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)

The aim of this research is to show the alterations of alpha-actinin in rabbit myocardium after DMF treatment administered by forced inhalation. Z-lines observed with light and phase-contrast microscopy, appeared to be intact and they were clearly displayed by the indirect PAP-reaction. But if you consider that in normal muscle Z lines do not get coloured by the PAP-reaction without a previous light treatment with trypsin. It may be inferred that, in this case, The DMF has had the same effect as the trypsin, causing alteration to the protein structure. Besides the sarcomeric structure is undoubtedly altered by the DMF, causing alterations, in our opinion, similar to those found in rabbit skeletal muscle, under conditions of acute experimental ischemia.
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PMID:[Structural and ultrastructural changes in the rabbit myocardium exposed to dimethylformamide vapors]. 676 21

1. Alterations in subcellular distribution of electrolytes were studied with particular emphasis on Ca++ in normal and ischemic myocardium produced by ligating the coronary artery in the dog, by means of the histochemical method using potassium pyroantimonate. 2. In the normal myocardium, the antimonate precipitates were observed most abundantly in TC of SR and on N-line within sarcomeric I-band, but found scarcely in mitochondria, M-line, Z-line, intercalated disc or T-system. 3. In the infarcted myocardium, the precipitates were strikingly increased in both number and size in disrupted mitochondria, while they were markedly decreased in swollen TC with the progress of ischemia. 4. Most of the precipitates in TC and on N-line were removed by chelation with EGTA but a few larger precipitates were consistently found mainly on N-line. And the presence of Ca++ in the antimonate precipitates was confirmed by energy dispersive X-ray microanalysis.
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PMID:Studies on the subcellular localization of electrolytes in normal and infarcted canine myocardium. With special reference to calcium ion. 746 23

Cardiac hypertrophy is associated with modifications in Ca2+ transport processes, enzymes of energy metabolism and antioxidant capacity. It is unknown whether these changes occur in infarct-induced hypertrophy with regard to an altered susceptibility to ischemia/reperfusion injury. We examined changes in sarcoplasmic reticulum (SR) Ca2+ transport, creatine kinase (CK) system, and the antioxidant enzymes glutathionperoxidase (GSH-Px) and superoxide dismutase (SOD) in rats 6 weeks after infarction due to coronary ligation (MI). Phenotypic modifications v sham operation (SHAM) were related to the contractile response of hypertrophied papillary muscle to hypoxia/reoxygenation for 30 min each. Under aerobic conditions we observed in MI v SHAM: decreases in isometric contraction and relaxation rate, a reduced Vmax-equivalent of sarcomeric shortening, a faster twitch-to-twitch decay of post-rest potentiation (PRC) which correlated closely to the decrease in SR Ca2+ uptake (-25%), a decrease in CK activity (-20%), reduced CK-MI and CK-MM, increased CK-MB and CK-BB, and enhanced activities of SOD (40%) and GSH-Px (50%). During hypoxia, an initial increase in peak force (PF) was followed by a slower PF decline in MI v SHAM. Reoxygenation caused a recovery of PF to approximately 30% in both groups; rates of contraction and relaxation recovered better in MI. In SHAM but not MI, twitch-to-twitch decay of PRC was accelerated after reoxygenation v aerobic control. The results suggest that adaptive changes in SR Ca2+ handling, CK isoenzymes and antioxidant enzymes may contribute to higher resistance against reduced oxygen supply and reoxygenation in hypertrophy due to MI.
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PMID:Decreased susceptibility of contractile function to hypoxia/reoxygenation in chronic infarcted rat hearts. 992 70

Stress proteins are assumed to protect cells against various kinds of stresses including ischemia. In this study, we focused on the behaviour of the most abundant myocardial stress protein, alpha B-crystallin, during ischemia and reperfusion of the pig heart in vivo, alpha B-crystallin constitutes 1-2% of the soluble protein pool and underwent, during severe but reversibly damaging ischemia (25 min), complete translocation to the Z-line area of myofibrils. Irreversibly damaging ischemia (60 min) was accompanied by extreme stretching of the majority of myofibrils, and by concomitant extension of alpha B-crystallin localization from the Z-line area to I-bands. This I-band shift correlated with displacement of the T12 epitope of titin from the vicinity of Z-lines into I-bands, indicating that the primary binding sites for alpha B-crystallin might also be located in juxtaposition to Z-lines and move into the I-bands during extreme sarcomeric stretching. During reperfusion after 25 min of ischemia, alpha B-crystallin disappeared rapidly from myofibrils: whereas reperfusion after irreversibly damaging ischemia (60 min) resulted in dissociation of alpha B-crystallin only from those myofibrils and myocardiocytes that were still able to contract, and alpha B-crystallin remained bound to the overstretched, damaged myofibrils no longer capable of contraction. The time course of translocation of alpha B-crystallin to myofibrils during ischemia correlated with phosphorylation of approximately 20% of the entire alpha B-crystallin pool. However, disappearance of alpha B-crystallin from myofibrils during reperfusion was not accompanied by dephosphorylation, indicating that phosphorylation alone does not explain myofibrillar binding of alpha B-crystallin. Ischemia-induced myofibrillar targeting of alpha B-crystallin probably requires additional structural and posttranslational modifications of myofibrillar components in juxtaposition to I-bands.
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PMID:Binding of the stress protein alpha B-crystallin to cardiac myofibrils correlates with the degree of myocardial damage during ischemia/reperfusion in vivo. 1019 88

Low plasma levels of taurine are associated with losses of cardiac sarcomeric proteins, leading to heart failure in mammals. Recently, it was proposed that cardiac taurine depletion serves to defend the heart against injury caused by regional ischemia in mammals. The role of taurine has not been well documented in broilers, particularly in relation to pulmonary hypertension syndrome (PHS; ascites). Three independent experiments evaluated plasma taurine in male broilers by utilizing the following treatments: unoperated controls (CONTROL; n = 10 in each experiment); sham operated (SHAM; n = 11, 12, and 10); or, unilaterally pulmonary artery clamped (PAC; n = 18, 29, and 24) that did (PAC-ascites) or did not (PAC-normal) develop ascites within 12 d postsurgery. Plasma samples were collected 9 and 11 d postsurgery in Experiments 1 and 2, respectively, and 2 d before and 4, 8, and 12 d after surgery in Experiment 3. Plasma taurine was analyzed by HPLC. Twelve days postsurgery, the birds were euthanatized, and ventricles were weighed for calculating the right:total ventricular weight ratio (RV:TV). The RV:TV of PAC birds (>0.35) consistently was higher (P < 0.01) than that of CONTROL and SHAM birds (<0.27 and 0.25, respectively). In Experiments 1 and 2, plasma taurine was higher (P < 0.05) in PAC-ascites (380 and 370 nmol/mL) than in SHAM broilers (183 and 186 nmol/mL), whereas CONTROL (262 and 278 nmol/mL) and PAC-normal (362 and 300 nmol/mL) broilers tended to have intermediate plasma taurine levels. In Experiment 3, PAC birds had higher (P < 0.05) plasma taurine at 8 and 12 d postsurgery when compared with presurgery levels, whereas plasma taurine was unchanged over time in CONTROL and SHAM birds. These results suggest cardiac taurine may be released into the plasma as a protective mechanism in response to the induction of pulmonary hypertension, hypoxemia, and right-side heart failure, similar to the mechanism reported for protecting cardiac muscle from ischemia in mammals.
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PMID:Plasma taurine levels in broilers with pulmonary hypertension syndrome induced by unilateral pulmonary artery occlusion. 1056 Aug 39

Endothelin-1 (ET-1) induces severe pathologic conditions such as coronary spasm followed by vasospastic angina pectoris and acute myocardial infarction. The related pathophysiologic mechanisms have remained obscure. Endothelin-1 receptor (ET(A) and ET(B)) is reported to couple with several types of G protein-involved pathways that participate in phospholipase C activation and atrial myofibrils organization into sarcomeric units. Here we demonstrate that ET-1 induces histologic and pathologic dysfunction in the rabbit myocardium and that such pathologic events are prevented by the Rho-kinase inhibitor fasudil. Although the bolus injection of ET-1 (1.4 nmol/kg) via the auricular vein of the rabbit induced only transient T-wave elevation, irreversible, severe histologic changes were observed in papillary muscles of the ventricle, and multifocal myocardial necrosis with infiltration of neutrophils and macrophages in the left ventricle occurred. Oral administration of fasudil (10 mg/kg) significantly reduced the occurrence of myocardial injury determinants, whereas conventional Ca2+ channel blockers (nifedipine, diltiazem) and a K+ channel opener (nicorandil; 10 mg/kg, p.o. each) showed a lesser or no effect on such determinants. These results suggest that ET-1 induces severe myocardial dysfunction based not only on the occurrence of vasospastic ischemia but also on its direct effects on the myocardium.
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PMID:The protein kinase inhibitor fasudil protects against ischemic myocardial injury induced by endothelin-1 in the rabbit. 1067 51

Cardiomyopathies are diseases of heart muscle that may result from a diverse array of conditions that damage the heart and other organs and impair myocardial function, including infection, ischemia, and toxins. However, they may also occur as primary diseases restricted to striated muscle. Over the past decade, the importance of inherited gene defects in the pathogenesis of primary cardiomyopathies has been recognized, with mutations in some 18 genes having been identified as causing hypertrophic cardiomyopathy (HCM) and/or dilated cardiomyopathy (DCM). Defining the role of these genes in cardiac function and the mechanisms by which mutations in these genes lead to hypertrophy, dilation, and contractile failure are major goals of ongoing research. Pathophysiological mechanisms that have been implicated in HCM and DCM include the following: defective force generation, due to mutations in sarcomeric protein genes; defective force transmission, due to mutations in cytoskeletal protein genes; myocardial energy deficits, due to mutations in ATP regulatory protein genes; and abnormal Ca2+ homeostasis, due to altered availability of Ca2+ and altered myofibrillar Ca2+ sensitivity. Improved understanding that will result from these studies should ultimately lead to new approaches for the diagnosis, prognostic stratification, and treatment of patients with heart failure.
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PMID:Molecular mechanisms of inherited cardiomyopathies. 1227 Sep 49

In the past decade, genetic modification has been extensively employed to define (patho)physiological roles of chaperones and the cytoskeleton in the heart, promoting dramatic advances in this field. Both loss-of-function and gain-of-function approaches have been used productively. alphaB-Crystallin (CryAB) is the most abundant small heat shock protein (HSP) in the heart. A missense mutation (R120G) in CryAB that is linked to human desmin-related myopathy (DRM), has proved in transgenic (TG) mice to be causative, likely through compromising the function of both CryAB and desmin filaments and inducing aberrant protein aggregation. For the molecular chaperones, the consensus gained is that up-regulation of each of the HSPs in the heart is protective against insults such as ischemia/reperfusion (I/R) injury. CryAB modulates protein aggregation of abnormal desmin. With respect to the cytoskeleton, disruption of the non-sarcomeric actin linkage at the intercalated discs via overexpressing the VASP-EHV1 domain is sufficient to cause dilated cardiomyopathy (DCM). Up-regulation of microtubule-associated protein 4 (MAP4) results in microtubule densification. Myocyte contractile malfunction characteristic of pressure overload hypertrophy is recapitulated by cardiac-restricted overexpression of MAP4. In contrast, overexpression of desmin filaments by itself is not detrimental to the heart. Although loss-of-function studies have been more limited, ablation of the desmin gene causes mitochondrial dysfunction and apoptosis, resulting in cardiomyopathy in mice. From function studies, abnormal desmin aggregation and disruption of the desmin networks resulting from expression of either mutant desmin or mutant CryAB have been shown to remodel the heart and compromise cardiac function, suggesting their synergistic roles in disease pathogenesis.
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PMID:Genetic modification of the heart: chaperones and the cytoskeleton. 1557 40

Brief periods of myocardial ischemia prior to timely reperfusion result in prolonged, yet reversible, contractile dysfunction of the myocardium, or "myocardial stunning". It has been hypothesized that the delayed recovery of contractile function in stunned myocardium reflects damage to one or a few key sarcomeric proteins. However, damage to such proteins does not explain observed physiological alterations to myocardial oxygen consumption and ATP requirements observed following myocardial stunning, and therefore the impact of alterations to additional functional groups is unresolved. We utilized two-dimensional gel electrophoresis and mass spectrometry to identify changes to the protein profiles in whole cell, cytosolic- and myofilament-enriched subcellular fractions from isolated, perfused rabbit hearts following 15 min or 60 min low-flow (1 mL/min) ischemia. Comparative gel analysis revealed 53 protein spot differences (> 1.5-fold difference in visible abundance) in reperfused myocardium. The majority of changes were observed to proteins from four functional groups: (i) the sarcomere and cytoskeleton, notably myosin light chain-2 and troponin C; (ii) redox regulation, in particular several components of the NADH ubiquinone oxidoreductase complex; (iii) energy metabolism, encompassing creatine kinase; and (iv) the stress response. Protein differences appeared to be the result of isoelectric point shifts most probably resulting from chemical modifications, and molecular mass shifts resulting from proteolytic or physical fragmentation. This is consistent with our hypothesis that the time course for the onset of injury associated with myocardial stunning is too brief to be mediated by large changes to gene/protein expression, but rather that more subtle, rapid and potentially transient changes are occurring to the proteome. The physical manifestation of stunned myocardium is therefore the likely result of the summed functional impairment resulting from these multiple changes, rather than a result of damage to a single key protein.
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PMID:Proteomics of ischemia/reperfusion injury in rabbit myocardium reveals alterations to proteins of essential functional systems. 1580 Aug 73

Ventricular hypertrophy develops in response to numerous forms of cardiac stress, including pressure or volume overload, loss of contractile mass from prior infarction, neuroendocrine activation, and mutations in genes encoding sarcomeric proteins. Hypertrophic growth is believed to have a compensatory role that diminishes wall stress and oxygen consumption, but Framingham and other studies established ventricular hypertrophy as a marker for increased risk of developing chronic heart failure, suggesting that hypertrophy may have maladaptive features. However, the relative contribution of comorbid disease to hypertrophy-associated systolic failure is unknown. For instance, coronary artery disease is induced by many of the same risk factors that cause hypertrophy and can itself lead to systolic dysfunction. It is uncertain, therefore, whether ventricular hypertrophy commonly progresses to systolic dysfunction without the contribution of intervening ischemia or infarction. In this review, we summarize findings from epidemiologic studies, preclinical experiments in animals, and clinical trials to lay out what is known-and not known-about this important question.
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PMID:Does load-induced ventricular hypertrophy progress to systolic heart failure? 1596 79


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