Contrasting Effects of Cyclic AMP Increase Caused by β-Adrenergic Stimulation or by Adenylate Cyclase Activation on Ventricular Fibrillation Threshold of Isolated Rat Heart

Mg, Worthington; Lh, Opie

doi:10.1097/00005344-199210000-00013

Cited by 25 publications

(3 citation statements)

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“…These authors also showed that although forskolin markedly raised cyclic AMP levels it did not induce arrhythmias in this model, calling into question the link between cyclic AMP and ischaemia-induced arrhythmias. Recently Worthington & Opie (1992) have reported that the mechanism by which cyclic AMP is elevated has a profound influence on the fibrillation threshold in isolated rat hearts. Large increases in cyclic AMP caused by forskolin did not cause such a large decrease in fibrillation threshold as that produced following the smaller increases in cyclic AMP caused by isoprenaline.…”

Section: Discussionmentioning

confidence: 99%

Effect of flosequinan on ischaemia‐induced arrhythmias and on ventricular cyclic nucleotide content in the anaesthetized rat

Jones¹,

Frodsham²,

Dickinson³

et al. 1993

British J Pharmacology

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1 Flosequinan, milrinone, isoprenaline and forskolin given intravenously at similarly hypotensive doses have been evaluated in separate studies for their effect on ischaemia-induced arrhythmias and on ventricular cyclic nucleotide content following coronary artery ligation in the pentobarbitone anaesthetized rat. 2 Flosequinan did not affect mortality or arrhythmias following coronary artery ligation in either study and no change in ventricular cyclic nucleotide content was observed. 3 Isoprenaline caused a significant increase in mortality (P<0.05) in both studies whereas milrinone and forskolin caused a significant increase in mortality in only one of the two studies conducted. All three agents caused significant increases in cyclic AMP which were associated with increased incidence of arrhythmias. 4 When compared at similarly hypotensive doses, flosequinan, in contrast to milrinone, isoprenaline and forskolin, did not influence ischaemia-induced arrhythmias or raise ventricular cyclic nucleotide levels in the anaesthetized rat.

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Section: Discussionmentioning

confidence: 99%

Effect of flosequinan on ischaemia‐induced arrhythmias and on ventricular cyclic nucleotide content in the anaesthetized rat

Jones¹,

Frodsham²,

Dickinson³

et al. 1993

British J Pharmacology

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“…However, this may be because forskolin increases cAMP in a compartmentalized manner. 24 The complete mechanical failure observed after repeated stimulation with isoproterenol may be a result of the well-established harmful effects of excess cAMP. 25 The mechanism of protection elicited by ␤-adrenergic agonists is complex.…”

Section: Mechanism Of Protection: Camp Related?mentioning

confidence: 99%

Ischemic Preconditioning and the β-Adrenergic Signal Transduction Pathway

et al. 1999

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Background-Previous studies from our laboratory showed cyclic increases in tissue cAMP during a multiple-cycle preconditioning (PC) protocol, followed by attenuated cAMP accumulation during sustained ischemia. The aim of this study was to determine whether ischemia-induced activation of the ␤-adrenergic signaling pathway could act as a trigger in eliciting protection. Methods and Results-Isolated perfused rat hearts were preconditioned by 3ϫ5 minutes of global ischemia, interspersed by 5 minutes of reperfusion. ␤-Adrenergic responsivity was assessed by measurement of tissue cAMP generation after ␤-adrenergic agonist administration at the end of the PC protocol. Tissue cAMP, adenylyl cyclase, and protein kinase A (PKA) activities and ␤-adrenergic receptor characteristics were assessed at different times. The role of cAMP generation in eliciting PC was studied by investigation of functional recovery during reperfusion after 25 minutes of global ischemia after (1) cAMP increases in the trigger period were prevented with the ␤-adrenergic blocker alprenolol 7.5ϫ10 Ϫ5 mol/L and (2) increases in cAMP were elicited by administration of forskolin 10 Ϫ7 and 10 Ϫ6 mol/L or isoproterenol 10

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“…Compartmentalisation of cyclic AMP may be an explication for these effects. 25 On the other hand it is known that CHF is associated with a high incidence ofventricular arrhythmias and sudden cardiac death. Although numerous treatments are used, no single agent appears to provide adequate symptomatic relief and protection from sudden death in all patients.…”

Section: Discussionmentioning

confidence: 99%

Combined phosphodiesterase inhibition and β-blockade in the GI104313, decreases ischemia-induced arrhythmias in the rat

Cárceles

Aleixandre

Fuente

et al. 2001

Can J Anesth/J Can Anesth

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Purpose:The purpose of the present study was to evaluate the effects of G1104313, a chimeric molecule containing a phosphodiesterase inhibiting pyradazinone and a blocking phenoxpropanolamine, on ischemia-induced arrhythmias in anesthetized rats.Method: The coronary artery was occluded 15 rain after commencing drug administration and myocardial ischemia was maintained for 30 rain during which the heart rate and mean blood pressure were recorded. Cyclic AMP and GMP were determined by radio-immunoassay.Results: G1104313 (0. I /~molkg i plus 0.01 /~molkg Imi~l or I /~molkg I plus 0. I /~molkg Imin i) decreased the incidence of ventricular tachycardia (86% and 75%), ventricular fibrillation (28%, P <0.01 and 12%, P <0.001) and premature ventricular beats (I 64 + 27.0 and 114 + 28.5, P <0.05) following coronary artery ligation, resulting in a decrease in mortality (29% and 12%, P <0.05).Changes in cyclic nucleotide concentrations have been implicated in the genesis of ischemia-induced arrhythmias. However, in the present study G1104313 did not change the concentrations of adenosine 3': 5'-cyclic monophosphate (cyclic AMP) (I.0 + 0.07 pmolmg I, 1.0 + 0.05 pmolmg) or guanosine 3' : 5'-cyclic monophosphate (cyclic GblP) (0.025 + 0.008 pmolmg i protein, 0.017 + 0.004 pmolmg I protein) in the left ventricle during ischemia-induced arrhythmias in anesthetized rats compared to saline (0.9 + 0.1 pmolmg I and 0.013 + 0.002 pmolmg I, respectively). Conclusion:Our results demonstrate that, in rats, G1104313 induced a decrease in both incidence of arrhythmias and mortality which was not associated with changes in ventricular cyclic nucleotide content. (I,0 + 0,07 pmolmg I,1,0 + 0,05 pmolmg i) ou de GMP cydique (0,025 + 0,008 pmolmg I de prot~ine, 0,017 + 0, (0,9 + O, I pmolm~ I et 0,013 + 0,002 pmolmg -I, respectivement). Objectif Conclusion :Nos r~sultats d~montrent que, chez les rats, la GI104313 a r~duit I'incidence des arythmies et de la mortalitY, consequence non associ~e aux changements du contenu en nucl~otides cycliques ventriculaires.

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Contrasting Effects of Cyclic AMP Increase Caused by β-Adrenergic Stimulation or by Adenylate Cyclase Activation on Ventricular Fibrillation Threshold of Isolated Rat Heart

Cited by 25 publications

References 0 publications

Effect of flosequinan on ischaemia‐induced arrhythmias and on ventricular cyclic nucleotide content in the anaesthetized rat

Effect of flosequinan on ischaemia‐induced arrhythmias and on ventricular cyclic nucleotide content in the anaesthetized rat

Ischemic Preconditioning and the β-Adrenergic Signal Transduction Pathway

Combined phosphodiesterase inhibition and β-blockade in the GI104313, decreases ischemia-induced arrhythmias in the rat

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