Peripheral plasma adenosine release in patients with chronic heart failure

Franceschi, Frédéric; Deharo, Jean‐Claude; Giorgi, Roch; By, Youlet; Monserrat, Colette; Condo, Jocelyne; Ibrahim, Zein Shaban; Saadjian, A; Guieu, Régis

doi:10.1136/hrt.2008.155242

Cited by 21 publications

(15 citation statements)

References 57 publications

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“…Recently, we reported that in the canine chronic heart failure model upregulation of A1R and GIRK4 expression in the RA is correlated with APD shortening and high occurrence of adenosine-induced AF, suggesting that an increased sensitivity of failing atria to adenosine may be a risk factor for AF in heart failure 12 . In the current study, we found A1R and GIRK4 protein expression gradients between lateral RA and LA are also highly present in hearts with history of heart failure and/or AF (Figure 7B and Supplemental Figure VI), which in combination with the elevated levels of endogenous adenosine reported in heart failure patients 11 may initiate AF with an RA-to-LA DF gradient. The variety of disease history within each group may limit the ability to show the effects of independent disease remodeling on protein expression, which requires further investigation.…”

Section: Discussionsupporting

confidence: 61%

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Adenosine-Induced Atrial Fibrillation

Csepe

Hansen

et al. 2016

Circulation

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Background Adenosine provokes atrial fibrillation (AF) with a higher activation frequency in right atria (RA) versus left atria (LA) in patients, but the underlying molecular and functional substrates are unclear. We tested the hypothesis that adenosine-induced AF is driven by localized reentry in RA areas with highest expression of adenosine A1 receptor (A1R) and its downstream GIRK channels (IK,Ado). Methods We applied bi-atrial optical mapping and immunoblot mapping of various atrial regions to reveal the mechanism of adenosine-induced AF in explanted failing and non-failing human hearts (n=37). Results Optical mapping of coronary-perfused atria (n=24) revealed that adenosine perfusion (10–100μM) produced more significant shortening of action potential durations (APD80) in RA (from 290±45ms to 239±41ms, 17.3±10.4%; p<0.01) than LA (from 307±24ms to 286±23ms, 6.7±6.6%; p<0.01). In ten hearts, adenosine induced AF (317±116 sec) that, when sustained (≥2 min), was primarily maintained by one/two localized reentrant drivers in lateral RA. Tertiapin (10–100nM), a selective GIRK channel blocker, counteracted adenosine-induced APD shortening and prevented AF induction. Immunoblotting showed that the superior/middle lateral RA had significantly higher A1R (2.7±1.7 fold; p<0.01) and GIRK4 (1.7±0.8 fold; p<0.05) protein expression than lateral/posterior LA. Conclusions This study revealed a three-fold RA-to-LA A1R protein expression gradient in the human heart, leading to significantly greater RA vs. LA repolarization sensitivity in response to adenosine. Sustained adenosine-induced AF is maintained by reentrant drivers localized in lateral RA regions with the highest A1R/GIRK4 expression. Selective atrial GIRK channel blockade may effectively treat AF during conditions with increased endogenous adenosine.

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Section: Discussionsupporting

confidence: 61%

“…Moreover, endogenous production of adenosine during metabolic stress conditions (e.g. ischemia 8, 9 and heart failure 10, 11 ) has been suggested as a trigger of AF. In clinical and animal model studies 6, 7, 12, 13 , adenosine was shown to shorten atrial action potential duration (APD) and refractoriness that could in turn provoke AF.…”

Section: Introductionmentioning

confidence: 99%

Adenosine-Induced Atrial Fibrillation

Csepe

Hansen

et al. 2016

Circulation

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“…A2BR mRNA was overexpressed in the left ventricle of minipigs with heart failure [475]. Adenosine release in CHF was found in the periphery and not in the myocardium [476]. In patients with CHF, following exercise the plasma levels of adenosine increased, while those of ammonia decreased and it was suggested that the enhanced cardioprotective actions of adenosine after exercise may be an adaptive response in patients with CHF [477].…”

Section: Pathophysiology and Therapeutic Potentialmentioning

confidence: 99%

Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

119

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This review is a historical account about purinergic signalling in the heart, for readers to see how ideas and understanding have changed as new experimental results were published. Initially, the focus is on the nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory nerves, as well as in intracardiac neurons. Control of the heart by centers in the brain and vagal cardiovascular reflexes involving purines are also discussed. The actions of adenine nucleotides and nucleosides on cardiomyocytes, atrioventricular and sinoatrial nodes, cardiac fibroblasts, and coronary blood vessels are described. Cardiac release and degradation of ATP are also described. Finally, the involvement of purinergic signalling and its therapeutic potential in cardiac pathophysiology is reviewed, including acute and chronic heart failure, ischemia, infarction, arrhythmias, cardiomyopathy, syncope, hypertrophy, coronary artery disease, angina, diabetic cardiomyopathy, as well as heart transplantation and coronary bypass grafts.

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“…Second, we did not clarify the origin of the plasma adenosine, although it has been reported that the plasma adenosine level is higher in plasma obtained from the brachial vein (peripheral) than in that obtained from the coronary sinus in patients with chronic HF, suggesting that adenosine release occurs at a peripheral level and not at the myocardial level. 16 Third, the number of cardiac patients examined was relatively small; in particular, there were few severe cases of NYHA class III or IV in the present study. A clinical study with a larger number of cardiac patients is required.…”

Section: Novel Issues Of the Present Study And Study Limitationsmentioning

confidence: 73%