Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early changes in lysosomal enzymes must occur if their role is significant in irreversible myocardial injury. Therefore, we ligated the anterior descending coronary artery in 14 dogs and after 60 min excised epicardial and endocardial samples from the ischemic and adjacent normal heart. The collateral flow measured with radioactive microspheres in the endocardial samples averaged 19% of control. The muscle was disrupted and fractionated by ultracentrifugation into nuclear pellet (NP), heavy lysosomal pellet (HL), light lysosomal pellet (LL), microsomal pellet (M) and supernate (S). Electron microscopy demonstrated changes characteristic of sichemia in whole tissues and sedimented fractions. Acid phosphatase reaction product was present in residual bodies in the HL fraction and membrane-bound vesicles in the LL fraction and in the intact tissue. Significant decreases in the specific activity of N-acetyl-beta-glucosaminidase and beta-glucuronidase occurred in the endocardial LL fraction, while significant increases in both were found in the ts fraction (P less than 0.05). Losses of acid phosphatase occurred in both LL and S fractions. Moreover, decreases of total N-acetyl-beta-glucosaminidase in the HL fraction and of total beta-glucuronidase and acid phosphatase in the LL fraction were positively correlated (P less than 0.01) with the degree of ischemia measured with radioactive microspheres. Only insignificant enzymatic changes were found when the collateral flow was greater than 40%, and the differences were less significant in epicardial samples where the flow averaged 29%. The early loss of enzymes from the lysosomal fractions in severe ischemia suggests a role for lysosomal hydrolases in the necrosis that follows coronary occlusion.
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PMID:Effect of collateral flow on epicardial and endocardial lysosomal hydrolases in acute myocardial ischemia. 115 94

This study was designed to clarify whether or not flecainide have cardioprotective effect on ischemic myocardium. Nineteen dogs anesthetized and subjected to 2 h coronary occlusion, were divided into 2 groups. In the control group, physiological saline was infused, and in the flecainide group, 2 mg/kg of flecainide acetate and followed by 100 micrograms/kg/min continuous infusion. To assess the cardioprotective effect, mitochondrial function and lysosomal enzyme activities were measured. Two hours after occlusion, mitochondria were prepared from both ischemic and non-ischemic areas in each group, and their function (respiratory control index, and the rate of oxygen consumption in state III respiration) were measured polarographically with succinate as substrate. Fractionation of myocardial tissue from both non-ischemic and ischemic areas was performed according to the method of Weglicki et al, and the activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase, and beta-glucuronidase) were measured. In the control group, mitochondrial dysfunction and leakage of lysosomal enzymes induced by 2 h occlusion were observed. On the contrary, administration of flecainide maintained significantly mitochondrial function, and prevented significantly leakage of lysosomal enzymes. These results indicated that flecainide had cardioprotective effect as well as antiarrhythmic effects in ischemic myocardium.
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PMID:[The effect of flecainide on 2 hour occlusion-induced myocardial damages in dog]. 250 Jun 90

Cardioprotective and antiarrhythmic effects of three beta-blockers with different pharmacological properties were investigated in 33 anesthetized dogs with a 2-h coronary occlusion. Dogs were divided into 4 groups and received physiological saline or one of the following drugs using a 10-min infusion at 25 min before the occlusion: saline or control (n = 12), propranolol (0.3 mg/kg, n = 7), bisoprolol (0.05 mg/kg, n = 7), and nipradilol (0.2 mg/kg, n = 7) groups. Blood pressure did not significantly differ among the 4 experimental groups throughout the entire observation period. On the contrary, the postocclusion change (fall) in heart rate from the preocclusion value was significantly (P less than 0.05-0.01) greater in the drug-treated groups than in the control group. Each of the beta-blockers effectively prevented the development of ventricular arrhythmias associated with the 2-h coronary occlusion. In terms of assessing a cardioprotective effect, the respiratory control index and rate of oxygen consumption in State III in mitochondria, and lysosomal enzyme activities (N-acetyl-beta-glucosaminidase or beta-glucuronidase) in myocardial tissues, all prepared from both ischemic and non-ischemic areas, were measured using the respective, established methods. The 2-h coronary occlusion induced a mitochondrial dysfunction and leakage of lysosomal enzymes in the control group, whereas each beta-blocker significantly (P less than 0.05-0.01) protected mitochondria against ischemia and prevented the lysosomal enzyme leakage. The results indicate that the antiarrhythmic effects of beta-blockers on ischemic myocardium are, at least in part, due to their cardioprotective action, and these effects appear to be unrelated to the ancillary pharmacological properties of these drugs.
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PMID:Cardioprotective and antiarrhythmic effects of beta-blockers, propranolol, bisoprolol, and nipradilol in a canine model of regional ischemia. 257 96

This study was designed to clarify the cardioprotective effects of various class I antiarrhythmic drugs, i.e., aprindine, disopyramide, flecainide, lidocaine, mexiletine, pentisomide and propafenone, on the ischemic heart. Sixty-one adult mongrel dogs were classified into eight groups according to premedication: 1) control group, physiologic saline solution was administered intravenously 25 min before left anterior descending coronary artery ligation; 2) aprindine group, 3 mg/kg body weight of aprindine intravenously; 3) disopyramide group, 2 mg/kg of disopyramide intravenously; 4) flecainide group, 2 mg/kg of flecainide intravenously followed by drip infusion of 100 micrograms/kg per min; 5) lidocaine group, 2 mg/kg of lidocaine intravenously followed by drip infusion of 100 micrograms/kg per min; 6) mexiletine group, 3 mg/kg per min of mexiletine intravenously followed by drip infusion of 15 micrograms/kg per min; 7) pentisomide group, 5 mg/kg intravenously; and 8) propafenone group, 2 mg/kg intravenously. Arterial blood pressure and electrocardiogram were monitored throughout the experiment. Two hours after coronary occlusion, the heart was excised. Myocardial mitochondria were prepared and mitochondrial function (the respiratory control index and the rate of oxygen consumption in state III) was measured polarographically. Fractionation of myocardial tissues was performed and the lysosomal enzyme (N-acetyl-beta-glucosaminidase and beta-glucuronidase) activities among fractions were measured. No significant hemodynamic changes were observed compared with the control group except for those in the disopyramide and flecainide groups; that is, decrease in heart rate without changes in blood pressure compared with the control group was observed. All antiarrhythmic drugs effectively prevented the development of ventricular arrhythmias associated with ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardioprotective effects of various class I antiarrhythmic drugs in canine hearts. 273 64

Leakage of lysosomal enzymes is associated with irreversible cellular damage. To determine the effect of prostaglandin I2 analogue and propranolol on the ischaemic myocardium in relation to changes in lysosomal integrity 26 anaesthetised mongrel dogs were divided into three treatment groups and subjected to 2 h coronary occlusion. In the control group (n = 12) physiological saline was infused throughout the experiment. In the prostaglandin I2 analogue group (n = 7) the prostaglandin I2 analogue, OP-41483-alpha-CD;5(E)-6-Deoxa-6,9 alpha-methylene-15-cyclopentyl-16,17,18,19,20-pentanor-PGI2. alpha-cyclodextrin clathrate (5 ng.kg-1.min-1) was infused from 25 min before occlusion until the end of the experiment. In the propranolol group (n = 7) propranolol (0.3 mg.kg-1) was injected for 10 min 25 min before occlusion. Two hours after occlusion mitochondria were prepared from both ischaemic and non-ischaemic areas in each group and their function measured polarographically with succinate as substrate. Fractionation of myocardial tissue from both non-ischaemic and ischaemic areas was performed and the activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase; beta-glucuronidase) were measured. In the control group, mitochondrial function in the ischaemic area was reduced compared with that from the non-ischaemic area. The activities of both lysosomal enzymes were increased significantly in the supernatant fraction obtained from the ischaemic area compared with those for the supernatant from the non-ischaemic area. The administration of prostaglandin I2 analogue or propranolol not only prevented the leakage of lysosomal enzymes but also maintained mitochondrial function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostaglandin I2 analogue and propranolol prevent ischaemia induced mitochondrial dysfunction through the stabilisation of lysosomal membranes. 304 92