Reduction in myocardial infarct size at 48 hours after brief intravenous infusion of ATL-146e, a highly selective adenosine A<sub>2A</sub> receptor agonist

Patel, Rajan A.G.; Glover, David K.; Broisat, Alexis; Kabul, Hasan Kutsi; Ruiz, Mirta; Goodman, Norman C.; Kramer, Christopher M.; Meerdink, Denis J.; Linden, Joel

doi:10.1152/ajpheart.00705.2008

Cited by 19 publications

(19 citation statements)

References 28 publications

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“…The exact role of adenosine and its receptors in the setting of exercise-mediated cardioprotection needs to be further evaluated. It has been previously reported that stimulation of A 2a R early after MI attenuates inflammation (73) and preserves cardiac function and that prereperfusion stimulation reduces infarct size (58) and attenuates contractile dysfunction in the remote LV. Subsequently, increased A 2a R signaling due to pre-MI exercise could be associated with cardioprotective effects in the early remodeling stages and may have paved the way for further antifibrotic mechanisms in the progressive remodeling progress.…”

Section: Adenosine Receptors Are Upregulated By Exercise: a Potentialmentioning

confidence: 97%

Exercise attenuates inflammation and limits scar thinning after myocardial infarction in mice

Puhl

Müller

Wagner

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Although exercise mediates beneficial effects in patients after myocardial infarction (MI), the underlying mechanisms as well as the question of whether an early start of exercise after MI is safe or even beneficial are incompletely resolved. The present study analyzed the effects of exercise before and reinitiated early after MI on cardiac remodeling and function. Male C57BL/6N mice were housed sedentary or with the opportunity to voluntarily exercise for 6 wk before MI induction (ligation of the left anterior descending coronary artery) or sham operation. After a 5-day exercise-free phase after MI, mice were allowed to reexercise for another 4 wk. Exercise before MI induced adaptive hypertrophy with moderate increases in heart weight, cardiomyocyte diameter, and left ventricular (LV) end-diastolic volume, but without fibrosis. In sedentary mice, MI induced eccentric LV hypertrophy with massive fibrosis but maintained systolic LV function. While in exercised mice gross LV end-diastolic volumes and systolic function did not differ from sedentary mice after MI, LV collagen content and thinning of the infarcted area were reduced. This was associated with ameliorated activation of inflammation, mediated by TNF-␣, IL-1␤, and IL-6, as well as reduced activation of matrix metalloproteinase 9. In contrast, no differences in the activation patterns of various MAPKs or adenosine receptor expressions were observed 5 wk after MI in sedentary or exercised mice. In conclusion, continuous exercise training before and with an early reonset after MI ameliorates adverse LV remodeling by attenuating inflammation, fibrosis, and scar thinning. Therefore, an early reonset of exercise after MI can be encouraged. exercise; remodeling; scar thinning; magnetic resonance imaging; fibrosis; myocardial infarction NEW & NOTEWORTHY Our data provide new insights into the exercise-mediated cardioprotection by implying that an early reinitiation of exercise after myocardial infarction attenuates left ventricular fibrosis and scar thinning, presumably by attenuating the coordinated proinflammatory response involving TNF-␣, IL-6, and IL-1␤. These findings could translate into clinical benefits in patients.CORONARY ARTERY DISEASE is the single most frequent cause of death worldwide. In Europe, every sixth man and every seventh woman will die of myocardial infarction (MI) (71). Those patients who survive MI frequently develop systolic heart failure due to the infarct-induced loss of functional myocardium per se and remodeling of the remainder of the left ventricular (LV) myocardium, which is frequently associated with thinning of the LV wall in the area of MI and its border zone, LV dilation, and systolic dysfunction. These parameters of myocardial remodeling are important prognostic markers for the long-term outcome of these patients. For instance, regional wall thinning is associated with postinfarction ventricular arrhythmia (36) and adverse outcome in patients undergoing coronary artery bypass surgery (87).Scar formation occurs secondary to isc...

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Section: Adenosine Receptors Are Upregulated By Exercise: a Potentialmentioning

confidence: 97%

Exercise attenuates inflammation and limits scar thinning after myocardial infarction in mice

Puhl

Müller

Wagner

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…Activation of A 1 and A 2A receptors has been shown to reduce ischemia-reperfusion injury in the heart (Schlack et al, 1993;Lozza et al, 1997). Brief intravenous infusion of ATL-146e, a selective adenosine A 2A receptor agonist (added 30 minutes before reperfusion), reduced myocardial infarct size at 48 hours after reperfusion after a period of ischemia (Patel et al, 2009). Selective A 3 receptor activation is cardioprotective in wild-type hearts and hearts overexpressing A 1 receptors.…”

Section: Ischemiamentioning

confidence: 99%

Purinergic Signaling and Blood Vessels in Health and Disease

2013

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“…A brief intravenous infusion of ATL-146e, a selective adenosine A2AR agonist (added 30 min before reperfusion), reduced myocardial infarct size at 48 h after ischaemiareperfusion perturbation [547]. Endogenous adenosine is an important mediator of ischaemic preconditioning and postconditioning (see [548]).…”

Section: Ischaemiamentioning

confidence: 99%

“…Infarct size was reduced after a brief intravenous infusion of a selective A2AR agonist, ATL-146e [547]. In a clinical trial, a high dose of intracoronary adenosine given during percutaneous coronary intervention (PCI) did not reduce infarct size [638].…”

Section: Myocardial Infarctionmentioning

confidence: 99%

Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

120

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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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Reduction in myocardial infarct size at 48 hours after brief intravenous infusion of ATL-146e, a highly selective adenosine A_2A receptor agonist

Abstract: Patel RA, Glover DK, Broisat A, Kabul HK, Ruiz M, Goodman NC, Kramer CM, Meerdink DJ, Linden J, Beller GA. Reduction in myocardial infarct size at 48 hours after brief intravenous infusion of ATL-146e, a highly selective adenosine A2A receptor agonist.

Cited by 19 publications

References 28 publications

Exercise attenuates inflammation and limits scar thinning after myocardial infarction in mice

Exercise attenuates inflammation and limits scar thinning after myocardial infarction in mice

Purinergic Signaling and Blood Vessels in Health and Disease

Cardiac purinergic signalling in health and disease

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