Role of adenosine in the treatment of myocardial stunning

Forman, Mervyn B.; Velasco, Carlos

doi:10.1007/bf00053551

Cited by 17 publications

(6 citation statements)

References 58 publications

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“…In this regard, adenosine has a high-affinity for nucleoside transporters and bypasses many of the preliminary reactions in the purine salvage pathways, thereby accelerating recovery of the intracellular adenine nucleotide pool (26,116). This hypothesis is confirmed in preparations of both regional and global ischemia in which adenosine with or without an adenosine deaminase inhibitor results in a rapid increase in ATP levels following reperfusion (56).…”

Section: Adenosine Restores Key Metabolic Substratesmentioning

confidence: 88%

Role of Adenosine as Adjunctive Therapy in Acute Myocardial Infarction

Forman

Stone

Jackson

2006

Cardiovascular Drug Reviews

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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

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Section: Adenosine Restores Key Metabolic Substratesmentioning

confidence: 88%

Role of Adenosine as Adjunctive Therapy in Acute Myocardial Infarction

Forman

Stone

Jackson

2006

Cardiovascular Drug Reviews

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“…20 Adenosine can reduce stunning. 21 Calcium channel blockers administered prior to experimental coronary oc clusion attenuate postischemic stunning. 22 · 23 Verapamil and nifedipine improve systolic func tion even when the calcium channel blocker is administered 30 minutes after reflow.…”

Section: Transduction Defectmentioning

confidence: 99%

Can Myocardial Stunning Contribute to Myocardial Infarction During Coronary Artery Bypass Surgery?

Jain

1993

Journal of Cardiac Surgery

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Myocardial stunning commonly occurs after cardiopulmonary bypass (CPB). Myocardial stunning can be cardioprotective under some conditions, but in other situations may actually contribute to myocardial infarction (MI). Vascular endothelial stunning may be one of the mechanisms by which myocardial stunning can cause MI. It has been found that 15 minutes of reversible ischemia is enough to cause elevations in vascular resistance and impairment of vasodilator responsiveness. However, no correlation between contractile dysfunction and microvascular stunning has been observed. Transduction defects (increased oxygen extraction and consumption despite normal regional oxygen blood flow and delivery) may be another mechanism by which stunning predisposes to MI, indicating uncoupling of substrate utilization from energy production. In addition, abnormalities in wall motion, oxygen free radical toxicity, hypotension, use of inotropic agents (leading to increased oxygen consumption, high heart rates, and arrhythmias) increase the risk of cellular necrosis. Following CPB, flow limitations due to diffuse atherosclerosis in some areas may result in poor contractility, and newly grafted areas have a high probability of becoming ischemic and stunned. These areas are likely to contribute to MI.

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“…[5][6][7] Indeed, adenosine has been reported to decrease infarct size and improve mechanical function after a prolonged (90 to 120 minutes) coronary occlusion in closed-chest8-10 and open-chest11 dogs and to mitigate contractile dysfunction after brief (<20 minutes) ischemic periods followed by reflow in isolated rat hearts12 and after prolonged global ischemia in models of cardiopulmonary bypass in dogs.13 Adenosine Al-receptor agonists have been found to be beneficial in isolated rat hearts subjected to global ischemia,'4"15 suggesting that adenosine enhances cardiac tolerance to ischemia via activation of Al-receptors. There is also indirect evidence for a salutary effect of adenosine in experiments where its production was stimulated by a-adrenoreceptor agonists.…”

mentioning

confidence: 99%

Augmentation of endogenous adenosine attenuates myocardial 'stunning' independently of coronary flow or hemodynamic effects.

et al. 1993

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This study demonstrates that (1) administration of an adenosine deaminase inhibitor plus a nucleoside transport blocker is remarkably effective in augmenting myocardial adenosine levels during regional ischemia and subsequent reperfusion in vivo, (2) this augmentation of adenosine results in a significant and sustained attenuation of myocardial stunning, and (3) the attenuation of stunning is not due to ATP repletion or to nonspecific actions on hemodynamic variables or coronary flow. These findings suggest that endogenous adenosine production during ischemia serves as an important pathophysiological mechanism that protects against myocardial stunning. The results also suggest that augmentation of endogenous adenosine (without exogenous adenosine administration) represents an effective therapeutic approach to the alleviation of reversible postischemic dysfunction.

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Role of adenosine in the treatment of myocardial stunning

Cited by 17 publications

References 58 publications

Role of Adenosine as Adjunctive Therapy in Acute Myocardial Infarction

Role of Adenosine as Adjunctive Therapy in Acute Myocardial Infarction

Can Myocardial Stunning Contribute to Myocardial Infarction During Coronary Artery Bypass Surgery?

Augmentation of endogenous adenosine attenuates myocardial 'stunning' independently of coronary flow or hemodynamic effects.

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