What does this research mean for the field?

The angiotensin II type 1 receptor blocker losartan protects the heart against ischemia/reperfusion injury through both bradykinin-dependent and bradykinin-independent mechanisms. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate the cardioprotective effects of preconditioning with the AT1 receptor blocker losartan against ischemia/reperfusion injury and examine the role of bradykinin B2 receptors in this process.

November 7, 2000Circulation

Myocardial Protection by Preconditioning of Heart With Losartan, an Angiotensin II Type 1-Receptor Blocker : Implication of Bradykinin-Dependent and Bradykinin-Independent Mechanisms

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Why the study?

Does losartan provide cardioprotection against ischemia/reperfusion injury in isolated rat hearts, and is it mediated by bradykinin B2 receptors?

Population

Isolated rat hearts subjected to 30 minutes of normothermic global ischemia followed by 2 hours of reperfusion

Comparison

Losartan and/or HOE 140 perfused via Langendorff… vs Control (Krebs-Henseleit buffer alone)

Design

Preclinical, randomly assigned

Follow-up

2 hours of reperfusion

Authors

MSMasa H. SatoKyoto Prefectural University RERichard M. EngelmanCardiac Surgery HOHajime OtaniKansai Medical University

Discussion

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Implication

Losartan may confer B2 receptor-mediated cardioprotection in rat hearts; leaves open translation to human ischemia/reperfusion injury.

Key Points

To evaluate the cardioprotective effects of preconditioning with the AT1 receptor blocker losartan against ischemia/reperfusion injury and examine the role of bradykinin B2 receptors in this process.
Isolated rat hearts were perfused in Langendorff mode with Krebs-Henseleit buffer with or without losartan (4.5 µmol/L), the bradykinin B2 receptor blocker HOE 140 (10 µmol/L), or both.
Randomly assigned hearts were switched to working mode and subjected to 30 minutes of normothermic global ischemia followed by 2 hours of reperfusion.
Functional recovery (developed pressure, aortic flow), myocardial infarct size, apoptotic cell death, and release of bradykinin and angiotensin were quantified during reperfusion.
Preconditioning with losartan significantly enhanced postischemic ventricular recovery by improving developed pressure and aortic flow while reducing myocardial infarct size and apoptotic cell death relative to control.
Treatment with HOE 140 exacerbated ischemia/reperfusion injury, partially attenuated losartan-induced functional recovery and infarct reduction, and completely blocked the antiapoptotic action of losartan.

Structured PICO

Does losartan provide cardioprotection against ischemia/reperfusion injury in isolated rat hearts, and is it mediated by bradykinin B2 receptors?

Population

Isolated rat hearts subjected to 30 minutes of normothermic global ischemia followed by 2 hours of reperfusion

Intervention

Losartan (4.5 micromol/L) and/or HOE 140 (10 micromol/L) perfused via Langendorff mode for 15 minutes prior to ischemia

Comparator

Control (Krebs-Henseleit buffer alone)

Outcome

Myocardial function (developed pressure and aortic flow), infarct size, cardiomyocyte apoptosis, and amount of bradykinin/angiotensin releasedsurrogate

Losartan provides cardioprotection against ischemia/reperfusion injury in rat hearts through both bradykinin-dependent and independent mechanisms.

Cite This Study

Sato et al. (2000) studied this question.

synapsesocial.com/papers/6a1a0eba05af093a17f6efda https://doi.org/10.1161/01.cir.102.suppl_3.iii-346

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Myocardial Protection by Preconditioning of Heart With Losartan, an Angiotensin II Type 1-Receptor Blocker : Implication of Bradykinin-Dependent and Bradykinin-Independent Mechanisms

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Myocardial Protection by Preconditioning of Heart With Losartan, an Angiotensin II Type 1-Receptor Blocker : Implication of Bradykinin-Dependent and Bradykinin-Independent Mechanisms

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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