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)

Although numerous interventions have been shown to exert a salutary effect on the ischemic myocardium, the severity of ischemia generally has been measured by indirect techniques. In the present investigation the effect of ischemia on intramural carbon dioxide tension (PmCO(2)) was measured directly in the open-chest, anesthetized dog with a mass spectrometer during repetitive 10-min coronary artery occlusions separated by 45-min periods of reflow; simultaneously, regional myocardial blood flow in the ischemic area was measured by (127)Xenon washout. In all dogs the increase in PmCO(2) from before to 10 min after the first occlusion (DeltaPmCO(2)) exceeded that during subsequent occlusions. In those dogs not receiving an intervention (controls), DeltaPmCO(2) during the third occlusion was similar to that during the second occlusion. When propranolol, hyaluronidase, and nitroglycerin were administered to different groups of dogs before the third occlusion, each caused significantly smaller elevations in DeltaPmCO(2) than those occurring during the control second occlusion, and the combination of all three interventions induced the smallest increase in DeltaPmCO(2). Regional myocardial blood flow rose with hyaluronidase and was unchanged with propranolol, nitroglycerin, and the three drugs in combination. In contrast to these beneficial interventions, isoproterenol infused with the third occlusion caused a higher DeltaPmCO(2) than during the control second occlusion. It is concluded, first, that interventions that modify the severity of ischemia can be evaluated by measuring intramural carbon dioxide tension; second, that propranolol, hyaluronidase, and nitroglycerin reduce ischemic injury, whereas isoproterenol increases it; and third, that the combination of propranolol, hyaluronidase, and nitroglycerin exerts an additive beneficial effect on ischemia.
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PMID:Assessment of the efficacy of interventions to limit ischemic injury by direct measurement of intramural carbon dioxide tension after coronary artery occlusion in the dog. 10 16

Both crude and highly purified testicular hyaluronidase preparations have been shown to contain a component which increases the permeability of the microcirculation in rat skin. This permeability activity had an isoelectric point of 7.4 while hyaluronidase was 9.4. It also could be separated from hyaluronidase by acrylamide gel electrophoresis. The permeability factor was not inhibited by serum and may explain previous observations that hyaluronidase preparations decrease the ischemia and necrosis appropriate to experimental myocardial infarction in vivo.
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PMID:Permeability factor contaminating hyaluronidase preparations. 51 Dec 98

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

Ischemia in the isolated perfused rat heart resulted in an increase in coronary vascular resistance. Studies were undertaken to determine the effect of hyaluronidase and methylprednisolone on this increase in resistance as well as on glycolytic rate and mechanical function of ischemic hearts. Neither hyaluronidase nor methylprednisolone affected the rate of glucose utilization in working perfused control or ischemic rat hearts. However, both agents prevented a reduction in coronary flow during a 2-hour ischemic period. Associated with the higher coronary flows were higher tissue concentrations of creatine phosphate and lower concentrations of lactate. These agents also prevented accumulation of tissue water in the ischemic hearts. Such changes would appear to be beneficial to the ischemic heart, although mechanical function of post-ischemic hearts was not enhanced by the presence of either hyaluronidase or methylprednisolone. The results, however, suggest that the reduction in myocardial infarct size noted with hyaluronidase and methylprednisolone may be due to their prevention of further reduction of coronary flow in marginally eschemic tissue.
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PMID:Effect of hyaluronidase and methylprednisolone on myocardial function, glucose metabolism, and coronary flow in the isolated ischemic rat heart. 89 Aug 92

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

During the course of experimentally induced myocardial ischaemia affected tissue initially suffers reversible ischaemic injury or, if ischaemia persists, injury of increasing severity before becoming irreversibly damaged. This state is characterized by tissue necrosis and referred to as myocardial infarction. The purpose of this study was to investigate whether it is possible to delay or perhaps even prevent the development of irreversible ischaemic injury. Ischaemia was induced by coronary artery occlusion (CAO) in canine hearts for 90 min or 24 h. The drug used for intervention was hyaluronidase. Ischaemic damage was assessed by p-NBT staining and ultrastructural evaluation of tissue biopsies. Development of irreversible ischaemic damage was prevented during 90 min of CAO. However, progression of reversible to irreversible ischaemic injury could not be prevented during 24 h of CAO. In conclusion, it is possible to prevent the development of irreversible ischaemic injury by a suitable intervention during the early stages of ischaemia in the canine heart and thus to gain time for additional intervention in the early treatment of myocardial infarction.
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PMID:Delay of development of transmural irreversible ischaemic injury in canine myocardium. 311 45

Effects of hyaluronidase on myocardial water content and distribution, and on coronary vascular hemodynamics and endothelial cell transport function were assessed in isolated rabbit hearts during 3.5 hours of reperfusion after 30 minutes of global, no-flow ischemia. In nonischemic control hearts, perfusion pressure, left ventricular end-diastolic pressure, maximum +dP/dt, and intravascular clearance of radiolabeled albumin remained constant during 5 hours of continuous perfusion, while the mean-transit time and vascular into extravascular space clearance of radiolabeled albumin increased 1.5X and 2.5X baseline, respectively. During reperfusion after 30 minutes of no flow, perfusion pressure increased 53% and interstitial fluid volume increased 2-fold, while left ventricular end-diastolic pressure and maximum +dP/dt returned to control levels. The rate of intravascular clearance of radiolabeled albumin decreased 38%, and the mean-transit time and vascular-into-extravascular space clearance of albumin increased approximately 3X and 5X baseline, respectively. Hyaluronidase blocked the ischemia-reperfusion-induced increases in total water content and in interstitial fluid volume and reduced the increases in perfusion pressure and mean-transit time of radiolabeled albumin by 40% and 45%, respectively, but did not prevent the increase in albumin vascular-into-extravascular space clearance and the decrease in albumin clearance from the coronary vasculature. These findings indicate that hyaluronidase does not prevent ischemia-reperfusion-induced increases in albumin permeation of the coronary vasculature, and suggest that its protective effect on ischemic myocardium is mediated, instead, by reducing interstitial edema and vascular resistance.
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PMID:Hyaluronidase does not prevent deterioration of vascular functional integrity during reperfusion after no-flow ischemia in isolated rabbit hearts. 400 93

During the past decade, efforts to limit the extent of myocardium exhibiting infarction once ischemia has been initiated have focused on manipulation of myocardial oxygen supply and demand as well as the process of injury itself. Interventions of promise range from the conventional, moderate increase in inspired oxygen content, to administration of hyaluronidase or intracoronary thrombolysis to augment oxygen supply; use of beta-adrenergic blocking drugs and nitroglycerin to diminish demand; and administration of calcium antagonists and prostaglandin synthesis inhibitors to limit the injury process. The ultimate effects on infarct size and long-term mortality have yet to be established unequivocally for any of these approaches in the clinical setting of acute myocardial infarction, but significant preservation of ischemic myocardium with hypothermia and with administration of nifedipine during coronary-artery bypass surgery have been documented. Several prospective, large-scale, blinded, and random sample selection clinical trials are currently in progress. Their results should definitively elucidate the clinical utility of specific interventions under defined conditions and should help to further improve the management of patients with ischemic heart disease.
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PMID:Pharmacological salvage of myocardium. 612 93

Hyaluronidase has been shown clinically and experimentally to reduce the effects of tissue ischemia in myocardial infarction and hemorrhagic shock. Dimethyl sulfoxide (DMSO) has been shown to reverse the effects of cerebral ischemia in the primate model. A caudally based dorsal skin flap in the rat was used to study the effects of these two drugs in physiological doses on skin flaps, and to investigate their mechanisms of action. This study demonstrates that both hyaluronidase and DMSO, which are nontoxic in physiological doses, can increase the surviving length of an experimental skin flap. It is hypothesized that these substances exert their effect by decreasing tissue edema and by aiding in the transport of nutritive substances to the flap during its acute phase.
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PMID:The effect of hyaluronidase and dimethyl sulfoxide (DMSO) on experimental skin flap survival. 663 21

Proper function of the coronary blood-tissue exchange system may be important in the preservation of myocardium threatened by ischemia. We have undertaken studies aimed at elucidating the functions of this system under baseline and ischemic conditions. The exchange of [14C]sucrose between the coronary capillaries and extravascular space has been studied with the multiple-tracer method. Protein transport has been examined by measuring the deposition of labeled albumin and by collecting cardiac lymph. Results indicate that reduced-flow ischemia decreases functioning capillary surface area but increases permeability to small molecules and protein. Hyaluronidase and adenosine can restore flow after partial occlusion of the coronary artery. However, only hyaluronidase restores capillary surface to its baseline value. Thus, ischemic effects on exchange are not controlled merely by hemodynamic factors. Reduced-flow ischemia in the heart can induce a vascular permeability change in the lung circulation. We conclude that capillary and interstitial transport are altered significantly by ischemia. Preservation of the proper function of these processes may be important in protecting the ischemic myocardium.
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PMID:Tracer exchange in the normal and ischemic coronary circulation. 669 35


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