The effects of intravenous infusions of selective adenosine A1-receptor and A2-receptor agonists on myocardial reperfusion injury

Norton, Elizabeth Daughtry; Jackson, Edwin K.; Turner, Michael; Virmani, Renu; Forman, Mervyn B.

doi:10.1016/0002-8703(92)90643-a

Cited by 103 publications

(70 citation statements)

References 22 publications

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“…It appears to be a receptor-mediated effect and involves inhibition of neutrophil-related processes. 27 Adenosine, administered before ischemia, exerts a protective effect similar to preconditioning, and preconditioning in an animal model can be blocked by selective A 1 receptor antagonists. 28 In this study, adenosine was administered after the onset of ischemia, so a preconditioning effect is not expected.…”

Section: Mechanisms For the Cardioprotective Effect Of Adenosinementioning

confidence: 99%

Beneficial Effects of Intracoronary Adenosine as an Adjunct to Primary Angioplasty in Acute Myocardial Infarction

et al. 2000

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Background —The benefits of vessel recanalization in acute myocardial infarction (AMI) are limited by reperfusion damage. In animal models, adenosine limits reperfusion injury, reducing infarct size and improving ventricular function. The aim of this study was to evaluate the safety and feasibility of adenosine adjunct to primary PTCA in AMI. Methods and Results —Fifty-four AMI patients undergoing primary PTCA were randomized to intracoronary adenosine or saline. The 2 groups were similar for age, sex, and infarct location. Adenosine administration was feasible and well tolerated. PTCA was successful in all patients and resulted in TIMI 3 flow in all patients given adenosine and in 19 given saline ( P <0.05). The no-reflow phenomenon occurred in 1 adenosine patient and in 7 saline patients ( P =0.02). Creatine kinase was lower in the adenosine group, and a Q-wave MI developed in 16 adenosine patients and in 23 saline patients ( P =0.04). Sixty-four percent of dyssynergic segments improved in the adenosine group and 36% in the saline group ( P =0.001). Function worsened in 2% of dyssynergic segments in the adenosine group and in 20% in the saline group ( P =0.0001). Adverse cardiac events occurred in 5 patients in the adenosine group and in 13 patients in the saline group ( P =0.03). Conclusions —Intracoronary adenosine administration is feasible and well tolerated in AMI. Adenosine adjunct to primary PTCA ameliorates flow, prevents the no-reflow phenomenon, improves ventricular function, and is associated with a more favorable clinical course.

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Section: Mechanisms For the Cardioprotective Effect Of Adenosinementioning

confidence: 99%

Beneficial Effects of Intracoronary Adenosine as an Adjunct to Primary Angioplasty in Acute Myocardial Infarction

et al. 2000

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“…13 Genetic deletion of A 1 and A 2a receptors attenuated the cardioprotective effects of ischemic postconditioning. 14,15 Furthermore, exogenous infusion of NECA, a nonselective A 1 /A 2 receptor agonist, 16 and CGS-21680, a selective A 2a receptor agonist, 17 immediately after prolonged ischemia had a pronounced infarct-limiting effect in the isolated rat heart and in vivo rabbit model, respectively. Taken together, these experimental data strongly suggest that adenosine can exhibit a potent cardioprotective effect when administered at the onset of myocardial reperfusion.…”

Section: Introductionmentioning

confidence: 99%

Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles

Galagudza¹,

Королев²,

Постнов³

et al. 2012

IJN

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Pharmacological agents suggested for infarct size limitation have serious side effects when used at cardioprotective doses which hinders their translation into clinical practice. The solution to the problem might be direct delivery of cardioprotective drugs into ischemic-reperfused myocardium. In this study, we explored the potential of silica nanoparticles for passive delivery of adenosine, a prototype cardioprotective agent, into ischemic-reperfused heart tissue. In addition, the biodegradation of silica nanoparticles was studied both in vitro and in vivo. Immobilization of adenosine on the surface of silica nanoparticles resulted in enhancement of adenosine-mediated infarct size limitation in the rat model. Furthermore, the hypotensive effect of adenosine was attenuated after its adsorption on silica nanoparticles. We conclude that silica nanoparticles are biocompatible materials that might potentially be used as carriers for heart-targeted drug delivery.

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“…Activation of A 1 and A 3 receptors before ischemia is cardioprotective (2,19,20,24,30,33,37,38,41), whereas A 2A and A 2B receptors appear to exert their effects during reperfusion (10,13,17,18,28,34,42,43). Adenosine A 3 receptor activation during reperfusion has been reported to be cardioprotective (8), but there are conflicting reports on whether A 1 receptor activation during reperfusion is beneficial (3,7,30,39,40). Likewise, all four adenosine receptors have been reported to activate protein kinases that appear to play a critical role in adenosine-mediated cardioprotection (9,17,33,35).…”

mentioning

confidence: 99%

Adenosine A_2A and A_2B receptors are both required for adenosine A₁ receptor-mediated cardioprotection

Zhan

McIntosh

Lasley

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Zhan E, McIntosh VJ, Lasley RD. Adenosine A2A and A2B receptors are both required for adenosine A1 receptor-mediated cardioprotection. Am J Physiol Heart Circ Physiol 301: H1183-H1189, 2011. First published July 8, 2011; doi:10.1152/ajpheart.00264.2011.-All four adenosine receptor subtypes have been shown to play a role in cardioprotection, and there is evidence that all four subtypes may be expressed in cardiomyocytes. There is also increasing evidence that optimal adenosine cardioprotection requires the activation of more than one receptor subtype. The purpose of this study was to determine whether adenosine A2A and/or A2B receptors modulate adenosine A1 receptor-mediated cardioprotection. Isolated perfused hearts of wildtype (WT), A2A knockout (KO), and A2BKO mice, perfused at constant pressure and constant heart rate, underwent 30 min of global ischemia and 60 min of reperfusion. The adenosine A1 receptor agonist N 6 -cyclohexyladenosine (CHA; 200 nM) was administrated 10 min before ischemia and for the first 10 min of reperfusion. Treatment with CHA significantly improved postischemic left ventricular developed pressure (74 Ϯ 4% vs. 44 Ϯ 4% of preischemic left ventricular developed pressure at 60 min of reperfusion) and reduced infarct size (30 Ϯ 2% with CHA vs. 52 Ϯ 5% in control) in WT hearts, effects that were blocked by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (100 nM). Treatments with the A2A receptor agonist CGS-21680 (200 nM) and the A2B agonist BAY 60-6583 (200 nM) did not exert any beneficial effects. Deletion of adenosine A2A or A2B receptor subtypes did not alter ischemia-reperfusion injury, but CHA failed to exert a cardioprotective effect in hearts of mice from either KO group. These findings indicate that both adenosine A2A and A2B receptors are required for adenosine A1 receptor-mediated cardioprotection, implicating a role for interactions among receptor subtypes.A2a adenosine receptor; A2b adenosine receptor; knockout mice THE BENEFICIAL EFFECTS of adenosine in the ischemic-reperfused myocardium have been recognized for Ͼ25 yr. Adenosine can exert protection when given either before ischemia or at the onset of reperfusion. Substantial evidence now exists that these cardioprotective effects are achieved by the activation of extracellular adenosine receptors. All four adenosine receptor subtypes (A 1 , A 2A , A 2B , and A 3 ) are expressed in the heart, and there is evidence that all four receptors may be expressed in ventricular myocytes (4,15,26,42).There is substantial evidence that the activation of all four adenosine receptors is cardioprotective, although there do appear to be differences in the specific roles of each receptor subtype. Activation of A 1 and A 3 receptors before ischemia is cardioprotective (2,19,20,24,30,33,37,38,41), whereas A 2A and A 2B receptors appear to exert their effects during reperfusion (10,13,17,18,28,34,42,43). Adenosine A 3 receptor activation during reperfusion has been reported to be cardioprotective (8), but there are conflicting reports on ...

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The effects of intravenous infusions of selective adenosine A1-receptor and A2-receptor agonists on myocardial reperfusion injury

Cited by 103 publications

References 22 publications

Beneficial Effects of Intracoronary Adenosine as an Adjunct to Primary Angioplasty in Acute Myocardial Infarction

Beneficial Effects of Intracoronary Adenosine as an Adjunct to Primary Angioplasty in Acute Myocardial Infarction

Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles

Adenosine A_2A and A_2B receptors are both required for adenosine A₁ receptor-mediated cardioprotection

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