Role of Adenosine as Adjunctive Therapy in Acute Myocardial Infarction

Abstract

Although early reperfusion and maintained patency is the mainstay therapy for ST elevation myocardial infarction, experimental studies demonstrate that reperfusion per se induces deleterious effects on viable ischemic cells. Thus "myocardial reperfusion injury" may compromise the full potential of reperfusion therapy and may account for unfavorable outcomes in high-risk patients. Although the mechanisms of reperfusion injury are complex and multifactorial, neutrophil-mediated microvascular injury resulting in a progressive decrease in blood flow ("no-reflow" phenomenon) likely plays an important role. Adenosine is an endogenous nucleoside found in large quantities in myocardial and endothelial cells. It activates four well-characterized receptors producing various physiological effects that attenuate many of the proposed mechanisms of reperfusion injury. The cardioprotective effects of adenosine are supported by its role as a mediator of pre-and postconditioning. In experimental models, administration of adenosine in the peri-reperfusion period results in a marked reduction in infarct size and improvement in ventricular function. The cardioprotective effects in the canine model have a narrow time window with the drug losing its effect following three hours of ischemia. Several small clinical studies have demonstrated that administration of adenosine with reperfusion therapy reduces infarct 116

Cardiac purinergic signalling in health and disease

“…Acute Myocardial Infarction Study of Adenosine (AMISTAD) clinical trials showed that infusion of adenosine for 3 h resulted in a striking reduction in infarct size [631]. However, long-term stimulation of A2BR commenced after MI prevented cardiac remodelling in rats [632] and contributed to post-infarction heart failure [633].…”

Liposomes in Diagnosis and Treatment of Cardiovascular Disorders

“…causes hypotension and bradycardia because of its vasodilatory and negative chronotropic effects. 22 an experimental infarction study in rats, however, showed that an infusion with PeGylated liposomes augmented the cardioprotective effects of adenosine against ischemia/reperfusion injury and reduced its unfavorable hemodynamic effects.…”

Acute Myocardial Injury: A Perspective on Lethal Reperfusion Injury

“…In addition, mitochondrial, and sarcolemmal KATP channels are also potential cellular protection targets and continue to be evaluated in clinical studies [101,111]. Adenosine receptors (A1 and A2 subtypes) as well as protein kinase C receptors also continue to be targeted [112][113][114][115]; mitogen activated protein kinase blockers have also been evaluated [116,117]. Pharmacologic treatments aimed at the Reperfusion Injury Salvage Kinase (RISK) and Survivor Activating Factor Enhancement (SAFE) pathways that activate pro-survival pathways possibly by inhibiting opening of mPTP at the level of the mitochondria are being studied [111,[118][119][120][121].…”