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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To date, most studies of the second window of protection against infarction (SWOP) have evaluated infarct size by staining with triphenyltetrazolium chloride (TTC) soon after reperfusion. However, early TTC staining has been found to be an unreliable indicator of the ultimate infarct size following some interventions. Therefore, we tested whether SWOP could induce a sustained limitation of infarct size. Instrumented, conscious rabbits underwent 30 min of coronary occlusion. Infarct size was determined by either TTC staining after 3 h of reperfusion or conventional histology after 72 h of reperfusion. In the TTC study, 43.5+/-3.1% of the risk zone infarcted in the control group. Four cycles of 5 min ischemia/10 min reperfusion 24 h prior to 30 min ischemia significantly reduced infarct size measured by TTC to 32.5+/-2.3% (P<0.05 v control). In the histological study 57.8+/-3.6% of the risk zone infarcted in the control group. However, ischemic preconditioning 24 h prior to the 30 min ischemia did not protect the heart (59.3+/-4.4% infarction). Thus the infarct-limiting effect of SWOP evaluated with early TTC staining could not be demonstrated when infarction was assessed by histology after 3 days of reperfusion. These data suggest that SWOP may not have a sustained anti-infarct effect, but rather may simply delay the progression to infarction.
J Mol Cell Cardiol 1999 Apr
PMID:Second window of protection against infarction in conscious rabbits: real or artifactual. 1032 8

Right ventricular pacing in lightly anaesthetized dogs (4x5 min periods at a pacing rate of 220 beats/min) protects against the consequences of coronary artery occlusion when this is initiated 24 h after the pacing stimulus. The main purpose of the present experiments was to determine whether repeating the pacing stimulus, at a time when protection from the initial stimulus had faded (48 h), prolonged the protection afforded against ischaemia-induced ventricular arrhythmias and other ischaemic changes (epicardial ST-segment mapping; changes in the degree of electrical inhomogeneity in the ischaemic region). Dogs were paced on two occasions, with a 48 h period between and, at different times (48, 72 and 96 h) after the second pacing stimulus, were re-anaesthetized and subjected to occlusion of the left anterior descending coronary artery. There was a marked reduction in the severity of ischaemia-induced arrhythmias 48 and 72 h after the second pacing stimulus (reduction in occlusion-induced and reperfusion-induced ventricular fibrillation, e.g. at 72 h 0/11 during occlusion and only 3/11 following reperfusion, compared to 7/21 and 10/21 respectively in the controls P<0.05). The protection had disappeared 96 h following the second pacing stimulus. Changes in ST-segment elevation and in the degree of inhomogeneity largely followed these changes in the severity of ventricular arrhythmias. The results suggest the possibility of maintaining protection against life-threatening arrhythmias following coronary occlusion by repeating a preconditioning pacing stimulus. We also demonstrate that this prolonged protection afforded by repeated cardiac pacing is mediated by nitric oxide, since the marked antiarrhythmic effect observed, e.g. 72 h after the second pacing stimulus, was abolished when S-(2-aminoethyl)-isothiourea (AEST), a particularly selective inhibitor of iNOS, had been administered before coronary artery occlusion.
J Mol Cell Cardiol 1999 Jun
PMID:Repeated cardiac pacing extends the time during which canine hearts are protected against ischaemia-induced arrhythmias: role of nitric oxide. 1037 97

Non-infarcted myocardium after coronary occlusion undergoes progressive morphological and functional changes. The purpose of this study was to determine whether non-infarcted myocardium exhibits (1) alteration of the substrate pattern of myocardial metabolism and (2) concomitant changes in the expression of regulatory proteins of glucose and fatty acid metabolism. Myocardial infarction was induced in rats by ligation of the left coronary artery. One day and eight weeks after coronary occlusion, glucose and palmitate oxidation were measured. Expression of selected proteins of metabolism were determined one day to 12 weeks after infarction. One day after coronary occlusion no difference of glucose and palmitate oxidation was detectable, whereas after eight weeks, glucose oxidation was increased (+84%, P<0.05) and palmitate oxidation did not change significantly (-19%, P=0.07) in infarct-containing hearts, compared with hearts from sham-operated rats. One day after coronary occlusion, myocardial mRNA expression of the glucose transporter GLUT-1 was increased (+86%, P<0.05) and the expression of GLUT-4 was decreased (-28%, P<0.05) in surviving myocardium of infarct-containing hearts. Protein level of GLUT-1 was increased (+81%, P<0.05) and that of GLUT-4 slightly, but not significantly, decreased (-16%, P=NS). mRNA expressions of heart fatty acid binding protein (H-FABP), and of medium chain acyl-CoA dehydrogenase (MCAD), were decreased by 36% (P<0.05) and 35% (P=0. 07), respectively. Eight weeks after acute infarction, the left ventricle was hypertrophied and, at this time-point, there was no difference in the expression of GLUT-1 and GLUT-4 between infarcted and sham-operated hearts. However, myocardial mRNA and protein content of MCAD were decreased by 30% (P<0.01) and 27% (P<0.05), respectively. In summary, in surviving myocardium, glucose oxidation was increased eight weeks after coronary occlusion. Concomitantly, mRNA and protein expression of MCAD were decreased, compatible with a role of altered expression of regulatory proteins of metabolism in post-infarction modification of myocardial metabolism.
J Mol Cell Cardiol 2000 Nov
PMID:Altered expression of proteins of metabolic regulation during remodeling of the left ventricle after myocardial infarction. 1104 Jan 6

Both free radicals (FRs) and adenosine receptor activation contribute to triggering a mechanism of preconditioning (PC) against infarction. This study examined the possibility that there is some interaction between FRs and adenosine generation during PC. In the first series of experiments, the effects of an FR scavenger, N-2-mercaptopropionyl glycine (MPG), on the interstitial adenosine level during PC and on the infarct size-limiting effect of PC were assessed in the rabbit heart in situ. PC with 5-min ischemia/5-min reperfusion limited infarct size after 30-min coronary occlusion (expressed as a percentage of area at risk, %IS/AR) from 33.2 +/- 4.7% (S.E.) to 10.8 +/- 1.1% (p < 0.05). This cardioprotection was blocked by MPG (1.5 mg/kg/min i.v.) infused before and during PC (%IS/AR = 27.4 +/- 3.6). However, the same dose of MPG did not suppress elevation of the adenosine and inosine levels in the microdialysate from the myocardium during 5-min ischemia/reperfusion. In the second series of experiments, the effect of an FR-generating system (1 mM hypoxanthine and 20 mU/ml xanthine oxidase) on the purine production was compared to that of PC in isolated rabbit hearts. Whereas PC increased the adenosine level in the coronary effluent from 0.17 +/- 0.16 microM under baseline to 1.68 +/- 0.53 microM, infusion of the FR generators over a period of 5 min did not increase the adenosine release. However, infarct size was similarly reduced by PC and by 5-min transient infusion of FR generators, and the cardioprotection by the FR generators was abolished by 300 microM MPG. These results suggest that there is no interaction between free radicals and adenosine during the trigger phase of PC in the rabbit heart.
Mol Cell Biochem 2000 Aug
PMID:Relationship between free radicals and adenosine in the mechanism of preconditioning: are they interrelated or independent triggers? 1105 47

Protein kinase C (PKC) has been known to play an important role in ischemic preconditioning (IP). This study was designed to examine whether the translocation of PKC is associated with the cardioprotective effects of IP in vivo on infarct size and ventricular arrhythmias in a rat model. Using anesthetized rats, heart rate, systolic blood pressure, infarct size and ventricular arrhythmias during 45 min of coronary occlusion were measured. PKC activity was assayed in both the cytosolic and cell membrane fraction. Brief 3-min periods ofischemia followed by 10 min ofreperfusion were used to precondition the myocardium. Calphostin C was used to inhibit PKC. Infarct size was significantly reduced by IP (68.1 (2.5)%, mean (S.E.) vs. 45.2 (3.4)%, p < 0.01). The reduction in infarct size by IP was abolished by pretreatment with calphostin C. The total number of ventricular premature complex (VPC) during 45 min of coronary occlusion was reduced by IP (1474 (169) beats/45 min vs. 256 (82) beats/45 min, p < 0.05). The reduction the total number of VPC induced by IP was abolished by the administration of calphostin C before the episode of brief ischemia. The same tendency was observed in the duration of ventricular tachycardia and the incidence of ventricular fibrillation. PKC activity in the cell membrane fraction transiently increased immediately after IP (100 vs. 142%, p < 0.01) and returned to baseline 15 min after IP. Pretreatment with calphostin C prevented the translocation of PKC. The translocation of PKC plays an important role in the cardioprotective effect of IP on infarct size and ventricular arrhythmias in anesthetized rats.
Mol Cell Biochem 2000 Nov
PMID:Protein kinase C is involved in cardioprotective effects of ischemic preconditioning on infarct size and ventricular arrhythmia in rats in vivo. 1119 88

Inflammation plays a key role in susceptibility to coronary atherosclerosis and response to therapy. A diverse array of factors modulates inflammation, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and CD14 receptors on the surface of macrophages. Genes encoding for inflammatory markers have variants that regulate their expression and are potential risk factors for atherosclerosis. We prospectively analyzed the possible association of CD14 -260C/T, TNF-alpha -308G/A, and IL-6 -174G/C variants, located in the promoter regions, with the severity, progression, and response to therapy of coronary atherosclerosis in a well-characterized cohort. We studied 375 subjects enrolled in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). Genotypes were determined by polymerase chain reaction (PCR) and restriction mapping. Fasting plasma lipids and quantitative coronary angiograms were obtained at baseline and 2.5 years following randomization to fluvastatin or placebo. Distributions of genotypes were--for CD14: 100 CC, 184 CT, and 86 TT; IL-6: 152 GG, 153 GC, and 62 CC; and TNF-alpha: 244 GG, 110 GA, and 17 AA. The CD14 CC genotype was associated with incidence of new coronary occlusion (P=0.026); TNF-alpha AA genotype with history of myocardial infarction (MI, P=0.04), and A allele with total occlusions at baseline (P=0.027), and systolic blood pressure (P=0.046); and IL-6-174 CC genotype with baseline minimum lumen diameter (P=0.043) and reduction in lipoprotein(a) with fluvastatin (P=0.03). Otherwise, no association between the genotypes and the biochemical, angiographic, and clinical phenotypes was detected, and neither were genotype-treatment interactions. Functional variants of CD14 -260C/T, TNF-alpha -308G/A, and IL-6 -174G/C, implicated in the susceptibility to infection, are unlikely to confer major risk for susceptibility to coronary atherosclerosis and its progression or response to therapy in the LCAS population.
J Mol Med (Berl) 2000
PMID:A prospective study of genetic markers of susceptibility to infection and inflammation, and the severity, progression, and regression of coronary atherosclerosis and its response to therapy. 1119 26

Brief episodes of tachycardia without myocardial ischemia prior to a coronary occlusion decrease myocardial infarct size in dogs. This non-ischemic preconditioning is mediated by adenosine. Because ischemic preconditioning is mediated through ATP dependent potassium channels, particularly the mitochondrial ones, we studied whether non-ischemic preconditioning is also mediated through these channels. In anesthetized dogs heart rate was kept constant at 120 cycles/min and aortic pressure changes were damped. Myocardial infarction was induced by occlusion of the anterior descending coronary artery for 60 min and reperfusion for 270 min. In a control group the infarct size (necrotic volume/risk region volume x 100) was 15.8+/-1.5%. Preconditioning with five periods of tachycardia, 5 min in duration each at 213 cycles/min with intervening periods of 5 min of basal heart rate at 120 cycles/min, reduced the infarct size by 45.6% (p < 0.05) with respect to the control group. This effect was completely reverted by the blockade of ATP dependent potassium channels with glibenclamide or 5 hydroxydecanoate (a specific blocker of mitochondrial ATP dependent potassium channels) prior to preconditioning. These effects were not due to differences in collateral flow, risk region size or hemodynamic variables between the groups. These results show that mitochondrial ATP dependent potassium channels mediate non-ischemic preconditioning by tachycardia in dogs.
Mol Cell Biochem 2001 Jan
PMID:Mitochondrial ATP dependent potassium channels mediate non-ischemic preconditioning by tachycardia in dogs. 1121 57

Our aim was to test the hypothesis that cardioprotection achieved with ischemic preconditioning (PC) involves increased activity of p38 mitogen-activated protein kinase (MAPK) early during sustained coronary artery occlusion. Using the isolated buffer-perfused rabbit heart model of regional ischemia, we quantified p38 MAPK activity (pmol/min/mg protein: by biochemical assay) at 5 and 10 min into coronary occlusion in hearts that first received PC ischemia or no intervention (controls), and in non-ischemic shams. Control hearts exhibited significant increases in p38 MAPK activity, averaging 883+/-142 and 1135+/-179 at 5 and 10 min of occlusion, v 144+/-49 in shams (P<0.05 and P<0.01). p38 MAPK activity was not, however, augmented with PC; rather, at 5 min into occlusion, activity was attenuated, averaging 432+/-72 (P=N.S. v sham). This early, modest reduction in p38 MAPK activity may be physiologically relevant: in additional hearts subjected to 30 min of sustained coronary occlusion and 2 h of reperfusion, infarct size (by tetrazolium staining: expressed as a % of the risk region) was 54+/-5% in hearts treated with SB 203580 (confirmed in our study to inhibit p38 MAPK activity at 5 min into occlusion) v 70+/-5% in vehicle controls (P<0.05). Thus, cardioprotection achieved with ischemic preconditioning in rabbit heart does not involve augmentation of p38 MAPK activity early during sustained coronary occlusion.
J Mol Cell Cardiol 2001 Apr
PMID:p38 MAPK activity is not increased early during sustained coronary artery occlusion in preconditioned versus control rabbit heart. 1127 21

FR167653 inhibits the production of inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) in human monocytes in a dose-dependent manner. We examined the effects of FR167653 on the propagation of myocardial infarction resulting from coronary occlusion-reperfusion and the time course of expression of these cytokines in myocardial tissue in rats. Myocardial infarction was induced by coronary ligation for 20 minutes followed by 2 hours of reperfusion. Although hemodynamic parameters did not differ significantly during coronary occlusion-reperfusion, the size of the infarct was significantly reduced by intravenous administration of FR167653 before occlusion (p < 0.01). mRNA levels of IL-1beta and TNF-alpha assessed by the reverse-transcriptase polymerase chain reaction method were significantly increased during coronary occlusion-reperfusion in the ischemic myocardium. Treatment with FR167653, however, significantly reduced the increased expression of these cytokines. These results indicate that the expression of inflammatory cytokines increases in the ischemic-reperfused myocardium and that the inhibition of the increased expression of cytokines by FR167653 effectively reduces myocardial ischemia-reperfusion injury.
Cytokines Cell Mol Ther 2000 Dec
PMID:FR167653, a cytokine-suppressive agent, reduces myocardial ischemia-reperfusion injury in rats. 1156 54

Recent evidence has shown that the cardioprotection afforded by the late phase of ischemic preconditioning (PC) is mediated by upregulation of inducible nitric oxide synthase (iNOS). However, the specific cardiac cell type(s) that express(es) iNOS in response to ischemic PC remains unknown. Thus, mice underwent a sequence of six cycles of 4-min coronary occlusion/4-min reperfusion, which induces late PC, and tissue samples were collected at serial times for measurement of mRNA (Northern) and protein levels (Western). In addition, whole heart samples were cryosectioned for in situ hybridization and immunohistochemistry. The steady-state levels of iNOS mRNA in the ischemic regions started to increase at 1 h after ischemic PC, peaked at 3 h (201+/-31% of sham, n=5 P<0.01) and remained elevated at 24 h (177+/-22% of sham, n=5 P<0.01). In accordance with these data, iNOS protein expression was increased at 24 h (219+/-41% of sham, n=5 P<0.01). In contrast, neither endothelial nitric oxide synthase (eNOS) mRNA levels nor its protein expression changed at any time-point. The magnitude of iNOS upregulation after ischemic PC was mild compared with that noted 66 h after permanent coronary occlusion (360+/-53% of sham) or 8 h after endotoxin (3117+/-61% of control). After ischemic PC, diffuse iNOS signals were detected with in situ hybridization and immunohistochemistry in the cytoplasmic space of cardiac myocytes and, to a lesser degree, in the wall of large vessels, but were absent in smooth muscle and endothelium of small vessels and in fibroblasts. This pattern contrasted with that observed in mouse hearts subjected to permanent coronary occlusion where strong iNOS signals were concentrated in inflammatory cells but absent in cardiac myocytes. Thus, not only the degree of iNOS expression but also its cellular distribution were profoundly different in reversibly injured (preconditioned) v infarcted myocardium. We conclude that iNOS is rapidly upregulated after ischemic PC and that cardiac myocytes are the main source of ischemic PC-induced iNOS expression. This study demonstrates, for the first time, a differential pattern of iNOS expression in sublethal (PC) v lethal ischemia, which may have important implication for the role of iNOS in these two settings.
J Mol Cell Cardiol 2002 Jan
PMID:Ischemic preconditioning upregulates inducible nitric oxide synthase in cardiac myocyte. 1181 60


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