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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although few surgeons dispute the benefits of high-potassium crystalloid cardioplegia, objective comparison of the efficacy of various formulations is difficult in clinical practice. We compared four commonly used cardioplegic solutions in the isolated rat heart (N = 6 for each solution) subjected to 180 minutes of hypothermic (20 degrees C) ischemic arrest with multidose cardioplegia (3 minutes every half-hour). The clinical solutions studied were St. Thomas' Hospital solution, Tyers' solution, lactated Ringer's solution with added potassium, and a balanced saline solution with glucose and potassium. Postischemic recovery of function was expressed as a percentage of preischemic control values. Release of creatine kinase during reperfusion was measured as an additional index of protection. St. Thomas' Hospital solution provided almost complete recovery of all indexes of cardiac function following ischemia including 88.1 +/- 1.6% recovery of aortic flow, compared with poor recovery for the Tyers', lactated Ringer's, and balanced saline solutions (20.6 +/- 6.5%, 12.5 +/- 6.4%, and 9.6 +/- 4.2%, respectively) (p less than 0.001). Spontaneous defibrillation was rapid (less than 1 minute) and complete (100%) in all hearts in the St. Thomas' Hospital solution group, but much less satisfactory with the other formulations. Finally, St. Thomas' Hospital solution had a low postischemic level of creatine kinase leakage, contrasting with significantly higher enzyme release in the other solutions tested (p less than 0.001). Although differences in composition are subtle, all potassium crystalloid cardioplegic solutions are not alike in the myocardial protection they provide. Comparative studies under controlled conditions are important to define which formulation is superior for clinical application.
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PMID:Comparison of the protective properties of four clinical crystalloid cardioplegic solutions in the rat heart. 647 50

The metabolic responses of rat hypoglossal nuclei to unilateral section of the 12th cranial nerve have been studied. Changes in the rates of protein synthesis and glucose utilization in the regenerating nucleus were determined with two quantitative autoradiographic techniques, the L-[1-14C]leucine method and the [14C] deoxyglucose method, respectively. The results show that both of these processes increase in the nucleus ipsilateral to the sectioned nerve and are unaffected in the contralateral nucleus as compared with sham-operated animals. The time courses of these metabolic changes have been compared with that of the return of functional innervation of the tongue. An increase in glucose utilization is first detected 24 hr postaxotomy. It is maximal between 1 and 3 days postaxotomy and constitutes an 84% increase over the rate in the contralateral control nucleus. The increase in protein synthesis is of smaller magnitude than that of glucose utilization. It is maximal at 48 hr after axotomy and constitutes a 25% increase over the rate in the contralateral nucleus. The increases in both of these metabolic processes persist even after functional recovery of the tongue at 21 days postaxotomy. Protein synthesis and glucose utilization return to normal levels between 24 and 35 days postaxotomy. Although the time courses of the changes in protein synthesis and glucose utilization are similar, the magnitude of the increase in glucose utilization is too large to be accounted for by the energy requirements of the relatively small increase in protein synthesis and probably reflects other processes as well, including altered function of the soma-dendritic membrane of regenerating neurons.
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PMID:Stimulation of protein synthesis and glucose utilization in the hypoglossal nucleus induced by axotomy. 649 19

To determine whether adding blood to a cardioplegic solution affects myocardial preservation, a randomized prospective study was carried out in 60 patients undergoing coronary revascularization to compare the effects of crystalloid potassium cardioplegics (group C) and potassium cardioplegic solutions to which blood has been added (group B) on markers of myocardial metabolism (lactate, inorganic phosphate, base deficit release, glucose and lactate uptake, oxygen extraction), myocardial damage (creatine kinase [CK]-MB levels), and cardiac performance (cardiac index and left atrial pressure). The solution with added blood had a significantly (p less than .05) greater oxygen content, a lower pH, and higher concentrations of potassium, calcium, sodium, and glucose. In group B patients there was a suggestion (p less than .06) of greater uptake of oxygen during the beginning of the initial cardioplegic infusion. During reperfusion there was no evidence of differential release of the metabolites of anaerobiosis and myocardial oxygen extraction and glucose and lactate uptake were similarly depressed in both groups. Likewise, CK-MB release after bypass was the same in both groups. Prompt, adequate functional recovery of cardiac index and left atrial pressure was observed in both groups. It was concluded that although there may be more oxygen available from the blood-containing solution during early infusion, there is no evidence that under the conditions of this investigation adding blood to cardioplegic solution improves myocardial preservation.
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PMID:A randomized comparison of crystalloid and blood-containing cardioplegic solutions in 60 patients. 660 19

The isolated working rat heart model of ischemic arrest was used to determine if the addition of carbohydrate substrate to our cardioplegic solution enhanced metabolic and functional myocardial protection. A single-dose cardioplegia technique, as used in earlier studies that showed glucose to have a harmful effect, and a multidose technique similar to that used clinically were studied and compared. Because recent data suggest that fructose-1,6-diphosphate(FDP) may have a protective effect with ischemia, this substrate was also tested and compared to glucose and fructose. In this model, single-dose cardioplegia resulted in poor protection from ischemic injury in all study groups. There was marked improvement in myocardial protection with multidose cardioplegia, and further substantial protection of myocardial function, high-energy phosphate levels, and glycogen stores when carbohydrate substrate was added to the arrest solution. The solution with a higher concentration of glucose (0.5%) provided the best overall metabolic and functional recovery and was clearly superior to fructose and FDP, both of which had about the same protective effect. Improved protection with carbohydrate substrate was accompanied by evidence of substantial increase in glycolytic flux, supporting the idea that increased anaerobic glycolysis can help protect the ischemic myocardium when intermittent reinfusion of cardioplegic solution is done.
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PMID:Metabolic and functional effects of carbohydrate substrate with single-dose and multiple-dose potassium cardioplegia. 661 70

Spontaneous recovery of function occurs in the syndrome of hemisensory neglect in monkeys. We produced this syndrome in 13 macaques by unilateral operative resection of the frontal polysensory association cortex. Using standardized behavioral measures, we documented severe acute neglect and followed the course of its improvement. Using the 2-deoxy[14C]glucose autoradiographic method, we studied animals in the acute phase of neglect and found decrements in local glucose utilization in subcortical structures, but not in cortical regions with known frontal connections. After spontaneous behavioral recovery, mild local glucose utilization decrements remained, but only in nucleus medialis dorsalis of the thalamus. The findings suggest that acute behavioral symptoms are based on widespread depression of neuronal activity in uninjured structures with synaptic relations to damaged cortex, and that return of neuronal activity in those structures is accompanied by restitution of behavioral function.
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PMID:Recovery from unilateral neglect. 688 82

Past studies have not established the optimal myocardial temperature range for hyperkalemic arrest but have generated controversy regarding the safety of exposing the myocardium to more profound levels of hypothermia. We therefore used the isolated working rat heart model of ischemic arrest to study the metabolic and functional effects of cardioplegia at the full range of temperatures pertinent clinically. Experimental conditions were designed to reliably control and maintain myocardial temperature during the 60 minute arrest period. We found that nearly full recovery of function occurred when hearts were arrested at or below 16 degrees C. High-energy phosphate levels measured immediately after arrest were better maintained at 4 degrees and 8 degrees C, despite evidence of decreased anaerobic glycolysis. When measured after the recovery period, high-energy phosphate levels returned to somewhat less than control levels in all groups arrested at or below 24 degrees C. Myocardial glucose utilization was best preserved in hearts arrested at or below 12 degrees C. We found no evidence that greater myocardial edema resulted from arrest at colder temperatures. Severe and permanent damage was observed when hearts were arrested at or above 28 degrees C. In this model, therefore, the best overall metabolic and functional protection occurred when hearts were maintained at 12 degrees C or below potassium-induced cardioplegia. Our results support the idea that cold injury to the heart does not occur and that colder temperatures provide better protection from ischemic myocardial injury.
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PMID:Effect of temperature during potassium arrest on myocardial metabolism and function. 709 10

The detrimental effect of exogenous lactate during ischaemia on post-ischaemic contractile function may be mediated either by a lactate-induced intracellular H+ load or by an increase in intracellular lactate. To distinguish between these two mechanisms, isolated rat hearts were perfused with lactate or pyruvate during low flow ischaemia, the rationale being that both would decrease H+ efflux via lactate/H+ cotransport and lead to decreased pH, but only exogenous lactate would decrease lactate efflux and lead to increased intracellular lactate. 31P NMR spectra were acquired sequentially while hearts were subjected to 32 min low flow (0.5 ml/min) ischaemia and 32 min reperfusion. During ischaemia, hearts were perfused with Krebs-Henseleit buffer containing 11 mM glucose (controls) or 11 mM glucose plus either 10 mM lactate or 10 mM pyruvate. Reperfusion of all hearts was with buffer containing only glucose. Intracellular volume, estimated to be 0.52 ml/heart using 31P NMR spectroscopy with phosphonate space markers, did not change under any of the ischaemic conditions during the protocol. Control and pyruvate hearts recovered approximately 85% of pre-ischaemic contractile function, but there was no recovery of function in lactate hearts. This lack of recovery correlated with a 57% loss of ATP during ischaemia, which was significantly greater (P < 0.001) than the 41% loss of ATP in control and pyruvate-perfused hearts. End-ischaemic intracellular pH was 6.60 in both lactate-perfused and control hearts, but significantly lower (P < 0.05) at pH 6.43 in pyruvate-perfused hearts. Both exogenous pyruvate and lactate should have decreased H+ efflux, however the higher pH in the lactate-perfused hearts could be explained by a 60% inhibition of glycolysis, determined by measurement of myocardial lactate production. Thus, the intracellular pH during ischaemia does not necessarily predict the extent of myocardial injury. We propose that lactate-induced damage is a consequence of increased intracellular lactate leading to inhibition of glycolysis, presumably via an increased NADH/NAD ratio. This study highlights the important role of glycolysis in the ischaemic rat heart.
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PMID:Is lactate-induced myocardial ischaemic injury mediated by decreased pH or increased intracellular lactate? 747 83

Previous studies have shown that exogenous lactate impairs mechanical function of reperfused ischaemic hearts, while pyruvate improves post-ischaemic recovery. The aim of this study was to investigate whether the diverging influence of exogenous lactate and pyruvate on functional recovery can be explained by an effect of the exogenous substrates on endogenous protecting mechanisms against oxygen-derived free radicals. Isolated working rat hearts were perfused by a Krebs-Henseleit bicarbonate buffer containing glucose (5 mM) as basal substrate and either lactate (5 mM) or pyruvate (5 mM) as cosubstrate. In hearts perfused with glucose as sole substrate the activity of glutathione reductase was decreased by 32% during 30 min of ischaemia (p < 0.10 versus control value), while the activity of superoxide dismutase and catalase was reduced by 27 and 35%, respectively, during 5 min of reperfusion (p < 0.10 versus control value). The GSH level in the glucose group was reduced by 29% following 30 min of ischaemia and 35 min of reperfusion (p < 0.10). In lactate- and pyruvateperfused hearts there were no significant decreases of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activity during 30 min of ischaemia, 5 min of reperfusion or 35 min of reperfusion. In pyruvate-perfused hearts the glutathione peroxidase activity was even increased by 43% during 30 min of ischaemia (p < 0.05). Glutathione levels (reduced and oxidized) did not markedly change in the lactate and pyruvate groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The influence of lactate, pyruvate and glucose as exogenous substrates on free radical defense mechanisms in isolated rat hearts during ischaemia and reperfusion. 756 44

During induced ischemia for cardiac surgery, myocardial stunning occurs and aerobic metabolism of glucose, fatty acids, and lactate is altered. Following reperfusion, stunned myocardium uses oxygen and substrate inefficiently, leading to poor functional recovery. However, amino acids may be used as anaplerotic metabolic substrates during and after ischemia, utilizing transamination of amino acids to form high-energy phosphates via the tricarboxylic acid cycle. We investigated if loading hearts with a physiologic spectrum of amino acids prior to ischemia could increase postischemic myocardial recovery. Isolated perfused rabbit hearts were subjected to 120 min of 34 degrees C cardioplegic ischemia. Hearts received cardioplegia alone as controls or were loaded with a 0.05, 0.1, 0.5, 1, 2, or 5% amino acid perfusion prior to cardioplegic ischemia. Following reperfusion, functional recovery revealed that hearts perfused with 0.05 and 0.1% amino acids had improved contractility and compliance vs untreated controls. To determine if the mechanism of amino acid loading in improving postischemic function was enhancement of high-energy phosphate resynthesis, nucleotides and nucleosides were measured. While all preischemic values were equivalent, amino-acid-loaded hearts had significantly greater high energy nucleotides at end ischemia and after reperfusion. These data demonstrate that metabolism, as well as function, is improved with amino acid loading prior to ischemia, which allowed for better internal reparative work during ischemia and external contractile work after ischemia. This strategy may have application in cardiac surgery.
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PMID:The mechanism of amino acid loading in improving postischemic myocardial recovery. 763 Jan 24

Ischemic contracture may be avoided by the provision of glucose under low flow conditions (Owen et al., 1990). However, accumulation of harmful metabolic end products may inhibit glycolytic flux and lessen the benefit of glucose. We assessed whether during increasingly severe flow restriction, provision of glucose might be harmful rather than beneficial, using the Langendorff perfused rat heart. Ischemic contracture (resting tension expressed as percent of preischemic developed pressure) was measured via a left ventricular balloon. Reductions in flow to 0, 0.015, 0.03, 0.06, 0.1, 0.2 or 0.4 ml/min/g wet wt over 60 min were tested. At zero flow, peak contracture was 61.4 +/- 3.5% (+/- S.E.) but fell to 15.6 +/- 6.3% with 0.4 ml/min/g wet wt (P < 0.05) in the presence of 11 mmol/l glucose. Time-to-onset of contracture was significantly delayed by the higher coronary flows. At coronary flows down to zero, the effect of glucose was inconstant or absent, but not harmful. With the residual flow at 0.2 ml/min/g wet wt, a dose response to glucose in ischemia was elicited, using concentrations of 0, 2.5, 5.5, 11 or 22 mmol/l. Maximum protection against ischemic contracture was found with 11 mmol/l glucose. However, once contracture occurred, functional recovery was severely impaired in all cases. Reducing glycogen prior to low flow ischemia (0.2 ml/min/g wet wt) with 11 mmol/l glucose increased peak contracture, and reduced the time-to-onset of contracture. Increased preischemic glycogen had little effect on contracture. Glycolytic flux fell in proportion to the coronary flow. However, there was an increased glucose extraction at lower flows of 0.1 and 0.2 ml/min/g wet wt, suggesting that it is the rate of delivery (i.e. coronary flow) which is the rate limiting step rather than enzyme inhibition by accumulated metabolites. If flow were further reduced, metabolite accumulation would become more important, such that with no flow, this would be the determinant of glycolytic flux rate. In our model, the two requirements for optimal protection from ischemia were (i) provision of glucose (11 mmol/l was optimal) and (ii) an adequate coronary flow to deliver the glucose and remove end product inhibition (greater than 0.06 ml/min/g wet wt).
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PMID:Coronary flow and glucose delivery as determinants of contracture in the ischemic myocardium. 776 Mar 88


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