate the production and/or the release of cyclo-oxygenase products in the effluent suggests that the PAF-induced production of prostaglandins may be mediated by intracellular leukotrienes or at sites not accessible to exogenously applied leukotrienes.

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Section: Introductionmentioning

confidence: 99%

Interaction of vasoactive substances released by platelet‐activating factor in the rat perfused heart

Man

1991

British J Pharmacology

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“…PAF also increased perfusion pressure indicating an increase in total coronary vascular resistance, and decreased developed tension during normal perfusion. Infusion or injection of PAF into intact dogs, pigs and rats has been shown to decrease coronary blood flow, myocardial contractility, blood pressure, cardiac output, heart rate, and myocardial oxygen consumption; to increase myocardial oxygen extraction and vascular resistance; and to produce metabolic acidosis and ST segment changes (Bessin et al, 1983;Feuerstein et al, 1984;Siren & Feuerstein, 1984;Sybertz et al, 1985;Ezra et al, 1987). Injection or perfusion of guinea-pig isolated hearts with PAF at concentrations up to 10-8M produced similar effects: reductions in coronary flow and myocardial contractile force, increases in perfusion pressure and coronary vascular resistance and also impaired atrioventricular conduction Levi et al, 1984;Baranes et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

“…Studies on intact animals and isolated hearts have shown the ability of PAF to increase the effects of myocardial ischaemia (Mickelson et al, 1988;Chakrabarty et al, 1988). Others have described the effects of exogenous PAF on myocardial contractility and vascular smooth muscle Bessin et al, 1983;Feuerstein et al, 1984;Levi et al, 1984;Sybertz et al, 1985; Baranes et al, 1986;Riedel et al, 1987;Ezra et al, 1987;Robertson et al, 1987;Siren & Feuerstein, 1989), while experiments performed on isolated, superfused papillary muscles suggest that PAF has direct myocardial electrophysiological effects, causing reductions in action potential duration, and increases in action potential amplitude and upstroke velocity (Camussi et al, 1984;Tamargo et al, 1985;Alloatti et al, 1986). Little is known about the cellular electrophysiological actions of PAF in intact hearts and an understanding of these is important if the effects of platelet activation are to be differentiated from those produced by PAF alone.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological and arrhythmogenic effects of platelet activating factor during normal perfusion, myocardial ischaemia and reperfusion in the guinea‐pig

Flores

Sheridan

1990

British J Pharmacology

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Platelet activating factor (PAF) is often used to study the effects of platelet activation. While direct myocardial electrophysiological effects of PAF have been described in superfused myocardial tissue, little is known about its actions on the whole heart. The cellular electrophysiological and arrhythmogenic effects of PAF (10−11 m, 10−10 m and 10−9 m) were studied during normal perfusion, global myocardial ischaemia and reperfusion in Langendorff‐perfused guinea‐pig hearts at 32°C. PAF (10−9 m) increased the incidence of ventricular fibrillation during ischaemia and reduced action potential duration (APD) during normal perfusion and early myocardial ischaemia (10−9 m and 10−10 m). PAF also reduced refractory period (RP) during normal perfusion (10−9 m) and early ischaemia (10−9 m and 10−10 m). PAF prevented recovery of APD (10−9 m) and RP (10−9 m and 10−10 m) during reperfusion. PAF at a concentration of 10−11 m had no electrophysiological effects. PAF (10−9 m) increased the QRS width of the electrocardiogram during late ischaemia while 10−10 m PAF raised pacing threshold during late ischaemia. Perfusion pressure was increased, and developed tension decreased by 10−9 m PAF. These results demonstrate that PAF has direct myocardial electrophysiological effects in the whole heart which occur during normal perfusion and are capable of augmenting the effects of myocardial ischaemia, but are independent of the presence of platelets.

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“…In isolated perfused hearts as well as in blood perfused in situ hearts, intracoronarily injected PAF produces a dose-related decrease in myocardial contractile force and a coronary constriction, resulting in a sustained coronary vasospasm at higher doses (12,13,16).…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular reactions and respiratory events during platelet activating factor-induced shock

et al. 1990

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The platelet activating factor (PAF), a low molecular phospholipid, plays an important role in inflammation, anaphylaxis, and shock state development. In the isolated perfused guinea pig heart, PAF induces a decrease in coronary flow and cardiac contractility and atrioventricular conduction disturbances. Furthermore, PAF mediates a powerful bronchoconstrictory action causing a severe impairment in respiratory function. In the present study an attempt was made to separate cardiac from respiratory events during PAF-induced shock in vivo. PAF was injected intravenously (0.1-10 micrograms/kg) into anesthetized guinea pigs ventilated with room air or 100% oxygen. Administration of 10 micrograms/kg PAF was uniformly lethal: already within 2 min, cardiac output decreased by 60% and end-diastolic left ventricular pressure increased markedly indicating cardiac failure. ECG recordings showed signs of acute myocardial ischemia. Arrhythmias occurred in terms of atrioventricular conduction delay. Blood pressure initially increased, then declined continuously to below baseline within 10 min. All animals died within 25 min. Ventilation with room air was paralleled by development of severe hypoxia. However, under ventilation with 100% oxygen a dissociation between PAF-mediated cardiac and respiratory effects occurred. It is concluded that the PAF-induced shock is primarily based on direct cardiac damage. Furthermore, the ECG signs of ischemia are most likely due to coronary spasms.

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Cardiac and coronary consequences of intracoronary platelet activating factor infusion in the domestic pig

Cited by 36 publications

References 23 publications

Interaction of vasoactive substances released by platelet‐activating factor in the rat perfused heart

Interaction of vasoactive substances released by platelet‐activating factor in the rat perfused heart

Electrophysiological and arrhythmogenic effects of platelet activating factor during normal perfusion, myocardial ischaemia and reperfusion in the guinea‐pig

Cardiovascular reactions and respiratory events during platelet activating factor-induced shock

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