Sheng-Mai-San is protective against post-ischemic myocardial dysfunction in rats through its opening of the mitochondrial KATP channels.
The present study used isolated rat hearts to investigate whether (1) Sheng-Mei-San (SMS), a traditional Chinese formulation comprising Radix Ginseng, Radix Ophiopogonis and Fructus Schisandrae, is protective against post-ischemic myocardial dysfunction, and (2) whether the cardioprotective effect of SMS is related to scavenging of hydroxyl radicals and opening the mitochondrial KATP channels. The excised hearts of male Sprague-Dawley rats were perfused on a Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O2 and 5% CO2. Left ventricular end-diastolic pressure (LVEDP, mmHg), left ventricular developed pressure (LVDP, mmHg), +/-dP/dt (mmHg/s) and coronary flow (ml/min) were continuously monitored. All hearts were perfused for a total of 120 min consisting of a 30-min pre-ischemic period followed by a 30-min global ischemia and 60-min reperfusion. Lactate, lactate dehydrogenase (LDH) and 2,5-dihydroxybenzoic acid (2,5-DHBA) concentrations in the effluent were measured during reperfusion. Three days' treatment with SMS (1.67 ml/kg per day) inhibited the rise in LVEDP and improved the post-ischemic LVDP and +/-dP/dt significantly better than in the untreated control hearts during reperfusion. SMS increased the coronary flow at baseline, and during reperfusion. Pretreatment with 5-hydroxydecanoic acid (5-HD), a mitochondrial KATP channel blocker, abolished the inhibition of the rise in LVEDP, the increase in coronary flow and the improvement in LVDP and +/-dP/dt induced by SMS. SMS significantly attenuated the concentrations of lactate, LDH and 2,5-DHBA during reperfusion, but the pretreatment with 5-HD restored them; 5-HD alone did not affect the concentrations. SMS improved the post-ischemic myocardial dysfunction through opening the mitochondrial KATP channels.
Wang
Ningyuan
N
Second Department of Internal Medicine, Gifu University School of Medicine, Japan.
Minatoguchi
Shinya
S
Arai
Masazumi
M
Uno
Yoshihiro
Y
Nishida
Yoshio
Y
Hashimoto
Kazuaki
K
Xue-Hai
Chen
C
Fukuda
Kazunori
K
Akao
Seigo
S
Takemura
Genzou
G
Fujiwara
Hisayoshi
H
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D009202:Cardiomyopathies / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005841:Gentisates; D062385:Hydroxybenzoates / Q000378:metabolism; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D016277:Ventricular Function, Left
D002316:Cardiotonic Agents; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D005841:Gentisates; D062385:Hydroxybenzoates; D015221:Potassium Channels; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; C010925:2,5-dihydroxybenzoic acid