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)

Previously, we reported that cardiac troponin T (TnT) can be detected and measured in coronary effluent from isolated rat hearts during hypoxia. The present study was designed to evaluate the release kinetics of TnT from post-ischemic rat hearts. Using the Langendorff technique, the hearts were reperfused for 4 h after 20 min or 60 min of global ischemia. Coronary flow was measured by timing the collection of the coronary perfusate that dripped from the hearts, and left ventricular pressure (LVP) was monitored continuously during the experiments. The amount of TnT released in 1 min was compared with the release of creatine kinase (CK) and lactate dehydrogenase (LD). The release kinetics of CK and LD showed a monophasic pattern and the levels at 4 h after reperfusion returned to baseline levels. By contrast, the release kinetics of TnT showed a small peak followed by a larger and more sustained peak. There were good negative correlations between developed pressure of LVP and both sigma TnT and the amount of TnT released within 1 min at 4 h after reperfusion. These results indicate that the release kinetics of TnT is different from that of CK and LD during reperfusion, and further that cardiac TnT is a useful indicator of myocardial cell damage and can be used to evaluate the degree of myocardial cell damage in both the early and late phase of acute myocardial infarction.
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PMID:Release kinetics and correlation with hemodynamic dysfunction of cardiac troponin T in coronary effluent from isolated rat hearts during reperfusion. 824 Feb 23

The present study was designed to test if prophylactic intravenous nifedipine or nitroglycerine could reduce myocardial damage after cardiopulmonary bypass. 45 patients scheduled for elective coronary artery bypass grafting were divided at random into three groups: Group 1: control; group 2: nifedipine (0.25 microgram/kg/min); group 3: nitroglycerine (1.5 micrograms/kg/min). Infusion period reached from the beginning of anaesthesia until crossclamp of the aorta. Myocardial damage was estimated by troponin T (TnT), CK-MB and ST-segment analysis of the ECG. TnT is a cardiospecific protein from the contractile apparatus of striated muscle cells. TnT-levels might provide a very sensitive marker of small amounts of cardiac muscle necrosis. It was tested with an ELISA/one-step sandwich-assay with streptavidin-technology [9]. Criteria for ischemia in the ST-segment analysis were (according to Smith et al. [19]): ST-depression > 1 mm from baseline or ST-elevation > 2 mm from baseline at J-point + 60 ms. Statistical interpretation was done by one- and two-factorial analyses of variance (including multivariate analyses of variance). Correlation between two variables was tested by regression analysis. A level of p < 0.05 was taken for indicating statistical significance. Biometrical data, circulation data and data from cardiopulmonary bypass were without significant differences among all groups (Tables 1 and 2). Starting from normal values (< 0.05 ng/ml) TnT significantly rose in all groups immediately after cardiopulmonary bypass and remained elevated until the forth day after operation (values between 0.4 and 0.6 microgram/ml) (Figure 1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cardiac protection in heart surgery interventions by preventive drug administration before extracorporeal circulation. Studies with troponin T as a parameter for perioperative myocardial damage]. 830 54

Myofibrillar proteins (MPs) were extracted from isolated and perfused rat hearts subjected to different periods of ischemia to investigate the occurrence of protein degradation and/or the association of cytosolic proteins with the myofibrillar pellet. A 23-kD band was detected by SDS-PAGE of MPs after 5 minutes of ischemia, with its density gradually increasing to a plateau after 20 minutes. Longer periods of ischemia were associated with the appearance of a 39-kD band. Irrespective of the duration of ischemia, both these bands persisted during reperfusion. A partial proteolytic degradation of troponin T (TnT) and troponin I (TnI) has been claimed to be responsible for the generation of these peptides. However, the N-terminal sequence of the 39-kD band was identical to that of GAPDH, whereas Edman sequencing after pepsin digestion showed that the 23 kD is alpha B-crystallin. The binding of the two cytosolic proteins to myofibrils was confirmed by immunofluorescence analysis on cryosections of ischemic hearts. In vitro studies showed that acidosis was sufficient to induce the binding of alpha B-crystallin, whereas the inhibition of ATP depletion prevented the binding of GAPDH. Thiol oxidation is unlikely to promote GAPDH binding, since perfusion with iodoacetate under aerobic conditions or treatment of homogenates with N-ethylmaleimide or diamide failed to induce GAPDH association with the myofibrils. These changes of the myofibrillar proteins could be considered as intracellular markers of the evolution of the ischemic damage. In addition, the binding of the 23-kD peptide might be involved in alterations of contractility.
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PMID:Binding of cytosolic proteins to myofibrils in ischemic rat hearts. 862 Jun 2

Myocardial stunning is characterized by decreased myofilament Ca2+ responsiveness. To investigate the molecular basis of stunned myocardium, we performed PAGE and Western immunoblot analysis of the contractile proteins. Isolated rat hearts were retrogradely perfused at 37 degrees C for either 50 minutes (control group) or for 10 minutes, followed by 20-minute global ischemia and 20-minute reperfusion (stunned group), or for 20-minute ischemia without reflow. Another group consisted of hearts subjected to 20-minute ischemia in which stunning was mitigated by 10-minute reperfusion with low Ca2+/low pH solution. Myocardial tissue samples subjected to PAGE revealed no obvious differences among groups. Western immunoblots for actin, tropomyosin, troponin C, troponin T, myosin light chain-1, and myosin light chain-2 showed highly selective recognition of the appropriate full-length molecular weight bands in all groups. Troponin I (TnI) Western blots revealed an additional band (approximately 26 kD, compared with 32 kD for the full-length protein) in stunned myocardial samples only. In parallel experiments, skinned trabeculae were treated with calpain I for 20 minutes; Western blots showed a TnI degradation pattern similar to that observed in stunned myocardium. Such TnI degradation was prevented by calpastatin, a naturally occurring calpain inhibitor. The results show that (1) TnI is partially and selectively degraded in stunned myocardium; (2) this degradation could be prevented by low Ca2+/low pH reperfusion, which also prevented the contractile dysfunction of stunning; and (3) calpain I could similarly degrade TnI, supporting the idea that Ca(2+)-dependent myofilament proteolysis underlies myocardial stunning.
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PMID:Role of troponin I proteolysis in the pathogenesis of stunned myocardium. 904 60

We tested the hypothesis that altered phosphorylation of myofibrillar proteins is involved in post-ischemic myocardial stunning. Myofibrillar proteins were isolated from Langendorff perfused control rabbit hearts, hearts submitted to 15 min normothermic ischemia and hearts submitted to 15 min ischemia followed by 10 min of reperfusion (stunned hearts). The in vivo level of phosphorylation of specific contractile proteins by protein kinases A and C was indirectly detected by the amount of 32P incorporated in vitro in the presence of these protein kinases and saturating concentration of [gamma-32P]-ATP (back-phosphorylation method). In control experiments the back-phosphorylation technique was able to detect PKA- or PKC-induced protein phosphorylation in hearts treated with isoproterenol and phorbol ester, respectively. In stunned hearts, contractile function was significantly suppressed compared to the period before ischemia. We found no difference in myofibrillar protein profile (on densitometry of the Coomassie-stained gels after SDS-PAGE) and in PKA mediated 32P incorporation when comparing control, ischemic and stunned myocardium. Three different PKCs were used for phosphorylation: commercial purified rat brain PKC, partially purified rat brain PKC or rabbit partially purified cardiac PKC. Cardiac PKC mainly phosphorylated troponin I, whereas brain PKC phosphorylated both troponin T and troponin I. No significant difference in 32P incorporation mediated by either brain or cardiac PKC was found between control, ischemic and ischemic/reperfused myofibrils. These data indicate that myocardial stunning does not cause changes in PKC- or PKA-mediated Pi incorporation into myofibrillar proteins detectable by the back-phosphorylation method.
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PMID:Phosphorylation by protein kinases A and C of myofibrillar proteins in rabbit stunned and non-stunned myocardium. 944 26

Our objective in experiments reported here was to identify myofilament proteins of rat hearts either lost or degraded by cardiac ischemia (15- or 60-minute duration) with and without 45 minutes of reperfusion. We correlated these changes with alterations in myofilament sensitivity to Ca2+ and maximum force generation. Protein degradation and loss were assessed by high-performance liquid chromatography, SDS-PAGE, Western blotting analysis, and amino acid sequencing. Compared with nonischemic control hearts, bundles of skinned fibers from hearts subjected to ischemia alone demonstrated a decrease in maximum force generation and an increase in sensitivity to Ca2+. These changes in function were increased with the duration of the ischemia and with reperfusion. With increasing duration of ischemia, there was an increased loss and degradation of myofibrillar alpha-actinin and troponin I (TnI) at its C-terminus. Alpha-actinin and TnI were most susceptible to ischemia, but with 60 minutes of ischemia/reperfusion, there was also degradation of myosin light chain-1 (MLC1) involving a clip of residues 1 to 19. The MLC1 degradation product was detected in the reperfusion effluent (along with troponin T, tropomyosin, and alpha-actinin) but not in the tissue with 60 minutes of ischemia with no reperfusion. Moreover, with ischemia the following proteins became associated with the myofibrils: GAPDH and proteins of the mitochondrial ATP synthase complex. Our results provide new evidence regarding the mechanism by which ischemia/reperfusion causes myocardial injury and support the hypothesis that an important element in the injury is altered activity and structure of the myofilaments.
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PMID:Breakdown and release of myofilament proteins during ischemia and ischemia/reperfusion in rat hearts: identification of degradation products and effects on the pCa-force relation. 946 97

The acute coronary syndromes represent a continuum of myocardial ischemia ranging from angina, reversible tissue injury --> unstable angina, frequently associated with minor myocardial damage --> myocardial infarction and extensive tissue necrosis. Historically, coronary artery disease assessment has been mainly binary, using WHO criteria of symptoms, electrocardiography, and biochemical markers. The creatine kinase-MB isoenzyme (CK-MB) has been a benchmark for markers, but it is not specific for myocardium. Cardiac-specific isoforms of troponin T and I have emerged as sensitive myocardial infarction (MI) indicators and, importantly, for risk stratification of acute coronary syndrome patients. In addition to markers of myocardial cell necrosis, markers of plaque disruption (C-reactive protein and serum amyloid A), "angry" platelets (P-selectin), ischemia (glycogen phosphorylase-BB isoenzyme), and the procoagulant state and thrombosis (soluble fibrin) have potential use. Also, CK-MB and myoglobin have been combined with clinical indicators for monitoring reperfusion after thrombolytic therapy. Biochemical markers will continue to be an important clinical adjunct for MI diagnosis, risk assessment, and reperfusion monitoring in the future.
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PMID:Biochemical markers of the acute coronary syndromes. 970 95

Experimental preconditioning is commonly regarded as a powerful protective phenomenon in case of subsequent ischemia. However, little is known about the applicability of preconditioning as an adjunct to cardioplegic myocardial protection in routine coronary surgery. For this reason, a prospective clinical study (611995 to 4/1996) was initiated to evaluate normothermic ischemic preconditioning prior to crystalloid or cold blood cardioplegic arrest. Preconditioning was performed in two cycles of 5 min ischemia and 10 min reperfusion. Four groups of 7 patients each were compared regarding release of troponin T, creatine kinase-myocardial isoform (CK-MB), lactate, and total CK in coronary sinus effluents over a 12-hour period. In the absence of perioperative myocardial infarction, there were no significant differences in these ischemic and metabolic parameters. Unexpectedly, the heed of postoperative pharmacological inotropic support was greater after preconditioning. These results may indicate that ischemic preconditioning as an adjunct to cardioplegic arrest may be associated with impairment of left-ventricular contractility, thus even exerting potentially detrimental functional effects. Overall, the proven beneficial effects of experimental preconditioning seem not to be directly transferable into the clinical settings.
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PMID:Ischemic preconditioning as an adjunct to crystalloid or blood cardioplegia for myocardial protection in routine coronary surgery. 982 83

Selective troponin I (TnI) modification has been demonstrated to be in part responsible for the contractile dysfunction observed with myocardial ischemia/reperfusion injury. We have isolated and characterized modified TnI products in isolated rat hearts after 0, 15, or 60 minutes of ischemia followed by 45 minutes of reperfusion using affinity chromatography with cardiac troponin C (TnC) and an anti-TnI antibody, immunological mapping, reversed-phase high-performance liquid chromatography, and mass spectrometry. Rat cardiac TnI becomes progressively degraded from 210 amino acid residues to residues 1-193, 63-193, and 73-193 with increased severity of injury. Degradation is accompanied by formation of covalent complexes between TnI 1-193 and, respectively, TnC residues 1-94 and troponin T (TnT) residues 191-298. The covalent complexes are likely a result of isopeptide bond formation between lysine 193 of TnI and glutamine 191 of TnT by the cross-linking enzyme transglutaminase. With severe ischemia, cellular necrosis results in specific release of TnI 1-193 into the reperfusion effluent and TnT degradation in the myocardium (25-, 27-, and 33-kDa products). Two-dimensional electrophoresis demonstrated that phosphorylation of TnI prevents ischemia-induced degradation. This study characterized the modified TnI products in isolated rat hearts reperfused after a brief or severe period of ischemia, revealing the progressive nature of TnI degradation, changes in phosphorylation, and covalent complexes with ischemia/reperfusion injury. Finally, we propose a model for ischemia/reperfusion injury in which the extent of proteolytic and transglutaminase activities ultimately determines whether apoptosis or necrosis is achieved.
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PMID:Troponin I degradation and covalent complex formation accompanies myocardial ischemia/reperfusion injury. 991 81

Ischemic preconditioning (IPC) is a potent mode of myocardial protection, but not in all models of cold cardioplegia. The present study investigates possible effects of hypothermia and hyperkalemia on the preconditioning response. Langendorff-perfused rat hearts were preconditioned (2 min global ischemia and 5 min reperfusion) or control-perfused prior to 35 min normothermic, global ischemia (series 1, n = 17 in each group); 50 min normothermic cardioplegia (St. Thomas's II) (series 2, n = 10 in each); 75 min 23 degrees C, global ischemia (series 3, n = 7 in each); or 5 h 6-8 degrees C, global ischemia (series 4, n = 9 in each). Left ventricular developed (LVDP) and end-diastolic (LVEDP) pressures, coronary flow (CF), heart rate, incidence of severe reperfusion arrhythmias, and release of troponin T (TnT) were measured. IPC attenuated reduction of LVDP and CF, and increase of LVEDP during reperfusion in series 1-3. TnT release was reduced by IPC in series 3 only. IPC did not attenuate dysfunction after hypothermic ischemia (series 4). Neither hyperkalemia nor moderate hypothermia alone inhibited the preconditioning response, but IPC was not protective in deep hypothermia.
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PMID:Does hypothermia or hyperkalemia influence the preconditioning response? 1022 9


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