The Cardioprotection Against Ischemic Injury By The Extract From Dendranthema Morifolium

BACKGROUNDAfter a certain period of myocardial ischemia, reperfusion can not absolutely recover its structure and function, on the contrary, aggravates the injury itself, such as appearing of arrhythmia, hemorrhagic necrosis, infarction extension, lower cardiac function, and so on. This phenomenon is called myocardial ischemia/reperfusion injury. Myocardial ischemia/reperfusion injury is a serious complication associated with cardiac intervention, such as coronary-artery bypass grafting, percutaneous transluminal coronary angioplasty and thromobolytic therapy, etc. So it is a very important problem to be solved to prevent against ischemia/reperfusion injury during myocardial ischemia/reperfusion injury and ischemia related heart diseases. Recent studies have indicated that oxygen paradox and calcium paradox elicit pathologic consequences during postischemic reperfusion.The flower of Dendranthema morifolium (ramat) tzvel. (DM) has been used as a folk medicine for sudorific, antidote and clearing away pathogenic heat in China. Previous studies showed that DM has beneficial effects on coronary heart disease and hypertension. The water extract of DM can dilate coronary artery, increase coronaryflow, reduce heart rates, influence myocardial contractility, alleviate the depression of ST segment induced by electrical stimulation at paraventricular nucleus, eliminate ventricular fibrillation in the isolated rabbit heart and recover the normal heartbeat. However, the effect of DM on ischemic myocardium has not been elucidated.OBJECTIVESTo investigate the effect of Dendranthema morifolium (Ramat) Tzvel (DM) on ischemic myocardium in different animal models.METHODS1. In vivo rat myocardial ischemia modelAnaesthetised rat was fixed and the heart was exposed. The left anterior descending coronary artery was ligated for 2 hours. The arterial blood was sampled for determination of the activities of creatine kinase (CK) and lactate dehydrogenase (LDH). At the end of the experiment, the hearts were isolated and the myocardial infarct area was measured.2. Recording of ST-T alterations in electrocardiogram of rats pretreated with pituitrin Lead II electrocardiogram was recorded in anaesthetised rat immediately after intravenous injection of pituitrin (0.6 U/kg) for 30 minutes. The alterations of ST-T were analyzed.3. In vivo canine myocardial ischemia modelAfter anaesthetization, the canine was fixed. A left thoracotomy was performed and a 4-0 suture was passed below the left descending coronary artery. The electrocardiogram was recorded before and after ligation of left descending coronary artery, respectively. The LDH and CK levels in plasma were measured befor the ligation and 1, 2, 3 hours after the ligation. At the end of the experiment, the canine was sacrifised and the heart was excised. The infarct area and heart weight weremeasured.4. Quantification of arrhythmiasQuantification of arrhythmias was achieved by using scoring systems of Curtis and Walker (1988).5. Langendorff perfused rat heart model and ischemia/reperfusion injury modelThe hearts were excised and immediately mounted on Langendorff apparatus, and were retrogradely perfused with a 95%02+5%CC>2 equilibrated Krebs-Henseleit (K-H) solution via the aorta at a constant pressure of 74 mmHg. The left anterior descending coronary artery was occluded for 120 min. Superoxide dismutase (SOD) and malondialdehyde (MDA) were determined as indicators of myocardial damage and membrane lipid peroxidation by using commercial analysis kits.RESULTS1. Myocardial ischemia model in rat induced by coronary artery ligation(1) Effect of DM on the myocardial infarct areas: Compared with the coronary artery ligation group, the myocardial infarct area was greatly decreased in all 3 DM groups after 2 hours of left anterior descending conory artery occlusion.(2) Effect of DM on the levels of serum LDH and CK in myocardial ischemia model: Compared with the coronary artery ligation group, the middle and high dose DM significantly decreased the levels of serum LDH and CK, and the low dose DM also significantly decreased the levels of serum LDH.2. Effects of DM on the changes of ST-T in ECG of rats pretreated with pituitrinAt 10 and 15 seconds after intravenous injection of pituitrin, in all 3 doses DM groups, the elevation of ST-T in ECG was depressed significantly.3. Effects of DM on MDA and SOD of isolated rat hearts subjected to ischemia/reperfusionTreatment with DM (0.5 g/L) significantly increased the activity of SOD anddecreased the content of MDA in the myocardium compared withischemia/reperfusion group.4. In vivo canine ischemic heart model(1) Effects of DM on the infarct sizeCompared with the coronary artery ligation group, the myocardial infarct area and weight were greatly decreased in all 3 DM groups after 3 hours of left anterior descending conory artery occlusion.(2) Effects of DM on serum LDH and CK after acute ischemia of canine hearts Compared with the coronary artery ligation group, within 3 hours ligation of left descending coronary artery, DM decreased the serum CKand LDH levels at 60min, 120min and 180min of ischemia.(3) Effects of DM on ischemic extent in myocardium determined by cardiac mapping Compared with the coronary artery ligation group, in all 3 DM groups, the elevation of ST summation (ZST), the summation of ST difference before and after ligation of left descending coronary artery, the number of mapping sites in which ST elevation was over 2mV (NST) and the ANST difference before and after the ligation decreased greatly.(4) Effects of DM on severity of arrythmia after occlusion of coronary artery of canine heartsCompared with the coronary artery ligation group, within 3 hours of ligation of left descending coronary artery, middle and high dose DM decreased the arrythmia score greatly.CONCLUTIONSIn the present study , it was demonstrated that the extract from Dendranthema morifolium (Ramat) Tzvel can protect myocardium against ischemia/reperfusion injury.