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)

To clarify the role of Na+i, pHi, and high-energy phosphate (HEP) levels in the initiation and maintenance of ischemia-induced ventricular fibrillation (VF), interleaved 23Na and 31P nuclear magnetic resonance spectra were collected on perfused rat hearts during low-flow ischemia (51 minutes, 1.2 mL/g wet wt). When untreated, 50% of the hearts from normal (sham) rats and 89% of the hypertrophied hearts from aorticbanded (band) rats (P < .01 versus sham) exhibited VF. Phosphocreatine content was significantly higher in sham than band hearts during control perfusion (53.3 +/- 1.6 versus 39.8 +/- 2.0 mumol/g dry wt). Before VF at 20 minutes of ischemia, Na+i accumulation was greater in hearts that eventually developed VF than in hearts that did not develop VF for both band and sham groups (144% versus 128% of control in sham; P < .005) and was the strongest metabolic predictor of VF; ATP depletion was also greater for VF hearts in the sham group. Infusion of the Na(+)-H+ exchange inhibitor 5-(N,N-hexamethylene)-amiloride prevented VF in sham and band hearts; reduced Na+i accumulation but similar HEP depletion were observed compared with VF hearts before the onset of VF. Rapid changes in Na+i, pHi, and HEP began with VF, resulting in intracellular Na+i overload (approximately 300% of control) and increased HEP depletion. A delayed postischemic functional recovery occurred in VF hearts, which correlated temporally with the recovery of Na+i. In conclusion, alterations in Na+i were associated with spontaneous VF transitions, consistent with involvement of excess Na+i accumulation in VF initiation and maintenance and with previously reported alterations in Ca2+i with VF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:23Na and 31P nuclear magnetic resonance studies of ischemia-induced ventricular fibrillation. Alterations of intracellular Na+ and cellular energy. 761 23

31P NMR spectroscopy was used to investigate whether improved functional recovery in ischaemic preconditioning was due to improved metabolic recovery in isolated rat hearts. The preconditioning stimulus was global ischaemia of 1 or 4 min followed by 12 min of reperfusion (Langendorff mode). The hearts were then subjected to a main ischaemic period of 16 min and 40 min of reperfusion. Functional and metabolic recoveries of hearts were compared to a control group subjected only to the main ischaemia. Preconditioning improved recovery of contractile function during the final reperfusion. Thus left ventricular developed pressure (LVDP) and heart rate (HR) product after 40 min of reperfusion recovered to 56, 67 and 68% in the control group, 1 min group and 4 min group, respectively. However, the metabolic recovery was comparable in all groups. CrP and ATP recovered to levels of 67-78% (CrP) and 35-41% (ATP), and pH to a level of 7.13-7.15 (not different from baseline values) at the end of the final reperfusion. We conclude that the improved functional recovery in preconditioning is not due to a higher level of high energy phosphates or less acidosis during the final reperfusion.
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PMID:Preconditioning by brief ischaemic episodes in the isolated rat heart assessed by 31P NMR spectroscopy: dissociation between metabolic and functional recovery? 762 39

We wished to determine whether histidine scavenges hydroxyl radical, H2O2, and superoxide anion in vitro and to investigate the protective effect of histidine on isolated perfused rat hearts after global ischemia (40 min) and reperfusion (30 min) (I/R). Left ventricular (LV) function was recorded and coronary effluent was collected for measurement of lactate dehydrogenase (LDH) before ischemia and at 5, 10, 15, and 30 min of reperfusion. At the end of the experiment, a portion of the LV wall was fixed with 2% glutaraldehyde for morphological analysis; the remaining heart was immediately frozen in liquid nitrogen for determination of adenine nucleotides. Histidine effectively quenched hydroxyl radicals and H2O2, but not superoxide anions, in in vitro and in vivo conditions. Hearts treated with histidine exhibited significantly greater functional recovery during reperfusion as compared with nontreated hearts (p < 0.05). Cell morphology was well preserved, and enzyme release was significantly attenuated by histidine treatment (p < 0.05). Histidine raised the ATP level to 73% and the creatine phosphate level to 68% of normal control during reperfusion. Total adenine nucleotide pool and energy charge rate in histidine-treated hearts significantly increased as compared with those in nontreated hearts (p < 0.05), but no effect on ATP and creatine phosphate was noted during ischemia, Histidine prevents postischemic reperfusion injury in isolated heart by inhibiting reactive O2 species and preserving high-energy phosphates (HEP).
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PMID:Antioxidative properties of histidine and its effect on myocardial injury during ischemia/reperfusion in isolated rat heart. 772 45

St Thomas' Hospital cardioplegic solution is commonly used to arrest hearts during surgery. Pursuing the hypothesis that the cardioprotective properties of adenosine could be a beneficial adjunct to a solution containing high K+ and Mg2+, we tested a low and a high adenosine concentration added to this cardioplegic solution, aiming at improved recovery of function and energy status. We arrested 18 working rat hearts by a 3-minute infusion with the solution without or with 50 microM or 5 mM adenosine. We induced 30 minute stop-flow ischemia at 37 degrees C, followed by 10 minute washout (Langendorff mode) and 20 minute reperfusion (working heart). Control cardioplegia induced electrical arrest in 19.8 +/- 5.5 s. This took 9.1 +/- 0.9* and 12.7 +/- 1.8 s in the presence of 50 microM and 5 mM adenosine, respectively (*p < 0.05 vs no adenosine). During reperfusion a regular electrocardiogram appeared after 1.9 +/- 0.3 minutes in controls, after 1.0 +/- 0.0* and 1.7 +/- 0.2 minutes in hearts treated with low and high-dose adenosine, respectively (*p < 0.05 vs no adenosine). After 20 minute reperfusion, the pressure-rate product had recovered to 65 +/- 17% in controls, and to 107 +/- 11** and 72 +/- 11% of preischemic values in hearts treated with 50 microM and 5 mM adenosine, respectively (**p < 0.05 vs other groups). There was a good correlation between reperfusion function recovery and the postischemic release of creatine kinase, an index for irreversible cellular damage. This association was absent with ATP content, which increased with the adenosine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine, added to St Thomas' Hospital cardioplegic solution, improves functional recovery and reduces irreversible myocardial damage. 774 86

Limitation of myocardial injury and infarction has been demonstrated by interventions such as ischemic preconditioning or the use of pyruvate as a substrate, which reduces glycogen content before, and acidosis during, ischemia. An isolated perfused rat heart model of global ischemia was employed to test the hypothesis that glycogen depletion reduces ischemic injury as measured by creatine kinase release. 31P-nuclear magnetic resonance spectroscopy was used to measure high-energy phosphates (ATP and phosphocreatine), phosphomonoesters (PME), and intracellular pH. Compared with control glucose-perfused hearts with normal glycogen content (1.49 +/- 0.13 mg Glc/g wet wt), glycogen-depleted pyruvate, ischemic preconditioned, and glycogen-depleted glucose hearts all had reduced glycogen content before ischemia (0.62 +/- 0.16, 0.81 +/- 0.10, and 0.67 +/- 0.12 mg Glc/g wet wt, respectively; P = 0.003) and significantly higher pH at the end of ischemia (5.85 +/- 0.02, 6.33 +/- 0.06, 6.24 +/- 0.04, and 6.12 +/- 0.02 in control, glycogen-depleted pyruvate, preconditioned, and glycogen-depleted glucose-perfused hearts, respectively; P < 0.01), although acidification during the initial phase of ischemia was differentially affected by the three interventions. Glycogen-depleted pyruvate and preconditioned hearts had reduced PME accumulation, greater recovery of function and phosphocreatine, and lower creatine kinase release on reperfusion, whereas glycogen-depleted glucose-perfused hearts were similar to control hearts. In summary, glycogen depletion by these three methods limits the fall in pH during global ischemia, although glycogen depletion in the absence of preconditioning does not limit ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of glycogen depletion on ischemic injury in isolated rat hearts: insights into preconditioning. 790 Aug 92

Preconditioning decreases ischemic injury, preserves tissue ATP content, and enhances the salutary effects of reperfusion. To evaluate whether preserved ATP is related to reduced utilization or increased production, 28 paced isolated rabbit hearts, perfused at constant flow, were subjected to 3 min of transient no-flow ischemia followed 12 min later by 1 h of low-flow ischemia and 45 min of reperfusion. Results were compared with those from 34 control hearts subjected to ischemia and reperfusion without preconditioning. Preconditioning delayed the onset of ischemic contracture and decreased its amplitude. At the end of ischemia, tissue ATP content was higher in hearts subjected to preconditioning (9.8 +/- 3.3 vs. 4.5 +/- 1.1 mumol/g dry wt; P < 0.01), accounted for by increased anaerobic ATP production using exogenous glucose. Preconditioning decreased ischemic damage (creatine kinase release 373 +/- 199 vs. 587 +/- 291 U/g dry wt; P < 0.05) and resulted in better functional recovery with reperfusion (74 +/- 11% of baseline developed pressure vs. 60 +/- 23%; P < 0.05). Thus preconditioning appears to protect ischemic myocardium by enhancing anaerobic glycolytic production of ATP using exogenous glucose.
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PMID:Ischemic preconditioning stimulates anaerobic glycolysis in the isolated rabbit heart. 794 81

Isolated rat hearts can be protected by preconditioning, although this has not been found when they are perfused with pyruvate. We addressed the question of whether pyruvate could increase the threshold for preconditioning in isolated rat hearts and whether this could be overcome with increased durations of ischemia. A protocol of four periods of 5 min of ischemic preconditioning (4 x 5 min) protected hearts (improved recovery of function, reduced lactate dehydrogenase release) not perfused with pyruvate from a subsequent 30-min period of global ischemia, but did not protect pyruvate-perfused hearts. Pilot studies indicated that hearts perfused in the presence of pyruvate must be ischemic for approximately 40% longer to produce equivalent ischemic damage in nonpyruvate-treated hearts. Thus the preconditioning period of 5 min was increased by approximately 40% to 7 min to produce equivalent degrees of preconditioning. Hearts preconditioned with the 4 x 7 min protocol with pyruvate were significantly protected against a subsequent severe global ischemia (enhanced recovery of function, reduced lactate dehydrogenase release). High-energy phosphates were measured at the end of the preconditioning protocol (before final global ischemia) to determine whether there was a correlation between cardioprotection and high-energy phosphate levels. There was no correlation between ATP, ADP, or AMP levels and the efficacy of preconditioning. However, an increase in creatine phosphate was associated with cardioprotection, although the importance of this in mediating preconditioning is doubtful. Thus the ability to precondition rat hearts is somewhat dependent on their energy source, but this appears to be due to changes in the severity of the ischemic preconditioning event.
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PMID:Pyruvate increases threshold for preconditioning in globally ischemic rat hearts. 794 85

This study investigates the hypothesis that inhibition of nucleoside transport during hypothermic storage elevates tissue adenosine (ADO) content and improves the function of the isolated rat heart. The hearts, flushed with a cardioplegic solution containing varying concentrations (0-100 nM) of a nucleoside transport inhibitor, S-(4-nitrobenzyl)-6-thioinosine (NBTI), were immersion-stored at 0 degrees C for 9 hr. Function was assessed after 30 min of working reperfusion. Function of unstored fresh hearts served as controls and poststorage recovery is reported as percentage of control function. Poststorage heart rate in all groups returned to control level after reperfusion. Recovery of other functional parameters in the no-NBTI group was as follows: aortic flow (AF), 56.2 +/- 4.6%; coronary flow (CF), 53.9 +/- 3.2%; cardiac output (CO), 55.5 +/- 4.0%; systolic pressure, 81.6 +/- 2.5%; work, 47.0 +/- 4.2%; and coronary vascular resistance (CVR), 157.1 +/- 7.8% of control. NBTI improved functional recovery in a dose-dependent fashion; the maximal improvement was seen at a dose of 5 nM, in which the recovery was: AF, 78.1 +/- 3.4%; CF, 73.5 +/- 4.4%; CO, 76.7 +/- 3.6%; work, 70.7 +/- 5.0%; and CVR, 127.5 +/- 4.5% of control (P < 0.05 vs. no-NBTI). The ADO A1-receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (0.1 microM) blocked the effects of 5 nM NBTI; the recovery of AF, CF, CO, work, and CVR decreased to 62.8 +/- 8.0%, 58.3 +/- 5.0%, 61.5 +/- 3.9%, 54.4 +/- 4.5%, and 163.8 +/- 12.7% of control, respectively (P < 0.05 vs. 5 nM NBTI). Tissue ADO content in 5 nM NBTI hearts at the end of storage was 0.075 +/- 0.025 mumol/g dry wt, which was significantly elevated from 0.016 +/- 0.004 mumol/g dry wt in no-NBTI hearts. Purine release during initial reperfusion was delayed in 5 nM NBTI hearts, indicating the inhibition of nucleoside transport by NBTI. But NBTI treatment did not improve end-storage or end-reperfusion myocardial ATP. In conclusion, the addition of NBTI to cardioplegic solution enhanced tissue ADO and improved poststorage function of the hypothermically stored rat heart. The effect is ADO A1-receptor mediated without invoking energy conservation.
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PMID:Enhanced functional preservation of cold-stored rat heart by a nucleoside transport inhibitor. 803 5

Hearts from treadmill-trained and sedentary rats were perfused in the working heart mode. Mechanical and metabolite status was evaluated before ischemia, after 25 min of global ischemia, and after 30 min of retrograde reperfusion. After reperfusion, hearts from trained rats were found to have better recovery of contractile function, lower diastolic stiffness, greater efficiency of work, and greater extracellular calcium responsiveness than hearts from sedentary rats. Training had no significant impact on bioenergetic status before or at the end of ischemia. However, after reperfusion, both phosphocreatine and ATP were significantly higher in hearts from trained rats than from sedentary control rats. Mitochondrial function in both subsarcolemmal and intermyofibrillar subpopulations was unaffected by ischemia-reperfusion. 45Ca2+ uptake during reperfusion was significantly higher in hearts from sedentary rats than from exercise-trained rats. No differences were found in free radical production or tolerance due to training. Therefore, hearts from exercise-trained rats demonstrated an increased metabolic tolerance to ischemic-reperfusion damage, which may contribute to the improved postischemic functional recovery.
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PMID:Exercise training improves metabolic response after ischemia in isolated working rat heart. 804 39

Functional recovery following ischemia and reperfusion in the isolated working rat heart perfused with glucose (11 mM) was examined in relation to pre- and postischemic levels of ATP, glycogen, glucose 6-phosphate, and the lactate-to-pyruvate ratio. The following variables were studied: feeding and fasting in vivo, addition of L-lactate (10 mM), dl-beta-hydroxybutyrate (10 mM), glucagon (0.01 and 1 micrograms/ml), and a 15-min anoxic perfusion before ischemia in vitro. Recovery was assessed as the percentage of preischemic power. Good correlation was found between functional recovery and the postischemic content of glycogen. Glycogen depletion by anoxia or glucagon before ischemia impaired recovery. There was no relationship among lactate produced, or the lactate-to-pyruvate ratio, and recovery. The addition of lactate or beta-hydroxybutyrate to hearts from fed rats increased the content of glycogen and glucose 6-phosphate, whereas addition of lactate, but not beta-hydroxybutyrate, improved recovery. There was a linear relationship between glycogen content and glucose 6-phosphate levels. In conclusion, the degree of return of oxidative metabolism and of net glycogen resynthesis reflects postischemic recovery of function. The results also suggest a role for anaplerosis of the citric acid cycle as an additional determinant of postischemic recovery.
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PMID:Metabolic recovery of isolated working rat heart after brief global ischemia. 806 97


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