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

Intermittent restoration of coronary flow during ischemia reduced myocardial damage and improved recovery of function. The mechanisms of the protective effects of intermittent perfusion were investigated in isolated rat hearts. Ventricular function was assessed as the product of developed pressure (left ventricular systolic pressure minus end-diastolic pressure) and heart rate. Recovery of function was calculated by division of the product at the end of reperfusion by that before ischemia. After 40 minutes of sustained global ischemia, intracellular Na+ (Nai) increased from 11 to 74 mumol/g dry wt. During 30 minutes of reperfusion, these hearts took up a large amount of 45Ca2+ (10 mumol/g dry wt), recovered only 24% of preischemic function, and had an increased left ventricular end-diastolic pressure (48 mm Hg). When the 40-minute period of ischemia was interrupted at 10-minute intervals by intermittent perfusion (three periods of 3 minutes) with either oxygenated or hypoxemic buffer, Nai increased to only 12 or 17 mumol/g dry wt, and reperfusion resulted in much lower 45Ca2+ uptake (0.5 and 0.5 mumol/g dry wt, respectively). Recovery of function was 100% of the preischemic value. When hypoxemic buffer without glucose was used for intermittent perfusion, Nai increased to 50 mumol/g dry wt, ATP was depleted, and reperfusion resulted in reduced recovery of function (76%) and moderately increased 45Ca2+ uptake (2.1 mumol/g dry wt). The role of Na(+)-K+ pump activity in maintaining low Nai was assessed by removing K+ from oxygenated or hypoxemic buffers used during intermittent perfusion. Under these conditions, Nai rose to 64 or 102 mumol/g dry wt, 45Ca2+ uptake increased to 4.4 or 9.4 mumol/g dry wt, and recovery of function was poor. There was a highly significant correlation between Nai during ischemia and reperfusion Ca2+ overload (r = 0.87) or impaired recovery of function (r = 0.96). These results indicate that prevention of an increase in Nai by maintenance of Na(+)-K+ pump activity is associated with a reduction of Ca2+ overload through Na+/Ca2+ exchange.
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PMID:Intermittent perfusion of ischemic myocardium. Possible mechanisms of protective effects on mechanical function in isolated rat heart. 237

It has been suggested that immature hearts are less well protected by conventional cardioplegic solutions than are adult hearts. In an attempt to develop an improved cardioplegic solution for use in the immature ischemic heart the authors investigated whether the addition of various concentrations of glucose or mannitol to St Thomas' Hospital cardioplegic solution can improve its protective ability. Hearts from immature (three- to five-day-old) rats were perfused as Langendorff preparations with an indwelling left ventricular balloon. Contractile function (left ventricular developed pressure, maximum rate of development of pressure, heart rate, rate-pressure product and coronary flow) was recorded before and after a period of normothermic global ischemia with preischemic infusion (2 mins) of St Thomas' Hospital cardioplegic solution. In preliminary experiments the post ischemic recovery of contractile function was related to the duration of ischemia. With 60, 75, 90 and 120 mins of ischemia the post ischemic recovery of developed pressure was 47.6 +/- 3.9%, 17.4 +/- 5.5%, 15.0 +/- 5.4% and 13.8 +/- 4.8%, respectively, of its preischemic control. Comparable results were obtained with the other indices of cardiac function. The effect on the post ischemic recovery of function and tissue water content of the addition of mannitol or glucose (10, 20, 40, 60 or 80 mmol/L) to the cardioplegic solution was examined after 60 mins of ischemia. The mannitol groups tended to show consistently better recoveries at all concentrations studied but the improvement was small and rarely achieved a degree of statistical significance. In contrast glucose gave a U-shaped dose response profile with a significant deleterious effect at 10, 20 and 40 mmol/L.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protection of the immature myocardium during ischemic arrest: dose dependent effects of glucose and mannitol when added to St Thomas' cardioplegic solution. 251 36

Ischemic injury results in proximal tubule (PT) dysfunction and loss of surface membrane (SM) polarity. Since epithelial vectorial transport requires SM polarity, we set out to determine if correction of renal cortical PT dysfunction following ischemia was dependent on the reestablishment of SM polarity. Acute renal failure was induced using a bilateral 50-min pedicle clamp. Serum creatinine and fractional sodium excretion were maximal on day 1, remained elevated on day 3, and returned toward base line by day 8. PT cellular ultrastructure was normal by day 3. Despite rapid morphological recovery, ischemia resulted in a prolonged defect in glucose reabsorption. The delayed recovery of normal glucose handling closely paralleled the slow normalization of apical membrane lipid polarity. Na+-K+-ATPase polarity was also lost secondary to ischemia as demonstrated cytochemically and biochemically by the redistribution of Na+-K+-ATPase to the apical membrane. The time required to reestablish normal Na+-K+-ATPase polarity (8 days) paralleled the recovery of normal PT Na+ reabsorption (8 days), as assessed by fractional lithium clearances. This finding supports the hypothesis that apical Na+-K+-ATPase is in part responsible for reduced Na+ reabsorption following ischemic injury. In summary, these data suggest that functional recovery of PT glucose and Na+ reabsorption following a reversible ischemic insult requires not only morphological recovery, but also the reestablishment of surface membrane lipid and protein polarity.
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PMID:Epithelial polarity following ischemia: a requirement for normal cell function. 253 79

A 72-hr preservation of canine pancreas by a 2-layer (Euro-Collins'/Perfluorochemical) cold storage method was tested in the canine model of segmental pancreas autotransplantation. The functional recovery of the grafts by this method (group 1) was determined by daily fasting blood glucose concentration and intravenous glucose tolerance test at 2 weeks after autotransplantation and compared with simple cold storage with Euro-Collins' solution (group 2) and control (no preservation) (group 3). Maintenance of normoglycemia for at least 5 days after transplantation was considered a successful preservation. The functional success rates after 72-hr preservation were 100%, 0%, and 100% for groups 1, 2, and 3, respectively. The mean K values of group 1 after 72-hr preservation was 1.78 +/- 0.42 compared with 2.05 +/- 0.32 for group 3 at 2 weeks after transplantation. Biopsies of grafts of group 2 after 72-hr preservation showed remarkable autolytic changes in exocrine and endocrine tissues. In contrast, biopsies of grafts of group 1 after 72-hr preservation showed almost normal architecture in both tissues. In addition, biopsies of 72-hr preserved grafts of group 1 at 4 weeks after after autotransplantation showed almost normal pancreas architecture with minimal fibrotic changes in the exocrine tissue. This study demonstrated the possibility of 72-hr preservation of the pancreas for transplantation.
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PMID:Seventy-two-hour preservation of the canine pancreas by the two-layer (Euro-Collins' solution/perfluorochemical) cold storage method. 233 97

The effect of the carnitine palmitoyltransferase 1 (CPT 1) inhibitor, Etomoxir, on glucose oxidation rates was determined in ischemic hearts reperfused in the presence of fatty acids. Isolated working rat hearts were perfused with 11 mM (14C)-glucose and 1.2 mM palmitate at a 15 cm H2O preload, 80 mm Hg afterload. Hearts were subjected to either 60 min aerobic perfusion, or 15 min work followed by 25 min global ischemia then 60 min of aerobic reperfusion. Steady state glucose oxidation rates in reperfused ischemic hearts were not significantly different from non-ischemic hearts. If 10(-9) M Etomoxir was added immediately prior to reperfusion no significant change in glucose oxidation occurred. Addition of 10(-8) M and 10(-6) M Etomoxir, however, significantly increased glucose oxidation. Etomoxir also significantly improved recovery of mechanical function at a concentration of 10(-8) M or greater. As we previously reported, no significant improvement of function was seen when 10(-9) M Etomoxir was added to the perfusate (Lopaschuk GD et al., Circ Res 63: 1036-1043, 1988). Long chain acylcarnitine levels were significantly reduced in the presence of both 10(-9) M and 10(-8) M Etomoxir. These data demonstrate that the beneficial effect of Etomoxir on reperfusion recovery of ischemic hearts is not due to a lowering of long chain acylcarnitine levels. Etomoxir may improve recovery of function by overcoming fatty acid inhibition of glucose oxidation.
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PMID:Glucose oxidation is stimulated in reperfused ischemic hearts with the carnitine palmitoyltransferase 1 inhibitor, Etomoxir. 277 37

The assessment of myocardial viability following interventions aiming at restitution of antegrade blood flow by PTCA and thrombolysis has become one of the most important goals to judge interventional success. Conventional markers as ECG, the extent of the regional wall motion abnormality and enzymes have conceptual limitations. We had shown previously that increased residual glucose metabolism in reperfused myocardium can be assessed by F-18 2-deoxy-glucose (FDG) and positron emission tomography (PET) and will predict functional recovery in reperfused myocardium. The present study introduces a novel concept for the evaluation of myocardial viability by the application of multiple tracer techniques and investigates tracer behaviour in relation to blood flow, regional wall motion, coronary anatomy and histology. The experimental data compare segmental uptake of F-18 FDG with the current most clinically important perfusion marker Tl-201 and Tc-99m (Sn) pyrophosphate (Tc-99mPPi) as a marker of myocardial necrosis in a canine model following a 3 hour intracoronary balloon occlusion and subsequent reperfusion and therefore in a clinically attributable occlusion and reperfusion scenario. Myocardial blood flow was assessed by microspheres, regional fractional tracer retention fractions were evaluated from tissue tracer concentrations, the arterial input function and quantitative blood flow measurements. The extent of ischemic damage was evaluated by TTC post mortem staining, histology, and histochemistry. Additional studies to illucidate the mechanism of increased glucose utilization were done by analysis of other substrates as lactate. The result within the area at risk was assessed in relation to the metabolic behaviour. PET methods were validated in the same dog model as a quantitative biochemical in-vivo assay and imaging procedure and demonstrate the ability of this noninvasive techniques to measure blood flow and myocardial metabolism, especially exogenous glucose utilization. Time dependent and repetitive PET studies may indicate a delayed recovery of myocardial metabolism following an ischemic event with a pattern of a blood flow-metabolism mismatch, characteristic for persistent viability. Metabolic data by imaging correlate with reference techniques as arterio-venous sampling and post mortem histochemical staining method using TTC, PAS, and glycogen techniques. The clinical part applies the proposed tracer concept to patients with acute myocardial infarction and following reperfusion interventions as well using conventional markers and again positron markers. These studies indicate possibilities to assess myocardial viability by the same simultaneou
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PMID:[Relation between myocardial perfusion, myocardial necrosis and residual glucose metabolism as a vitality parameter in the post-ischemic myocardium following coronary reperfusion]. 278 48

In a prospective study of 86 patients with acute stroke, blood glucose and HbA1 were estimated within 72 h of onset. The prevalence of previously diagnosed diabetes mellitus was 8% whereas 28% could be assumed to have had unrecognized hyperglycaemia preceeding the acute event as identified by a stable HbA1 raised more than two SD above the mean reference value. Complete functional recovery of the limbs within 4 weeks of the stroke was confined to those patients with a normal admission blood glucose. None of the patients with a raised admission blood glucose regained full functional recovery within 4 weeks. Cumulative mortality at 4 weeks was significantly raised in patients with an elevated blood glucose value irrespective of their HbA1 values (p less than 0.05). The prevalence of unrecognized hyperglycaemia as a risk factor for acute stroke is greater than previously reported in the UK and admission blood glucose concentration is of greatest importance in predicting early mortality and morbidity.
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PMID:The prognostic value of stress hyperglycaemia and previously unrecognized diabetes in acute stroke. 295 26

Fatty acids are known to increase the severity of injury during acute myocardial ischemia. In this study, we determined the effects of a carnitine palmitoyltransferase I inhibitor, ethyl 2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate (Etomoxir) on reperfusion recovery of fatty acid perfused hearts. Following a 25-minute period of global ischemia, isolated working hearts reperfused with 1.2 mM palmitate, 11 mM glucose exhibited depressed function compared to hearts perfused with 11 mM glucose alone. A low dose of Etomoxir (10(-9) M) decreased long chain acylcarnitine and long chain acyl-coenzyme A (CoA) levels but did not prevent depressed function. In contrast, a high dose of Etomoxir (10(-6) M) prevented the palmitate-induced depression of function but did not decrease myocardial long chain acylcarnitine or long chain acyl-CoA levels. At this high dose of Etomoxir, oxygen consumption per unit work was decreased during reperfusion recovery, and ATP and creatine-phosphate levels were significantly higher after reperfusion. In aerobic hearts not subjected to ischemia, Etomoxir (10(-6) M) increased glucose oxidation both in the presence and absence of palmitate, while 10(-9) M Etomoxir had no effect. In these aerobic hearts, only the low dose of Etomoxir decreased long chain acylcarnitine and long chain acyl-CoA levels. These data demonstrate that Etomoxir (10(-6) M) increases functional recovery of fatty acid perfused ischemic hearts. This protection is unrelated to changes in levels of long chain acylcarnitines but may be due to increased glucose use by the reperfused heart, resulting in decreased oxygen consumption per unit work.
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PMID:Etomoxir, a carnitine palmitoyltransferase I inhibitor, protects hearts from fatty acid-induced ischemic injury independent of changes in long chain acylcarnitine. 319 71

The myocardial oxidation of fatty acids and glucose, the predominant substrates for aerobic metabolism, is impaired after cardioplegic arrest for coronary revascularization. Because lactate can be readily metabolized to pyruvate, it may be the preferred substrate for aerobic metabolism after cardioplegic arrest when arterial concentrations are elevated. Nineteen patients undergoing elective coronary revascularization with blood cardioplegia were randomized to receive LOW (nine patients, no exogenous lactate) or HIGH (10 patients, a perioperative infusion of Ringer's lactate) arterial lactate concentrations. Coronary sinus catheterization and lactate labeled with carbon 14 permitted calculation of myocardial oxygen consumption and lactate oxidation which were significantly increased during reperfusion in the group with HIGH arterial lactate concentrations. Atrial pacing at 110 beats/min on cardiopulmonary bypass resulted in myocardial lactate production (suggesting ischemic anaerobic metabolism) in the LOW lactate group, but atrial pacing increased lactate consumption and oxidation in the HIGH lactate group (suggesting increased aerobic metabolism). Systolic function (the relation between end-systolic pressure and volume) as assessed by nuclear ventriculography 3 hours postoperatively was significantly better (p less than 0.05 by analysis of covariance) in the HIGH lactate group. Postoperative myocardial creatine kinase release was significantly lower in the HIGH lactate group, which suggested less perioperative ischemic injury. Lactate was the preferred substrate for myocardial oxidative metabolism after cardioplegic arrest, and the higher arterial lactate concentrations improved myocardial metabolic and functional recovery and reduced perioperative ischemic injury.
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PMID:Improving myocardial metabolic and functional recovery after cardioplegic arrest. 328 60

Previous studies from this laboratory demonstrated that the use of an oxygenated cardioplegic solution in the hypothermic arrested rat heart resulted in improved preservation of high-energy phosphate stores (adenosine triphosphate and creatine phosphate), mechanical recovery during reperfusion, and preservation of myocardial ultrastructure. In the current study the effect of cardioplegic solutions oxygenated with 30%, 60%, and 95% oxygen was evaluated in the isolated rat heart with reference to the maintenance of adenosine triphosphate, creatine phosphate, oxygen consumption, functional recovery, and mitochondrial oxidative phosphorylation in vitro. Results indicate that the hearts receiving cardioplegic solutions supplemented with 95% oxygen and 5% carbon dioxide maintained adenosine triphosphate and creatine phosphate at control values for at least 5 hours. The oxygen consumption during elective cardiac arrest, mechanical performance during reperfusion, and in vitro mitochondrial oxygen uptake and phosphorylation rate were highest in the hearts receiving cardioplegic solutions supplemented with 95% oxygen when compared to solutions with 30% and 60% oxygen. Addition of glucose and insulin to the cardioplegic solution (95% oxygen) increased the adenosine triphosphate levels but failed to improve function after reperfusion. Although myocardial adenosine triphosphate and creatine phosphate were well preserved by the oxygenated cardioplegic solution, there was a discrepancy between the adenosine triphosphate levels at the end of the arrest period, which represents the potential for mechanical function, and the actual function of the hearts after 5 hours.
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PMID:Oxygen requirements of the isolated rat heart during hypothermic cardioplegia. Effect of oxygenation on metabolic and functional recovery after five hours of arrest. 281 24


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