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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We can summarize the results of our studies as follows (Fig. 15). The critical cellular factors involved in the loss of reversibility following ischemia appear to be the mechanisms involved in the membrane function of energy transduction. Irreversibility appears to correlate with an irrepairable defect in energy transduction. This could involve both the mitochondrial energy transduction functions and those in the plasma membrane. The mechanisms involved in this transition are not presently clear but they are associated with increased leakiness or permeability of these membranes accompanied by changes in lipid content, alterations in membrane proteins, and presumably in lipid-protein interactions. There are two prominent theories to explain energy transduction. These are the "proton pump" hypothesis of Mitchell (1972) and the "paired moving charge" hypothesis of Blondin and Green (1975). Both of these hypotheses require integrated function of membrane components, i.e., lipid and protein. The hypothesis of Blondin and Green, however, can work even with discontinuous membrane sheets because it involves the concept of ribbons of protein embedded in the protein-lipid membrane matrix. The characteristic finding of our studies following ischemic injury, namely, the continuous electron flow well into the irreversible phase while the energy transduction is impaired, could be explained by both hypotheses. What do these observations have to say about theories of energy conservation? We have observed that the vectorial nature of the proton separation is stopped. Charge separation may not occur at this time across the membrane since proton gradient and possible membrane potential are abolished. Electron transport, however, continues indicating the generation of protons. Since the decline of P/O ratio, decline of proton gradient and the cellular "point-of-no-return" coincide, these observations point toward the important membrane defects acquired at that particular time. The "paired moving charge" model which involves moving ions encapsulated in endogenous ionophores such as lecithin and maintenance of magnesium is favpred by the observation that phosphatidyl choline and phosphatidyl ethanolamine are lost in correlation with irreversibility. Furthermore, the decrease in magnesium content of cells is closely associated with the loss of viability following ischemia. The "paired moving charge" hypothesis has the attractive feature in that it involves antagonistic effects of calcium and magnesium. During reflow, calcium may inhibit magnesium mediated transport of inorganic phosphate by lecithin. Also, according to this theory fatty acids or their cyclic anions which act as uncouplers may foster the loss of phosphorylation capacity.
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PMID:Recent studies on the pathophysiology of ischemic cell injury. 79 Dec 45

Ischemia induced by cross-clamping the aorta during open-heart operations initiates progressive metabolic derangement. If the duration of ischemia is short, these derangements are easily reversed by restoring the flow of blood containing oxygen and substrate. If ischemia is prolonged, treatment designed to ameliorate ischemic damage may be necessary. Three problems are discussed: (1) loss of adenine nucleotides, particularly adenosine triphosphate, (2) impairment of calcium sequestration, and (3) formation of microemboli in coronary vessels. The rationale for postbypass treatment is presented.
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PMID:Postbypass treatment. 80 69

The x-ray microanalysis technique was used to determine the chemical composition of intramitochondrial electron-dense deposits in ischemic myocardial cells. Semi-thin sections were cut from Araldite-embedded tissue and analyzed in a scanning electron microscope equipped with energy- and wavelength-dispersive spectrometers. The energy dispersive spectrum revealed calcium and phosphorus peaks over many mitochondrial deposits. Peak to background ratios of calcium, phosphorus and magnesium obtained with the wavelength dispersive spectrometer were 1.7, 8.8 and 1.2, respectively. There was no consistent relationship in the characteristic peaks of calcium and phosphorus in a given mitochondrial granule. Magnesium appears to be negligible, except in some mitochondrial deposits which lacked calcium, where it was present with a peak to background ratio of two. These results suggest formation of calcium or magnesium phosphate in the mitochondria during ischemia. X-ray microanalysis can provide detailed information on subcellular electrolyte distribution in normal and ischemic myocardial cells and should be attempted with improved methods of tissue preparation.
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PMID:X-ray microanalysis of mitochondrial deposits in ischemic myocardium. 82 7

Ischemic liver tissue was produced by clamping the portal venous and hepatic arterial blood supply to the left lateral and median lobes of rat liver. If, after 2 to 3 hours of ischemia, reflow to the liver was established by removing the clamp, two-thirds or more of the liver cells were histologically dead 24 hours later. Pretreatment with chlorpromazine (20 mg/kg) 30 minutes before inducing ischemia for up to 3 hours virtually completely prevented this ischemic cell death. If the animals were kept alive for an additional 24 hours with no further treatment, the extent of liver cell necrosis at 48 hours was still markedly less than that seen in the untreated ischemic controls. Administration of chlorpromazine after induction of ischemia and immediately prior to the onset of reflow reduced but did not completely prevent ischemic cell death as determined at 24 hours. This protective action of chlorpromazine was confirmed by the ability of the treated animals to regenerate cellular ATP levels after 3 hours of ischemia. In addition, chlorpromazine was shown to significantly reduce the increases in total liver cell and mitochondrial calcium ion contents that accompany the return of blood flow to irreversibly injured liver cells. The protective effect of chlorpromazine could not be attributed to any effect either on the rate or extent to which the liver cells became ischemic or on the perfusion patterns following release of the obstruction, and it is concluded that the action of chlorpromazine must be on some component(s) of the reaction of the cells to the ischemia itself. The possible basis of this action is discussed.
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PMID:Prevention by chlorpromazine of ischemic liver cell death. 88 8

This study was based on the concept that intracellular accumulation of calcium plays a role in mediating ischemic myocardial injury and that inhibition of entry of calcium into cells may have a salutary effect on the ischemic heart. Nifedipine, a potent vasodilator and inhibitor of transmembrane calcium flux, was infused into the aortic root of 6 dogs (5 microgram/kg/hr) during 2 hours of myocardial ischemia while on cardiopulmonary bypass. Seven control animals received normal saline at the same flow rate and temperature (20 degrees C). The results showed that none of the 7 control animals were able to maintain adequate aortic pressure or cardiac output after 30 to 60 minutes of normothermic reperfusion. All had marked left ventricular failure and were unresponsive to large doses of inotropic agents. In contrast, the 6 dogs treated with nifedipine were weaned from bypass either without difficulty or requiring small doses of calcium chloride and norepinephrine. Light microscopy demonstrated more marked ischemic damage in the control group than in the group of drug-treated dogs. We conclude that the concept of inhibition of transmembrane calcium flux offers a new and potent method for myocardial preservation during ischemia.
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PMID:Pharmacological preservation of the ischemic heart. 90 99

Isolated blood-perfused rabbit interventricular septa were adapted for studies of global ischemia by enclosure in a constant-humidity nitrogen atmosphere. During ischemia, developed tension (DT) and maximal rate of relaxation (-dP/dt) declined monoexponentially, lambda = 0.39 min-1 at 37 degrees C and 72 beats/min with a Q10 of 1.4 for DT and a Q10 of 1.9 for -dP/dt. After a 60- to 90-s delay the maximal rate of tension development (+dP/dt) declined at the same rate as DT. Time-to-peak tension (TPT) shortened immediately with ischemia but action potential duration shortened after 60-90 s. Calcium at a concentration of 5 mM slowed the rate of decline of +dP/dt to lambda = 0.26 min-1. Upon reperfusion after 10 min of ischemia the rates of recovery of DT, +dP/dt, and -dP/dt were similar, lambda = 0.21-0.23 min-1, and were not temperature dependent. The magnitude of recovery was 10-17% less at 37 degrees C than 28 degrees C. Potassium at a concentration of 10 mM did not alter the rate of decline of mechanical function, but significantly (P less than 0.01) increased the magnitude of mechanical recovery. The results suggest depletion and/or repletion of single compartments as the rate-limiting steps in ischemia and reperfusion.
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PMID:Ischemia in isolated interventricular septa: mechanical events. 98 8

This study determines the effect of ischemia and reperfusion on energy-linked Ca2+ uptake by myocardial mitochondria. The left anterior descending coronary artery was occluded in 14 mature pigs for 2 hr. In seven animals the ligature was released and the ischemic zone reperfused for 2 additional hours. After sacrifice, mitochondrial function was measured in normal and reperfused or ischemic areas of the left ventricle, using a polarographic method. Mitochondria were prepared without EDTA by standard procedures and Ca2+ uptake measured by 45Ca2+ isotope tracer. Uptake of Ca2+ by mitochondria derived from ischemic myocardium is markedly impaired with or without phosphate. Reperfusion may accentuate this impairment. The presence of exogenous Ca2+ inhibits the ability of ischemic or reperfused mitochondria to phosphorylate ADP.
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PMID:Alteration in calcium metabolism in mitochondria isolated from ischemic and reperfused myocardium. 103 50

Mitochondrial respiration, succinate dehydrogenase coenzyme Q reductase, and myosin B were investigated in ischemic myocardium from experimental myocardial infarction in dogs. Respiratory control ratio of mitochondria was impaired by ischemia at 60 min after coronary ligation, and oxygen consumption was inhibited 120 min later. Enzyme activity of succinate dehydrogenase coenzyme Q reductase was decreased at 6 hr after coronary ligation. Calcium ion sensitivity of myosin B declined 12 hr after coronary ligation. However, adenosine triphosphatase activity of myosin A from infarcted myocardium was not different from that of the intact one. These results suggest that interaction in the sequence of enzyme complexes was first impaired in ischemic myocardium and that deterioration of enzyme activity was then manifested.
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PMID:Relationship between energy liberation and utilization in ischemic cardiac muscle. 103 51

X-ray microanalytical techniques using wavelength dispersive (WDS) and energy dispersive spectrometry (EDS) indicate that Ca2+ is present in intramitochondrial granules which occur in myocardial cells following irreversible ischemic injury. Preliminary results using tissue prepared for routine electron microscopy suggest that the degree of calcium binding that occurs in the mitochondria increases with increased duration of ischemia. Free ions are leached out of the tissue during processing; hence, the role of ion redistribution in producing myocardial necrosis cannot be elicited from a study of this nature. However, with continued progress in the development of techniques of tissue preparation x-ray spectrometry may provide a means of assessing quantitative ion alterations that occur during ischemia.
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PMID:X-ray microanalysis of mitochondrial calcium. 103 82

Colloidal lanthanum salts have an average particle size of 40 degrees A; consequently, this electron-opaque marker remains extracellular and does not cross the intact plasma membrane. The affinity of lanthanum for calcium-binding sites on mitochondrial membranes makes it possible to demonstrate loss of plasma membrane integrity at the cellular level in ischemic myocardium. Biopsies were obtained from infarcted, marginal and normal areas 3 1/2 hours after ischemia was produced in 9 anesthetized closed-chest dogs by electrically induced thrombosis of the left anterior descending coronary artery. The tissue was immediately fixed in 4% glutaraldehyde and 0.1 M cacodylate buffer containing 1.3% La(NO3)3, pH 7.4, for 2 hours. In normal control tissue prepared this way the lanthanum tracer, as expected, was confirmed to the extracellular spaces, including, basement membranes, gap junctions and portions of the intercalated discs. Specimens taken near the center of frank infarctions all contained intracellular as well as extracellular lanthanum. Intracellular lanthanum could be seen evenly distributed around lipid droplets and in focal deposits around mitochondria. Only when mitochondria were disrupted did lanthanum gain access to internal sites on mitochondrial membranes. Areas marginal to the infarct contained cells in varying stages of degeneration including many that appeared normal by morphologic criteria alone. Intracellular lanthanum was present in many but not all of the marginal cells in which degenerative changes could be seen. Similarly a few of the cells that appeared morphologically normal contained intracellular lanthanum. The entry of lanthanum into some of these marginal cells and its exclusion from adjacent cells demonstrated that ischemic injury affects the permeability properties of the plasma membrane and independently of other intracellular morphologic changes and that lanthanum can be a sensitive indicator of such alteration in membrane permeability.
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PMID:Colloidal lanthanum as a marker for impaired plasma membrane permeability in ischemic dog myocardium. 114 60


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