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)

This study examined whether N-acetylcysteine, a low molecular weight compound used clinically to replenish glutathione, could limit tissue necrosis during acute myocardial infarction in hearts with minimal coronary collateral flow. Fifty rabbits underwent 45 mins ischemia with and without coronary reperfusion for 3h. Four groups were studied. Saline or N-acetylcysteine (140 mg/kg) was administered intravenously 10 mins before occlusion and continued for 35 mins after occlusion. The area at risk of necrosis was assessed with fluorescent particles and the area of tissue necrosis was defined using triphenyltetrazolium chloride staining. No differences were observed for tissue necrosis expressed as a percentage of the risk zone size (mean +/- SEM, 46.7 +/- 8.2% versus 46.3 +/- 8.2%) for saline and N-acetylcysteine treated rabbits subjected to 45 mins coronary occlusion. Tissue necrosis in rabbits with 45 mins ischemia followed by 3 h reperfusion was not significantly reduced with N-acetylcysteine treatment (36.4 +/- 5.1%) compared to untreated controls (36.5 +/- 6.4%). Risk zone size and hemodynamic parameters were similar between the treatment groups. Thus, treatment before and during short term coronary occlusion did not limit tissue necrosis during acute myocardial infarction.
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PMID:Effect of N-acetylcysteine on tissue necrosis during acute myocardial infarction in rabbits. 279 May 79

Zomepirac sodium (ZS) (5 mg/kg i.v.) was used to evaluate the effects of preischemia cyclooxygenase inhibition on CBF (as assessed by 133Xe clearance), CBF-PaCO2 responsiveness, and electrophysiologic (EEG) parameters before and after a 15-min period of complete global ischemia produced by four-vessel occlusion and mild hypotension. During the 15-min period of ischemia, CBF was essentially zero. Following reflow all groups displayed an initial hyperemia as compared with control (92 +/- 11 vs. 141-146 ml/100 g/min). Saline-treated animals during reflow displayed a delayed hypoperfusion (26 +/- 3 ml/100 g/min), which showed no improvement during the 2-h reflow period prior to death. In contrast, ZS-treated animals during reflow displayed significantly higher flows during the hypoperfusion phase (72 +/- 9 ml/100 g/min). The CBF-PaCO2 response displayed an approximately sevenfold reduction in slope at 2 h after reflow in saline-treated animals. This decrease in PaCO2 reactivity was not observed in the ZS-pretreated animals. With regard to EEG, all animals showed a total flattening during the 15 min of ischemia. In saline-treated animals only one of seven showed any sign of even marginal recovery. In ZS-treated animals EEG activity showed prominent recovery in seven of seven. Brainstem auditory evoked potentials were monitored and showed prominent recovery of amplitude and latency in ZS but not saline-treated animals during reflow.
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PMID:Effect of preischemia cyclooxygenase inhibition by zomepirac sodium on reflow, cerebral autoregulation, and EEG recovery in the cat after global ischemia. 309 46

Myocardial 201Tl redistribution after transient ischemia may be too slow to allow identification of a reversible myocardial defect within the routine 201Tl imaging period. To determine whether 201Tl redistribution could be affected by a metabolic intervention, intravenous ribose was administered postischemia. Seventeen domestic swine were subjected to a 10-min ischemic period followed by either a 30-min i.v. ribose (n = 8) or saline (n = 9) infusion. Thallium-201 was injected during ischemia and myocardial 201Tl activity was continuously monitored in ischemic and nonischemic regions with miniature CdTe radiation detection probes. Coronary flow in the ischemic region was reduced to 25% of that in the nonischemic regions in both saline and ribose groups. The 201Tl time-activity curves demonstrated a significant enhancement of % 201Tl redistribution in the ribose-treated animals at the end of ribose infusion: Ribose (48 +/- 11%), Saline (20 +/- 4%), p less than 0.05. Alteration of 201Tl kinetics by ribose may permit earlier recognition of 201Tl myocardial redistribution after transient ischemia.
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PMID:Effect of ribose on thallium-201 myocardial redistribution. 314 74

The aim of this study was to differentiate myocardial reperfusion injury from that of ischemia. We assessed the role of the myocardial adenosine 5'-triphosphate (ATP) catabolites, hypoxanthine and xanthine, generated during ischemia and the early phase of reperfusion, in reperfusion injury by modulating adenosine transport and metabolism with specific metabolic inhibitors. This was followed by intracoronary infusion of exogenous hypoxanthine and xanthine. Twenty-four dogs instrumented with minor-axis piezoelectric crystals and intraventricular pressure transducers were subjected to 30 minutes of normothermic global myocardial ischemia and 60 minutes of reperfusion. In Group 1 (n = 7), normal saline was infused into the cardiopulmonary bypass reservior before ischemia and before reperfusion. Saline solution containing 25 microM p-nitrobenzylthioinosine (NBMPR) and 100 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) was infused in Group 2 (n = 10) dogs. Group 3 (n = 7) dogs were treated exactly like those in Group 2 except, at the end of the ischemic period and immediately before releasing the cross-clamp, a solution of EHNA-NBMPR containing 100 microM hypoxanthine and 100 microM xanthine was infused into the aortic root. Left ventricular performance and myocardial adenine nucleotide pool intermediates were determined before and after ischemia. ATP was depleted by about 50% (p less than 0.05 vs. preischemia) in all groups after 30 minutes of ischemia. Inosine was the major ATP catabolite (9.29 +/- 1.2 nmol/mg protein) in Group 1, while adenosine (9.91 +/- 0.7 nmol/mg protein) was the major metabolite in EHNA-NBMPR-treated dogs (Groups 2 and 3). Hypoxanthine levels were fivefold more in Group 1 compared with Groups 2 and 3 (p less than 0.05). Left ventricular performance in Group 1 decreased from 76.8 +/- 7.6 to 42.9 +/- 9.8 and 52.3 +/- 8.4 dynes/cm2 x 10(3) (p less than 0.05), while myocardial ATP decreased from 30.9 +/- 2.2 to 17.2 +/- 1.0 and 16.5 +/- 1.0 nmol/mg protein during 30 and 60 minutes of reperfusion, respectively (p less than 0.05 vs. preischemia). Ventricular function in Group 2 dogs completely recovered within 30 minutes of reperfusion, and myocardial ATP recovered to the preischemic level at 60 minutes of reperfusion. In Group 3, left ventricular performance was depressed by 39% and 30% during 30 and 60 minutes of reperfusion (p less than 0.05), respectively, and myocardial ATP did not recover during reperfusion despite a significant intramyocardial adenosine accumulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Myocardial reperfusion injury. Role of myocardial hypoxanthine and xanthine in free radical-mediated reperfusion injury. 318 Apr 2

A previous study by the authors showed that myocardial infarct size in the rabbit, measured after 45 mins of ischemia and 3 h of reperfusion, could be limited by administration of superoxide dismutase (SOD) plus catalase. The present study examined whether this infarct size limitation is sustained for the following three days. Under anesthesia, a coronary branch of the Japanese white rabbit was occluded for 45 mins and then reperfused. Three days after surgery, the heart was excised and the volume of myocardium supplied by the occluded coronary branch (ischemic zone size) was assessed with fluorescent particles and the infarct size was estimated by hematoxylin and eosin and with Mallory's staining. The SOD plus catalase group (n = 14) received 15,000 units/kg of SOD plus 50,000 units/kg of catalase in saline over 90 mins, starting 15 mins before the coronary occlusion. Saline was infused in the control group (n = 15). Three rabbits in the control group and three in the SOD plus catalase group died of ventricular fibrillation during the ischemic period. Three control and two SOD plus catalase rabbits were excluded because the ischemic zone was ambiguous. The percentage of the ischemic zone which was infarcted was 59.4 +/- 6.9% (mean +/- SE) in the control group (n = 9) and 49.4 +/- 5.1% in the SOD plus catalase group (n = 9). These were not statistically different. Ischemic zone size and hemodynamic parameters were similar in the two groups. These findings suggest that SOD plus catalase may serve only to delay rather than prevent myocardial infarction.
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PMID:Effect of superoxide dismutase plus catalase on myocardial infarct size in rabbits. 322 70

A method to determine migration of phagocytic cells in vivo has been evaluated. It was used to analyze leukocyte migration during ischemia, peritonitis, and after pretreatment with methylprednisolone. Phagocytic cells were labeled in vitro with 150 megabecquerel (4.05 mCi) of technetium Tc 99m colloid and reinfused. Saline 0.03 mg and 3.0 mg of endotoxin per kilogram per rat were injected subcutaneously in duplicate. Four hours later, a standardized amount of skin and subcutaneous tissue from the area of injection was removed and weighed. A dose-related accumulation of radiolabeled leukocytes to endotoxin was found in healthy controls but not in animals with hypoperfusion or peritonitis or those pretreated with methylprednisolone. This in vivo method to calculate leukocyte migration will give reproducible results with a mean difference between duplicate samples of less than 6%.
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PMID:In vivo determination of modulated migration of radiolabeled leukocytes. 330 99

The cerebral protective effects of lidocaine were evaluated using a rat model of severe (near-complete) global ischemia produced by 10 min of bilateral carotid artery occlusion combined with systemic hypotension (MAP 45-55 mmHg). Prior to the induction of ischemia, 16 rats were given incremental doses of lidocaine intravenously until EEG slowing with sharp wave activity became evident. An equal number of rats (controls) received saline prior to the ischemic insult. Normoxia, normocapnia, and normothermia were maintained at all times. Following ischemia, the animals were allowed to recover. At 1.5 h post-ischemia, eight rats from each treatment group were reanesthetized, and regional brain water content was assessed gravimetrically. Brain specific gravity was significantly reduced from normal values in both treatment groups, and was unaltered by pre-ischemic lidocaine administration. Seven days post-ischemia, the remaining animals were reanesthetized; the brains were formalin fixed and processed for identification of irreversibly injured neurons in the hippocampus, neocortex, and caudate nucleus. Saline-treated rats displayed 75 +/- 4% (mean +/- SD) dead cells in the hippocampus (CA1); lidocaine-treated rats had similar injury (78 +/- 7%). In the neocortex and caudate nucleus, injury was graded as moderate, and no difference in severity could be distinguished between the treatment groups. The authors conclude that pre-ischemic treatment with maximal sub-epileptogenic doses of lidocaine had no effect on either early post-ischemic cerebral edema or delayed neuronal necrosis in this rat model of near-complete global ischemia.
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PMID:Failure of pre-ischemic lidocaine administration to ameliorate global ischemic brain damage in the rat. 333 92

The effect of MCl-176 [2-(2,5-dimethoxyphenylmethyl)-3-(2-dimethylaminoethyl)-6- isopropoxy-4(3H)-quinazolinone hydrochloride], a novel calcium channel blocker, on ischemic myocardial acidosis was studied in the dog heart, in which the left anterior descending coronary artery was partially occluded for 90 min (partial occlusion). Myocardial pH (measured by a micro glass pH electrode) was about 7.60 in the nonischemic normal heart. The myocardial pH decreased rapidly in response to partial occlusion, and reached the steady state of about 6.85 within 30 min (i.e., the myocardial [H+] increased after partial occlusion). Saline or drug was injected i.v. 30 min after partial occlusion, and the drug effect was observed till the end of partial occlusion. Myocardial [H+], that had been increased by partial occlusion, restored slightly after the saline injection, and the restoration was about 30% 60 min after the injection. MCl-176 increased this spontaneous restoration of myocardial [H+] with a decrease in blood pressure and heart rate; the restoration induced by 0.1 mg/kg of MCl-176 was 74% 60 min after the injection. Even in the paced heart, MCl-176 (0.1 mg/kg) attenuated the ischemia-induced myocardial acidosis. Propranolol (1 mg/kg) also attenuated the myocardial acidosis, the restoration being 82%. These results indicate that MCl-176 attenuates the myocardial acidosis during ischemia as does propranolol, and that the mechanism of action of MCl-176 is not due primarily to a decrease in heart rate.
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PMID:MCl-176, a novel calcium channel blocker, attenuates the ischemic myocardial acidosis induced by coronary artery occlusion in dogs. 336 49

This study examines the extent of endothelial damage following a period of irrigation with various crystalloid irrigation fluids. Both arteries and veins were evaluated after irrigation with normal saline, lactated Ringer's, Balanced Salt Solution (BSS), and Balanced Salt Solution Plus (BSS+). The arterial and venous endothelia were examined with the scanning electron microscope. Using a randomized blind observer scoring system, micrographs were evaluated for changes in nuclear shape, cell junction integrity, cytoplasm changes, and sloughing of the endothelial cell layer. BSS+ and BSS produced statistically significant (P less than .001) improvement over the other two irrigation fluids in the arteries. BSS+ and BSS were statistically superior (P less than .001) in the venous vessels. The compositions of BSS and BSS+ tend to maintain a physiologic environment in the presence of ischemia. These fluids maintained a morphologic appearance closer to that of perfusion-fixed controls. The data suggest a protective effect of such physiologic preparations on the endothelium. The preservation of intact endothelium may play a role in decreased platelet activation, continued production of prostacyclin, and maintenance of an intact barrier between the intracellular and extracellular spaces. This could enhance the survival of transplanted or transferred tissue, by helping to maintain nearly normal endothelium during surgery.
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PMID:Effect of irrigation fluids on arterial and venous endothelium after ischemia. 368 25

Effects of glucagon and prostacyclin (PGI2) were studied in anesthetized dogs during sequential occlusive and postocclusive mesenteric ischemia induced by 90 min of tourniquet stenosis of the superior mesenteric artery (SMA). After 30 min of SMA stenosis, glucagon (1 microgram/kg/min, n = 7), PGI2 (30 ng/kg/min, n = 7), or saline (1 ml/min, n = 3) was infused intravenously for 30 min, followed by 30 min of continued ischemia. SMA flow and distal SMA pressure ( SMAP ) decreased 76% with SMA stenosis (P less than 0.01). Ileal wall flow measured by radiolabeled microspheres decreased from 45 to 13 ml/min/100 g (P less than 0.01); mesenteric AV O2 difference ( AVDO2 ) increased from 5.1 to 10.1 ml/dl (P less than 0.01); and mesenteric O2 consumption (VO2) decreased by 48% (P less than 0.05). Glucagon infusion caused a further decrease in ileal wall flow, to 10 ml/min/100 g (P less than 0.05), and an increase in AVDO2 to 11 ml/dl (P less than 0.05), despite a 22% increase in cardiac output. PGI2 caused a similar decrease in ileal wall flow and an increase in AVDO2 , although these were not statistically significant. Saline infusion caused no change in measured variables. In the second phase of this study, SMA blood flow was restored by tourniquet release. After animals had stabilized for 30 min, a repeat 30-min drug infusion was studied. In this postocclusive period, persistent gut ischemia was indicated by a reduction in VO2 to 76% of original baseline, associated with a 50% decrease in both CO and SMAQ . Intravenous infusion of glucagon at this time increased SMAQ by 195% (P less than 0.05) and resulted in a return of VO2 to its original baseline level. PGI2 infusion caused a 21% increase in SMAQ and a 16% decrease in AVDO2 (NS), but had no significant effect on VO2. Glucagon was effective in the management of postocclusive mesenteric ischemia but appeared to have a detrimental effect on ileal blood flow in severe occlusive ischemia.
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PMID:Effects of glucagon and prostacyclin in acute occlusive and postocclusive canine mesenteric ischemia. 637 91


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