Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of brief myocardial ischemia on the expression of heat shock protein (HSP 70) was examined in an in vivo rabbit model of myocardial ischemia using Northern blotting. Functional studies were carried out in the open-chested anesthetized rabbit. The large marginal branch of the left circumflex was occluded four times for 5 min. Using piezoelectric crystals implanted midwall in the ischemic zone, end-diastolic length, end-systolic length, and percent segmental shortening were assessed. Expression of HSP 70 was measured by Northern blotting. A single 5-min coronary occlusion doubled the expression of HSP 70 whereas four cycles of 5 min of ischemia/5 min of reperfusion resulted in a threefold increase in HSP 70 mRNA (P less than 0.001). Measurements with the piezoelectric crystals showed mild myocardial dysfunction concomitant with the increase in HSP 70. This increase in HSP 70 mRNA after repetitive brief ischemia was transient, occurring as early as 1 h and returning to baseline by 24 h after ischemia. Western blot analysis with a monoclonal antibody to HSP 70 was used to compare sham and postischemic myocardial HSP 70 levels. Changes in the amount of HSP 70 were evident as early as 2 h and were even more striking at 24 h.
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PMID:Rapid expression of heat shock protein in the rabbit after brief cardiac ischemia. 198 91

We investigated whether ischemic preconditioning (PC) produced a second window of protection by delayed synthesis of cardioprotective proteins. Anesthetized open-chest rabbits were subjected to 30 min of coronary occlusion and 3 h of reperfusion. PC was elicited by 5 min of ischemia and was separated from sustained ischemia by 5 min, 2 h, or 24 h of reperfusion. Infarct size (% area at risk) was markedly limited by PC with 5 min of reperfusion when compared with controls (13.3 +/- 2.5 vs. 46.8 +/- 7.0%; P < 0.05). This protective effect was lost when the interval between PC and sustained ischemia was extended to 2 h (47.8 +/- 4.8%; P = NS vs. control) and did not reoccur even when it was extended to 24 h (44.2 +/- 6.5%; P = NS vs. sham-operated control). To potentiate induction of heat shock proteins (HSPs), a PC protocol involving four 5-min episodes of ischemia and reperfusion was also used and was separated from sustained ischemia by 24 or 48 h of reperfusion. However, neither of these protocols was protective, and limitation of infarct size was not observed (55.5 +/- 5.9 and 53.4 +/- 6.5% in 24 and 48 h of reperfusion, respectively; P = NS vs. corresponding sham-operated control). Myocardial expression of HSPs was examined using a monoclonal antibody against 72- to 73-kDa HSP in additional rabbits. Immunoreactivity was observed in the myocardium at 24 and 48 h after PC, but not immediately after PC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ischemic preconditioning elevates cardiac stress protein but does not limit infarct size 24 or 48 h later in rabbits. 794 94

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

If a coronary occlusion long enough to produce a myocardial infarction is preceded by one or more brief periods of occlusion, the infarct size is reduced with respect to the area at risk. Also the ischaemia reperfusion injury is remarkably reduced. Such effects form the ischaemic preconditioning. Ischaemia-reperfusion injury is attributed to a Ca2+ overload of the myocardial fibres together with an inadequate resynthesis of ATP, a loss of membrane phospholipids and a release of free oxygen radicals. The inadequate resynthesis of ATP is responsible for an increased concentration of nucleosides and purinic bases with swelling of the myocardial fibres. The cell Ca2+ overload depends on a reduced activity of the ionic pumps caused by the oxygen lack during ischaemia. During reperfusion the vascular endothelial cells of the previously ischaemic area release free oxygen radicals in response to the activity of the xanthine-oxidase on hypoxanthine produced by the ischaemic myocardium. This initial release of oxygen radicals is responsible for the adhesion of neutrophils to the endothelium. After adhesion also the neutrophils release free radicals due to the activity of NADPH-oxidase on molecular oxygen. Myocardial, neural and endothelial mechanisms account for the protective effect of preconditioning. Myocardial mechanisms include the release of adenosine as well as of antioxidant enzymes. Adenosine, which activates protein-kinase C, favours the phosphorylation of a protective protein, whereas the antioxidant enzymes impair the activity of the free oxygen radicals. Preconditioning may also involve the synthesis of a heat shock protein. Neural mechanisms are represented by a reduced release of noradrenaline from the sympathetic nerve endings and a reduced sensitivity of myocardium to noradrenaline. Finally, vascular endothelial cells take part in preconditioning by means of an increased production of nitric oxide which seems to exert a protection against arrhythmias.
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PMID:[Mechanisms of ischemic preconditioning: relation with ischemia-reperfusion injury]. 924 32

Hearts hypertrophied by pressure-overload are more susceptible to ischemia than nonhypertrophied hearts, which may result from the attenuation of self-protective responses. Because heat shock proteins (HSPs) are reported to protect against ischemic injuries, we hypothesized that HSP expression by coronary occlusion may be attenuated in hypertrophied hearts. We banded the ascending aorta to develop ventricular hypertrophy and put a snare around the left coronary artery in rats. After 4 wk, coronary occlusion was applied by tightening the snare for 5 or 10 min in rats with and without aortic banding. The hearts were excised 0, 0.5, 1, 2, 4, 8, 12, and 24 h after coronary occlusion. Ischemic and nonischemic myocardial tissues were obtained after the snare was tightly tied, and dye was infused from the aorta. The mRNAs and protein of 72-kDa HSP (HSP 72) and/or 73-kDa HSP (HSP 73) were detected by Northern and Western blot analyses. Protein and mRNA levels of HSPs expressed by 5-min coronary occlusion in hypertrophied hearts (left ventricular weight, 577 +/- 16 mg) were lower compared with those in control hearts (462 +/- 9 mg). A longer period of coronary occlusion (10 min) elevated the attenuated expression to a level similar to that in control hearts. Treatment with an angiotensin-converting enzyme (ACE) inhibitor (cilazapril, 10-15 mg.kg(-1).day(-1)) for 4 wk preserved HSP mRNA expression even in hearts with ascending aortic banding. In hypertrophied hearts, HSP 72 and 73 expression by coronary occlusion was attenuated and was modulated by the duration of coronary occlusion and by ACE inhibitor treatment.
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PMID:Attenuation of heat shock protein expression by coronary occlusion in hypertrophied hearts. 927 65

Experimental studies examining the effects of regular exercise on cardiac responses to ischemia and reperfusion (I/R) are limited. Therefore, these experiments examined the effects of endurance exercise training on myocardial biochemical and physiological responses during in vivo I/R. Female Sprague-Dawley rats (4 mo old) were randomly assigned to either a sedentary control group or to an exercise training group. After a 10-wk endurance exercise training program, animals were anesthetized and mechanically ventilated, and the chest was opened by thoracotomy. Coronary occlusion was achieved by a ligature around the left coronary artery; occlusion was maintained for 20 min, followed by a 10-min period of reperfusion. Compared with untrained, exercise-trained animals maintained higher (P < 0.05) peak systolic blood pressure throughout I/R. Training resulted in a significant (P < 0.05) increase in ventricular nonprotein thiols, heat shock protein (HSP) 72, and the activities of superoxide dismutase (SOD), phosphofructokinase (PFK), and lactate dehydrogenase. Furthermore, compared with untrained controls, left ventricles from trained animals exhibited lower levels (P < 0. 05) of lipid peroxidation after I/R. These data demonstrate that endurance exercise training improves myocardial contractile performance and reduces lipid peroxidation during I/R in the rat in vivo. It appears likely that the improvement in the myocardial responses to I/R was related to training-induced increases in nonprotein thiols, HSP72, and the activities of SOD and PFK in the myocardium.
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PMID:Exercise training improves myocardial tolerance to in vivo ischemia-reperfusion in the rat. 979 Oct 63

Effects of bimoclomol, the novel heat shock protein (HSP) coinducer, was studied in various mammalian cardiac and rabbit aortic preparations. Bimoclomol decreased the ST-segment elevation induced by coronary occlusion in anesthetized dogs (56% and 80% reduction with 1 and 5 mg/kg, respectively). In isolated working rat hearts, bimoclomol increased coronary flow (CF), decreased the reduction of cardiac output (CO) and left ventricular developed pressure (LVDP) developing after coronary occlusion, and prevented ventricular fibrillation (VF) during reperfusion. In rabbit aortic preparations, precontracted with phenylephrine, bimoclomol induced relaxation (EC(50)=214 microM). Bimoclomol produced partial relaxation against 20 mM KCl, however, bimoclomol failed to relax preparations precontracted with serotonin, PGF(2) or angiotensin II. All these effects were evident within a few minutes after application of bimoclomol. A rapid bimoclomol-induced compartmental translocation of the already preformed HSPs may explain the protective action of the compound.
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PMID:In vivo and in vitro acute cardiovascular effects of bimoclomol. 1136 93

The abundantly expressed small molecular weight proteins, CRYAB and HSPB2, have been implicated in cardioprotection ex vivo. However, the biological roles of CRYAB/HSPB2 coexpression for either ischemic preconditioning and/or protection in situ remain poorly defined. Wild-type (WT) and age-matched ( approximately 5-9 mo) CRYAB/HSPB2 double knockout (DKO) mice were subjected either to 30 min of coronary occlusion and 24 h of reperfusion in situ or preconditioned with a 4-min coronary occlusion/4-min reperfusion x 6, before similar ischemic challenge (ischemic preconditioning). Additionally, WT and DKO mice were subjected to 30 min of global ischemia in isolated hearts ex vivo. All experimental groups were assessed for area at risk and infarct size. Mitochondrial respiration was analyzed in isolated permeabilized cardiac skinned fibers. As a result, DKO mice modestly altered heat shock protein expression. Surprisingly, infarct size in situ was reduced by 35% in hearts of DKO compared with WT mice (38.8 +/- 17.9 vs. 59.8 +/- 10.6% area at risk, P < 0.05). In DKO mice, ischemic preconditioning was additive to its infarct-sparing phenotype. Similarly, infarct size after ischemia and reperfusion ex vivo was decreased and the production of superoxide and creatine kinase release was decreased in DKO compared with WT mice (P < 0.05). In permeabilized fibers, ADP-stimulated respiration rates were modestly reduced and calcium-dependent ATP synthesis was abrogated in DKO compared with WT mice. In conclusion, contrary to expectation, our findings demonstrate that CRYAB and HSPB2 deficiency induces profound adaptations that are related to 1) a reduction in calcium-dependent metabolism/respiration, including ATP production, and 2) decreased superoxide production during reperfusion. We discuss the implications of these disparate results in the context of phenotypic responses reported for CRYAB/HSPB2-deficient mice to different ischemic challenges.
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PMID:CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice. 1787 8