Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental myocardial infarction was induced in rats. The myocardial accumulation of hyaluronan (HA) and water during the development of infarction was measured. The extractable HA content of the infarcted area increased progressively from day 1 and on day 3 reached a threefold increase compared with the HA amounts in myocardium of sham operated controls. The relative water content of infarcted areas also increased progressively reaching a maximum value by day 3 and was strongly correlated with the HA accumulation. Affinity histochemistry visualized a thin rim of HA in the endoperimysium in healthy myocardium. By day 2 an interstitial edema with inflammatory cells was apparent. The widened endoperimysium stained extensively for HA. By its water-binding ability, interstitial accumulation of HA will contribute to the interstitial edema in infarcted myocardial tissue. An interstitial edema is likely to influence the electromechanical characteristics of the myocardium and facilitate reentry phenomena due to a loss of contact between muscle cells. The edema also induces an increased extracellular pressure and an altered myocardial wall compliance that might impair myocardial microcirculation. The findings are relevant to an understanding of the beneficial effect of hyaluronidase treatment in limiting cellular damage during myocardial ischemia.
 ...
PMID:Accumulation of hyaluronan and tissue edema in experimental myocardial infarction. 193 49

Active drainage of cardiac lymph using hyaluronidase was attempted in dogs. The results were satisfactory and the ischemic myocardium was salvaged. The infarct risk area (I/R) ratio decreased after drainage. Regional myocardial ischemia and infarction were provided by means of ligature of the left coronary artery for 120 and 240 minutes respectively. Cardiac lymph was collected by conventional procedures. Enzymes released from the myocardium increased significantly in the cardiac lymph. The volume of cardiac lymph gradually increased after ligature of the coronary artery. Administration of hyaluronidase further increased the cardiac lymph flow and significantly decreased the I/R ratio as determined by triphenyl tetrazolium chloride (TTC) and methylene blue staining. Drainage of the cardiac lymph salvaged the ischemic myocardium. Reduction of interstitial edema and augmentation of cardiac lymph flow with the hyaluronidase prevented the development of the infarction. This is the first documentation of the effect of active drainage of cardiac lymph on the development of infarction through observation of the I/R ratio.
 ...
PMID:Active drainage of cardiac lymph in relation to reduction in size of myocardial infarction: an experimental study. 227 98

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.
 ...
PMID:Hyaluronidase therapy for acute myocardial infarction: results of a randomized, blinded, multicenter trial. MILIS Study Group. 287 94

Hyaluronic acid, a principal glycosaminoglycan of the cardiac interstitium, may have a role in interstitial hydration, interstitial plasma protein exclusion and microvascular transport process (Wiederhielm, 1976b). We have investigated whether hyaluronidase reduces myocardial hyaluronate concentrations and thereby alters these several physical aspects in the isolated rat heart. Studies were conducted in ischemic, as well as aerobic hearts because of the reported therapeutic efficacy of the enzyme in myocardial ischemia. Two hours of perfusion with hyaluronidase significantly reduced myocardial hyaluronate content. Additionally, hyaluronidase decreased interstitial volume of both aerobic and otherwise edematous ischemic hearts, and prevented ischemic induced increased coronary vascular resistance in ischemic hearts. However, hyaluronidase did not effect the albumin interstitial exclusion volume or microvascular albumin and sorbitol exchange in aerobic hearts. In ischemic hearts, the enzyme did not prevent nor enhance the increase in microvascular permeability which occurred. We conclude that hyaluronate is neither a determinant of interstitial protein exclusion nor microvascular permeability, but plays an important role in interstitial hydration.
 ...
PMID:The effects of hyaluronidase on interstitial hydration, plasma protein exclusion, and microvascular permeability in the isolated perfused rat heart. 391 Oct 32

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.
 ...
PMID:Pharmacological salvage of myocardium. 612 93

Over a 34.5-month period, all admissions to 5 university hospital coronary care units were screened for eligibility for the Multicenter Investigation of the Limitation of Infarct Size (MILIS), an ongoing study of the effects of hyaluronidase, propranolol and placebo on myocardial infarct (MI) size. Of 3,697 patients with greater than or equal to 30 minutes of discomfort that was thought to reflect myocardial ischemia who were assessed for the presence or absence of certain electrocardiographic abnormalities at the time of hospital admission, the electrocardiogram was considered predictive of acute MI if greater than or equal to 1 of the following abnormalities was present: new or presumably new Q waves (greater than or equal to 30 ms wide and 0.20 mV deep) in at least 2 of the 3 diaphragmatic leads (II, III, aVF), or in at least 2 of the 6 precordial leads (V1 to V6), or in I and aVL; new or presumably new ST-segment elevation or depression of greater than or equal to 0.10 mV in 1 of the same lead combinations; or complete left bundle branch block. In the screened population, the diagnostic sensitivity of the electrocardiographic criteria was 81%, whereas the overall infarct rate in the total population screened was 49%. The diagnostic specificity of these entry criteria was 69% and the predictive value 72%.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Electrocardiographic and clinical criteria for recognition of acute myocardial infarction based on analysis of 3,697 patients. 635 62

Bovine testicular hyaluronidase (BTH) reduces experimental myocardial infarct size and ameliorates electrocardiographic signs of ischemia. This study was done to determine if heparin, an in vitro inhibitor of hyaluronidase activity, blocks the action of BTH in the myocardium of dogs after coronary artery occlusion. BTH was administered intravenously as 5,000 NF units/kg at 0.5 and 2.5 hours after coronary occlusion. Heparin was administered intravenously as a 150-unit/kg loading dose, followed by 10 units/kg per hour i.v., beginning 15 minutes before coronary occlusion. The area of myocardial ischemia at risk was assessed by a radiolabeled microsphere technique; the area that developed necrosis was assessed by a histochemical technique. In vivo activity of BTH was assessed by a colorimetric analysis of the BTH substrate, i.e., hyaluronic acid (HA), extracted from myocardial tissue. For biochemical analysis of HA, the heart was divided into anterior myocardium, which included ischemic tissue and posterior nonischemic myocardium. The myocardial HA content of dogs treated with BTH plus heparin (anterior, 3.44 +/- 0.40 micrograms HA/mg protein; posterior, 3.69 +/- 0.33 micrograms HA/mg protein) was not significantly different from control (anterior, 3.61 +/- 0.29 micrograms HA/mg protein; posterior, 3.55 +/- 0.23 micrograms HA/mg protein). In contrast, BTH lowered myocardial HA content (anterior, 2.16 +/- 0.21 micrograms HA/mg protein; posterior, 2.08 +/- 0.14 micrograms HA/mg protein) compared with either BTH plus heparin or control groups in both anterior myocardium (p = 0.006) and posterior myocardium (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Heparin inhibits bovine testicular hyaluronidase activity in myocardium of dogs with coronary artery occlusion. 670 49

Testicular hyaluronidase prevents increased coronary vascular resistance (CVR) during prolonged myocardial ischemia. The mechanism is unknown, but edema and contracture both have been suggested to increase CVR. Additionally, the extent of contracture has been inversely related to ATP levels. Therefore, isolated perfused ischemic rat hearts were treated with hyaluronidase, following a 25% increase in CVR, to determine whether 1) increased CVR was reversed, 2) edema or contracture was reduced, and 3) tissue ATP levels were increased. Three hours of low-flow ischemia decreased coronary flow (CF) from 17.4 +/- 0.13 to 12.6 +/- 0.2 ml X min-1 X g dry tissue-1. During the subsequent 2 h of ischemia, CF of vehicle-treated hearts continued to decline to 8.0 +/- 0.76 ml X min-1 X g dry tissue-1, whereas CF of hyaluronidase-treated hearts increased to 15.6 +/- 1.17 ml X min-1 X g dry tissue-1. These changes in CF persisted during postischemic perfusion. Furthermore, restoration of coronary vascular resistance by hyaluronidase was associated with a 19% reduction in tissue water compared with control ischemic hearts but not with a reduction in cardiac contracture or an increase in tissue ATP. These results suggest that treatment of ischemic hearts with hyaluronidase reverses increased CVR through a reduction in tissue edema.
 ...
PMID:Hyaluronidase reversal of increased coronary vascular resistance in ischemic rat hearts. 688 54

The value of three agents in reducing the area of myocardial ischemia in rabbit hearts perfused with crystalloid solution was examined. Ten hearts received crystalloid solution with methylprednisolone (M), 0.25 mg/ml; 18 with hyaluronidase (H), 4 U/ml; and 10 with propranolol (P), 1 microgram/ml. Thirty-six hearts served as controls. The mitral valves were excised, the hearts were paced at 240 beats/min and a coronary artery was ligated. The ischemic area was evaluated by nicotinamide adenine dinucleotide autofluorescence photography, an intrinsic, high-resolution display of anoxic tissue. The ischemic area was determined by computer from standardized photographs. Myocardial oxygen consumption (MVO2) was determined and photographs were taken before and at 10-minute intervals after ligation. At 60 minutes, each heart was perfused with rhodamine dye and quick-frozen. In hearts treated with M and H, coronary blood flow increased by 151% (51.7 +/- 3 to 77.9 +/- 3 ml/min) and 150% (48.3 +/- 2 to 72.3 +/- 2 ml/min), respectively (p less than 0.001), whereas in hearts treated with U and P, coronary flow decreased at 60 minutes. In the control hearts, the ischemic area did not change between 5 and 40 minutes of ischemia. The ischemic area of H-treated hearts decreased from 136 +/- 4 mm2 to 110 +/- 9 mm2 between the postligation control and the end of the experiment (p less than 0.01). The ischemic area of M-treated hearts decreased from 131 +/- 5 mm2 to 113 +/- 5 mm2 (p less than 0.05). P produced no change in ischemic area (p greater than 0.4). There was no change in the oxygen-diffusion zone of P-treated or control hearts (439 +/- 13 vs 383 +/- 12 mu, p greater than 0.1). The oxygen-diffusion zone between perfused and anoxic tissue in the M and H hearts increased from 383 +/- 12 mu to 861 +/- 76 mu and 681 +/- 62 mu, respectively (p less than 0.001). We conclude that significant volumes of myocardium remain normoxic within nonperfused areas of M-, P- and H-treated hearts.
 ...
PMID:Pharmacologic modification of myocardial ischemia. 709 66

The influence of hyaluronidase (H) on subacute experimental myocardial ischemia was studied in isolated perfused rabbit hearts. Changes in ischemic area were assessed by epicardial nicotinamide adenine dinucleotide (NADH) fluorescence photography, an intrinsic high-resolution display of myocardial ischemia. Computerized determination of ischemic area was made from standardized photographs. Hyaluronidase was begun 20 minutes after coronary artery occlusion at 4 units/ml perfusate. NADH fluorophotographs were taken at 10-minute intervals up to 60 minutes of ischemia. Coronary sinus oxygen tension (PcsO2), myocardial oxygen consumption (MVO2), and coronary flow were determined. After 70 minutes, the hearts were perfused with rhodamine solution to identify areas of myocardial perfusion. In 13 H-treated hearts 54.3% +/- 3.7% (mean +/- SEM) of the nonperfused area (rhodamine stained) was ischemic (NADH fluorescent). In 14 untreated hearts 79.8% +/- 3.2% of the nonperfused area was ischemic (p less than 0.0001) and the ischemic areas were uniform. The distance between perfused and ischemic tissue was 952 +/- 78 micrometers in the H hearts and 504 +/- 35 micrometers in the untreated heart (p less than 0.0001). In the H hearts PcsO2 increased to 155% of the post-ligation control while it decreased to 79% in the untreated hearts (p less than 0.0001). MVO2 decreased in the H-treated hearts to 62%; the untreated hearts had no further change. In the H-treated hearts, coronary flow increased to 146% of the post-ligation control while it fell to 91% in the untreated group (p less than 0.0001). We conclude that H increases coronary flow while decreasing MVO2 during subacute ischemia. In H-treated hearts, significant amounts of myocardium remain normoxic within the nonperfused areas, and may potentially be salvaged after prolonged myocardial ischemia.
 ...
PMID:Mechanism of action of hyaluronidase in decreasing myocardial ischemia post coronary occlusion in the isolated perfused rabbit heart. 711 92


1 2 Next >>