Pyrroloquinoline quinone (PQQ) decreases myocardial infarct size and improves cardiac function in rat models of ischemia and ischemia/reperfusion.
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.
Zhu
Bo-Qing
BQ
Cardiology Section, VA Medical Center, San Francisco, California 94121, USA.
Zhou
Hui-Zhong
HZ
Teerlink
John R
JR
Karliner
Joel S
JS
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006334:Heart Function Tests / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008315:Malondialdehyde / Q000737:chemistry / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D045542:PQQ Cofactor / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control
D008315:Malondialdehyde; D045542:PQQ Cofactor