Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.36 (hyaluronidase)
4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results of experiments with indirect methods have suggested that various interventions reduce infarct size after coronary artery occlusion. To determine and quantify directly both the short- and long-term effects of several interventions on myocardial salvage without relying on indirect methods, the left coronary artery was occluded in 880 rats; they were then given either no treatment or one of the following interventions: (a) hyaluronidase, an enzyme that hydrolyzes interstitial glycoproteins, 1,500 National Formulary (NF) U/kg i.v. 5 min and 24 h after occlusion; (b) cobra venom factor, a protein that depletes the third component of complement, 20 U/kg i.v. 5 min after occlusion; (c) a glucocorticoid: hydrocortisone, 50 mg/kg i.v. 5 min after occlusion; or the five-fold more potent methylprednisolone (MP): (i) 50 mg/kg i.v. 5 min after occlusion or (ii) 50 mg/kg i.v. 5 min after occlusion followed by 50 mg/kg i.m. 3, 6, and 24 h after occlusion; or (d) reserpine, an agent that depletes the heart of catecholamines, 0.5 mg/kg i.m. once on each of the 3 days before occlusion. The animals were sacrificed either 2 days after occlusion, i.e., at the time of peak necrosis, or after 3 wk, i.e., after the infarct was completely healed. The amount of preserved myocardium was then assessed by two independent techniques: planimetric measurement of serial histologic sections and creatine kinase activity of the whole left ventricle. The amount of normal myocardium preserved at 21 days postocclusion was significantly increased, by 22.3+/-7.8% (P < 0.025) after the administration of hyaluronidase, by 25.3+/-5.8% (P < 0.005) after cobra venom factor, by 14.5+/-6.9% (P < 0.05) after hydrocortisone, by 20.8+/-8.2% (P < 0.025) after the single dose of MP, by 20.9+/-3.9% (P < 0.001) after the four doses of MP, and by 10.2+/-3.7% (P < 0.05) as a result of pretreatment with reserpine. The four doses of MP significantly thinned the infarct-by 25.6+/-2.9% (P < 0.001)-and although ventricular rupture did not occur, the intervention caused distension of the left ventricle as a result of stretching of the infarcted tissue during scar formation. Thus, myocardium acutely jeopardized by ischemia can be preserved on a long-term basis.
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PMID:Long-term preservation of ischemic myocardium after experimental coronary artery occlusion. 64 Nov 37

In order to measure the protective effect of interventions following coronary artery occlusions in dogs, the creatine kinase activity of myocardial tissue was assayed after 24 h and related to the myocardial blood flow of that tissue measured with 85Sr labelled microspheres injected 15 min after occlusion. This assay showed normal levels when flow exceeded 50 cm3.min-1.100 g-1. In myocardium with flow reduced to 0 to 15 cm3. min-1.100g-1, creatine kinase activity was 7.6 +/- 0.6 IU.mg-1 protein in control dogs and 13.1 +/- 1.8 IU.mg-1 protein (P less than 0.01) in dogs given 500 NF units.kg-1 of hyaluronidase 20 min after occlusion. Where myocardial blood flow was reduced to 16 to 50 cm3. min-1. 100g-1, creatine kinase activity was increased from 14.1 +/- 1.1 to 20.5 +/- 1.4 IU.mg-1 protein by hyaluronidase. This method therefore assesses ischaemic damage independent of electrophysiological measurements and confirms myocardial preservation by hyaluronidase.
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PMID:A method for demonstrating the efficacy of interventions designed to limit infarct size following coronary occlusion: beneficial effect of hyaluronidase. 69 85

The effects on the evolution of canine myocardial infarction (MI) of the lymphagogues hyaluronidase (hyaluronate glucanohydrolase) (known to reduce the size of MIs) and calcium dobesilate (calcium, 2,5-dihydroxybenzenesulfonate, CLS 2210) were compared in a coded, placebo-controlled study in 48 dogs, during the first 24 h after coronary occlusion. MI was induced by embolization of the anterior descending branch of the left coronary artery. The animals were given either a placebo, CLS 2210, or hyaluronidase by intravenous infusion begun immediately after embolization and continued for 24h. The volume of myocardial tissue at risk was evaluated at 2 and 24 h by ungated computed tomography (CT), and after necropsy by staining myocardial sections with triphenyl tetrazolium chloride (TTC). Electrocardiography and estimation of serum creatine kinase (CK) activity were also performed. In the 25 animals that survived 24 h, the results of all tests showed that there was less myocardial damage in the animals treated with the two lymphagogues than in those treated with placebo, and less damage with CLS 2210 than with hyaluronidase. The good correlation between the volume of ischemic tissue as assessed by CT in vivo and as assessed by TTC staining after necropsy (r = 0.959) confirms that the CT perfusion phase defect accurately reflects the volume of tissue at risk during the evolution of MI. This study has shown that CLS 2210 is at least as effective as hyaluronidase in reducing myocardial damage due to coronary artery occlusion in dogs.
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PMID:Myocardial infarction treated with two lymphagogues, calcium dobesilate (CLS 2210) and hyaluronidase: a coded, placebo-controlled animal study. 169 85

A randomized, double-blind, multicenter study was conducted of the value of hyaluronidase therapy for acute myocardial infarction (AMI). Patients were eligible for enrollment if they were less than 76 years old, had at least 30 minutes of pain typical of myocardial ischemia and had electrocardiographic changes suggestive of acute ischemia or evolving infarction. A total of 851 patients were randomly assigned to hyaluronidase (500 National Formulary units/kg intravenously every 6 hours for 48 hours) or placebo therapy with a mean of 9.4 +/- 0.1 hours after the onset of pain. There were no significant differences between the hyaluronidase- and placebo-treated patients in incidence of AMI (86 vs 88%), creatine kinase-MB infarct size index (14.6 +/- 0.8 vs 15.1 +/- 0.7 CK-MB-gEq/m2), change in total R wave from time 0 to 72 hours for anterior transmural ischemia or infarction (-34 +/- 7 vs -35 +/- 8 mV), infarct size determined by pyrophosphate scintigrams (27 +/- 1 vs 27 +/- 1 cm2), change in left ventricular ejection fraction from day 0 to day 10 (+ 2.4 +/- 0.7 vs + 1.2 +/- 0.7%) or cumulative proportion surviving 4 years (0.70 +/- 0.03 vs 0.68 +/- 0.03). These findings indicate there is no overall benefit from administration of hyaluronidase more than 9 hours after the onset of AMI, but do not exclude the possibility that such therapy could be of value if given earlier, or if given to a subgroup of patients with sufficient residual flow to the area of AMI.
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PMID:Hyaluronidase therapy for acute myocardial infarction: results of a randomized, blinded, multicenter trial. MILIS Study Group. 287 94

A multicentred, randomised, blind study was started in 1978 to compare propranolol or hyaluronidase with placebo in patients with acute myocardial infarction admitted within 18 hours of onset of symptoms. Patients were randomised to group A and received hyaluronidase, propranolol, or placebo, or, if propranolol was contraindicated, to group B and received hyaluronidase or placebo. Hyaluronidase (500 U/kg given every six hours for 48 hours) had no effect on mortality or infarct size in the overall population. Because spontaneous reperfusion was more common in patients with early peaking of plasma creatine kinase MB or non-transmural electrocardiographic changes or both, the results were reanalysed for two subgroups: those in whom plasma creatine kinase peaked less than 15 hours after the onset of symptoms (early peak, n = 184) and those with a peak greater than 15 h after the onset of symptoms (late peak, n = 546). The distribution of time to peak activity of creatine kinase MB was similar in the hyaluronidase and placebo groups. In the early peak patients who were given hyaluronidase (groups A and B) total mortality and cardiac-specific four year mortality were significantly lower. This was most pronounced in group B in which the total mortality was 45% and cardiovascular mortality was 47% less than in the placebo group. Similarly, mortality from cardiovascular disease in patients (groups A and B) with nontransmural ischaemia (ST-T changes) given hyaluronidase was significantly lower, with group B showing a 50% reduction. In the subsets of patients with late peaking of creatine kinase MB or those presenting with transmural electrocardiographic changes there was no difference in total mortality or deaths from cardiac disease between those given hyaluronidase and those given placebo. Hyaluronidase was associated with improved survival in patients with early peaking of plasma creatine kinase MB, suggesting the possibility of salvage of myocardium in patients who have early spontaneous reperfusion and possibly after therapeutic reperfusion.
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PMID:Effect of hyaluronidase on mortality and morbidity in patients with early peaking of plasma creatine kinase MB and non-transmural ischaemia. Multicentre investigation for the limitation of infarct size (MILIS). 305 76

The induction of myocardial infarction in rats by ligation of the left-anterior coronary artery was confirmed by measurement of increased plasma levels of creatine kinase, aspartate aminotransferase and lactate dehydrogenase. Using this model system it has been established that intravenous administration of 125I-labelled hyaluronidase to rats resulted in a preferential uptake of the enzyme by damaged myocardium as compared to normal heart tissue.
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PMID:Preferential uptake of intravenously administered hyaluronidase (Hyalosidase) by damaged rat myocardium. 402 52

79 patients with suspected myocardial infarction entered a randomised trial to establish the safety of early intravenous administration of a highly purified hyaluronidase preparation (GL enzyme) and to assess its effects on eventual infarct size as measured by electrocardiographic, enzymatic, and scintigraphic criteria. Of the 71 patients with infarction, 35 received GL enzyme and 36 placebo within 6 h of the onset of chest pain. GL enzyme injected into a peripheral vein produced no adverse changes in the clinical, haemodynamic, biochemical, or haematological variables studied. GL enzyme reduced precordial electrocardiographic indices of infarct size as reflected by a diminution (p less than 0.02) in the degree of both R wave loss and Q wave development. In addition, the number of leads developing pathological Q waves (N delta Q greater than or equal to 2), a sign of progression from ischaemia to necrosis, was reduced (p less than 0.05) after GL enzyme treatment. However, there were no significant differences in infarct size as measured by cumulative creatine kinase MB isoenzyme release or technetium-99m pyrophosphate scintigraphic infarct area, or in clinical outcome during the hospital stay. Interpretation of the enzymatic and scintigraphic data was complicated by chance bias in pre-treatment randomisation which resulted in more (p less than 0.05) patients with severe haemodynamic impairment (and hence probably larger infarct sizes) entering the GL enzyme group. Nonetheless, a favourable effect of GL enzyme on infarct size was demonstrated by precordial electrocardiographic QRS mapping, here each patient acts as his or her own control.
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PMID:Effects of early administration of a highly purified hyaluronidase preparation (GL enzyme) on myocardial infarct size. 612 98

A procedure is described for the production of large numbers of Ca2+-tolerant adult canine ventricular myocytes. Gentle tissue dissociation is achieved in Spinner flasks using 320 mosM enzyme buffer containing collagenase hyaluronidase, and trypsin in the presence of millimolar levels of Ca2+. The technique allows for the complete removal of erythrocytes, the gentle removal of closely adhering nonmuscle cells (less than 3% contamination), and the selective removal of damaged from nondamaged myocytes. Total myocyte yields averaged 4-6 x 10(6)/g wet wt; 61.0 +/- 6.5% of the cells have rod-shaped morphology and are "viable" based on trypan blue exclusion. Only 3.9 +/- 1.1% of the rod-shaped cells beat spontaneously when challenged with 2 mM Ca2+. Exposure to 2 mM Ca2+ at 37 degrees C results in minimal loss of viability (2.1 +/- 1.3%/h) based on both trypan blue uptake and creatine kinase release. Simulation of cellular (i.e., membrane) injury in vitro is performed by the separate application of the perturbations of anoxia, acidosis, and low glucose to the canine myocyte suspensions; the data suggest that these myocytes are affected independently by these perturbations and are in good agreement with the results obtained by others using the isolated rat myocyte system.
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PMID:Ca2+-tolerant adult canine myocytes: preparation and response to anoxia/acidosis. 628 68

The goal of this investigation was to determine whether hyaluronidase administration can alter the size, morbidity, and mortality of experimental acute cerebral infarctions. Accordingly, the left common carotid artery was occluded in 1205 ether-anesthetized Mongolian gerbils. The gerbils were randomized into hyaluronidase-treated (4000 National Formulary units per kg., intravenously, 5 minutes after occlusion) or control groups. All were examined for clinical signs of cerebrovascular accident three times during the 24 hours and then decapitated, and each hemibrain was analyzed for its total creatine kinase activity. In the control group, 90 of 601 gerbils died, whereas in the hyaluronidase-treated group only 61 of 604 gerbils died. This reduction in mortality was highly significant (chi 2 = 6.53, p less than 0.02). In the surviving gerbils with cerebrovascular accidents, infarct size was calculated by creatine kinase depletion (normal right hemibrain creatine kinase minus infarcted left hemibrain creatine kinase divided by right hemibrain creatine kinase and corrected for "residual" (nondepletable) creatine kinase). In controls, infarct size was 36.5 +/- 1.8 per cent (n = 105), and in the hyaluronidase-treated gerbils it was significantly lower, 31.4 +/- 1.7 per cent (n = 117, p less than 0.05). Thus, in gerbils with experimental cerebrovascular accidents, hyaluronidase significantly reduced mortality (by one-third) and reduced "enzymatic" infarct size by 14.0 +/- 4.6 per cent (p less than 0.01).
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PMID:Effect of hyaluronidase on experimental cerebral infarct size and mortality. 707 54

A series of thirteen patients with acute myocardial infarction was studied. In the 12 patients heparinised on admission, there was a fall in serum hyaluronidase activity, free amino sugar and uronic acid levels. This contrasted with a rise in creatine kinase activity. In a single unheparinised patient, the hyaluronidase level rose. This suggests that necrotic cardiac tissue releases hyaluronidase. Any beneficial effects of the local release of hyaluronidase may be minimized by heparin therapy. Study of patients on a trial of intravenous bovine testicular hyaluronidase following acute myocardial infarction could detect no rise in hyaluronidase levels. This confirms previous reports that human serum inhibits bovine testicular hyaluronidase.
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PMID:Glycosaminoglycan metabolism following acute myocardial infarction and the effects of intravenous hyaluronidase therapy. 738 76


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