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

The purpose of this study was to evaluate the protective effect of a new endotoxin analogue, monophosphoryl lipid A (MLA) in a rabbit model of myocardial ischemia/reperfusion and to show if this protection was mediated via synthesis of 70 kDa heat shock protein (HSP 70). Three groups of New Zealand White rabbits underwent 30 min coronary occlusion, followed by 4 hours reperfusion. First group of rabbits (n = 6) were treated with 0.35 ml vehicle (40 % propylene glycol, 10 % ethanol in water). The second and third group of rabbits (n = 6-8) were treated with MLA (35 micrograms/kg, i.v.) 12 and 24 hours prior to ischemia and reperfusion. MLA treatment either 12 or 24 h prior to ischemia/reperfusion demonstrated significantly reduced infarct size (12.5 +/- 1.7 and 14.7 +/- 2.1% for 12 and 24 h) when compared with vehicle control (40.4 +/- 8.6%, mean +/- S.E.M, p < 0.05). No significant differences in the infarct size was observed between the 12 and 24 h MLA treated groups. The area at risk was not significantly different between the three groups. Baseline values of heart rate, systolic and diastolic blood pressure were not significantly different between the control and MLA treated groups. However, the systolic as well as diastolic blood pressure during reperfusion were significantly lower in rabbits treated with MLA. Western blot analysis of the protein extracts of the hearts (n = 2/group) demonstrated no increase in the expression of the inducible form of HSP 70 following treatment with MLA. We conclude that MLA has significant anti-infarct effect in rabbit which is not mediated by the cardioprotective protein HSP 70. The anti-infarct effect of this drug is superior to the reported protective effects of delayed ischemic or heat stress preconditioning. We hypothesize that the pharmacologic preconditioning afforded by MLA is accomplished via a unique pathway that bypasses the usual intracellular signaling pathways which lead to the myocardial protection with the expression of heat shock proteins.
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PMID:Monophosphoryl lipid A induces pharmacologic 'preconditioning' in rabbit hearts without concomitant expression of 70-kDa heat shock protein. 870 70

The purpose of this study was to evaluate the protective effect of a new endotoxin analogue, monophosphoryl lipid A (MLA) in a rabbit model of myocardial ischemia/reperfusion and to show if this protection was mediated via synthesis of 70 kDa heat shock protein (HSP 70). Three groups of New Zealand White rabbits underwent 30 min coronary occlusion, followed by 4 hours reperfusion. First group of rabbits (n = 6) were treated with 0.35 ml vehicle (40% propylene glycol, 10% ethanol in water). The second and third group of rabbits (n = 6-8) were treated with MLA (35 micrograms/kg, i.v.) 12 and 24 hours prior to ischemia and reperfusion. MLA treatment either 12 or 24 h prior to ischemia/reperfusion demonstrated significantly reduced infarct size (12.5 +/- 1.7 and 14.7 +/- 2.1% for 12 and 24 h) when compared with vehicle control (40.4 +/- 8.6%, mean +/- S.E.M, p < 0.05). No significant differences in the infarct size was observed between the 12 and 24 h MLA treated groups. The area at risk was not significantly different between the three groups. Baseline values of heart rate, systolic and diastolic blood pressure were not significantly different between the control and MLA treated groups. However, the systolic as well as diastolic blood pressure during reperfusion were significantly lower in rabbits treated with MLA. Western blot analysis of the protein extracts of the hearts (n = 2/group) demonstrated no increase in the expression of the inducible form of HSP 70 following treatment with MLA. We conclude that MLA has significant anti-infarct effect in rabbit which is not mediated by the cardioprotective protein HSP 70. The anti-infarct effect of this drug is superior to the reported protective effects of delayed ischemic or heat stress preconditioning. We hypothesize that the pharmacologic preconditioning afforded by MLA is accomplished via a unique pathway that bypasses the usual intracellular signaling pathways which lead to the myocardial protection with the expression of heat shock proteins.
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PMID:Monophosphoryl lipid A induces pharmacologic 'preconditioning' in rabbit hearts without concomitant expression of 70-kDa heat shock protein. 881 12

Nitrite and nitrate (NO2 and NO3), the oxidative products of nitric oxide (NO), were elevated in the plasma of rabbits on the third day following ligation of a coronary artery. This elevation coincided with increased activity of the inducible form of nitric oxide synthase (iNOS) in infarcted heart muscle. Data are reported which relate the elevated plasma concentrations of NO2+NO3 (NO(x)) to the increased induction of iNOS in an infarcted heart. NO2 and NO3 in plasma were measured by chemiluminescence. Nitrate was converted to nitrite by nitrate reductase. Plasma from the ear vein, right and left ventricle, and coronary sinus were analyzed for NO(x), and iNOS activity was enzymatically determined in infarcted, risk, and normal areas of the heart. The production equivalent of NO(x) by the heart and lung was also calculated. In addition, the effect of a specific inhibitor of iNOS, S-methylisothiourea sulfate (SMT) on plasma concentration and myocardial production of NO(x) was determined. It was concluded that the elevation of plasma NO(x) following onset of myocardial ischemia was directly related to increased induction of iNOS in the heart. This conclusion was based on a proportional and simultaneous increase in NO(x) plasma concentration with myocardial iNOS activation. The inhibitory effect of SMT furnished additional confirmation of the relationship between myocardial iNOS activation and NO(x) plasma levels in experimental myocardial infarction.
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PMID:Oxidation products of nitric oxide, NO2 and NO3, in plasma after experimental myocardial infarction. 904 16

We compared the time course of tolerance to myocardial ischemia-reperfusion injury with the time course of heat shock protein 72 (hsp72; inducible form) induction after heat stress in a rat model. The size of the infarct resulting from ischemia-reperfusion was increased 12 h after whole-body hyperthermia (42 degrees C for 15 min), but was significantly decreased 48 and 72 h after hyperthermia, compared with the sham control. The infarct size was decreased as late as 96 h after hyperthermia, although the infarct-limiting effect was smaller at that time. The myocardial content of hsp72 was markedly increased for 3-72 h after hyperthermic treatment, and was decreased after 72 h in association with an increase in the infarct size. The hsp72 content remained elevated during the period of tolerance to ischemia-reperfusion injury, but the infarct size decreased after the hsp72 content peaked. Pretreatment with a protein kinase C (PKC) inhibitor, chelerythrine chloride, immediately before hyperthermia, significantly suppressed the delayed cardioprotective effect of hyperthermia and reduced hsp72 induction. These results suggest that newly synthesized hsp72 through PKC activation after heat stress may have to be post-translationally modified and compartmentalized prior to assuming to the development of the delayed tolerance to ischemia-reperfusion injury in rats.
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PMID:Time course of tolerance to ischemia-reperfusion injury and induction of heat shock protein 72 by heat stress in the rat heart. 923 36

The effect of dexamethasone (DEX) on the activation of the inducible form of nitric oxide synthase (iNOS) and its relation to the formation of oxidation products of nitric oxide (NO2-+ NO3-, NOx) in infarcted heart muscle of rabbits was investigated. Myocardial infarction was produced by ligation of the first anterior branch of the left circumflex coronary artery. NOx was determined by chemiluminescence and iNOS by conversion of L-[14C]-arginine to L-[14C]-citrulline. The rise in myocardial iNOS production, which followed onset of myocardial ischemia, was suppressed by DEX. In addition, following coronary artery ligation, coronary arterial venous differences of NOx increased markedly; this effect was also partially abolished by DEX. Cardiac origin of NOx was confirmed by the linear relationship between coronary A-V NOx difference and myocardial formation of iNOS. This relationship was preserved after administration of DEX. Therefore glucocorticoids interfere with the myocardial NO production and thus diminish the concentration of its oxidative products in plasma.
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PMID:Dexamethasone on inducible nitric oxide synthase and nitrite/nitrate production in myocardial infarction. 979 Jan 71

This report reviews the author's involvement in the growth of ideas and basic concepts in myocardial ischemia resulting in the histological changes of myocardial infarction. Concepts arising from the study of myocardial substrate utilization, activation of the inducible form of nitric oxide synthase and production of prostacyclin and thromboxane in the infarcted heart are presented. New approaches are discussed dealing with the effects of nonsteroidal anti-inflammatory drugs on myocardial production of nitric oxide and prostanoids, and with the relevance of the inducible form of cyclooxygenase. The review also records a number of significant similarities between angiogenesis in the ischemic heart and some cancers. Angiogenesis in both instances originates from inflammatory reactions, illustrating how different tissues and organs such as ischemic heart muscle and cancer react to similar pathological stimuli in an identical manner. This multifocal approach opens new concepts on myocardial ischemia and cancer.
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PMID:Myocardial ischemia and infarction: growth of ideas. 1139 43