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December 21, 1999Circulation

Inhibition of the Na+/H+Exchanger Confers Greater Cardioprotection Against 90 Minutes of Myocardial Ischemia Than Ischemic Preconditioning in Dogs

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Key result

NHE-1 inhibition with BIIB 513 was more efficacious than ischemic preconditioning at reducing infarct size after a 90-minute ischemic insult (P<0.05).

Why the study?

Does NHE-1 inhibition reduce infarct size more effectively than ischemic preconditioning in a canine model of myocardial ischemia?

Population

Canine infarct model undergoing 60- or 90-minute coronary artery occlusion followed by 3 hours of reperfusion

Comparison

Specific NHE-1 inhibitor BIIB 513 administered… vs Ischemic preconditioning produced by 1 or four…

Design

Preclinical

Follow-up

3 hours of reperfusion

Authors

RGRichard J. GuminaThe Ohio State UniversityEBErich BuergerBoehringer Ingelheim (Germany)CEChristian EickmeierBoehringer Ingelheim (Germany)

Discussion

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Implication

Should not change clinical practice; leaves open translation of NHE-1 inhibition to human cardioprotection trials.

Structured PICO

Does NHE-1 inhibition reduce infarct size more effectively than ischemic preconditioning in a canine model of myocardial ischemia?

P
Population
Canine infarct model subjected to 60- or 90-minute coronary artery occlusion followed by 3 hours of reperfusion.
I
Intervention
Specific NHE-1 inhibitor BIIB 513 (0.75 or 3.0 mg/kg) administered 15 minutes before occlusion, alone or in combination with ischemic preconditioning
C
Comparator
Ischemic preconditioning (IPC) produced by 1 or four 5-minute coronary artery occlusions
O
Outcome
Infarct size as a percentage of the area at risk (IS/AAR) determined by TTC stainingsurrogate

Main Result

p-value: p=<0.05

NHE-1 inhibition provides greater cardioprotection than ischemic preconditioning against prolonged (90-minute) myocardial ischemia in a canine model, and their combination yields greater-than-additive benefits.

Cite This Study

Gumina et al. (1999) studied Myocardial ischemia. NHE-1 inhibitor BIIB 513 vs. Ischemic preconditioning (IPC) was evaluated on Infarct size as a percentage of the area at risk (IS/AAR) (p=<0.05). NHE-1 inhibition with BIIB 513 was more efficacious than ischemic preconditioning at reducing infarct size after a 90-minute ischemic insult (P<0.05).

synapsesocial.com/papers/6a33643f5d2f1ecbcf8b1bcfhttps://doi.org/10.1161/01.cir.100.25.2519
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Also Consider

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

  1. 1Preischaemic as well as postischaemic application of a Na+/H+ exchange inhibitor reduces infarct size in pigs1995 · 40 citations
  2. 2Protective effects of HOE642, a selective sodium-hydrogen exchange subtype 1 inhibitor, on cardiac ischaemia and reperfusion1995 · 422 citations
  3. 3Role of Activation of Protein Kinase C in the Infarct SizeLimiting Effect of Ischemic Preconditioning Through Activation of Ecto-5′-nucleotidase1996 · 122 citations
  4. 4Ischemic preconditioning preserves creatine phosphate and intracellular pH.1991 · 213 citations
  5. 5Characterization of high affinity binding sites for charybdotoxin in synaptic plasma membranes from rat brain. Evidence for a direct association with an inactivating, voltage-dependent, potassium channel.1990 · 89 citations