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Pyrroloquinoline Quinone (PQQ) Decreases Myocardial Infarct Size and Improves Cardiac Function in Rat Models of Ischemia and Ischemia/Reperfusion

  • Basic Pharmacology
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Summary

As pyrroloquinoline quinone (PQQ) is a redox cofactor in mammals, we asked if it is cardioprotective. Rats were subjected to 2 h of left anterior descending (LAD) coronary artery ligation without reperfusion (model 1, ischemia). In model 2 (ischemia/reperfusion), rats were subjected to 17 or 30 min of LAD occlusion and 2 h of reperfusion. PQQ (15–20 mg/kg) was given i.p., either 30 min before LAD occlusion (Pretreatment) or i.v. at the onset of reperfusion (Treatment). In model 1, PQQ reduced infarct size (10.0 ± 1.5 vs 19.1 ± 2.1%, P < 0.01). In model 2, either PQQ Pretreatment or Treatment also reduced infarct size (18.4 ± 2.3 and 25.6 ± 3.5% vs 38.1 ± 2.6%, P < 0.01). PQQ resulted in higher LV developed pressure and LV (+)dP/dt after 1–2 h of reperfusion (P < 0.05), and fewer ventricular fibrillation episodes. PQQ dose (5–20 mg/kg) was inversely related to infarct size. PQQ reduced myocardial tissue levels of malondialdehyde (MDA), an indicator of lipid peroxidation (316 ± 88 vs 99 ± 14 nmol/g, P < 0.01). PQQ given either as Pretreatment or as Treatment at the onset of reperfusion is highly effective in reducing infarct size and improving cardiac function in a dose-related manner in rat models of ischemia and ischemia/reperfusion. The optimal dose in this study, which exhibited neither renal nor hepatic toxicity, was 15 mg/kg, but lower doses may also be efficacious. We conclude that PQQ, which appears to act as a free radical scavenger in ischemic myocardium, is a highly effective cardioprotective agent.

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Abbreviations

PQQ:

pyrroloquinoline quinone

ANOVA:

analysis of variance

LV:

left ventricle

VF:

ventricular fibrillation

LAD:

left anterior descending coronary artery

LVSP:

left ventricular systolic pressure

LVDP:

left ventricular developed pressure

MDA:

malondialdehyde

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Authors and Affiliations

  1. Cardiology Section, VA Medical Center; Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco

    Bo-qing Zhu, Hui-zhong Zhou, John R Teerlink & Joel S Karliner MD

  2. VA Medical Center, Cardiology 111C5, 4150 Clement Street, San Francisco, CA, 94121

    Joel S Karliner MD

Authors
  1. Bo-qing Zhu
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  2. Hui-zhong Zhou
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  3. Joel S Karliner MD
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Corresponding author

Correspondence to Joel S Karliner MD.

Additional information

This study was supported by the Charitable Leadership Foundation

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Zhu, Bq., Zhou, Hz., Teerlink, J.R. et al. Pyrroloquinoline Quinone (PQQ) Decreases Myocardial Infarct Size and Improves Cardiac Function in Rat Models of Ischemia and Ischemia/Reperfusion. Cardiovasc Drugs Ther 18, 421–431 (2004). https://doi.org/10.1007/s10557-004-6219-x

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