Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study we examined factors affecting the reversal of the ischemia-induced protonic inhibition of the mitochondrial ATPase described earlier (Rouslin, W. (1983) J. Biol. Chem. 258, 9657-9661). It was found that ATPase reactivation and accompanying inhibitor protein release during the re-energization of intact mitochondria isolated from 20-min ischemic canine heart muscle could be blocked completely by either carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) or nigericin but was unaffected by valinomycin at 35 mM K+. At higher K+ concentrations, valinomycin also blocked ATPase reactivation but not quite as completely as did nigericin. These observations suggest that ATPase reactivation and inhibitor protein release are particularly dependent upon either the trans-inner membrane pH gradient (delta pH) or possibly upon matrix pH per se and slightly less dependent upon membrane potential (delta psi) in intact cardiac muscle mitochondria. The addition of FCCP at the end of the re-energization incubations limited partially the extent of both ATPase reactivation and inhibitor protein release. This latter effect appears to have been mediated by a partial reassociation of the inhibitor protein with the enzyme, and it was accentuated (when FCCP was added at the end of the incubations) or mimicked (when FCCP was absent) by lowering the pH of the re-energization medium. A close examination of the first 10 min of the time course of enzyme activation and of inhibitor protein release revealed that while the former process was essentially finished in 1 min or less, the latter required approximately 10 min for completion. This observation led to the proposal of a two-site model of enzyme-inhibitor interaction which is discussed.
 ...
PMID:Factors affecting the reactivation of the oligomycin-sensitive adenosine 5'-triphosphatase and the release of ATPase inhibitor protein during the re-energization of intact mitochondria from ischemic cardiac muscle. 295 98

A survey of 12 species has revealed that reversible ischemia-induced protonic inhibition of the cardiac muscle mitochondrial adenosine 5'-triphosphatase (ATPase) described by this author earlier (Rouslin, W. J. Biol. Chem. 258: 9657-9661, 1983) occurs only in animals with heart rates lower than approximately 200 beats/min. It was thus fully demonstrable in rabbit, dog, sheep, human, pig, and beef heart mitochondria. In contrast, the in situ ATPase inhibition was completely absent in six smaller species capable of heart rates of approximately 300 or more beats/min. These were chicken, pigeon, guinea pig, rat, hamster, and mouse. Analyses of the cardiac muscle mitochondria of 9 of the 12 species studied showed them to contain normal levels of mitochondrial ATPase inhibitor; the three smallest species, rat, hamster, and mouse contained only very low levels of inhibitor. Thus, although chicken, pigeon, and guinea pig heart mitochondria contained normal levels of ATPase inhibitor, they (like the rat, hamster, and mouse) showed no in situ ischemia-induced ATPase inhibition. This and other observations suggest that the lack of in situ ATPase inhibition in hearts capable of 300 or more beats/min may be due to the presence of either an in situ nonfunctional ATPase inhibitor protein or to an in situ uninhibitable form of the mitochondrial ATPase in the faster-paced hearts. Alternatively, the mitochondria of the fast-paced hearts may be insulated somehow against the cytosolic acidosis which develops during ischemia and which triggers the ATPase inhibition in the slow heart-rate hearts. In the faster paced hearts, ATP hydrolysis does not appear to be regulated by inhibitor binding to the ATPase under nonenergizing conditions.
 ...
PMID:The mitochondrial adenosine 5'-triphosphatase in slow and fast heart rate hearts. 295 Jul 75

Twenty minutes of ischemia in canine cardiac muscle produced a 50% to 60% inhibition of the mitochondrial ATPase. The inhibition has been shown to be triggered by a drop in cell pH under the non-energizing conditions which prevail in ischemic cells (Rouslin, W J Biol Chem 258, 9657-9661 (1983). In the present study we showed that the ATPase inhibition produced in situ in ischemic cardiac muscle was preserved in submitochondrial particles (SMP) prepared from mitochondria isolated from the ischemic tissue. The ischemic SMP ATPase was 45 +/- 3% as active as that of control particles. Measurements of the amounts of ATPase inhibitor protein of Pullman and Monroy present in extracts of control and ischemic SMP by two independent methods, titration of rat heart SMP ATPase and radioimmunoassay, revealed that control SMP contained 62 +/- 4% as much inhibitor as ischemic SMP as estimated by the titration procedure and 66 +/- 3% as much as estimated by the RIA. The results suggest that about one-third of the inhibitor was displaced from the control SMP. Finally, submitochondrial particles prepared from 20 min ischemic heart muscle showed a 2.5-fold increase in ATPase specific activity and a concomitant release of 35% of their inhibitor as a result of subsequent reenergization in vitro. Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) prevented both ATPase reactivation and inhibitor release. These findings support the hypothesis that the observed in situ ATPase inhibition is inhibitor protein mediated. Moreover, they suggest a pathophysiological function for the inhibitor protein in cardiac muscle.
 ...
PMID:Protonic inhibition of the mitochondrial adenosine 5'-triphosphatase in ischemic cardiac muscle. Reversible binding of the ATPase inhibitor protein to the mitochondrial ATPase during ischemia. 296 Aug 23

Ventricular late potentials are regarded as an expression of delayed impulse conduction in an area of myocardial ischemia and, accordingly, indicative of a preformed reentry circuit. Late potentials can be detected in chronic, stable coronary artery disease and their presence correlates closely with impairment of ventricular function and with the probability of future occurrence of tachyarrhythmic events or sudden cardiac death. While repetitive ventricular arrhythmias in the chronic stage of coronary artery disease result almost invariably from circling intraventricular wavefronts, tachyarrhythmias associated with acute myocardial infarction appear attributable to differing pathomechanisms. According to experimental studies, in acute myocardial infarction, three phases of arrhythmogenesis can be differentiated: phase 1 encompasses the first hours after vessel occlusion which generally corresponds with the prehospital phase. Due to the difference in potential of up to 25 mV between ischemic and nonischemic cardiac muscle areas, an injury current is called into existence which leads to depolarization of normal cardiac muscle tissue. The ectopic impulses so precipitated, the conduction of which is supported by the functional inhomogeneity of the infarcted region, are capable of initiating reentry tachycardia. During phase 2, a few hours to days after the ischemic event, only the subendocardial Purkinje fibers in the infarcted region exhibit focal arrhythmogenicity. In contrast to the working myocardial cells, the latter survive due to their immediate proximity to the cardiac chamber and show, ischemia-induced, a propensity to high-frequency impulse formation in terms of abnormal automaticity. Similar to the experimental findings, the cause of the frequently-observed ventricular arrhythmias in the early hospital phase appears predominantly attributable to a focal arrhythmia mechanism. During phase 3, several days to weeks after the acute myocardial ischemic event, reentry mechanisms again are in the foreground in which the electrophysiologic changes in the Purkinje fibers, in terms of increasing desynchronization, together with conduction barriers arising through the infarct scar, pave the way for reentry phenomenon. After abrupt restoration of patency of a previously occluded vessel the very frequent "reperfusion arrhythmias" are also attributable primarily to reentry mechanisms due to inhomogeneous improvement of the conduction properties in the region of the reperfused myocardium. Ventricular late potentials can be registered both invasively by means of epi- or endocardial leads as well as noninvasively from the body surface.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Ventricular late potentials in acute myocardial infarct]. 304 72

Electrocardiographic abnormalities have been known to occur in the context of neurologic disease for a long time. These changes fall into 2 categories: arrhythmias and repolarization abnormalities. However, until relatively recently these changes were believed to represent purely electrophysiologic alterations and not real heart disease. It is now clear that some patients with neurogenic electrocardiographic changes show cardiac enzyme release and myofibrillar degeneration at autopsy. There are 4 major methods for producing myofibrillar degeneration (i.e., contraction band necrosis or coagulative myocytolysis): catecholamine infusion, stress-steroid, nervous system stimulation and reperfusion. The common thread connecting these 4 methods is the opening of receptor-operated calcium channels, resulting in intense contraction of cardiac muscle. Thus, neurogenic influence over cardiac function may represent a continuum. In the mild reversible circumstance, only the electrocardiographic change will be seen, whereas in the severe, irreversible situation, myofibrillar degeneration will ensue with release of cardiac enzymes. Cardiac cell death may be caused by oxygen free radicals produced by metabolism of catecholamines or reperfusion or both, after variable periods of ischemia. This concept represents a unifying hypothesis, tying together the clinical, physiologic, biochemical and pathologic findings in neurogenic heart disease.
 ...
PMID:Neurogenic heart disease: a unifying hypothesis. 332 64

Reperfusion of cardiac muscle after an ischemic episode results in the cells becoming overloaded with Ca2+. Gross ultrastructural changes, including the formation of contraction bands, also occur. The present study investigates the relationship, if any, between contractile activity during reperfusion and Ca2+ gain. Contractile activity was inhibited with 2,3-butanedione monoxime (BDM). Isolated perfused rat hearts were subjected to 30 minutes ischemia before reperfusion in the presence or absence of BDM. BDM (10 MIN) significantly reduced the Ca2+ gained during reperfusion. It also enhanced the ATP and creatine phosphate supplies. Ultrastructural examination of cells from hearts reperfused in the presence of BDM for 30 minutes revealed cells with relaxed myofibrils, some glycogen and intact sarcolemmal membranes, compared with cells from hearts reperfused in the absence of BDM which showed contraction bands, sarcolemmal discontinuities and swollen mitochondria. The 'protection' afforded by BDM did not result in a restoration of the cells to their normal state. Removal of BDM and continued reperfusion with Krebs-Henseleit buffer resulted in a gain in Ca2+ and ultrastructural damage, including contraction band formation. These findings suggest a role for contractile activity in the Ca2+ gain. However, preventing the damage which occurs as a result of contractile activity is not sufficient to restore the cells to their preischemic state. This suggests that the damage caused as a result of contractile activity is secondary to some other primary deleterious event.
 ...
PMID:Contractile activity and reperfusion-induced calcium gain after ischemia in the isolated rat heart. 337 13

31P magnetic resonance spectroscopy, using surface coils placed on perfused or surgically exposed animal hearts, shows that unequivocal changes in phosphocreatine (PCr) and adenosine triphosphate (ATP) occur during interventions, such as ischemia. Similar measurements seem warranted in man. We have used a modification of the rotating-frame imaging technique to measure PCr-to-ATP ratio non-invasively in human heart. The subject lay prone on a double-surface coil probe with the apex and the anterior surface of the heart covered by the coil in a 1.9 T magnet. 31P spectra were obtained from slices of tissue approximately 6 cm in diameter and 2 cm in thickness. Though skeletal and cardiac muscle contain similar phosphorus metabolites, animal studies show that the ratio in the two are different. We argued that the ratio should start high (skeletal muscle) and plateau at a low value representing cardiac muscle. Using this criterion, which makes no assumption on what the ratio is in heart muscle, the PCr:ATP in six normal subjects was 1.55 +/- 0.2. This protocol has been used in a preliminary study in patients with cardiomyopathies.
 ...
PMID:Measurement of phosphocreatine to ATP ratio in normal and diseased human heart by 31P magnetic resonance spectroscopy using the rotating frame-depth selection technique. 343 7

The isolated, perfused ventricles of guinea-pig and rat hearts stimulated at the rate of 60/min were equilibrated for 60 min with 45Ca containing solution. Thereafter some of them were perfused for the last 10 min of experiment with deoxygenated (pO2 = 35 not equal to 7 mm Hg) radioactive solution. Hypoxia resulted in decrease of exchangeable calcium (45Ca) content by 0.90 mmol/kg w.w. in guinea-pig and by 0.26 mmol/kg w.w. in the rat. The amount of 15Ca lost by guinea-pig ventricles is equal to the content of rate-dependent fraction Ca2 described in the previous papers [Pytkowski et al., 1983; Lewartowski et al., 1984]. The isolated papillary muscles of the right ventricles of guinea-pig and rat hearts were subjected to 90 min of ischemia simulated by immersion in the warm, deoxygenated paraffin oil. Some of the guinea-pig muscles were deprived of Ca2 fraction by means of prolonged rest (20 min) immediately prior to ischemia. All the preparations were quiescent during ischemia. The guinea-pig muscles deprived of fraction Ca2 and the rat muscles developed much weaker contracture during ischemia and showed better recovery of phasic contraction upon reperfusion than the guinea-pig muscles containing Ca2 fraction prior to ischemia. We propose that Ca2 fraction is released from its binding sites at the early phases of ischemia contributing to the disturbances in Ca homeostasis and to mechanism of damage of ischemic cardiac muscle.
 ...
PMID:The role of intracellular calcium in the ischemic myocardial damage. 345 9

This study evaluates the capacity of regional substrate-enriched blood cardioplegic reperfusion (without bypass) to salvage cardiac muscle subjected to 40 minutes of regional ischemia. Results are compared with those obtained by normal blood reperfusion at either systemic or reduced perfusion pressure (i.e., simulating acute angioplasty or streptokinase thrombolysis). All studies were carried out in beating, working hearts when the conditions of reperfusion were not controlled. The results show that regional cardioplegic reperfusion without cardiopulmonary bypass reduces the incidence of perfusion ventricular fibrillation (15% versus 55%, p less than 0.05), increases recovery of subendocardial creatine phosphate (35.3 versus 14.0 mumol/gm, p less than 0.05) and adenosine triphosphate (6.0 versus 3.1 mumol/gm, p less than 0.05), reduces histochemical damage evaluated by triphenyltetrazolium chloride (0% versus 43% transmural nonstaining, p less than 0.05), and improves myocardial contractile reserve capacity (91% versus 41%, p less than 0.05). Normal blood reperfusion restored immediate systolic shortening in only 3 of 18 hearts (17%), and regional cardioplegic reperfusion without bypass produced early recovery of regional systolic shortening in only 10 of 16 hearts (63%, p greater than 0.05). Thus the value of controlling reperfusate composition without simultaneous control of reperfusion conditions is limited.
 ...
PMID:Metabolic and histochemical benefits of regional blood cardioplegic reperfusion without cardiopulmonary bypass. 374 81

This study assesses the regional oxygen requirements of muscle segments that are beating and working, beating and empty, arrested and decompressed, and nonischemic that move dyskinetically. Regional oxygen demands were evaluated by producing a dyskinetic segment by infusing regional cardioplegic solution through a left anterior descending coronary artery catheter with and without extracorporeal circulation. The results show that the O2 demands of the perfused dyskinetic cardiac muscle segment (4 to 8 ml/100 gm/min) are approximately 55% of the contracting (beating, working) segment (7 to 12 ml/100 gm/min) and are fivefold more than when the same muscle segment is arrested and decompressed by total vented bypass (0.8 to 1.2 ml/100 gm/min). Additional studies showed that ischemia for 2 hours (left anterior descending coronary artery ligation) produced severe dyskinesia (-24% control systolic shortening), which failed to recover after reperfusion with the heart in the beating, working state. In contrast, lowering O2 demands by reperfusion during bypass restored occasional contractile function as a consequence of left ventricular decompression. Dyskinetic muscle segments have a high oxygen requirement that may affect their capacity to be salvaged if reperfusion is conducted without left ventricular decompression. These observations suggest that the value of revascularization in the working heart (i.e., streptokinase with or without angioplasty) may be limited unless the left ventricle is decompressed during reperfusion and provide an explanation for the delayed recovery of mechanical function in hearts reperfused surgically with normal blood during cardiopulmonary bypass.
 ...
PMID:High oxygen requirements of dyskinetic cardiac muscle. 374 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>