What question did this study set out to answer?

To evaluate whether acadesine elevates endogenous interstitial fluid adenosine levels during ischaemia and limits myocardial infarct size through adenosine receptor-mediated mechanisms.

April 1, 1995Cardiovascular Research

Acadesine reduces myocardial infarct size by an adenosine mediated mechanism

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Why the study?

Does acadesine reduce myocardial infarct size in an anesthetized rabbit model of ischemia-reperfusion?

Population

Anaesthetised rabbits subjected to 30 min left coronary artery occlusion and 120 min reperfusion.

Comparison

Acadesine infused intravenously beginning 30 min… vs Untreated group.

Design

Preclinical

Follow-up

120 min reperfusion

Authors

ZZZeyi ZhaoYunnan Observatories MWM. W. WilliamsUniversity of Edinburgh HSHiroki SatoOkayama University

Discussion

Member takes

Implication

Hypothesis-generating in rabbits; leaves open clinical translation of acadesine for human infarct reduction.

Key Points

To evaluate whether acadesine elevates endogenous interstitial fluid adenosine levels during ischaemia and limits myocardial infarct size through adenosine receptor-mediated mechanisms.
Anaesthetised rabbits underwent 30 minutes of left coronary artery occlusion followed by 120 minutes of reperfusion (n=33), with acadesine infused intravenously from 30 minutes preischaemia until 30 minutes into reperfusion.
Cardiac microdialysis in a separate cohort (n=22) measured interstitial fluid adenosine and metabolite concentrations across baseline, ischaemia, and early reperfusion.
The nonselective adenosine receptor antagonist 8-p-sulphophenyltheophylline (SPT) was administered during ischaemia-reperfusion or during reperfusion alone to assess receptor dependence.
Acadesine significantly reduced myocardial infarct size to 19.7 (SEM 2.9)% of the risk area compared with 29.4 (SEM 1.3)% in untreated controls (P < 0.05, n=8 per group).
The cardioprotective effect was prevented by SPT administered during ischaemia-reperfusion [infarct size 46.2 (SEM 3.0)%, n=8] or during reperfusion alone [42.7 (SEM 2.6)%, n=9].
Acadesine did not significantly increase dialysate adenosine levels preischaemia [0.094(0.032) microM] or during ischaemia [0.542(0.262) microM] compared to untreated ischaemic controls [0.339(0.146) microM].

Structured PICO

Does acadesine reduce myocardial infarct size in an anesthetized rabbit model of ischemia-reperfusion?

Population

Anaesthetised rabbits (n=55 total; 33 for infarct size, 22 for microdialysis) subjected to 30 min left coronary artery occlusion and 120 min reperfusion.

Intervention

Acadesine (1 mg.kg-1.min-1 for 5 min, then 0.2 mg.kg-1.min-1) infused intravenously beginning 30 min before coronary occlusion and ending 30 min after reperfusion, with or without adenosine receptor blocker 8-p-sulphophenyltheophylline (SPT).

Comparator

Untreated group.

Outcome

Myocardial infarct size (as % of risk area) and interstitial fluid (ISF) adenosine levels.surrogate

Acadesine reduces myocardial infarct size through an adenosine-mediated mechanism, despite not significantly augmenting interstitial fluid adenosine levels.

Cite This Study

Zhao et al. (1995) studied this question.

synapsesocial.com/papers/6a8975ddf8670bac6e334486 https://doi.org/10.1016/s0008-6363(96)88525-7

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Acadesine reduces myocardial infarct size by an adenosine mediated mechanism

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Acadesine reduces myocardial infarct size by an adenosine mediated mechanism

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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