Effects of sasanquasaponin on ischemia and reperfusion injury in mouse hearts.
We investigated effects of sasanquasaponin (SQS), a traditional Chinese herb's effective component, on ischemia and reperfusion injury in mouse hearts and the possible role of intracellular Cl- homeostasis on SQS's protective effects during ischemia and reperfusion. An in vivo experimental ischemia model was made in mice (weight 27-45 g) using ligation of left anterior descending coronary artery, and in vitro models were made in perfused hearts by stopping flow or in isolated ventricular myocytes by hypoxia. The in vivo results showed that SQS inhibited cardiac arrhythmias during ischemia and reperfusion. Incidence of arrhythmias during ischemia and reperfusion, including ventricular premature beats and ventricular fibrillation, was significantly decreased in the SQS-pretreated group (P<0.05). Results in perfused hearts showed that SQS suppressed the arrhythmias, prevented against ischemia-induced decrease in contract force and promoted the force recovery from reperfusion. Furthermore, intracellular Cl- concentrations ([Cl-]i) were measured using a MQAE fluorescence method in isolated ventricular myocytes in vitro. SQS slightly decreased [Cl-]i in non-hypoxic myocytes and delayed the hypoxia/reoxygenation-induced increase in [Cl-]i during ischemia and reperfusion (P<0.05). Our results showed that SQS protected against ischemia/reperfusion-induced cardiac injury in mouse hearts and that modulation of intracellular Cl- homeostasis by SQS would play a role in its anti-arrhythmia effects during ischemia and reperfusion.
Lai
Zhong-Fang
ZF
Department of Cell and Biological Pharmacology, Graduate School of Medical Sciences, Kumamoto University, Japan. lai-zf@gpo.kumamoto-u.ac.jp
Shao
Zhanqiang
Z
Chen
Yu-Zhen
YZ
He
Ming
M
Huang
Qiren
Q
Nishi
Katsuhide
K
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D003331:Coronary Vessels / Q000293:injuries / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007511:Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D010210:Papillary Muscles / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010477:Perfusion / Q000379:methods; D010946:Plants, Medicinal / Q000737:chemistry; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
C497504:22-O-angeloylcamelliagenin C-3-O-(glucopyranosyl-1-2)(glucopyranosyl-1-2-O-arabinopyranosyl-1-3-)glucopyranosiduronic acid; D002712:Chlorides; D004365:Drugs, Chinese Herbal; D012503:Saponins