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

Lack of a reproducible model to quantitatively assess hepatocellular injury following ischemia has made it difficult to assess new strategies for minimizing hepatic injury. We studied the progression of hepatocellular injury after ischemia and ischemia with reperfusion in rats. Irreversible injury was quantitated using a triphenyltetrazolium chloride assay that was shown to correlate with ultrastructural changes. Adenosine triphosphate decreased to 36% of basal values after 30 minutes, but returned to normal with reperfusion with no decrease in viability. In contrast, viability fell by 30% after 60 minutes of ischemia, and by 64% when 60 minutes of ischemia was followed by reperfusion. We conclude that reperfusion of ischemic liver increases the degree of irreversible damage. The model employed here seems to be useful for studying ischemic and reperfusion injury in the liver.
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PMID:Liver viability after ischemia-reperfusion. 203 66

Eighteen dogs underwent transmural left ventricular biopsies for adenosine triphosphate and suturing of the noncoronary cusp, creating valvular aortic stenosis. Three months after aortic stenosis and the subsequent development of left ventricular hypertrophy, animals underwent repeat transmural left ventricular biopsies followed by total myocardial ischemia at 37 degrees C. Left ventricular tissue samples for adenosine triphosphate and lactate levels were determined at 15-minute intervals and compared with 15 control animals. No significant difference between subendocardial and subepicardial adenosine triphosphate levels was found between left ventricular samples taken before left ventricular hypertrophy and 3 months after left ventricular hypertrophy. Significant differences in adenosine triphosphate utilization occurred between subendocardial and subepicardial layers in control and left ventricular hypertrophy myocardium, however. The gradient between the subendocardium and the subepicardium was significantly increased by left ventricular hypertrophy (p less than 0.05). Significant differences also occurred within the same layer when left ventricular hypertrophy and control groups were compared. During total ischemia, lactate concentration was significantly greater within the subendocardium than within the subepicardium in left ventricular hypertrophy. The onset of ischemic contracture was 48.2 +/- 2.1 minutes in left ventricular hypertrophy versus 62.3 +/- 1.8 minutes in control hearts (p less than 0.01). Subendocardial intramyocardial pressure increased significantly earlier than subepicardial in both left ventricular hypertrophy and control hearts. Adenosine triphosphate was used, and lactate accumulated more rapidly in animals with a more pronounced hemodynamic gradient. These data show that after left ventricular hypertrophy, adenosine triphosphate stores in the subendocardium and the subepicardium are unchanged from control values, yet the rates of adenosine triphosphate utilization and lactate accumulation during total ischemia are significantly increased. Furthermore, the subendocardial to subepicardial gradient of adenosine triphosphate utilization during ischemia found in normal hearts is markedly increased by left ventricular hypertrophy.
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PMID:Accelerated transmural gradients of energy compound metabolism resulting from left ventricular hypertrophy. 214 78

The lower extremity may be exposed to prolonged periods of ischemia, resulting in depletion of intracellular energy stores in the affected skeletal muscle. The role of adenine nucleotide reduction and failure of resynthesis on reperfusion in determining the extent of muscle necrosis was investigated in this study, in addition to the possible beneficial effects of the addition of exogenous adenosine triphosphate-magnesium chloride during early reperfusion. The isolated paired canine gracilis muscle model was used. After 4 hours of normothermic ischemia in group I, a perfusate Krebs-Henseleit solution plus the gradual reintroduction of oxygenated blood flow was compared to standard reperfusion. In group II, a similar infusion protocol was used, with the addition of 2 mmol/L adenosine triphosphate-magnesium chloride and compared to normal reperfusion. Adenosine triphosphate-magnesium chloride resulted in the salvage of skeletal muscle, 57% +/- 12% versus 44% +/- 14% (p less than 0.05, n = 6 pairs). Reperfusion with the solution alone increased the resulting necrosis (42% +/- 13% vs 60% +/- 20%, n = 6 pairs). Adenine nucleotide stores were not increased, but oxygen consumption was increased by magnesium chloride-adenosine triphosphate (p less than 0.05, analysis of variance [ANOVA]). A clear relationship was demonstrated between the fall in energy stores, as measured by a change in energy charge potential from preischemia to end ischemia levels, and the extent of resulting necrosis (p less than 0.01). In summary, the addition of 2 mmol/L to an infusion of Krebs-Henseleit solution during reperfusion results in significant salvage of skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exogenous magnesium chloride-adenosine triphosphate administration during reperfusion reduces the extent of necrosis in previously ischemic skeletal muscle. 231 33

Prolonged ischemia to skeletal muscle as occurs after an acute arterial occlusion results in alterations in adenine nucleotide metabolism. Adenosine triphosphate continues to be used for cellular functions, and an ischemia-induced degradation of phosphorylated adenine nucleotides is initiated. In this experiment we demonstrated the time-dependent aspect of adenine nucleotide depletion during ischemia and the production of large quantities of soluble precursors. In addition, we studied the rate of conversion of xanthine dehydrogenase to xanthine oxidase, a potential source of oxygen-free radicals, after controlled periods of total normothermic ischemia (4 hours and 5 hours) and during the reperfusion phase. During ischemia complete depletion of creatine phosphate occurred in both groups, and adenosine triphosphate fell from 22.1 +/- 1.3 to 10.3 +/- 1.4 mumol/gm dry weight after 4 hours and from 21.6 +/- 0.7 to 3.9 +/- 0.8 mumol/gm dry weight after 5 hours (p less than 0.05). During reperfusion, creatine phosphokinase resynthesis occurred in both groups, but adenosine triphosphate levels were not significantly increased (p greater than 0.05). A washout of lipid soluble products of adenine nucleotide metabolism occurred equally in both groups. The relationship between phosphorylated adenine nucleotides as measured by the energy charge potential fell significantly in both groups (p less than 0.05), but after the shorter period of ischemia (4 hours it returned to normal during early reperfusion but did not after 5 hours of ischemia. There was 21% +/- 4% necrosis after 4 hours and 51% +/- 8% after 5 hours of ischemic stress when assessed at 48 hours. In conclusion, the degree of adenine nucleotide degeneration as determined primarily by the length of the ischemic period, may be the most important determinant of the ultimate extent of skeletal muscle ischemic necrosis that results from an acute interruption of circulation.
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PMID:The effect of ischemia/reperfusion on adenine nucleotide metabolism and xanthine oxidase production in skeletal muscle. 237 59

Hypothermic total circulatory arrest for repair of congenital heart lesions in neonates requires a period of rapid core cooling on cardiopulmonary bypass during which the myocardium is also exposed to hypothermic perfusion. Myocardial hypothermia in the nonarrested state results in an increase in contractility due to elevation of intracellular calcium levels. This study was designed to test the hypothesis that rapid myocardial cooling before cardioplegic ischemic arrest results in damage, with impaired recovery during reperfusion. Two groups of 10 rabbit hearts were perfused on an isolated Langendorff apparatus. Group N (normothermia) was perfused at 37 degrees C before 2 hours of cardioplegic ischemic arrest at 10 degrees C. Group C (cooling) was perfused at 15 degrees C in the unarrested state for 20 minutes before the same cardioplegic arrest conditions as group N. Left ventricular isovolumic pressure measurements, biochemical measurements from right ventricular biopsy specimens, and ventricular necrosis as defined by tetrazolium staining were used to compare the groups at 30 and 60 minutes of normothermic reperfusion. Developed pressure at a constant volume was preserved in group N at 90.7 +/- 4.5 mm Hg versus 76.9 +/- 6.3 in group C after reperfusion (p less than 0.05). Diastolic compliance showed significant deterioration in group C, with marked elevation of diastolic pressure during reperfusion (group N = 6.8 +/- 2.5 mm Hg versus group C = 38.9 +/- 6.1 after reperfusion; p less than 0.001). Adenosine triphosphate levels were significantly higher in group N both at end-ischemia and after reperfusion versus group C (group N = 17.0 +/- 1.1 nmol/mg protein versus group C = 7.7 +/- 1.0 after reperfusion; p less than 0.001). Group N had 0.4% +/- 0.4% necrosis of ventricular mass versus 19.3% +/- 2.2% with prearrest cooling in group C (p less than 0.0001). These results indicate that, when combined with cardioplegic ischemic arrest, rapid myocardial cooling in the unarrested state results in significant damage. The mechanism may be related to the cytosolic calcium loading effect of hypothermia that is not relieved during the subsequent period of cardioplegic arrest. Although hypothermia is an essential component to ischemic preservation, rapid cooling contracture can adversely influence cardioplegic myocardial protection.
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PMID:Rapid cooling contracture of the myocardium. The adverse effect of prearrest cardiac hypothermia. 239 83

Myocardial dysfunction after induced ischemic arrest is an important problem in cardiac surgery. Adenosine-5'-triphosphate content in myocardial tissue remains depressed for days after ischemia, perhaps because of reperfusion washout of diffusable purine substrates. Left ventricular function is also depressed after ischemia, but its relationship to absolute tissue adenosine triphosphate content is unclear. We tested the hypothesis that arresting hearts with a cardioplegic solution containing adenosine, hypoxanthine, and ribose would result in improved tissue adenosine triphosphate content and left ventricular function after 1 hour of normothermic global ischemia in dogs supported by cardiopulmonary bypass. Animals with ischemic arrest initiated with a crystalloid cardioplegic solution containing adenosine 100 mumol/L, hypoxanthine 100 mumol/L, and ribose 2 mmol/L demonstrated significant improvement (p less than 0.05) during postischemic reperfusion. A significant correlation (p less than 0.05) existed between myocardial adenosine triphosphate content and the recovery of left ventricular function. These experiments demonstrate that an asanguineous cardioplegic solution containing adenosine, hypoxanthine, and ribose maintains myocardial adenosine triphosphate content during ischemia and reperfusion and enhances functional recovery during the postischemic period.
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PMID:Purine-enriched asanguineous cardioplegia retards adenosine triphosphate degradation during ischemia and improves postischemic ventricular function. 249 76

Rats were bled to a mean arterial pressure of 40 mm Hg until the onset of decompensatory shock (marked by the need to return some blood in order to maintain the blood pressure) at which time all the shed blood was returned. 31P-nuclear magnetic resonance (NMR) spectra of their livers were collected during the shock and a subsequent 60 min recovery period. Adenosine triphosphate (ATP) levels fell linearly with time, in some instances to zero during shock. ATP recovery was very rapid after return of shed blood but did not return to its preshock values. Levels of ATP remained stable during the 60 min of recovery. From the rapid recovery after total depletion of ATP in this study and in other NMR studies on perfused ischemic livers, as well as the discrepancy in residual levels of ATP during shock and ischemia as measured by in vivo NMR or by extraction techniques, we argue in favor of metabolically inaccessible pools of adenine nucleotides during these hepatic stresses.
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PMID:Rat liver metabolism in hemorrhagic traumatic shock. 259 15

Quantitative assessment of high-energy phosphate levels, including degradation or utilization during ischemia, has not previously been performed in infants and children. Animal experiments suggest that high-energy phosphate metabolism varies with maturation. To help answer these questions, 24 patients aged 2 months to 8 years underwent myocardial biopsy immediately after the institution of cardiopulmonary bypass (16 to 20 degrees C). Additional samples were obtained at 16 and 45 minutes after aortic cross-clamping and administration of cardioplegia (St. Thomas's solution) (in vivo ischemia). Seven patients also underwent major myocardial resection. Resected specimens were placed in a 37 degrees C bath and divided into equal-sized samples that were removed at ten-minute intervals (in vitro ischemia). All samples were immersed in liquid nitrogen and analyzed for adenine nucleotide pool metabolites using high-performance liquid chromatography. Levels of adenosine triphosphate were high before cross-clamping but diminished during the period of protected ischemia. Adenosine triphosphate loss was much more pronounced in patients less than 18 months old (p less than 0.05) and was associated with accumulation of adenosine monophosphate and inosine, a finding not seen in patients more than 18 months old (p less than 0.05). The same trends documented during in vivo ischemia were noted during in vitro ischemia. Immaturity of 5'-nucleotidase results in accumulation of adenosine monophosphate during ischemia. It is known that 5'-nucleotidase is present in neonatal myocardial cell membranes and absent from the cytosol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial adenine nucleotide metabolism in pediatric patients during hypothermic cardioplegic arrest and normothermic ischemia. 273 Jan 89

The effect of captopril on energy-rich phosphates and pH during normothermic ischemic arrest, hypothermic cardioplegic arrest and subsequent reperfusion was investigated in the isolated rat heart using 31P-nuclear magnetic resonance. The hearts remained in the probe during all perfusion procedures and captopril (80 ml.l-1) treatment was started directly after cannulation. After normothermic ischemic arrest (15 min), the ATP content of captopril-treated hearts was not significantly different from that of untreated hearts (53 +/- 9% and 52 +/- 8%, respectively). Accumulation of inorganic phosphate at the end of ischemia was significantly less in treated hearts, suggesting a higher end-ischemic nucleotide content in treated hearts. Hypothermic cardioplegic arrest (St. Thomas' Hospital solution, 4 degrees C) lasted for 3 h at 10 degrees C. Adenosine triphosphate in untreated hearts was significantly lower at the end of ischemia; 36 +/- 6% compared to 53 +/- 9% for untreated hearts. Adenosine triphosphate in untreated hearts recovered to 76 +/- 9% after normothermic ischemia and to 72 +/- 7% after hypothermic ischemia at the end of 30 min reperfusion. Captopril significantly improved adenosine triphosphate recovery in both treated groups; 89 +/- 4% after normothermic and 83 +/- 4% hypothermic ischemia. We conclude that captopril has a beneficial effect on recovery of adenosine triphosphate both after normothermic and after hypothermic ischemia.
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PMID:Captopril improves recovery of adenosine triphosphate during reperfusion of the ischemic isolated rat heart; a 31-phosphorus-nuclear magnetic resonance study. 306 91

Postoperative low cardiac output is the most common cause of death in patients undergoing elective repair of tetralogy of Fallot. The incidence is much higher than in elective adult bypass operations for coronary artery disease. To explain this difference, we investigated 16 children having elective repair of tetralogy (mean age 6.3 years). Myocardial biopsy specimens obtained during bypass before arrest, at the end of cold arrest by blood cardioplegia, and after 30 minutes of reperfusion were studied for adenosine triphosphate and lactate levels. Myocardium was submitted for microscopic study shortly after the onset of ischemia. The operation was successful in reducing right ventricular-pulmonary artery gradients from 82 +/- 28 to 9 +/- 1 mm Hg, yet seven patients required significant inotropic support (dopamine, greater than 5 micrograms/kg/min) for more than 24 hours and 12 patients needed prolonged use of digoxin and diuretics for right ventricular failure. Tissue levels of adenosine triphosphate and lactate in the tetralogy groups were compared with those in 20 adults with coronary artery disease having similar myocardial protection techniques. Adenosine triphosphate levels in the tetralogy group decreased during cross-clamping (41 +/- 8 minutes) from 24 +/- 3 to 16 +/- 2 mmol/kg dry weight (mean +/- 1 standard error), with a marked further drop after reperfusion to 9 +/- 2 mmol/kg (p less than 0.01). Adenosine triphosphate levels in the group with coronary disease also decreased from 20 +/- 1 to 16 +/- 1 mmol/kg after a longer cross-clamp time (70 +/- 17 minutes) but remained at 15 +/- 2 mmol/kg after reperfusion. Tissue lactate levels in the tetralogy group rose markedly during ischemia and remained elevated after reperfusion. In contrast, lactate levels in the group with coronary disease rose moderately during ischemia and returned to normal early on reperfusion. Microscopic study revealed focal myocyte necrosis in tetralogy of Fallot. Our findings, which demonstrate inadequate myocardial protection of patients with tetralogy during repair, with depression of adenosine triphosphate and increased lactate during ischemia and reperfusion, suggest a defect in oxidative metabolism. The drop in adenosine triphosphate after reperfusion in the patients with tetralogy implicates reperfusion injury as a mechanism of myocardial damage.
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PMID:Inadequate myocardial protection with cold cardioplegic arrest during repair of tetralogy of Fallot. 325 36


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