Comparison of pyrroloquinoline quinone and/or metoprolol on myocardial infarct size and mitochondrial damage in a rat model of ischemia/reperfusion injury.
The cardioprotective effectiveness of low-dose pyrroloquinoline quinone (PQQ, 3 mg/kg) was compared with metoprolol, a beta(1)-selective adrenoceptor antagonist. Rats underwent 30 minutes of left anterior descending coronary artery occlusion and 2 hours of reperfusion. Metoprolol and/or PQQ were given at the onset of reperfusion to mimic clinical treatment. Metoprolol and/or PQQ reduced infarct size and protected against ischemia-induced left ventricular dysfunction after 2 hours of reperfusion. Combined therapy augmented left ventricular developed pressure at the end of reperfusion. Metoprolol or PQQ alone enhanced mitochondrial respiratory ratios in ischemic and nonischemic myocardium. Although the PQQ/metoprolol combination therapy increased respiratory ratio values, the effects were small when compared with PQQ alone. Only PQQ decreased lipid peroxidation. Metoprolol and/or PQQ given at the onset of reperfusion reduce infarct size and improve cardiac function. Combination therapy further reduces infarct size. PQQ is superior to metoprolol in protecting mitochondria from ischemia/reperfusion oxidative damage.
Zhu
Bo-qing
BQ
Cardiology Section, VA Medical Center, Department of Medicine, University of California-San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.
Simonis
Ursula
U
Cecchini
Gary
G
Zhou
Hui-zhong
HZ
Li
Luyi
L
Teerlink
John R
JR
Karliner
Joel S
JS
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000097:blood; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008790:Metoprolol / Q000008:administration & dosage / Q000627:therapeutic use*; D008929:Mitochondria, Heart / Q000187:drug effects; D009203:Myocardial Infarction / Q000401:mortality / Q000473:pathology* / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000401:mortality / Q000473:pathology* / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D045542:PQQ Cofactor / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014693:Ventricular Fibrillation / Q000473:pathology
D000319:Adrenergic beta-Antagonists; D000975:Antioxidants; D002316:Cardiotonic Agents; D008315:Malondialdehyde; D045542:PQQ Cofactor; D003402:Creatine Kinase; D008790:Metoprolol