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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

An approach to intraoperative protection of the myocardium is described that attempts to increase glucose utilization by infusion of high-energy solutions during aortic cross-clamping. Infusion of hypertonic glucose or glucose plus insulin prior to aortic cross-clamping has enhanced contractility and increased high-energy phosphate moieties in animals with induced ischemia. Recent pilot experiments in our laboratory suggest that infusions of creatine may result in increased production of creatine phosphate, which in turn induces phosphorylation of adenosine diphosphate to adenosine triphosphate, possibly enhancing myocardial contractility. The intraoperative clinical benefits of these infusions remain to be proved, however.
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PMID:Protection of the myocardium with high-energy solutions. 80 61

Cardioplegia induced with an osmotically balanced solution of high potassium concentration appears to lower the oxygen requirements of the heart, slows high-energy phosphate depletion to some extent, and is associated with increased survival in prolonged normothermic ischemia. To date no obvious detrimental effects have been observed from injecting this solution.
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PMID:Potassium-induced cardioplegia. 80 63

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

The effects of occlusion of the left anterior descending coronary artery on a variety of metabolic parameters was examined in both infarcted and noninfarcted areas of the dog heart. These included mitochondrial performance, glycolysis, in vitro contractility, and regional myocardial blood flow. Measurements were made at 1 and 3 h after onset of ischemia. Regional coronary blood flow was measured in infarcted, noninfarcted and borderline regions using radioactive microspheres. Blood flow through the ischemic area was reduced by an average of 69% after 1 h of ischemia, and 75% after 3 h. After 3 h the subendocardium of the borderline region also revealed a significantly reduced blood flow. Mitochondria isolated from the ischemic region of the heart exhibited a substantial decrease in the rate of respiration (QO2), and minor reductions in the coupling between oxidative phosphorylation and electron transport (RCI), and in the amount of ADP phosphorylated per oxygen reduced (ADP:O ratio). Levels of hexose monophosphates were elevated 1 and 3 h after ischemia was initiated. At the same time, the concentration of fructose-1,6-diphosphate declined markedly, reflecting inhibition of glycolysis at the phosphofructokinase level. Concentrations of the adenosine phosphate moieties, as well as creatine phosphate, were reduced, while levels of free fatty acids were elevated in ischemic tissue. The in vitro contractility of glycerinated ischemic muscle fibers was also depressed. Significant changes were found in maximal tension development (P0), maximal rate of tension development (dp/dtmax), time to peak tension (t0), and shortening velocity at zero load (Vmax).
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PMID:Regional blood flow, contractility and metabolism in early myocardial infarction. 87 51

To evaluate whether elevated arterial free fatty acids (FFA) increase myocardial oxygen demand and ischemia, 15 fasting patients with coronary artery disease underwent a standardized atrial pacing test before (PTI) and during (PT2) heparin infusion. The patients were monitored for clinical and electrocardiographic (ECG) manifestations of ischemia. Myocardial extraction of lactate, inorganic phosphate, oxygen and FFA was measured before and during each PT. The control arterial FFA was 0.65 +/- 0.03 micromole/ml and rose to 1.83 +/- 0.16 micromole/ml during heparin influsion. Myocardial oxygen extraction at rest and during PT was not affected by the increase in arterial FFA. Seven patients asymptomatic during PT1 did not develop ischaemic manifestations during PT2. In eight patients with angina during both PTs, increased arterial FFA concentration did not modify the severity of anginal pain, the amount of ST-segment depression and the myocardial balance of lactate or inorganic phosphate. Elevation of arterial FFA by heparin neither increased myocardial oxygen extraction at rest or during pacing nor accentuated ischemic manifestations during PT.
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PMID:Effect of increased free fatty acids on myocardial oxygen extraction and angina threshold during atrial pacing. 87 27

There has been considerable controversy concerning the relative merits of intermittent coronary perfusion vs. continuous aortic cross-clamping for cardiac procedures requiring ischemic arrest. Using the isovolumic ventricular balloon model and "stop-freeze" biopsy techniques, myocardial contractility (LV dp/dt max, length-tension, and force-velocity relationships) and metabolism (adenine nucleotides, creatine phosphate, and glycogen) were studied in 46 intact dogs supported by normothermic cardiopulmonary bypass and subjected to either 60 minutes of continuous ischemic arrest or to four 15-minute intervals of ischemia each followed by 5 minutes of reperfusion. Following ischemia the hearts were reperfused for 30 minutes and defibrillated after the first 10 minutes. There were no significant differences in either metabolic parameters or contractile function between the groups. Although partial regeneration of adenosine triphosphate and glycogen occurred during reperfusion, only creatine phosphate achieved normal values and the end result was no difference between the two techniques. These data indicate that 5 minutes of coronary reperfusion between consecutive episodes of ischemic arrest affords no greater intraoperative protection of the myocardium than does continuous aortic cross-clamping.
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PMID:Does intermittent coronary perfusion offer greater myocardial protection than continuous aortic cross-clamping? 87 56

Whole-heart ischemia has been induced in isolated working rat heart. The distribution of the reduced coronary flow was even, as judged by 3H-antipyrine autoradiographs. Reducing the coronary flow resulted in myocardial ischemia, as indicated by a lowered tissue content of glycogen, ATP and creatine phosphate and accumulation of lactate. After a reperfusion period of 30 min there was a restoration of glycogen, ATP and creatine phosphate for hearts that were ischemic for 5 and 10 min, with a concomitant normalization of tissue lactate. Hearts that were ischemic for 30 min did not show restoration of high energy phosphates and glycogen. There was a leakage of ASAT, CK and LD in all groups of hearts, suggesting that a release of these enzymes does not necessarily indicate an irreversibly damaged myocardial cell.
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PMID:Significance of enzyme release from ischemic isolated rat heart. 87 8

Ischemia in the isolated perfused rat heart resulted in an increase in coronary vascular resistance. Studies were undertaken to determine the effect of hyaluronidase and methylprednisolone on this increase in resistance as well as on glycolytic rate and mechanical function of ischemic hearts. Neither hyaluronidase nor methylprednisolone affected the rate of glucose utilization in working perfused control or ischemic rat hearts. However, both agents prevented a reduction in coronary flow during a 2-hour ischemic period. Associated with the higher coronary flows were higher tissue concentrations of creatine phosphate and lower concentrations of lactate. These agents also prevented accumulation of tissue water in the ischemic hearts. Such changes would appear to be beneficial to the ischemic heart, although mechanical function of post-ischemic hearts was not enhanced by the presence of either hyaluronidase or methylprednisolone. The results, however, suggest that the reduction in myocardial infarct size noted with hyaluronidase and methylprednisolone may be due to their prevention of further reduction of coronary flow in marginally eschemic tissue.
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PMID:Effect of hyaluronidase and methylprednisolone on myocardial function, glucose metabolism, and coronary flow in the isolated ischemic rat heart. 89 Aug 92

Organ perfusion methods offer a number of advantages in biologic studies but require full characterization before application. Two new methods for perfusing rat testes were characterized and compared with recirculating hemicorpus system. These preparations, selective and isolated testicular perfusion, are nonrecirculating and consequently, allow direct measurement of testosterone secretion. In both systems, testosterone production was a fuction of the dose of human chorionic gonadotropin in the perfusion medium up to 1000 mIU per ml which appeared to be inhibitory. The isolated testis method, in comparison with the selective, is more sensitive to human chorionic gonadotropin, requires less perfusion medium, maintains normal blood flow rates and water content, and is associated with no ischemia at commencement of perfusion. However, this system does not retain normal levels of ATP and GTP after 3 hr of perfusion. Whereas both procedures may be used for studies of testosterone secretion and androgen receptors, the inability to maintain testicular ATP and GTP levels indicates that present methods are not suitable for study of processes dependent upon high energy phosphate metabolism.
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PMID:Evaluation of methods for perfusing rat testes. 90 14


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