What question did this study set out to answer?

To compare the cardioprotective efficacy of AMP579 versus adenosine administered at reperfusion on neutrophil activation, coronary endothelial injury, and final myocardial infarct size.

August 1, 2000Cardiovascular ResearchOpen Access

Comparative study of AMP579 and adenosine in inhibition of neutrophil-mediated vascular and myocardial injury during 24 h of reperfusion

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Why the study?

Does AMP579 reduce myocardial and vascular reperfusion injury compared to adenosine in a canine model of ischemia-reperfusion?

Population

Anesthetized dogs undergoing 1 hour of left anterior descending coronary artery occlusion followed by 24…

Comparison

AMP579 administered intravenously at reperfusion. vs Adenosine or saline control.

Design

Preclinical

Follow-up

24 hours

Authors

JBJason M. BuddeDavidson College

Discussion

Member takes

Implication

AMP579 merits testing in human reperfusion trials; leaves open translation from canine infarct reduction.

Key Points

To compare the cardioprotective efficacy of AMP579 versus adenosine administered at reperfusion on neutrophil activation, coronary endothelial injury, and final myocardial infarct size.
Anesthetized dogs underwent 1 h left anterior descending coronary artery occlusion followed by 24 h reperfusion.
Animals received interventions at reperfusion: saline control (n=8), AMPI (AMP579 50 µg/kg bolus + 3 µg/kg/min for 2 h; n=7), AMPII (AMP579 bolus only; n=7), AMPIII (AMP579 3 µg/kg/min for 2 h; n=7), or adenosine (140 µg/kg/min for 2 h; n=7).
Assessed in vitro superoxide production, neutrophil adherence to postischemic endothelium, myocardial blood flow, myeloperoxidase activity, and infarct size via triphenyltetrazolium chloride staining.
In vitro, AMP579 inhibited neutrophil superoxide generation more potently than adenosine (IC50 0.09±0.02 µM vs 3.9±1.1 µM; P<0.05).
Neutrophil adherence was significantly attenuated in AMPI (60±3 PMNs/mm²) and AMPIII (58±3 PMNs/mm²) versus Control (110±4 PMNs/mm²; P<0.05), whereas adenosine showed only modest attenuation (98±3 PMNs/mm²; P<0.05).
Infarct size was significantly reduced in AMPI (21±4%) and AMPIII (22±3%) compared to Control (38±3%; P<0.05) alongside lower myeloperoxidase activity, whereas adenosine did not significantly alter infarct size, myocardial blood flow, or myeloperoxidase.

Structured PICO

Does AMP579 reduce myocardial and vascular reperfusion injury compared to adenosine in a canine model of ischemia-reperfusion?

Population

Anesthetized dogs undergoing 1 hour of left anterior descending coronary artery occlusion followed by 24 hours of reperfusion (n=36).

Intervention

AMP579 administered intravenously at reperfusion (Group I: 50 microg/kg bolus followed by 3 microg/kg/min for 2 h; Group II: 50 microg/kg bolus alone; Group III: 3 microg/kg/min for 2 h).

Comparator

Adenosine (140 microg/kg/min i.v. for 2 h) or saline control.

Outcome

Inhibition of polymorphonuclear neutrophil (PMN) activation, PMN-mediated injury to coronary artery endothelium, and final infarct size.surrogate

Continuous infusion of AMP579 at reperfusion is more potent than adenosine in reducing infarct size and attenuating neutrophil-mediated reperfusion injury in a canine model.

Cite This Study

Jason M. Budde (2000) studied this question.

synapsesocial.com/papers/6a11e7ebdb195b84738e18a7 https://doi.org/10.1016/s0008-6363(00)00115-2

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Comparative study of AMP579 and adenosine in inhibition of neutrophil-mediated vascular and myocardial injury during 24 h of reperfusion

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Comparative study of AMP579 and adenosine in inhibition of neutrophil-mediated vascular and myocardial injury during 24 h of reperfusion

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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