Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used a new technique for extraction of myocardial membranes (0.25 M sucrose, 0.6 M KCl) to isolate particulate and soluble proteins and enzymatic activities in an effort to quantify changes characteristic of progressive ischemia. Myocardial blood flow (MBF) was measured with microspheres (15 micrometer diameter) in all samples of tissue used for assay of proteins and enzymatic activities; MBF to the moderately ischemic areas (M-ischemia) was 53% of control (H-control); MBF to the severely ischemic areas (L-ischemia) was 9% of control. Significant decreases (P less than 0.001) in content of protein were seen in all post 1,000 g pellets and supernatant fluids in the L-ischemia zones; particulate lysosomal enzymatic activity was significantly decreased (P less than 0.001) in all four post 1,000 g pellets (2,500 g to 140,000 g) of the L-ischemic areas (for N-acetyl-beta-glucosaminidase and beta-glucuronidase). The increase in percent free activity of lysosomal enzymes (index of loss of latency) also was highly significant (P less than 0.001) in all particulate fractions of the L-ischemic areas. In addition, about 45% of the total activity of the microsomal marker enzyme, rotenone-insensitive NADH cytochrome C reductase (RINCR), was found in the 140,000 g pellet of H-control tissue (9.9 micronmol/min per g); this activity fell to 8.1 micronmol/min per g in M-ischemic areas (P less than 0.001) and to 5.3 micronmol/min per g in L-ischemic areas (P less than 0.001). This study demonstrates that changes in myocardial proteins, lysosomes, and other membrane-bound enzymes (RINCR) may provide reproducible bichemical parameters for assessing ischemic myocardial injury.
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PMID:Effects of well-defined ischemia on myocardial lysosomal and microsomal enzymes in a canine model. 21 2

The pathobiology of the process of myocardial injury during ischemia comprises a series of events that results in the release of lysosomal enzymes from their subcellular locations within the myocardium. We have developed a canine model of acute myocardial ischemia in which the anterior descending coronary artery is ligated, myocardial blood flow is measured using radioactive microspheres, and tissues from subendocardium and subepicardium are assayed for activity of lysosomal hydrolases:N-acetyl-beta-glucosaminidase (NAG), beta-glucuronidase (beta-gluc), and acid phosphatase (AP). Particulate fractions of subendocardium revealed significant depletion of of total acid hydrolases (NAG, beta-gluc, and AP) after one and two hours of ischemia. In addition, after two hours of ischemia, the total activity of these three hydrolases in the subendocardial supernatant was decreased, correlating significantly with diminished myocardial blood flow (NAG: r =0.96; beta-gluc: r = 0.95; AP: r = 0.75). The diminished enzymatic levels in thesupernatant suggested "washout" of the hydrolases that was more efficient in those ischemic areas that had higher myocardial flow (greater than 20% of control). These changes in distribution of lysosomal hydrolases indicate early involvement of these enzymes in the pathobiology of myocardial injury and demonstrate the dynamic relationship of "washout" of acid hydrolases with the degree of diminished blood flow.
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PMID:Release of lysosomal enzymes during ischemic injury of canine myocardium. 103 97

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

We have induced acute renal failure (ARF) in barbiturate anesthetized rabbits, through warm ischaemia of 30 or 60 min duration caused by transient bilateral occlusion of renal arteries. In this model we have monitored some renal performance parameters, before and 4 hours after reperfusion, aiming to characterize ARF in this animal species. Glomerular filtration rate (determined by the inulin clearance technique) was of 9.74 +/- 0.48 ml min-1 in 4 rabbits before injury and declined by 91% (60 min ischemia) during the first reperfusion hour. In 6 rabbits undergoing 30 min occlusion, pre-ARF values of 10.70 +/- 0.98 ml min-1 declined by 47%. In both groups no recovery was observed in the following hours. Tubular enzymes (alanine-amino-peptidase, AAP and N-acetyl-beta-glucosaminidase, NAG) were released into urines before injury at the rate of 1.11 +/- 0.18 and 1.32 +/- 0.41 mU min-1, respectively, in the 30 min model (3 animals/group). During ARF, maximal AAP output was five-fold increased (5.83 +/- 0.35 mU min-1), whereas NAG was unmodified. On the other hand, renal haemodynamics in 5 rabbits did not change after the ischaemic procedure: total renal blood flow (44 +/- 5 ml min-1) and renal vascular resistances (225 +/- 26 Pa ml-min) displayed less than 10% variations throughout the reperfusion period. We concluded that ARF in rabbits can be reliably and reproducibly monitored and that the pathogenesis of the disease, in our situation, is attributable mainly to tubular cell damage and not to impairment of the vascular component of renal performance.
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PMID:[Parameters of tubulo-glomerular function in anesthetized rabbits with acute kidney insufficiency]. 197 49

In this study the role of free radicals, lipid peroxidation, and neutrophil infiltration as mediators of ischemia and reperfusion-induced intestinal mucosal damage were investigated. We used a rat experimental model in which a ligated loop of the distal ileum was subjected to ischemia and reperfusion and the ensuing mucosal damage was assessed by means of lysosomal enzyme release and intestinal permeability measurements. We also determined the mucosal content of malondialdehyde, a lipid peroxidation product, and the mucosal activity of myeloperoxidase, a neutrophil granulocyte marker. Ischemia and revascularization alone caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa, and increased myeloperoxidase activity in the mucosa. Intravenous injection of enzymatic antioxidant, superoxide dismutase, together with xanthine oxidase inhibitor, allopurinol, prevented the malondialdehyde accumulation and caused attenuation of all the other effects of ischemia. Intravenous pretreatment of hydrocortisone sodium succinate (Solu-Cortef), a steroid and also a nonenzymatic antioxidant, prevented not only malondialdehyde accumulation but also neutrophil infiltration and mucosal damage. These data support a concept that neutrophil infiltration is an important element in ischemic mucosal damage. In addition, the blocking of this phenomenon may have clinical significance in attempts to modulate the potential damaging effects of the increased neutrophil infiltration associated with small-intestinal ischemia.
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PMID:Oxygen radicals, lipid peroxidation, and neutrophil infiltration after small-intestinal ischemia and reperfusion. 253 52

We have examined how a Ginkgo biloba extract influences the damaging effects of ischaemia in the small-intestinal mucosa. We used a rat experimental model in which a ligated loop of the distal ileum was subjected to ischaemia and revascularization, and the ensuing mucosal damage assessed by lysosomal enzyme release and intestinal permeability measurements. We also determined the mucosal content of malondialdehyde, a lipid peroxidation product, and the mucosal activity of myeloperoxidase, a neutrophil granulocyte marker. Ischaemia and revascularization alone caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa, and increased myeloperoxidase activity in the mucosa. Intravenous injection of G. biloba extract caused a dose-dependent attenuation of all these effects of ischaemia. It is suggested, therefore, that G. biloba extract may protect the intestinal mucosa against ischaemic damage by reducing neutrophil infiltration and lipid peroxidation.
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PMID:Ginkgo biloba extract prevents mucosal damage associated with small-intestinal ischaemia. 255 86

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

The antiarrhythmic and cardioprotective effects of cibenzoline (4,5-dihydro-2-(2,2-diphenylcyclopropyl)-1H-imidazole) were investigated. Nineteen adult mongrel dogs were divided into 2 groups; in the control group, physiological saline (25 ml) was administered, and 20 min after, the left anterior descending coronary artery (LAD) was occluded for 2 h; in the cibenzoline group, cibenzoline (2 mg/kg), was administered 10 min before 2 h LAD occlusion. Blood pressure and appearance of arrhythmias were monitored throughout the experiment. Two h after occlusion, mitochondria were prepared from both ischemic and non-ischemic areas in each group, and their functions were measured polarographically. Fractionation of myocardial tissue from both ischemic and non-ischemic areas was performed, and activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase and beta-glucuronidase) were measured in each fraction. Administration of cibenzoline significantly reduced the appearance of ventricular arrhythmias in association with ischemia. Cibenzoline did not change significantly blood pressure and heart rate. In the control group, mitochondrial dysfunction and leakage of lysosomal enzymes induced by 2 h occlusion were observed. Administration of cibenzoline maintained significantly mitochondrial function and prevented significantly leakage of lysosomal enzymes. These results indicated that cibenzoline has a cardioprotective as well as an antiarrhythmic effect on ischemic myocardium.
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PMID:The effect of cibenzoline on myocardial damages in dogs. 275 58

Long-chain acylcarnitines are membrane-active intermediates of fatty acid metabolism whose intracellular accumulation has been implicated in the myocardial injury associated with both streptozotocin-induced diabetes and acute ischemia. In the present study, rats treated with streptozotocin (50 mg/kg i.v.) exhibited increases in myocardial long-chain acylcarnitines comparable to those previously reported to occur in moderate to severe ischemic injury. With the exception of a reduction in the sedimentable (lysosome-associated) fraction of myocardial N-acetyl-beta-glucosaminidase and a decrease in sarcoplasmic reticulum K+, Ca++-stimulated ATPase activity, other characteristic indices of myocardial ischemic damage, notably inhibition of sarcolemmal and mitochondrial ATPase activities as well as alterations in the ionic composition of myocardial tissue, were not apparent in the hearts of the streptozotocin-diabetic animals. On the basis of in vitro studies using palmitylcarnitine, it does not seem that differential sensitivity to long-chain acylcarnitine inactivation can explain the preferential inhibition of the sarcoplasmic reticulum ATPase enzyme observed in vivo. Our data are consistent with the findings of others suggesting that long-chain acylcarnitines are unlikely to be the most important or sole mediators of myocardial ischemic injury. However, a modulatory role of these substances in myocardial ischemic injury or in determining the increased susceptibility of diabetics to the complications of ischemic heart disease cannot be excluded at present.
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PMID:Subcellular myocardial abnormalities in experimental diabetes: role of long-chain acylcarnitines. 294 27


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