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December 1, 1993Journal of Cardiovascular Pharmacology

Role for the Na+/H+ Exchanger in Reperfusion Stunning in Isolated Perfused Rat Heart

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Why the study?

Does inhibition of Na+/H+ exchange with HOE 694 or amiloride improve recovery of aortic output and reduce arrhythmias in isolated perfused rat hearts subjected to ischemia-reperfusion?

Population

Isolated perfused working rat hearts subjected to 20-min global ischemia and reperfused for 30 min

Comparison

HOE 694 or amiloride administered as… vs Untreated controls subjected to the same…

Design

Preclinical

Follow-up

30 minutes

Key result

Pretreatment with HOE 694 (10-7M) increased recovery of aortic output after 30-minute reperfusion compared to controls (50.6% vs 38.5%, p<0.05) in isolated rat hearts.

Authors

ETEugene F. Du ToitLOLionel H. Opie

Discussion

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Overview

Hypothesis-generating for Na+/H+ inhibition in ischemia-reperfusion; leaves open translation to human cardioprotection.

Key Points

  • This research investigates how Na+/H+ exchange affects reperfusion stunning and arrhythmias in heart tissue.
  • Evaluated the effects of amiloride and HOE 694 on isolated perfused rat hearts.
  • Hearts underwent 20 minutes of global ischemia followed by 30 minutes of reperfusion.
  • Measurements included aortic output recovery during various pretreatment and reperfusion conditions.
  • HOE 694 pretreatment improved aortic output from 38.5% to 50.6% after reperfusion (p<0.05).
  • Reperfusion with HOE 694 raised aortic output recovery to 62.4% (p<0.002).
  • Amiloride showed lesser effectiveness, improving recovery to 55.8% during pretreatment (p<0.05).

Structured PICO

Does inhibition of Na+/H+ exchange with HOE 694 or amiloride improve recovery of aortic output and reduce arrhythmias in isolated perfused rat hearts subjected to ischemia-reperfusion?

P
Population
Isolated perfused rat hearts subjected to 20-minute global ischemia and 30-minute reperfusion to evaluate Na+/H+ exchange inhibitors.
I
Intervention
HOE 694 (10-7M or 10-6M) or amiloride (10-5M or 10-3M) administered as pretreatment (for 5 min before ischemia) or during reperfusion (initial 2 min)
C
Comparator
Untreated controls subjected to the same ischemia-reperfusion protocol
O
Outcome
Recovery of aortic output (AO) after 30-min reperfusionsurrogate

Main Result

Absolute Event Rate: 50.6% vs 38.5%

p-value: p=<0.05

The Na+/H+ exchange inhibitor HOE 694 limits reperfusion stunning and arrhythmias even when administered only during early reperfusion in isolated rat hearts.

Cite This Study

Toit et al. (1993) studied Reperfusion stunning and arrhythmias. HOE 694 and amiloride vs. Control was evaluated on Recovery of aortic output (AO) after 30-min reperfusion (p=<0.05). Pretreatment with HOE 694 (10-7M) increased recovery of aortic output after 30-minute reperfusion compared to controls (50.6% vs 38.5%, p<0.05) in isolated rat hearts.

synapsesocial.com/papers/6a237a3d96b50e6ae79ece76https://doi.org/10.1097/00005344-199312000-00016
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Comparative Effects of Na+/H+ Exchange Inhibitors Against Cardiac Injury Produced by Ischemia/Reperfusion, Hypoxia/Reoxygenation, and the Calcium Paradox1993 · 58 citations
  2. 2New Na(+)-H+ exchange inhibitor HOE 694 improves postischemic function and high-energy phosphate resynthesis and reduces Ca2+ overload in isolated perfused rabbit heart.1994 · 171 citations
  3. 3Na+/H+ exchange and reperfusion arrhythmias: protection by intracoronary infusion of a novel inhibitor1994 · 85 citations
  4. 4Effects of proton buffering and of amiloride derivatives on reperfusion arrhythmias in isolated rat hearts. Possible evidence for an arrhythmogenic role of Na(+)-H+ exchange.1990 · 101 citations
  5. 5Amiloride enhances postischemic ventricular recovery: possible role of Na+-H+ exchange1988 · 186 citations