The influence of prostacyclin on coronary occlusion induced arrhythmia in cats

Dix, Robert K.; Kelliher, Gerald J.; Jurkiewicz, Nancy K.; Lawrence, Theodore

doi:10.1016/0161-4630(79)90101-0

Cited by 26 publications

(5 citation statements)

References 12 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.

108

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.

108

105

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“…In the present study, concentrations greater than 1 pg kg-' min-' could not be examined since in some animals they precipitated excessive decreases in mean arterial blood pressure, sometimes to below 40mm Hg. Dix et al (1979) have shown that in cats, prostacyclin can have both antiarrhythmic and arrhythmogenic activity, depending on dosage. In dogs prostacyclin in a dose of 0.5 pg kg-I min-1, has been shown to be antiarrhythmic (Au et al, 1979).…”

Section: Discussionmentioning

confidence: 99%

THE EFFECTS OF PROSTAGLANDINS E₂, F_2α, PROSTACYCLIN, FLURBIPROFEN AND ASPIRIN ON ARRHYTHMIAS RESULTING FROM CORONARY ARTERY LIGATION IN ANAESTHETIZED RATS

Coker

Parratt

1981

British J Pharmacology

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1 Various prostaglandins and inhibitors of prostaglandin synthesis were administered prior to acute coronary artery ligation in anaesthetized rats and their effects were assessed on the number and severity of the resulting early arrhythmias (ventricular ectopic activity; incidence and duration of ventricular tachycardia and of ventricular fibrillation). 2 Prostaglandin E2 (PGE2), PGF2c and prostacyclin all showed antiarrhythmic activity; in contrast flurbiprofen increased the incidence of ventricular fibrillation and mortality. 3 Both the number of ventricular ectopic beats and the incidence of ventricular fibrillation were reduced by aspirin.4 The results suggest that the release of endogenous PGE2, PGF2", and prostacyclin could reduce early post-infarction ventricular arrhythmias whilst the protective effect of aspirin in this model adds further support for the hypothesis that thromboxane release is involved in the genesis of these arrhythmias.

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“…Therefore one might suggest that both PGI2 and ASN decrease the small vascular resistance compartment of the myocardium, e.g., a decrease in vascular tone of arterioles most probably via the same mechanism. The effect on resistance vessels seems to be the major hemodynamic effect of PGI 2 in most peripheral organs, as can be concluded from hemodynamic studies in different animal species (1,2,6,7,12,15,17,18,24,38,39,46), where systemic blood pressure is profoundly decreased due to peripheral vasodilation.…”

Section: Discussionmentioning

confidence: 91%

“…Besides the potent inhibition of platelet aggregation (27), PGIe markedly decreases systemic blood pressure in a dose-dependent manner in several species under anaesthesia (1,2,6,7,12,15,17,18,24,38,46) and in conscious rats (39) and humans (43), indicating powerful vasodilator properties. This has led to a re-evaluation of the control mechanisms for the regulation of coronary blood flow (35).…”

Section: Introductionmentioning

confidence: 98%

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Effects of prostacyclin (PGI2) and adenosine (ASN) on total and regional blood flow of isolated, collateralized dog hearts

Scholtholt¹,

Birringer²,

Fiedler³

et al. 1981

Basic Res Cardiol

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Dogs were subjected to chronic occlusion of the left circumflex and the right coronary artery by ameroid-type constrictors 4-5 weeks before the experiments. The hearts were isolated, fibrillated and perfused with blood (100 mm Hg) from a support dog. Total and regional myocardial blood flow as well as peripheral coronary pressure (circumflex artery) were determined before and during infusion of PGI2 and ASN into the isolated hearts. Both drugs increased total and regional blood flow to all parts of the myocardium in a dose-dependent manner, PGI2 being 2-3 times more potent than ASN. The perfusion pressure for the collateral-dependent myocardium, the peripheral coronary pressure, decreased following high doses of both drugs. For PGI2 a dose level existed where total flow was increased, while peripheral coronary pressure remained unaffected. After termination of the infusion of PGI2, a peripheral coronary pressure rose above predrug level with the total blood flow still being elevated. These findings indicate a PGI2-induced dilatation of collateral vessels. In general, the hemodynamic profile within the isolated hearts and the support dogs was characterized by the pronounced vasodilatory effects of PGI2 on arterioles. However, these effects did not deteriorate further the non-homogenous blood flow distribution in the collateralized portions of the myocardium.

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The influence of prostacyclin on coronary occlusion induced arrhythmia in cats

Cited by 26 publications

References 12 publications

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

THE EFFECTS OF PROSTAGLANDINS E₂, F_2α, PROSTACYCLIN, FLURBIPROFEN AND ASPIRIN ON ARRHYTHMIAS RESULTING FROM CORONARY ARTERY LIGATION IN ANAESTHETIZED RATS

Effects of prostacyclin (PGI2) and adenosine (ASN) on total and regional blood flow of isolated, collateralized dog hearts

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The influence of prostacyclin on coronary occlusion induced arrhythmia in cats

Cited by 26 publications

References 12 publications

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

THE EFFECTS OF PROSTAGLANDINS E2, F2α, PROSTACYCLIN, FLURBIPROFEN AND ASPIRIN ON ARRHYTHMIAS RESULTING FROM CORONARY ARTERY LIGATION IN ANAESTHETIZED RATS

Effects of prostacyclin (PGI2) and adenosine (ASN) on total and regional blood flow of isolated, collateralized dog hearts

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THE EFFECTS OF PROSTAGLANDINS E₂, F_2α, PROSTACYCLIN, FLURBIPROFEN AND ASPIRIN ON ARRHYTHMIAS RESULTING FROM CORONARY ARTERY LIGATION IN ANAESTHETIZED RATS