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

Energy reserves (TAN) and anaerobic substrates (glucose, glycogen) are lower in renal than in myocardial tissue. Euro-Collins-solution contains nearly 200 mmol/l glucose, while the HTK-solution of Bretschneider contains none. Therefore the influence of glucose on kidney lactate production, on energy reserves (TAN), intrarenal pH and on morphology during the protection of ischemic kidneys was analysed using either Euro-Collins-solution, or modified "Euro-Collins-solution", containing mannitol instead of glucose, or HTK-solution with and without the addition of 5, 10 and 20 mmol/l glucose. Glucose content changed during kidney perfusion with Euro-Collins-solution from about 60 to 800 mumol/gdw. While intrarenal pH decreased from 7.1 to 5.1 in Euro-Collins-kidneys during 420 min of ischemia at 25 degrees C, pH decreased to 6.7 with the modified, mannitol containing "Euro-Collins-solution". In HTK-protected kidneys intrarenal pH decreased with increasing glucose addition to the solution. Although Total Adenine Nucleotides are highest at the end of ischemia with Euro-Collins-solution, structural protection after the same ischemic stress was best in HTK-protected kidneys without glucose addition. We conclude that glucose stimulated lactate production, reduced interstitial pH in the kidney even in combination with a highly buffered solution and that it might cause greater membrane permeability leading to a structural deterioration. Mannitol seemed more appropriate than glucose in this respect, although other substances, which provide energy substrate and prevent structural damage, may exist.
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PMID:Effects of glucose in protected ischemic kidneys. 311 45

To assess the warm ischemia time of kidneys with obscure donor histories we attempted to develop an index for the duration of ischemia by analysis of adenine nucleotides and their degradation products in cortical biopsies of canine kidneys. Two biopsy harvesting techniques were compared. The use of a laboratory technique (dentist's drill) resulted in higher concentrations of adenosine triphosphate (ATP) in normoxic tissue specimens as compared with a clinical method of harvesting biopsies (wedge biopsy). However the sum of adenine nucleotides (AN) (ATP, adenosine diphosphate [ADP], and adenosine monophosphate [AMP]) was not significantly different in both groups (P less than 0.05). Therefore, wedge biopsies were used to study the degradation of AN following 0, 30, 60, 90, and 120 min of ischemia. Adenine nucleotides and their degradation products were assayed by high-performance liquid chromatography. Concentrations of individual adenine nucleotides did not show a consistent correlation with warm ischemia time. However, as the sum of the AN and the sum of their degradation products (DP) decreased and increased, respectively, the balance between these metabolites offered a good correlation with duration of warm ischemia. The ratio of DP to AN was significantly different at each interval (P less than 0.05). To study the influence of temperature on the degradation process, ischemia was induced at 37 degrees C and 32 degrees C. Lowering of the temperature reduced the catabolic rate of the AN. The ratio of DP to AN was significantly different from corresponding values at 37 degrees C. In biopsies of nonischemic human donor kidneys, concentrations of adenine nucleotides and their degradation products were measured. Biopsies weighing less than 0.01% of total renal mass were large enough to meet analytical demands. The ratio of DP to AN in human kidney biopsies was in the same range as in the corresponding dog kidney biopsies. These findings demonstrate that the ratio of DP to AN, as determined from concentrations of purine metabolites in canine cortical wedge biopsies, is a sensitive and potentially useful index of warm ischemia time.
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PMID:Determination of warm ischemia time at donor nephrectomy. 327 44

The relation between adenine nucleotide liver concentrations and the viability of liver allografts after cold preservation and warm ischemia was studied. A rat model was used with storage times defined in terms of allograft viability. Livers were excised and stored for 4 hr at 4 degrees C or 1 hr at 37 degrees C (viable if transplanted) or for 8 hr at 4 degrees C or 2 hr at 37 degrees C (not viable if transplanted) in a solution containing 0.9% NaCl and 2 mM CaCl2. Adenine nucleotide, malondialdehyde, and glutathione concentrations were measured in liver biopsies at the end of the storage periods and in control livers. During cold preservation, ATP concentrations decline, but degradation is largely halted at AMP, and this is independent of the length of storage or viability of the allograft. Graft failure is not due to lack of availability of intramitochondrial substrate (AMP) for rephosphorylation to adenosine triphosphate (ATP), nor is it likely that provision of such substrate will be helpful. On the other hand, with warm ischemia, degradation to inosine, hypoxanthine and xanthine occurs and nonviable livers develop higher levels of xanthine than viable ones; in fact, xanthine concentrations provide 100% discrimination between viable and nonviable warm preserved livers. Malondialdehyde concentrations were also significantly greater in the warm preserved nonviable livers, indicating that some lipid peroxidation may occur even before reperfusion of allografts. Glutathione concentrations were similar in all experimental groups.
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PMID:Adenine nucleotide tissue concentrations and liver allograft viability after cold preservation and warm ischemia. 328 45

Effects of S-adenosyl-L-methionine (SAM) on the improvement of cerebral energy metabolism and microcirculation were examined in postischemic rat brain. Male Wistar rats, whose vertebral arteries were electrically cauterized last day, were subjected to forebrain ischemia by temporary clipping of both common carotid arteries. After 60 min of ischemic insult, they were intravenously administered with SAM at doses of 30 or 100 mg/kg; this was followed by recirculation for 60 min. To determine cerebral concentrations of energy metabolites, the brain was frozen in situ. Adenine nucleotides (ATP, ADP, AMP) were assayed by anion-exchange HPLC system, and other metabolites (PCr, glucose, lactate, pyruvate) were analyzed by enzymatic fluorometry. In order to estimate regional cerebral blood flow (rCBF) and glucose utilization, double-tracer autoradiography was undertaken using 14C-iodoantipyrine (14C-IAP) and 18F-fluorodeoxyglucose (18F-FDG). In animals without SAM treatment (60-60 group), energy metabolites did not recover and neither CBF nor glucose uptake restored during 60 min of recirculation. In contrast, in SAM-treated animals (60-60 SAM group), values of the energy metabolites improved significantly and both CBF and glucose uptake recovered, though incompletely. These results indicate that SAM is able to improve postischemic cerebral microcirculation and energy metabolism. For mechanisms of the effects, it is suggested to the enhancement of erythrocyte deformability by phospholipid methylation, the stabilization of mitochondria, and the normalization of injured metabolic reactions. Therefore, we conclude that SAM is able to be effective clinically as a drug treated for the acute phase of cerebrovascular diseases.
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PMID:[Effects of S-adenosyl-L-methionine on the cerebral energy metabolism and microcirculation in the rats subjected to transient forebrain ischemia]. 344 52

The energy and redox states of placentas in newly anesthetized or sacrificed guinea pigs and sheep were compared with that of human placentas immediately after delivery. Subsequently the effect of ischemia was observed in both human and animal placentas. The influence of perfusion, using a fluid containing oxygenated red cells (adult human) was studied in the human placenta. Adenine nucleotide precursors were added to the perfusion fluid in an attempt to improve the energy and redox states and the mixed protein synthetic rate of the tissue. The ATP and lactate concentrations in guinea pig placental tissue taken immediately after nembutal anesthesia were 1.16 and 3.59 mmol kg-1 wet weight respectively. One minute's ischemia caused a fall in ATP to 0.7 and a rise in lactate to 6.5 mmol kg-1. The concentration of ATP in human placental tissue, 30 secs to 3 minutes after delivery of the organ, was 0.52 and of lactate 4.8 mmol kg-1 wet weight, suggesting that some biochemical deterioration had already occurred. A further fall in ATP to 0.21 and rise in lactate to 6.4 mmol kg-1 wet weight took place during 20 mins of ischemia; thereafter the ATP level remained constant while the lactate continued to rise to 11 mmol kg-1 wet weight by 1 1/2 hours. The initial energy charge was similar in both animal and human placentas, 0.8-0.9, and was only reduced during prolonged hypoxia at 37 degrees C. Since the AMP did not rise to the same extent as in other tissues, it is suggested that the Atkinson equation used in the calculation of energy charge may not be applicable to the placenta, and that the most sensitive indication of deterioration in energy status is the swift fall in ATP concentration. Rapid establishment of maternal intervillous perfusion of an isolated lobule of the human placenta using ixygenated RBCS in the perfusion fluid, enabled the ATP and lactate levels to be maintained near to 'in vivo' values during one hour, with a protein turnover rate of 40% day-1, two thirds of that observed 'in vivo' in the sheep. The addition of 1.0-50 microM adenosine to the perfusion fluid improved the energy state of the tissue, but not its redox state nor protein synthetic rate. 1.5 microM inosine in the perfusion medium did not alter the energy state but caused a marked reduction in lactate production.
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PMID:Observations on the energy and redox state and protein synthetic rate in animal and human placentas. 358 80

Carbohydrates are an important source of energy for the immature myocardium. Since dipyridamole (DPY) has been reported to facilitate glucose uptake in the adult heart, the present study was designed to determine whether DPY could enhance glucose uptake in the nonischemic newborn. In anesthetized, open chest lambs (n = 8), circumflex coronary blood flow (CBF), myocardial adenine nucleotide content, and aortic and coronary sinus concentrations of glucose, lactate, and pyruvate were determined before and after a single dose of DPY (0.2 mg/kg, intravenously). Adenine nucleotides were measured by HPLC. The consumption of substrates was calculated as the product of CBF and the aortic-coronary sinus difference in substrate concentration. Coronary blood flow averaged 114 +/- 6 ml/min/100 g in the untreated animals, and increased by 44% following treatment with dipyridamole (P less than 0.01). This was associated with a 32% decrease in coronary vascular resistance (P less than 0.01). Glucose uptake increased from 9 to 46 mumoles/min/100 g (P less than 0.01) following dipyridamole treatment; lactate uptake decreased by 97% (P less than 0.01). There was a net release of pyruvate from the neonatal hearts; this increased from 18 to 25 mumole/min/100 g (P less than 0.05). Myocardial ATP content averaged 4.08 mumole/g wet wt in the untreated animals, and increased 11% to 4.52 following DPY (P less than 0.01). The agent had no effect on the myocardial tissue levels of AMP or ADP. These data indicate that DPY is a coronary vasodilator in the newborn lamb and augments both glucose uptake and myocardial ATP content. These metabolic effects provide a rationale for further studies during periods of hypoxia and ischemia.
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PMID:Effects of dipyridamole on myocardial glucose uptake in the newborn lamb. 374 88

Recovery of adenosine triphosphate after myocardial ischemia is limited by the slow adenine nucleotide de novo synthesis and the availability of precursors of the nucleotide salvage pathways. We determined the adenine nucleotide de novo synthesis in the dog by infusion of [14C]glycine and the acceleration of adenine nucleotide built up by intracoronary infusion of ribose together with [14C]glycine or radiolabeled 5-amino-4-imidazolcarboxamide riboside or adenosine in the same animal model and with the same dosage of substrates (9 mmol) in postischemic and nonischemic myocardial tissue. After 45 minutes of occlusion of a side branch of the left coronary artery, the ischemic area was reperfused for 3 hours, and needle biopsies were taken for biochemical analysis. Adenine nucleotide de novo synthesis was found to be very slow (1.5 nmol/g wet weight per hour). The rate was doubled after ischemia. Adenine nucleotide synthesis was accelerated 5-fold by ribose, the basic substrate of the adenine nucleotide de novo synthesis, 9-fold by 5-amino-4-imidazolcarboxamide riboside, an intermediate of the adenine nucleotide de novo synthesis and 90-fold by adenosine, a substrate of the nucleotide salvage pathway. Therefore, only adenosine infusion resulted in a measurable increase of adenosine triphosphate levels after 3 hours of reperfusion, but over a longer time period, ribose or 5-amino-4-imidazol-carboxamide riboside also can be expected to replenish reduced myocardial adenosine triphosphate faster than adenine nucleotide de novo synthesis. Studies with radiolabeled 5-amino-4-imidazol-carboxamide riboside showed significant incorporation of radioactivity into 5-amino-4-imidazol-carboxamide ribose triphosphate which had also risen measurably during 5-amino-4-imidazol-carboxamide ribose infusion, and which is not normally found in heart muscle.
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PMID:Influence of ribose, adenosine, and "AICAR" on the rate of myocardial adenosine triphosphate synthesis during reperfusion after coronary artery occlusion in the dog. 391 4

An important question in energy metabolism of the reperfused, previously ischemic myocardium is whether the return of a normal tissue adenosine triphosphate (ATP) content is a prerequisite for normal rates of oxygen consumption (that is, ATP turnover) and cardiac function. To study this problem, isolated working rat hearts were perfused with bicarbonate saline solution containing glucose (10 mM) at near physiologic work load. After 20 minutes, hearts were made totally ischemic by clamping the aortic and atrial lines for 5, 10 or 20 minutes and then were reperfused for another 10 minutes. Heart rate, aortic pressure, cardiac output and myocardial oxygen consumption were measured continuously. Adenine nucleotides, phosphocreatine, glycogen and the products of glycolysis were determined in freeze-clamped tissue extracts. Functional recovery was assessed by return of aortic pressure and oxygen consumption to preischemic values. Time required for return of function after reperfusion was 90 seconds after 5 minutes and 124 seconds after 10 minutes of ischemia. No recovery was observed after 20 minutes of ischemia. Tissue ATP content decreased significantly at the end of 5 (-38%) and 10 (-56%) minutes of ischemia and did not increase significantly at return of aortic pressure and oxygen consumption to preischemic values. Glycogen stores decreased by more than 50% at the end of 10 minutes of ischemia and did not normalize on recovery. In contrast to ATP or glycogen, the phosphocreatine content decreased to even lower levels at the end of ischemia, but returned to levels higher than the control level after recovery from 5 to 10 minutes of ischemia in association with return of function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Energy metabolism in reperfused heart muscle: metabolic correlates to return of function. 403 1

Postischemic acute renal failure was induced by 1 hr of clamping of the renal vasculature. Adenine nucleotide (ATP, ADP, AMP) and lactate (Lac) levels were measured after 0, 0.25, 1, 6, 24, and 48 hr of reflow to determine the time necessary for recovery to control levels. After 1 hr of ischemia with no reflow, [ATP] was 18% and [Lac] was 10-fold control levels. Control levels were restored after 24 hr of reflow. Variable ischemic times (5, 15, 30, 60, 90, and 120 min) followed by (1) no reflow or (2) 24 hr of reflow were also studied. [ATP] decreased to 25 and 13% of controls after 5 and 120 min of ischemia, respectively, and [Lac] increased to 5- and 13-fold controls after 5 and 120 min. Five to ninety minutes of ischemia followed by 24 hr of reflow resulted in a trend toward restoration of ATP and Lac levels; whereas, 120 min of ischemia followed by 24 hr of reflow resulted in death. The results indicate that: (1) In vivo ischemia results in a drastic and rapid shift in the ATP-ADP-AMP equilibrium; (2) the absolute concentration of ATP is not a reliable criterion of cell viability, but the ability to resynthesize ATP may be determinant in the reversibility of the lesion; (3) 1 hr of ischemia is reversible with respect to restoration of [ATP] and [Lac], but 24 hr of reflow are needed for restoration; and (4) ischemia for 90 min results in a metabolic derangement which is partially reversible in that metabolite levels are partially restored after 24 hr of reflow. However, 90 min of vascular clamping is not functionally reversible since the majority of animals exhibit severe azotemia and do not survive.
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PMID:Metabolic studies of postischemic acute renal failure in the rat. 670 89

A method was developed for tissue preservation and evaluation of the adenine nucleotide metabolism in small samples of myocardium after 45 min of ischaemia. Ischaemia was produced by coronary artery occlusion in anaesthetized cats. Adenine nucleotides and their metabolites were measured by isocratic liquid chromatographic systems which allow quantitative analysis of the nucleotides and their metabolites inosine, hypoxanthine and xanthine in biopsies of 5-20 mg tissue. Regional myocardial blood flow was measured in the tissue surrounding the biopsies by the distribution of 15 micron radiolabelled microspheres. In central ischaemic regions the ATP level was approximately 1 mumol/g wet weight, whereas in normally perfused myocardium the ATP level was approximately 5 mumol/g tissue. In tissue with intermediate flow values, intermediate ATP levels were found. Energy charge, which summarizes all adenine nucleotide concentrations, was reduced from 0.88 to 0.50, and the molar concentrations of inosine, hypoxanthine and xanthine increased in ischaemic tissue. We conclude that this method provides reliable characterization of the local cellular energy status in cat hearts with ischaemic regions.
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PMID:Relationship between myocardial adenine nucleotide catabolism and tissue blood flow rate in experimental ischaemia. 671 18


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