The antiarrhythmic effect of PGE2 on premature ventricular beats (PVBs) in man

Mest, H.‐J.; Rausch, J

doi:10.1016/0262-1746(82)90083-x

Cited by 8 publications

(3 citation statements)

References 14 publications

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“…Infusion of PGI 2 or PGE 2 analogs restrains pharmacological and ischemia-induced arrhythmogenesis in animal models (41)(42)(43), and infusion of PGE 2 depresses premature ventricular beats dose-dependently in humans (44). However, despite the baroreflex effects of PGI 2 and PGE 2 , vagotomy and adrenergic blockade fail to modify their inhibitory effects on ouabain-induced arrhythmias in cats (45), suggesting a direct cardiac action.…”

Section: Discussionmentioning

confidence: 99%

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

Wang

Patel

Ricciotti

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

110

105

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Nonsteroidal anti-inflammatory drugs selective for inhibition of COX-2 increase heart failure and elevate blood pressure. The COX-2 gene was floxed and crossed into merCremer mice under the ␣-myosin heavy-chain promoter. Tamoxifen induced selective deletion of COX-2 in cardiomyocytes depressed cardiac output, and resulted in weight loss, diminished exercise tolerance, and enhanced susceptibility to induced arrhythmogenesis. The cardiac dysfunction subsequent to pressure overload recovered progressively in the knockouts coincident with increasing cardiomyocyte hypertrophy and interstitial and perivascular fibrosis. Inhibition of COX-2 in cardiomyocytes may contribute to heart failure in patients receiving nonsteroidal anti-inflammatory drugs specific for inhibition of COX-2.arrhythmia ͉ heart failure ͉ knockout ͉ NSAIDs ͉ fibrosis R andomized, placebo-controlled trials indicate that nonsteroidal antinflammatory drugs (NSAIDs) specific for inhibition of cyclooxygense (COX)-2 confer an increased risk of myocardial infarction and stroke (1-5), effects explicable by suppression of COX-2-derived products, such as prostacyclin (PGI 2 ) and prostaglandia E 2 (PGE 2 ) (6). While, the clinical spectrum of hazard is dominated by a predisposition to thrombosis, an additional feature has been congestive heart failure (1-4). NSAIDs may variably increase blood pressure (7): studies in rodents (8, 9) and a meta-analysis of clinical studies (10) suggest that this reflects inhibition of COX-2 and the specificity with which this is attained (11). Elevation of blood pressure by manipulation of the prostaglandin pathway is conditioned by genetic background in rodents (12). However, given this caveat, deletion or inhibition of COX-2 (8, 13) and deletion of the E prostanoid (EP)-2 receptor (14, 15) or the I-prostanoid receptor (IP) (16) for the COX-2 products, PGE 2 and PGI 2 respectively, may each result in hypertension. Indeed, deletion of the IP in these mice also results in cardiac hypertrophy and fibrosis, effects ameliorated by coincident deletion of the receptor for thromboxane A 2 , the TP, a maneuver that does not, alone, affect blood pressure (16). By contrast, inhibition or deletion of COX-1 attenuates the hypertensive response to infusion of angiotensin II (8) or treatment with a COX-2 inhibitor (13). Although placebo-controlled trials provide unequivocal evidence that COX-2-specific NSAIDs confer a cardiovascular hazard, the number of events within each trial are insufficient to permit analysis of covariates. Thus, it is unknown whether congestive heart failure on NSAIDs results solely from or is exacerbated by hypertension.Although suppression of COX-2-derived prostanoids is sufficient to explain the cardiovascular hazard conferred by purposedesigned and older NSAIDs specific for inhibition of COX-2 (17), there has been interest in the possibility that some or all of these effects might reflect ''off target'' effects. One such example was an overview-trial analysis interpreted to suggest that arrhythmia, cardiac arrest, ...

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Section: Discussionmentioning

confidence: 99%

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

Wang

Patel

Ricciotti

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

110

105

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“…The study performed on rabbits demonstrated that PGE 2 prevented drug-induced torsade de pointes, which is life-threatening arrhythmia (Farkas and Coker, 2003). Antiarrhythmic effect of PGE 2 was also demonstrated in humans (Mest and Rausch, 1983). In contrast, microinjection of PGE 2 in rats or superfusion of the rat cardiac myocytes with PGE 2 resulted in tachycardia (Li et al, 1997;Zaretskaia et al, 2003), whereas 41% of women receiving misoprostol, EP2/EP3/EP4 agonist, had late decelerations or bradycardias (Kolderup et al, 1999).…”

Section: Cardiovascular Systemmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin E₂Receptors (EP1–4) and Prostacyclin Receptor (IP): Specific Roles in Pathophysiologic Conditions

et al. 2020

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“…propranolol and 34% ajmaline) (Mest et al, 1977). PGE2 dose-dependently decreased the incidence of premature ventricular beats in men (Mest et Rausch, 1983) and reduced druginduced TdP ventricular tachyarrhythmia that action was not mediated by ATP-dependent K + channels (Farkas and Coker, 2003).…”

Section: Other Possible Mechanism Of Cardiac Actions Of Ibuprofenmentioning

confidence: 94%

The possible proarrhythmic effects of some non-antiarrhythmic drugs

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Human Embryonic Kidney cells hERG: human ether-a-go-go-related gene channel ICa,L: inward calcium current If: 'funny current' (the hyperpolarizing-activated current) IK1: inward rectifier potassium current IK-ACh: muscarinic-gated potassium current (acetylcholine-regulated potassium current) IK-ATP: ATP-sensitive potassium current IKr: rapid delayed rectifier potassium current IKs: slow delayed rectifier potassium current IKur: ultra-rapid delayed rectifier potassium current INa,L: 'window' or late sodium current INa/K: sodium-potassium pump current INa: voltage-dependent sodium current I NCX : sodium/calcium exchange current Ito,f: fast component of the transient outward potassium current Ito,s: slow component of the transient outward potassium current Kir: inward rectifier potassium channel Kv: voltage-dependent potassium channel LQTS: long QT syndrome M cell: midmyocardial cells Nav: voltage-dependent sodium channel NSAID(s): non-steroidal anti-inflammatory drug(s)

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The antiarrhythmic effect of PGE2 on premature ventricular beats (PVBs) in man

Cited by 8 publications

References 14 publications

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin E₂Receptors (EP1–4) and Prostacyclin Receptor (IP): Specific Roles in Pathophysiologic Conditions

The possible proarrhythmic effects of some non-antiarrhythmic drugs

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The antiarrhythmic effect of PGE2 on premature ventricular beats (PVBs) in man

Cited by 8 publications

References 14 publications

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin E2Receptors (EP1–4) and Prostacyclin Receptor (IP): Specific Roles in Pathophysiologic Conditions

The possible proarrhythmic effects of some non-antiarrhythmic drugs

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About

International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin E₂Receptors (EP1–4) and Prostacyclin Receptor (IP): Specific Roles in Pathophysiologic Conditions