HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Pharmacological prevention of reperfusion injury in acute myocardial infarction. A potential role for adenosine as a therapeutic agent.

Abstract
The concept of reperfusion injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. Although the pathophysiology of reperfusion injury is complex, the major role that neutrophils play in this process is well known. Neutrophils generate free radicals, degranulation products, arachidonic acid metabolites and platelet-activating factors that interact with endothelial cells, inducing endothelial injury and neutralization of nitrous oxide vasodilator capacity. Adenosine, through its multi-targeted pharmacological actions, is able to inhibit some of the above-mentioned detrimental effects. The net protective of adenosine in in vivo models of reperfusion injury is the reduction of the infarct size, the improvement of the regional myocardial blood flow and of the regional function of the ischemic area. Additionally, adenosine preserves the post-ischemic coronary flow reserve, coronary blood flow and the post-ischemic regional contractility. In small-scale studies in patients with acute MI, treatment with adenosine has been associated with smaller infarcts, less no-reflow phenomenon and improved LV function. During elective PCI adenosine reduced ST segment shifts, lactate production and ischemic symptoms. During the last years, three relatively large placebo-controlled clinical trials have been conducted: Acute Myocardial Infarction Study of Adenosine Trial (AMISTAD) I and II and Attenuation by Adenosine of Cardiac Complications (ATTACC). In the AMISTAD trials, the final infarct size was reduced and the LV systolic function was improved by adenosine treatment, mainly in patients with anterior MI localization. However, morbidity and mortality were not affected. In the ATTACC study, the LV systolic function was not affected by adenosine, however, trends towards improved survival were observed in patients with anterior MI localization. The possibility of obtaining a Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the infarct-related artery in up to 95% of patients with acute MI (increasing the occurrence of reperfusion injury) has turned back the interest towards the protection of myocardial cells from the impending ischemic and reperfusion injury in which adenosine alone or together with other cardio-protective agents may exert important clinical effects.
AuthorsMiguel Quintana, Thomas Kahan, Paul Hjemdahl
JournalAmerican journal of cardiovascular drugs : drugs, devices, and other interventions (Am J Cardiovasc Drugs) Vol. 4 Issue 3 Pg. 159-67 ( 2004) ISSN: 1175-3277 [Print] New Zealand
PMID15134468 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Receptors, Adenosine A2
  • Vasodilator Agents
  • Adenosine
Topics
  • Adenosine (therapeutic use)
  • Clinical Trials as Topic (trends)
  • Humans
  • Myocardial Infarction (physiopathology, therapy)
  • Myocardial Reperfusion (adverse effects)
  • Myocardial Reperfusion Injury (etiology, physiopathology, prevention & control)
  • Primary Prevention (trends)
  • Receptors, Adenosine A2 (drug effects)
  • Vasodilator Agents (therapeutic use)
  • Ventricular Dysfunction, Left (physiopathology, therapy)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: