Effects of the PAF antagonists BN50726 and BN50739 on arrhythmogenesis and extent of necrosis during myocardial ischaemia/reperfusion in rabbits

Chakrabarty, S.; Fluck, David; Flores, Nicholas A.; Sheridan, Desmond J.

doi:10.1111/j.1476-5381.1992.tb14510.x

Cited by 13 publications

(7 citation statements)

References 24 publications

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“…Because PAF is present in the inflammatory milieu following coronary ischemia (32), there has been interest in investigating PAFR antagonists as antiarrhythmic agents in ischemia-reperfusion injury. Indeed, PAFR antagonism has been shown to be effective in preventing post-ischemia arrhythmias ex vivo (33) and in vivo (34,35). Unfortunately, one PAFR antagonist has been shown to promote QT interval prolongation and coronary vasodilation, resulting in hypotension and arrhythmogenic potential (33).…”

Section: Discussionmentioning

confidence: 99%

Ability to Induce Atrial Fibrillation in the Peri-operative Period Is Associated with Phosphorylation-dependent Inhibition of TWIK Protein-related Acid-sensitive Potassium Channel 1 (TASK-1)

Harleton

Besana

Comas

et al. 2013

Journal of Biological Chemistry

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Background: Peri-operative atrial fibrillation (AF) is a common complication of thoracic surgery linked to inflammation. Results: TASK-1 current is absent from atrial myocytes isolated from AF dogs. The inhibition is phosphorylation-dependent, and threonine 383 is a PKC target in this model. Conclusion: TASK-1 inhibition and phosphorylation are associated with peri-operative AF. Significance: TASK-1 inhibition and phosphorylation are markers of peri-operative AF and are potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Ability to Induce Atrial Fibrillation in the Peri-operative Period Is Associated with Phosphorylation-dependent Inhibition of TWIK Protein-related Acid-sensitive Potassium Channel 1 (TASK-1)

Harleton

Besana

Comas

et al. 2013

Journal of Biological Chemistry

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“…In the isolated rabbit heart, the effects of PAF were platelet dependent (291). When reperfusion was performed in the presence of autologous platelets, there was a significant worsening of left ventricular function and an increased rate of ventricular arrhythmias, which were prevented by a PAF receptor antagonist (90). The effect of platelets was due to the release of histamine, thromboxane A 2 , and leukotrienes (291).…”

Section: B Role Of Paf In Ischemia-reperfusion Injury Of the Heartmentioning

confidence: 99%

Role of Platelet-Activating Factor in Cardiovascular Pathophysiology

Montrucchio

Alloatti

Camussi

2000

Physiological Reviews

336

310

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Platelet-activating factor (PAF) is a phospholipid mediator that belongs to a family of biologically active, structurally related alkyl phosphoglycerides. PAF acts via a specific receptor that is coupled with a G protein, which activates a phosphatidylinositol-specific phospholipase C. In this review we focus on the aspects that are more relevant for the cell biology of the cardiovascular system. The in vitro studies provided evidence for a role of PAF both as intercellular and intracellular messenger involved in cell-to-cell communication. In the cardiovascular system, PAF may have a role in embryogenesis because it stimulates endothelial cell migration and angiogenesis and may affect cardiac function because it exhibits mechanical and electrophysiological actions on cardiomyocytes. Moreover, PAF may contribute to modulation of blood pressure mainly by affecting the renal vascular circulation. In pathological conditions, PAF has been involved in the hypotension and cardiac dysfunctions occurring in various cardiovascular stress situations such as cardiac anaphylaxis and hemorrhagic, traumatic, and septic shock syndromes. In addition, experimental studies indicate that PAF has a critical role in the development of myocardial ischemia-reperfusion injury. Indeed, PAF cooperates in the recruitment of leukocytes in inflamed tissue by promoting adhesion to the endothelium and extravascular transmigration of leukocytes. The finding that human heart can produce PAF, expresses PAF receptor, and is sensitive to the negative inotropic action of PAF suggests that this mediator may have a role also in human cardiovascular pathophysiology.

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“…30 Likewise, platelet-activating factor antagonists ameliorated ischemia-induced VF in vivo in 2 study, 31 but not in others. 32,33 Moreover, platelet-activating factor and plateletactivating factor antagonists possess platelet-independent effects on ischemia-induced VF. 28 In most published studies, the IZ was not determined.…”

Section: Platelets and The Pathophysiological Reserve For Vfmentioning

confidence: 99%

Trapped Platelets Activated in Ischemia Initiate Ventricular Fibrillation

Dhanjal

Medina

Leem

et al. 2013

Circ: Arrhythmia and Electrophysiology

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Background-We tested the hypothesis that ischemia-induced ventricular fibrillation (VF) is facilitated by platelets, trapped regionally in the ischemic zone and activated to release arrhythmogenic secretome. Methods and Results-In a randomized study in blood-free, buffer-perfused isolated rat hearts, ischemic zone territory (34±1% of left ventricle) was selected so that ischemia evoked VF in only 42% of controls. VF incidence was increased to 91% (P<0.05) by coronary ligation-induced trapping of freshly prepared autologous platelets (infused before and during coronary ligation, with trapping confirmed by 111 In-labeled platelet autoradiographic imaging). Trapping of platelet secretome prepared ex vivo, or platelet-sized fluorospheres, did not increase ischemia-induced VF incidence. Secretome alone did, however, evoke VF in 2 sham coronary-ligated hearts. Perfusion did not activate infused platelets in sham coronary-ligated hearts, whereas ligation activated trapped platelets (assessed by thromboxane release). In a separate study, trapping whole-heparinized blood mimicked the ability of trapped platelets to increase VF incidence. This effect was not prevented by >5 days oral pretreatment in vivo with clopidogrel (10 mg/kg per day) or indomethacin (2.4 mg/kg per day). Conclusions-Platelets facilitate VF during acute ischemia independently of their ability to participate in occlusive thrombosis.Moreover, the effect is unresponsive to antiplatelet drugs commonly used. Labile secretome constituents appear to be responsible. This opens a novel avenue for antiarrhythmic drug research. (Circ Arrhythm Electrophysiol. 2013;6:995-1001.)

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Effects of the PAF antagonists BN50726 and BN50739 on arrhythmogenesis and extent of necrosis during myocardial ischaemia/reperfusion in rabbits

Cited by 13 publications

References 24 publications

Ability to Induce Atrial Fibrillation in the Peri-operative Period Is Associated with Phosphorylation-dependent Inhibition of TWIK Protein-related Acid-sensitive Potassium Channel 1 (TASK-1)

Ability to Induce Atrial Fibrillation in the Peri-operative Period Is Associated with Phosphorylation-dependent Inhibition of TWIK Protein-related Acid-sensitive Potassium Channel 1 (TASK-1)

Role of Platelet-Activating Factor in Cardiovascular Pathophysiology

Trapped Platelets Activated in Ischemia Initiate Ventricular Fibrillation

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