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)

Opioids introduced at reperfusion (R) following ischemia (I) reduce infarct size much like postconditioning, suggesting the hypothesis that postconditioning increases cardiac opioids and activates local opioid receptors. Anesthetized male rats subjected to 30 min regional I and 3 h R were postconditioned with three cycles of 10 s R and 10 s reocclusion at onset of R. Naloxone (NL), its peripherally restricted analog naloxone methiodide, delta-opioid receptor (DOR) antagonist naltrindole (NTI), kappa-opioid receptor antagonist norbinaltorphimine (NorBNI), and mu-opioid receptor (MOR) antagonist H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) were administered intravenously 5 min before R. The area at risk (AAR) was comparable among groups, and postconditioning reduced infarct size from 57 +/- 2 to 42 +/- 2% (P < 0.05). None of the antagonists alone altered infarct size. All antagonists abrogated postconditioning protection at higher doses. However, blockade of infarct sparing by postconditioning was lost, since tested doses of NL, NTI, NorBNI, and CTAP were lowered. The efficacy of NorBNI declined first at 3.4 micromol/kg, followed sequentially by NTI (1.1), NL (0.37), and CTAP (0.09), suggesting likely MOR and perhaps DOR participation. Representative small, intermediate, and large enkephalins in the AAR were quantified (fmol/mg protein; mean +/- SE). I/R reduced proenkephalin (58 +/- 9 vs. 33 +/- 4; P < 0.05) and sum total of measured enkephalins, including proenkephalin, peptide B, methionine-enkephalin, and methionine-enkephalin-arginine-phenylalanine (139 +/- 17 vs. 104 +/- 7; P < 0.05) compared with shams. Postconditioning increased total enkephalins (89 +/- 8 vs. 135 +/- 5; P < 0.05) largely by increasing proenkephalin (33 +/- 4 vs. 96 +/- 7; P < 0.05). Thus the infarct-sparing effect of postconditioning appeared to involve endogenously activated MORs and possibly DORs, and preservation of enkephalin precursor synthesis in the AAR.
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PMID:Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation. 1820 44

Using The globally ischaemic isolated guinea-pig heart we conducted studies to assess the role of activated neutrophils (PMNs) and the role of the endothelium in reperfusion injury. Reperfusion injury was induced by a 20 min period of global ischaemia followed by a 30 min reperfusion with Krebs' buffer supplemented with f-Met-Leu-Phe (fMLP) and heparinized blood. Ischaemia alone or blood alone resulted in a complete recovery in contractile function measured by developed pressure, fMLP (500 muM) and blood, administered to normoxic hearts did not affect contractile function. The combination of 100 muM fMLP and blood beginning at reperfusion and continuing for 30 min decreased the recovery in contractile function (max. 33 +/- 6% reovery) while buffer and 100 pM fMLP resulted in a complete recovery in function. In hearts infused with buffer and neutropenic blood incubated with 100 muM fMLP a complete recovery in function was observed. Isolated peritoneal neutrophils, 7-70 x 10(5) PMN/ min, incubated with 100 muM fMLP and Krebs' solution decreased contractile function in a concentration-related manner (max. 44 +/- 11% recovery). Platelets, plasma or red blood cells alone incubated with fMLP did not decrease recovery in developed pressure. Platelets and PMN incubated with 100 muM fMLP did not, while red blood cells and PMN did, elicit a reduction in recovery in contractile function (34 +/- 4% recovery). A 20 min period of global ischaemia destroys the functional integrity of the endothelium (response to Ach). Pre-treatment of the heart with sufficient H(2)O(2) to functionally damage the endothelium, followed by infusion of Krebs' solution supplemented with blood and 100 muM fMLP also elicited a reduction in recovery of contractile function (42 +/- 15% recovery). In summary, partially activated neutrophils play a major role in reperfusion injury and there exists a cooperativity between the RBC and PMN in this model.
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PMID:The role of the neutrophil and formed elements of the blood in an in vitro model of reperfusion injury. 1847 8

The efficacy of copper aspirinate against thrombotic diseases has been tested in animal models. The results show that copper aspirinate, following ig pretreatment for 7 days at 0.012mmol/kg markedly prolonged the bleeding time and inhibited the mortality induced by arachidonic acid (AA) in mice. On cereral ischemia model pretreatment with 0.018mmol/kg copper aspirinate ig significantly increased survival of animals and the density of intact hippocampal CA1 cells and decreased brain calcium concentration. Its anticerebral ischemia activity was superior to or equal to nimodipine. It is, therefore, suggested that copper aspirinate is very promising in becoming an antithrombotic drug in preventing and treating thrombotic diseases.
Met Based Drugs 1998
PMID:Potential application of copper aspirinate in preventing and treating thromboembolic diseases. 1847 33

The cerebroprotective effects of copper aspirinate [dimeric copper(II) bis(o-acetoxybenzoate)] were investigated in gerbils subjected to 10-min global cerebral ischemia followed b 60-min reperfusion. The results showed that intragastric copper aspirinate (7.5, 15.0 and 30.0 mg Kg(-1)) markedly promoted the recovery of the electroencephalogram amplitude, attenuated the increase of lipid peroxide content and the decrease of superoxide dismutase activity in the cortex during ischemia-reperfusion injury. It suggested that copper aspirinate possesses potential neuroprotective properties, the mechanism of which might be related to an increase of the activity of endogenous superoxide dismutase.
Met Based Drugs 2002
PMID:Cerebroprotective Effects of Dimeric Copper(II) Bis(o-acetoxybenzoate) on Ischemia-reperfusion Injury in Gerbils. 1847 2

Puerarin, a major isoflavonoid derived from the Chinese medical herb Radix puerariae (kudzu root), has been reported to be useful in the treatment of various cardiovascular diseases. In the present study, we examined the detailed mechanisms underlying the inhibitory effects of puerarin on inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAO) in rats. Treatment of puerarin (25 and 50 mg/kg; intraperitoneally) 10 min before MCAO dose-dependently attenuated focal cerebral ischemia in rats. Administration of puerarin at 50 mg/kg, showed marked reduction in infarct size compared with that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor-1alpha (HIF-1alpha), inducible nitric oxide synthase (iNOS), and active caspase-3 protein expressions as well as the mRNA expression of tumor necrosis factor-alpha (TNF-alpha) in ischemic regions. These expressions were markedly inhibited by the treatment of puerarin (50 mg/kg). In addition, puerarin (10-50 microM) concentration-dependently inhibited respiratory bursts in human neutrophils stimulated by formyl-Met-Leu-Phe. On the other hand, puerarin (20-500 microM) did not significantly inhibit the thiobarbituric acid-reactive substance reaction in rat brain homogenates. An electron spin resonance (ESR) method was conducted on the scavenging activity of puerarin on the free radicals formed. Puerarin (200 and 500 microM) did not reduce the ESR signal intensity of hydroxyl radical formation. In conclusion, we demonstrate that puerarin is a potent neuroprotective agent on MCAO-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both HIF-1alpha and TNF-alpha activation, followed by the inhibition of inflammatory responses (i.e., iNOS expression), apoptosis formation (active caspase-3), and neutrophil activation, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, puerarin treatment may represent a novel approach to lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders.
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PMID:Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats. 1927 72

Coronary artery disease either presents with acute chest pain or with exercise induced chest symptoms or shortness of breath. The differentiation between stable and unstable Angina pectoris is prognostically important, unstable angina is managed as an acute coronary syndrome including hospital admission, patients with stable symptoms can be further evaluated in an outpatient setting. A broad differential diagnosis of other cardiac and non-cardiac causes must be considered. Important initial diagnostic steps are cardiovascular risk stratification and prove of ischemia (or scar, necrosis) either at rest or usually exercise-induced, if necessary by additional imaging. Exercise capacity is assessed by physiological parameters (watt, VO2max., MET and distance) during exercise tests like ergometry, spiroergometry or 6-minute walking test (e.g. heart failure patients). Additional factors must be considered for the assessment of working capacity.
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PMID:[Outpatient diagnosis of coronary artery disease]. 1935 34

The present study investigated the possible role of Janus kinase-2 (JAK-2) in hyperhomocysteinemia-induced attenuation of the cardioprotective effects of ischemic preconditioning (IPC). Rats were administered L-methionine (1.7 g/kg/day, p.o.) for 4 weeks to produce hyperhomocysteinemia. Isolated Langendorff's perfused normal and hyperhomocysteinemic rat hearts were subjected to global ischemia for 30 min, followed by reperfusion for 120 min. Myocardial infarct size was assessed macroscopically using triphenyltetrazolium chloride staining. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK) release to assess the extent of cardiac injury. The oxidative stress in the heart was assessed by measuring thiobarbituric acid-reactive substances (TBARS), superoxide anion generation and the reduced form of glutathione. Ischemia-reperfusion (I/R) induced oxidative stress by increasing TBARS, superoxide anion generation and decreasing reduced form of glutathione in normal and hyperhomocystenemic rat hearts. Moreover, I/R produced myocardial injury, which was assessed in terms of the increase in myocardial infarct size, LDH and CK release in coronary effluent, and decrease in coronary flow rate in normal and hyperhomocysteinemic rat hearts. The hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with a high degree of oxidative stress as compared with normal rat hearts subjected to I/R. Four episodes of IPC (5 min each) afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts as assessed in terms of improvement in coronary flow rate and reduction in myocardial infarct size, levels of LDH, CK, and oxidative stress. On the other hand, IPC-mediated myocardial protection against I/R-injury was abolished in hyperhomocysteinemic rat hearts. Tyrphostin AG490 (5 microM), a selective inhibitor of JAK-2, did not affect the cardioprotective effects of IPC in normal rat hearts, but its administration markedly restored the cardioprotective potential of IPC in hyperhomocysteinemic rat hearts. Administration of diazoxide (30 microM), an ATP-sensitive potassium (K(ATP)) channel opener, also restored the cardioprotective effects of IPC in hyperhomocysteinemic rat hearts. In conclusion, it is suggested that the high degree of oxidative stress produced in hyperhomocysteinemic rat hearts during reperfusion and consequent activation of JAK-2 and closure of K(ATP) channels may be responsible for abolishing the cardioprotective potential of IPC against I/R-induced myocardial injury.
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PMID:Possible role of JAK-2 in attenuated cardioprotective effect of ischemic preconditioning in hyperhomocysteinemic rat hearts. 1942 Aug 83

The present study was designed to investigate the effect of hyperhomocysteinemia (Hhcy) on cardioprotective potentials of ischemic preconditioning (IPC) and postconditioning (IPost). Rats were administered L-methionine (1.7 g/kg/day orally) for 4 weeks to produce Hhcy. Isolated Langendorff-perfused normal and hyperhomocysteinemic rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 120 min. Myocardial infarct size was assessed macroscopically by volume method using triphenyltetrazolium chloride staining. Coronary effluent was analyzed for the release of lactate dehydrogenase (LDH) and creatine kinase (CK) to assess the degree of cardiac injury. Moreover, oxidative stress in the heart was assessed by measuring lipid peroxidation, superoxide anion generation and reduced glutathione. Ischemia-reperfusion (I/R) was noted to produce myocardial injury, as assessed in terms of increase in myocardial infarct size, LDH and CK in coronary effluent and oxidative stress in normal and hyperhomocysteinemic rat hearts. In addition, the hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with a high degree of oxidative stress in comparison with normal rat hearts subjected to I/R. Four episodes of IPC (5 min each) and six episodes of IPost (10 s each) afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts, as assessed in terms of reduction in myocardial infarct size, LDH, CK and oxidative stress. However, surprisingly, IPC- and IPost-mediated myocardial protection against I/R injury was abolished in the hyperhomocysteinemic rat heart. It may be concluded that Hhcy may make the heart susceptible to oxidative stress induced by I/R, and that the high degree of oxidative stress produced in the hyperhomocysteinemic rat heart in response to reperfusion may be responsible for abolishing the cardioprotective potential of IPC and IPost against I/R injury.
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PMID:Modulation of cardioprotective effect of ischemic pre- and postconditioning in the hyperhomocysteinemic rat heart. 1945 61

The changes of functional state isolated by Lanhendorf old rat hearts with low content of ubiqinone--coenzyme Q (CoQ) under activation of it endogenous synthesis through administration of precursors--4-hydroxybenzoic acid, methionine and modulator vitamin E were studied. The activation of ubiqinone biosynthesis contribute to cardioprotective effect due to reduce the degree of the ischemia-reperfusion injury in old rat heart, namely the restoration of myocardial contractile function and coronary flow as well as decrease the end diastolic pressure and oxygen cost of the heart compared with control group of the animals during ischemia-reperfusion. Thus the results allow to conclude that the activation of KoQ biosynthesis under administration of it precursors has protective effect in the development of the heart postreperfusion damages in aging.
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PMID:[Cardioprotective action of coenzyme Q in conditions of its endogenous synthesis activation in cardiac ischemia-reperfusion in old rats]. 1982 31

The present study has been designed to investigate the possible role of protein kinase C-delta (PKC-delta) in hyperhomocysteinemia-induced attenuation of cardioprotective potential of ischemic preconditioning (IPC). Rats were administered L-methionine (1.7 g/kg/day, p.o.) for 4 weeks to produce hyperhomocysteinemia. Isolated Langendorff perfused normal and hyperhomocysteinemic rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 120 min. Myocardial infarct size was assessed macroscopically using triphenyltetrazolium chloride (TTC) staining. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK) release to assess the degree of cardiac injury. Moreover, the oxidative stress in heart was assessed by measuring lipid peroxidation and superoxide anion generation. The ischemia-reperfusion (I/R) was noted to produce myocardial injury as assessed in terms of increase in myocardial infarct size, LDH and CK in coronary effluent and oxidative stress in normal and hyperhomocysteinemic rat hearts. In addition, the hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with high degree of oxidative stress as compared with normal rat hearts subjected to I/R. Four episodes of IPC (5 min each) afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts as assessed in terms of reduction in myocardial infarct size, LDH, CK and oxidative stress. On the other hand, IPC mediated myocardial protection against I/R-injury was abolished in hyperhomocysteinemic rat hearts. Treatment with rottlerin (10 microM), a selective inhibitor of PKC-delta did not affect the cardioprotective effects of IPC in normal rat hearts; but its treatment significantly restored the cardioprotective potentials of IPC in hyperhomocysteinemic rat hearts. The high degree of oxidative stress produced in hyperhomocysteinemic rat hearts during reperfusion may activate PKC-delta, which may be implicated in the observed paradoxically abrogated cardioprotective potentials of IPC in hyperhomocysteinemic rat hearts.
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PMID:Possible involvement of PKC-delta in the abrogated cardioprotective potential of ischemic preconditioning in hyperhomocysteinemic rat hearts. 1991 92


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