Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic and functional recovery following 60 minutes of low flow (0.1 ml/min) ischemia were compared in rabbit hearts perfused with normal sodium and potassium, low sodium (120 mM NaCl replaced by 120 mM LiCl), or zero potassium perfusate during ischemia. During the control, pre-ischemic, and reperfusion periods, all hearts were perfused identically with normal sodium and potassium. 31P NMR was used to monitor intracellular pH (pHi), ATP, and phosphocreatine (PGr). Developed pressure, end diastolic pressure, pHi, and the integrated areas of ATP and PCr were equivalent in the three groups in the pre-ischemic period. The fall in pHi, PCr, ATP, and developed pressure and the rise in end diastolic pressure during 60 min ischemia also did not differ among the three groups. In contrast to the lack of an effect of perfusate sodium and potassium on the decline in parameters of metabolism and function during ischemia, there was a marked difference in the recovery of these indices during reperfusion. Hearts perfused with low sodium during ischemia exhibited the best recovery (expressed as percent of control) of developed pressure (95 +/- 4%), PCr (106 +/- 6%), and ATP (51 +/- 2%) and the smallest rise in end diastolic pressure (229 +/- 50%); hearts perfused with normal sodium and potassium during ischemia had intermediate recovery values for developed pressure (53 +/- 10%), PCr (78 +/- 9%), ATP (45 +/- 4%) and end diastolic pressure (487 +/- 73%) and the hearts perfused with zero potassium solution during ischemia exhibited the poorest recovery of developed pressure (23 +/- 6%), PCr (49 +/- 6%), ATP (39 +/- 5%) and end diastolic pressure (968 +/- 185%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Perfusate sodium during ischemia modifies post-ischemic functional and metabolic recovery in the rabbit heart. 649 72

Previous studies from this laboratory utilized mass spectrometry to measure myocardial oxygen (PO2) and carbon dioxide (PCO2) tensions in isolated feline hearts subjected to periods of global ischemia and reperfusion. Myocardial carbon dioxide tension was found to increase during ischemia, and its rate of increase was found to correlate inversely with subsequent recovery of myocardial function following reflow. The present study utilized phosphorus-31 nuclear magnetic resonance (NMR) to assess whether the severity of intracellular acidosis or the depletion of high energy phosphate stores would show a similar correlation with recovery of function. Hyperkalemic cardioplegia employed as a myocardial preservation technqiue in combination with hypothermia was compared with hypothermia alone as the control intervention. The experimental results demonstrated that intracellular pH fell to 6.09 +/- 0.13 with hypothermia alone and to 6.31 +/- 0.09 with cardioplegia plus hypothermia. Furthermore, myocardial ATP content fell to 22% +/- 2% of control with hypothermia alone, while falling to 36% +/- 4% of control with the combined therapy. Recovery of myocardial performance was found to correlate inversely with the severity of intracellular acidosis and depletion of ATP during ischemia. In contrast, no relationship was observed between preservation of phosphoryl-creatinine levels either during ischemia or after reflow and recovery of ventricular function. These results suggest that, similar to mass spectrometry, which allows monitoring of myocardial PCO2, 31P NMR permits the on-line monitoring of intracellular pH as well as high energy phosphate compounds, and thereby provides useful metabolic indices of the severity of ischemia. Since tight coupling was found between changes in these parameters and subsequent recovery of contractile performance, further development of 31P NMR for evaluation of techniques designed to minimize the severity of ischemic damage would seem indicated.
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PMID:Mass spectrometry and phosphorus-31 nuclear magnetic resonance demonstrate additive myocardial protection by potassium cardioplegia and hypothermia during global ischemia. 677 61

Phosphorus-31 nuclear magnetic resonance (31P NMR) can estimate tissue intracellular pH as well as the content of high-energy phosphate metabolites in isolated perfused hearts. We used 31P NMR to examine mechanisms associated with the recovery of ventricular function in hearts subjected to global ischemia and reperfusion, with special emphasis on intracellular pH, a previously unreported variable. Single-dose and multiple-dose administration of a hyperkalemic cardioplegic solution were compared with hypothermia alone in 18 isolated perfused rabbit hearts. Hearts in group 1 were subjected to 24 degrees C hypothermia during 60 minutes of global ischemia; group 2 hearts received a single injection of 37-mM KCL cardioplegic solution at 10 degrees C at the onset of ischemia; and group 3 hearts received a similar initial cardioplegic injection followed by two subsequent 24 degrees C injections at 20-minute intervals during the ischemic period. Using an intraventricular balloon, maximal dP/dt provided a quantitative index of left ventricular performance before and after ischemia. Return of ventricular function expressed as a percentage of control was 54 +/- 11% for group 1, 84 +/- 6% for group 2, and 101 +/- 18% for group 3. Differences in the rate of development of intracellular acidosis were noted during the 60-minute ischemic period. Intracellular pH fell to 6.09 +/- 0.12 in group 1, 6.31 +/- 0.09 in group 2, an 6.79 +/- 0.03 in group 3. In all three groups intracellular pH returned to control (pH 7.20) within 10 minutes of reflow. The metabolic correlates of functional recovery appeared to be the tissue content of ATP at the end of ischemia and after reflow. ATP content at the end of ischemia was 22 +/- 2% of control in group 1 hearts, 31 +/- 4% in group 2 and 64 +/- 2% in group 3. After 45 minutes of reperfusion, ATP levels recovered to 33 +/- 9% of control in group 1, to 71 +/- 9% in group 2 and to 86 +/- 6% in group 3. Although there were no differences between groups in the content of creatine phosphate after 60 minutes of ischemia, the rates of creatine phosphate decline were dissimilar. Further, during the early reflow period, a marked overshoot in tissue creatine phosphate was detected, especially in groups 1 and 2. Histologic damage assessed by light microscopy correlated with the metabolic data, confirming that multidose cardioplegia provided the best preservation of cellular morphology. These results demonstrate that the magnitude of intracellular acidosis and the associated increase in inorganic phosphate correlate inversely with recovery of postischemic ventricular structure and function. ATP, but not creatine phosphate, content correlates with return of contractile performance after reperfusion. The overshoot in creatine phosphate during early reperfusion might impede optimal restoration of ATP content and, as a result, optimal recovery of cell functions.
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PMID:Mechanisms of ischemic myocardial cell damage assessed by phosphorus-31 nuclear magnetic resonance. 679 21

The degradation of adenine nucleotide levels and impairment of functional recovery associated with exposure to hypothermic (20 degrees C) cardioplegia was studied in 84 isolated working rat hearts. After a 1-hour control period, hearts were exposed to 1 hour of cardioplegia that consisted of increasingly longer periods of cardioplegic solution (CPS) infusion (30 seconds and 10, 30 and 60 minutes), followed by increasingly shorter periods of global ischemia (591/2 minutes and 50, 30 and 0 minutes). Hearts were then reperfused for 1 hour with control perfusate, during which recovery of cardiac output was monitored. Additional hearts were freeze-clamped at various points in the protocols to determine adenine nucleotide levels (ATP, ADP, AMP and their sum TAN). Exposure to increasingly longer periods of CPS perfusion resulted in proportionally greater degradation of nucleotides and poorer recovery of cardiac output. Addition of inosine to the recovery perfusate as well as the CPS further improved nucleotide levels and recovery of cardiac output. These results suggest that washout of nucleotide degradation products in the CPS or reperfusion prevents their salvage for nucleotide resynthesis and impairs functional recovery from cardioplegia.
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PMID:Nucleotide degradation and functional impairment during cardioplegia: amelioration by inosine. 684 95

C3a and its C-terminal hexapeptide lead to a dose dependent release of biogenic amines and nucleotides stored in platelet's granules. The release reaction can be measured by tritiated serotonin or by ATP, indicated by an ATP specific bioluminescence assay. We tested the capability of C3a to induce aggregation of washed platelets. The recently described phenomenon of low dose, stimulus specific desensitization of platelets to the anaphylatoxic peptides C3a and C5a could be shown by measuring the release reaction as well as the aggregation. Further we could demonstrate the reversibility of the stimulus specific desensitization within 2 to 3 hours. The desensitization was proven to be temperature dependent. The recovery of function was independent of newly synthetized protein and is discussed as the result of receptor-recycling.
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PMID:C3a induced activation and stimulus specific reversible desensitization of guinea pig platelets. 698 27

The effect of ATP-MgCl2 treatment was investigated on the biochemical changes of preserved kidneys and on the functional recovery of hypoxically damaged and autotransplanted canine kidneys. We observed that ATP-MgCl2 administered before or during simple hypothermic storage did not protect the integrity of preserved kidney cells, as measured by enzyme wash-out (LDH and NAG) or by lactate release. If the compound was administered after 120 min or 180 min clamping of the renal artery, the solitary kidney showed a faster regeneration as measured by changes in serum creatinine level. The survival rates were significantly higher in the treated groups. Without warm ischemia of the kidney all of the autotransplanted dogs survived after surgery. After 60 min of warm ischemia the mortality rate was 100%, and the mean survival time in average 5 days. If ATP-MgCl2 was administered after the 60 min of warm ischemia, an improved recovery of the graft function was observed
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PMID:Effect of ATP-MgCl2 treatment on kidney preservation and on recovery of graft function. 701 Apr 79

Isolated rat hearts reperfused after 25 min of ischemia have 23% of control mechanical function, 65% of control nucleotides, 52% of control ATP, and 75% of control creatine phosphate, whereas cellular calcium is increased 2.3-fold. Initiating reperfusion with verapamil or low Ca2+-containing buffer did not alter these tissue parameters or improve function over hearts reperfused with control buffer only. Also, when verapamil was present before and during ischemia, improvement in cardiac function resulted, and the adenine nucleotides, tissue ATP, and creatine phosphate concentrations were increased while cellular Ca2+ was reduced compared with the other reperfused ischemic hearts. Verapamil apparently improves recovery of function by decreasing energy demand during ischemia rather than by blocking Ca2+ influx during reprefusion. The respiration of isolated mitochondria and homogenates from reperfused ischemic hearts and homogenates of ischemic hearts was decreased by 20-30%, possibly due to sarcolemmal damage, although the respiration of isolated cells from ischemic hearts was normal. Cells isolated from ischemic hearts may represent a selected population lacking sarcolemmal damage.
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PMID:Effects of Ca2+ antagonism on energy metabolism: Ca2+ and heart function after ischemia. 738 50

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

Blockers of ATP-sensitive K+ channels (KATP) abolish preconditioning in several species. Glyburide does not abolish preconditioning in rat hearts, but this may be due to a loss of its activity during ischemia. We determined the effect of a KATP blocker, which is more active during ischemia (sodium 5-hydroxydecanoate, 5-HD), on preconditioning in isolated rat hearts. Rat hearts were subjected to 4 periods of 5 min global ischemia followed by 30 min of global ischemia and reperfusion. Preconditioning significantly enhanced post-ischemic recovery of function and reduced lactate dehydrogenase (LDH) release vs. sham. 5-HD (100 microM) did not abolish preconditioning. Cromakalim (20 microM) was protective in this ischemic model and this was abolished by 5-HD. This is further evidence that KATP opening is not the mechanism of preconditioning in rats.
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PMID:The KATP blocker sodium 5-hydroxydecanoate does not abolish preconditioning in isolated rat hearts. 749 19

Reperfusion following a period of ischemia can salvage the myocardium only if the ischemic episode has not exceeded a certain time limit; beyond this point damage becomes irreversible. A key feature of the transition from reversible to irreversible injury is mitochondrial dysfunction which may involve the opening of a non-specific pore in the mitochondrial inner membrane. Pore opening can be induced in vitro by exposure of isolated mitochondria to high [Ca2+] and Pi. Such pore formation is sensitized by adenine nucleotide depletion and oxidative stress and can be blocked by the immunosuppressant cyclosporin A. Here we show that in isolated perfused rat hearts subjected to 30 min ischemia and 15 min reperfusion, 0.2 microM cyclosporin A restored the ATP/ADP ratio and AMP content (decreased and increased respectively during ischemia) to pre-ischemic values. In separate experiments functional recovery was assessed by monitoring the restoration of left ventricular developed pressure (LVP) during reperfusion after 30, 40 or 45 min ischemia. LVP was substantially improved in the presence of 0.2 microM cyclosporin A but did not return to pre-ischemic levels. The cyclosporin analogues G and H were less effective than cyclosporin A in protecting the heart during reperfusion. This is consistent with their reduced ability to protect isolated mitochondria from damage caused by Ca2+ overload. Surprisingly, reperfusion of hearts with 1 microM cyclosporin A reversed the protective effect seen at 0.2 microM.
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PMID:Protection by Cyclosporin A of ischemia/reperfusion-induced damage in isolated rat hearts. 751 54


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