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Cardiovascular Drugs and Therapy

, Volume 18, Issue 6, pp 421–431 | Cite as

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

  • Bo-qing Zhu
  • Hui-zhong Zhou
  • John R Teerlink
  • Joel S Karliner
Basic Pharmacology

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.

Key Words

myocardial infarct size ischemia-reperfusion (I/R) pyrroloquinoline quinone (PQQ) hemodynamics 

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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Copyright information

© Springer Science + Business Media, Inc. 2004

Authors and Affiliations

  • Bo-qing Zhu
    • 1
  • Hui-zhong Zhou
    • 1
  • John R Teerlink
    • 1
  • Joel S Karliner
    • 1
    • 2
  1. 1.Cardiology Section, VA Medical Center; Department of Medicine, and Cardiovascular Research InstituteUniversity of CaliforniaSan Francisco
  2. 2.VA Medical Center, Cardiology 111C5San Francisco

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