The objective of the study was to investigate whether the lysosomal enzyme, N-Acetyl-beta-D-glucosaminidase (NAG) activity is increased in plasma of patients with acute myocardial infarction (AMI) and to determine if there is any association between plasma levels of NAG and severity of myocardial infarction (MI). NAG activity in plasma was monitored in 69 patients with AMI and 135 normal healthy subjects using a spectrofluorimetric method. A modified Aldrich ST elevation score was used to gauge the severity of MI in terms of size of the infarct. Plasma NAG levels in AMI patients and normal healthy subjects were found to be 10.92+/-7.5 U/l and 6.8+/-2.2 U/l, respectively. These two mean value when compared by Student's t-test were significantly different P = 0.0001. No statistically significant differences in NAG activity were observed in patients in terms of gender, age, location of infarct, time from onset of chest pain to blood sampling in the hospital and size of the infarct.
Acetylglucosaminidase/blood/*metabolism ; Adult ; Aged ; Female ; Human ; Male ; Middle Aged ; Myocardial Infarction/*enzymology/metabolism/physiopathology

OBJECTIVETo investigate the clinical implications of relationship between myeloperoxidase and acute coronary syndromes (ACS).

METHODS176 consecutive patients who underwent coronary angiography for coronary atherosclerosis were divided into four groups according to the quartile of MPO Level. The characters and the relationship between MPO and the elements were studied in every group.

RESULTS(1) ACS rate (36.2%) in the fourth quartile group of MPO level was 6 times higher than that (5.2%) in the first quartile group of MPO level, P < 0.01. (2) Gensini score (65.6 +/- 30.3) in the fourth quartile group of MPO level was significantly higher than that (17.3 +/- 10.2) in the first quartile group (P < 0.01). WBC [(7.7 +/- 1.6) x 10(9)/L] in the fourth quartile group was also significantly higher than that [(6.6 +/- 1.8) x 10(9)/L] in the first quartile group, P < 0.05. (3) When TnI < or = 0.05 ng/ml, MPO level had a positive correlation with Gensini score (r = 0.321, P = 0.002) and WBC (r = 0.230, P = 0.025). (4) Kaplan-meier event rate curve showed that there was a significant difference of the terminus incident (death, no causing death AMI, vessel reestablish and incidence rate of CABG add up) between the groups > or = 62.9 AUU/L and < 62.9 AUU/L of MPO serum level at 6-month follow-up visit (chi(2) = 13.5, P = 0.01).

CONCLUSIONActivity level of MPO in human serum seems a good biomarker for diagnosing and predicting ACS, which may be especially helpful in predicting the risk of myocardial infarction in patients with acute chest pain during 6-month follow up.

Acute Coronary Syndrome ; diagnostic imaging ; enzymology ; physiopathology ; Adult ; Angina, Unstable ; diagnostic imaging ; enzymology ; Coronary Angiography ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; enzymology ; Myocardial Ischemia ; diagnostic imaging ; enzymology ; Peroxidase ; blood ; Troponin I ; metabolism

OBJECTIVETo clarify the impact of increased heme oxygenase-1 (HO-1) expression on cardiac function of diabetic rats with myocardial infarction and its mechanism.

METHODSSixty adult male Wistar rats were randomly divided into five groups (n = 12): sham operation group (sham), diabetes + sham operation group (DM + sham), diabetes + MI group (DM + MI) , diabetes + myocardial infarction + cobalt original porphyrin (CoPP) group (DM + MI + CoPP), diabetes + myocardial infarction + CoPP+ tin porphyrin (SnMP) group (DM + MI + CoPP + SnMP). CoPP 4.5 mg/kg or SnMP 15 mg/kg were administered at the day next to MI operation, for six weeks, once a week. At the 28th week post operation, the echocardiography, left heart via the carotid artery indoor intubation were used to observe the long-term influence of HO-1 inducer (cobalt protoporphyrin, CoPP) and activity of HO inhibitor (tin porphyrin, SnMP) on the indices of left ventricular remodeling and cardiac function after the intervention. Blood glucose (GLU), total cholesterol (TC), C-reactive protein (CRP), serum creatinine (Cr), aminotransferase (ALT) and other indicators were measured. ELISA was used to test interleukin-6 (IL-6), tumor necrosis factor (TNF), nitric oxide (NO), prostacyclin (PGI2), adiponectin, and ultra sensitive CRP (HsCRP) level.

RESULTSHO-1 inducer, CoPP, could ameliorate ± dp/dtmax, left ventricular ejection fraction and left ventricular shortening fraction in diabetic myocardial infarction rats. It could also decrease left ventricular end-diastolic diameter. The serum bilirubin, NO and PGI2 levels, myocardial phosphorylated endothelial nitric oxide synthasee(peNOS), phosphorylated activated protein kinase (pAkt), phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) expression were also significantly elevated, and the serum hs-CRP and TNF levels were significantly inhibited. Compared to inducer group, cardiac function were worse in the inhibitor group.

CONCLUSIONUpregulated HO-1 level can improve the endothelial function, inhibite of the inflammatory response and enhance the antioxidant substances in serum bilirubin via peNOS-pAMPK pathway, which effectively inhibit ventricular remodeling and improve the long-term cardiac function after infarction in diabetic rats.

Animals ; Antioxidants ; metabolism ; Bilirubin ; blood ; Diabetes Mellitus, Experimental ; physiopathology ; Heme Oxygenase (Decyclizing) ; metabolism ; Male ; Myocardial Infarction ; enzymology ; Myocardium ; enzymology ; Rats ; Rats, Wistar ; Signal Transduction ; Up-Regulation ; Ventricular Function, Left ; Ventricular Remodeling ; drug effects

The aim of the present study was to investigate the protective effect of polydatin against myocardial ischemia/reperfusion injury in rats and the underlying mechanism. In anesthetized rats, ischemia and reperfusion arrhythmia produced by ligating and loosing the coronary artery was recorded and myocardial infarct size was measured. In Langendorff isolated rat heart, cardiac function was recorded before and after 30 min of global ischemia followed by 60 min of reperfusion. The parameters of cardiac function include left ventricular developed pressure (LVDP), maximal differentials of LVDP (±LVdp/dt(max)) and coronary flow (CF) were measured. Myocardial superoxide dismutase (SOD) activity, the contents of myocardial malondialdehyde (MDA) and nitric oxide (NO) as well as the activity of nitric oxide synthase (NOS) were measured in isolated heart. The results showed: (1) Arrhythmia score and myocardial infarct size were significantly lower in polydatin group than that in the control group (P<0.05, P<0.01); (2) The recovery of LVDP, ±LVdp/dt(max) and CF during reperfusion in polydatin group were significantly better than that in the control rats (P<0.05, P<0.01); (3) SOD activity in polydatin group was significantly higher than that in the control group, but MDA content was lower in polydatin group than that in the control group (P<0.05); (4) NO content and NOS activity, especially constitutive nitric oxide synthase (cNOS) activity in polydatin group were higher than that in the control group (P<0.05); (5) L-NAME, the NOS inhibitor, reversed the protective effect of polydatin against ischemia/reperfusion injury. The results suggest that polydatin has a protective effect against ischemia/reperfusion injury in rat heart. The cardioprotection of polydatin is mainly mediated by cNOS which leading to an increase in NO production.
Animals ; Glucosides ; pharmacology ; Heart ; drug effects ; physiopathology ; Malondialdehyde ; metabolism ; Myocardial Infarction ; pathology ; Myocardial Reperfusion Injury ; drug therapy ; Myocardium ; enzymology ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; antagonists & inhibitors ; metabolism ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; pharmacology ; Superoxide Dismutase ; metabolism

OBJECTIVES: The aging process affects responsiveness and other functions of endothelium and vascular smooth muscle cells, predisposing the old vessels to the development of atherosclerotic lesions. Endothelial nitric oxide synthase (ecNOS) gene polymorphisms were shown to affect the occurrence of acute myocardial infarction (AMI). We hypothesized that aging may affect the association between the ecNOS gene polymorphism and AMI. METHODS: We investigated the age-related distribution of the ecNOS gene a/b polymorphism in 121 male AMI patients and 206 age-matched healthy male controls. RESULTS: The aa, ab and bb genotypes were found in 1, 49 and 156 cases among the control subjects and 5, 23 and 93 cases among the AMI patients, respectively. There was a significant correlation between the ecNOS polymorphism and AMI (p +AD0- 0.045). When the correlation was analyzed by age, the significance remained only in the group below the age of 51 (p +AD0- 0.009). The proportion of smokers was increased in the young patients when compared to the old patients (p +AD0- 0.033), indicating that smoking also has greater effect on the younger population. The incidences of hypertension and diabetes mellitus, however, were similar in both populations. CONCLUSION: Our work provides the first evidence that links ecNOS polymorphism to the risk of AMI in relation to age. Young persons who smoke or have ecNOSaa genotype may have an increased risk of developing AMI. The functional as well as structural changes associated with aging in the vascular endothelium may mask the effect of the ecNOS polymorphism in the development of AMI in old persons.
Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Aging/physiology+ACo- ; Chi-Square Distribution ; Comorbidity ; Diabetes Mellitus/epidemiology ; Endothelium, Vascular/enzymology+ACo- ; Genotype ; Human ; Hypertension/epidemiology ; Korea/epidemiology ; Male ; Middle Age ; Myocardial Infarction/physiopathology+ACo- ; Myocardial Infarction/epidemiology ; Nitric-Oxide Synthase/metabolism+ACo- ; Nitric-Oxide Synthase/genetics+ACo- ; Polymerase Chain Reaction ; Polymorphism (Genetics)+ACo- ; Risk Assessment ; Statistics, Nonparametric

BACKGROUNDThe traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo.

METHODSMiniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively.

RESULTSTongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA.

CONCLUSIONSTongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.

Animals ; Antigens, CD ; analysis ; Blood Pressure ; drug effects ; Cadherins ; analysis ; Drugs, Chinese Herbal ; therapeutic use ; Heart Rate ; drug effects ; Microscopy, Fluorescence ; Myocardial Infarction ; drug therapy ; physiopathology ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium ; enzymology ; pathology ; Neutrophil Infiltration ; Nitric Oxide ; physiology ; Nitric Oxide Synthase ; metabolism ; Peroxidase ; metabolism ; Swine ; Swine, Miniature

BACKGROUNDMesenchymal stem cells (MSCs) transplantation is of therapeutic potential after ischemic injury in both experimental and clinical studies. Clinically, elderly patients are more vulnerable to acute myocardial infarction (AMI). But little is known about the characteristics of young donor-derived MSCs transplanted to old patients with AMI. The present study was designed to investigate the effect of transplanted MSCs from rats of different ages on the improvement of heart function after AMI.

METHODSMSCs from Sprague-Dawley (SD) rats were isolated and cultured in vitro. The apoptosis characteristics of MSCs were observed under conditions of ischemia and anoxia. SD rats underwent MI received intramyocardial injection of MSCs from young donor rats (n = 8), old donor rats (n = 8), respectively. AMI control group received equal volume physiological saline. Immunofluorescence was used to observe the differentiation of the grafted cells into cardiomyocytes. Four weeks after cell transplantation, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry for vascular endothelial growth factor (VEGF), VIII-factor immunohistochemistry for vessel density, TUNEL, caspase-3 for cardiomyocyte apoptosis, echocardiography and hemodynamic detection for heart function were performed.

RESULTSThe apoptosis rate of the old donor-derived MSCs group was significantly higher than that of the young donor-derived MSCs group under conditions of ischemia and anoxia (P < 0.05). Engrafted MSCs survived, proliferated and differentiated into myocardium-like cells. VEGF gene expression and capillary density in the old donor-derived group were lower than those in the young donor-derived group but higher than those in the control group (P < 0.05). The transplantation of old donor-derived MSCs attenuated apoptosis of cardiomyocytes in the peri-infarct region compared with the control group and the effect was elevated in young donor-derived MSCs (P < 0.05). The heart functions (left ventricle ejection fraction (LVEF), left ventricle fractional shortening (LVFS)) were improved more significantly in the old donor-derived MSCs group than in the control group and the heart function in the young donor-derived MSCs group further improved (P < 0.05).

CONCLUSIONSYoung donor-derived MSCs can improve heart function significantly through angiogenesis and decreasing cardiomyocyte apoptosis when transplanted to the infarcted area.

Age Factors ; Animals ; Apoptosis ; Caspase 3 ; metabolism ; Cells, Cultured ; Flow Cytometry ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology ; Myocardial Infarction ; physiopathology ; surgery ; Myocytes, Cardiac ; cytology ; enzymology ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism