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 aim of this study was: (1) to elucidate in more detail the relationship between stress protein expression and brief periods of ischaemia and reperfusion, such as occur during early (classical) ischaemic preconditioning (PC) in the rabbit myocardium; (2) to determine whether stress protein expression is affected by adenosine receptor modulation, since adenosine is a mediator of the preconditioning response. We have studied the expression of the 60 kDa (hsp60); 70 kDa (hsp70-inducible and constitutive isoforms) and 27 kDa (hsp27) stress proteins and the mitochondrial ATP-synthase beta-subunit using Northern blotting. Hsp60, hsp70 and hsp27 expression were also determined at the protein level by Western blotting. Total RNA and proteins were prepared from frozen samples of ischaemic left ventricle and non-ischaemic right ventricle rabbit myocardium after the following treatments (1) sham-operated; (2) 15 min stabilization + 5 min coronary occlusion + 10 min reperfusion (PC); (3) PC + 30 min coronary occlusion (I); (4) PC + 30 min coronary occlusion + 2 h reperfusion (I/R) (5) the adenosine receptor antagonist 8-(p-sulpho-phenyl) theophyline (SPT) given 5 min prior to PC; (6) the adenosine receptor agonist 2-chlorocyclopentyl-N6-adenosine (CCPA) given in place of PC. A transient, approximately two-fold elevation in hsp60 mRNA occurred following 5 min coronary occlusion + 10 min reperfusion (PC) which was stable during a subsequent 30 min ischaemia (I), but returned to baseline during the second (2 h) reperfusion (I/R). An inducible hsp70 mRNA species appeared within 10 min of the second (30 min) coronary occlusion (I) which continued to increase to high levels during the second (2 h) reperfusion (I/R). Hsp27 mRNA expression was not altered following PC or subsequent ischaemia and reperfusion (I/R). ATP synthase beta-subunit mRNA did not change during PC or I but decreased during the subsequent 2 h reperfusion (I/R). Western blot analysis showed no change in left ventricle ischaemic zone hsp60, hsp70i/hsc70 or hsp27 protein during PC compared to an approximately two-fold elevation of hsp70i 24 h following whole body heat stress or 24 h following 4 x 5 min coronary occlusion (as reported by Marber et al., 1993). However, hsp70i, hsp60 and hsp27 showed significant decreases in immunodetectable protein following subsequent ischaemia and reperfusion (I/R). SPT inhibited the increase in hsp60 mRNA following PC (P < or = 0.05), but had no effect on hsp70, hsp27 or ATP-synthase mRNA levels. Therefore, differential expression of mRNAs for hsp60 and hsp70 occurred following ischaemia and reperfusion, with hsp70 mRNA expression involving a significant reperfusion-dependent component. CCPA had no effect on expression of mRNAs for hsp60, hsp70, hsp27 or ATP-synthase. We conclude that the early phase of adenosine receptor-dependent preconditioning in the rabbit heart is not mediated via stress protein expression. However, brief ischaemia and reperfusion resulted in differential changes in individual stress protein gene expression which may be due to different physiological and/or biochemical components of ischaemia and reperfusion in the heart. In addition, partial dependence of hsp60 expression on adenosine receptor modulation was observed.
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PMID:Differential stress protein mRNA expression during early ischaemic preconditioning in the rabbit heart and its relationship to adenosine receptor function. 857 30

Brief periods of ventricular pacing during the early reperfusion phase (pacing-induced postconditioning, PPC) have been shown to reduce infarct size as measured after 2 h of reperfusion. In this study, we investigated (1) whether PPC leads to maintained reduction in infarct size, (2) whether abnormal mechanical load due to asynchronous activation is the trigger for PPC and (3) the signaling pathways that are involved in PPC. Rabbit hearts were subjected to 30 min of coronary occlusion in vivo, followed by 6 weeks of reperfusion. PPC consisted of ten 30-s intervals of left ventricular (LV) pacing, starting at reperfusion. PPC reduced infarct size (TTC staining) normalized to area at risk, from 49.0 +/- 3.3% in control to 22.9 +/- 5.7% in PPC rabbits. In isolated ejecting rabbit hearts, replacing LV pacing by biventricular pacing abolished the protective effect of PPC, whereas ten 30-s periods of high preload provided a protective effect similar to PPC. The protective effect of PPC was neither affected by the adenosine receptor blocker 8-SPT nor by the angiotensin II receptor blocker candesartan, but was abrogated by the cytoskeletal microtubule-disrupting agent colchicine. Blockers of the mitochondrial K(ATP) channel (5HD), PKC (chelerythrine) and PI3-kinase (wortmannin) all abrogated the protection provided by PPC. In the in situ pig heart, PPC reduced infarct size from 35 +/- 4 to 16 +/- 12%, a protection which was abolished by the stretch-activated channel blocker gadolinium. No infarct size reduction was achieved if PPC application was delayed by 5 min or if only five pacing cycles were used. The present study indicates that (1) PPC permanently reduces myocardial injury, (2) abnormal mechanical loading is a more likely trigger for PPC than electrical stimulation or G-coupled receptor stimulation and (3) PPC may share downstream pathways with other modes of cardioprotection.
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PMID:Long-term protection and mechanism of pacing-induced postconditioning in the heart. 2033 4