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)

Ischemia and ischemic stress hormones induce endogenous cardiac protection against ischemia-reperfusion (I/R) injury. Although ischemia and ischemic stress hormones are accompanied by increased [Ca2+], it is unknown whether either opening of the sarcoplasmic reticular ryanodine Ca2+ channel (SR RyR) or inhibition of Ca2+ uptake by the sarcoendoplasmic reticular Ca(2+)-ATPase (SERCA) prior to I/R can similarly induce post-I/R functional protection. To study this, isolated, crystalloid perfused Sprague-Dawley rat hearts were used to assess the effects of inducing a pre-ischemic [Ca2+]i load by either priming the SR RyR with ryanodine (Ry, 5 nM/2 min) or by transient blockade of the SERCA 10 min prior to global I/R (20 min). A pre-ischemic Ca2+ load by either SR RyR activation or SERCA blockade improved post-ischemic myocardial functional recovery (developed pressure, end diastolic pressure, coronary flow, heart rate, and left ventricular creatine kinase activity). We conclude that 1) Ca(2+)-induced myocardial functional protection involves the SR Ca2+ source, 2) a pre-ischemic Ca2+ load induced with either Ry or thapsigargin constructively primes against myocardial I/R injury, and 3) Ca(2+)-induced cardioadaptation to I/R injury may have important therapeutic implications prior to planned ischemic events such as cardiac allograft preservation and cardiac bypass surgery.
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PMID:Constructive priming of myocardium against ischemia-reperfusion injury. 890 38

Many studies suggest that single-dose and multidose cardioplegia are protective in the ischemic adult heart, but in the neonatal heart single-dose cardioplegia is only protective, whereas multidose cardioplegia is damaging. We examined three clinically used cardioplegic solutions to compare the protective properties of single-dose and multidose cardioplegia in the neonatal rabbit heart (aged 7 to 10 days). The clinical solution studied were St. Thomas', Typers' and Bretschneider's solutions. In isolated working hearts (n = 8/group), cardiac function was assessed prior to 10 hours of ischemia (20 degrees C) and again after 35 min reperfusion (15 min Langendorff, 20 min working). All hearts received a pre-ischemic infusion (10 ml) of cardioplegic solution. The cardioplegic solution was given either as a single infusion (single-dose) or as repeated infusions (multidose) with 5 ml of cardioplegic solution every hour. The changes in coronary vascular resistance (CVR) during repeated cardioplegic infusions were measured in the multidose groups. During 15 min of Langendorff reperfusion, creatine kinase (CK) leakage and CVR were evaluated in all hearts. The results revealed that single-dose cardioplegia provided significantly better functional recovery than multidose cardioplegia in hearts given St. Thomas' or Tyers' solutions, while using Bretschneider solution single-dose cardioplegia Tended to provide better functional recovery. Post-ischemic CK leakages were higher in hearts given Bretschneider's solution in both single-dose and multidose cardioplegia. In hearts given St. Thomas' and Tyers' solutions, post-ischemic CVR in the single-dose group is lower than that in the multidose group, whereas post-ischemic CVR was lowest in the multidose group using Bretschneider's solution. Among multidose groups, CVR prior to reperfusion was lowest in Breschneider's solution as well. In conclusions, these results confirmed that, using the clinical solutions studied, single-dose cardioplegia provided better functional recovery than multidose cardioplegia in the neonatal rabbit heart. However, low CVR in Bretschenider's multidose cardioplegia suggested the better protection in coronary vasculature although functional recovery was poor.
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PMID:[Comparison of the protective prorerties of St. Thomas', Tyers', and Bretschneider's cardioplegic solutions in the neonatal rabbit heart]. 895 17

To evaluate the resistance of physiologically hypertrophied hearts to hypoxic insult, we quantified the development of functional deficits during hypoxia and reoxygenation in hypertrophied hearts from swim-trained female rats and we correlated this with assessment of high-energy phosphate (HEP) metabolites from simultaneous 31P nuclear magnetic resonance (NMR) measurements. Furthermore, in vivo enzymatic studies were carried out with saturation transfer NMR under well-oxygenated perfusion conditions for both beating and KCl-arrested hearts. Finally, in vitro enzymatic assays were performed. During hypoxia, the trained hearts exhibited improved systolic and diastolic function compared with hearts from sedentary animals. After 16 min of hypoxia, left ventricular (LV) developed pressure fell to 9% of baseline in control hearts but to only 21% of baseline in trained hearts (P < 0.01). LV diastolic function was also improved by training, increasing during hypoxia from a baseline of 10 to 71.0 +/- 3.3 mmHg in control hearts and to 55.3 +/- 4.8 mmHg in trained hearts (P < 0.05). Trained hearts also showed more rapid and complete recovery of function during reoxygenation and greater coronary flow per gram of heart throughout the entire protocol. Functional differences were not accompanied by differences in HEP at baseline; moreover, ATP and phosphocreatine (PCr) loss during hypoxia was similar between control and trained hearts, as was the recovery of PCr during reoxygenation. Saturation transfer experiments showed an increase in the forward creatine kinase (CrK) rate constant in trained hearts of 18% while beating, whereas in vitro enzymatic analysis revealed a 16% increase in the ratio of mitochondrial CrK to citrate synthase activity in LV tissue. Thus the relative preservation of function in hearts from trained rats could not be accounted for by overall HEP levels but may reflect adaptations in the CrK system.
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PMID:Function and bioenergetics in isolated perfused trained rat hearts. 903 63

In isolated working rat hearts we have evaluated the effects of preconditioning on postischemic coronary endothelial permeability. Isolated Wistar male rat hearts were used and subdivided into three groups: Group A, control hearts submitted to 20 min global normothermic ischemia; Group B, hearts subjected, before ischemia, to preconditioning (three phases of 3 min ischemia, each one followed to 2 min Langendorff reperfusion; Group C, hearts submitted to preconditioning and hypertonic reperfusion (by adding 80 mM sucrose to normal perfusion buffer), in order to increase the effects on postischemic interstitial fluid accumulation (osmotic forces balance). A 65 min working heart reperfusion was also performed to assess functional response. We have evaluate the hemodynamic changes (coronary and aortic flows, systolic aortic pressure, work minute), reperfusion arrhythmias, heart weight changes (ww/dw), myocardial enzyme release (creatine phosphokinase and lactic dehydrogenase) and microcirculation permeability changes (FITC.albumin diffusion), as an index of endothelial function. In Group B, a significant reduction of ischemia-reperfusion damage (functional recovery, enzyme release and arrhythmias) was detected with respect to Group A. In Group C this reduction was significantly more evident with respect to groups A and B. In Groups B and C, a significant reduction in myocardial reperfusion (ww/dw: A: 5.9 +/- 0.5, B: 4.9 +/- 1.1, p < 0.02 vs A, C: 4.4 +/- 0.6, p < 0.01 vs A) edema and FITC-albumin diffusion (A: 32.8 +/- 5.9% area; B: 16.3 +/- 6.1% area, p < 0.01 vs A; C: 13.3 +/- 4.5% area, p < 0.01 vs A), especially in perimyocytic space was also observed. Data show that preconditioning may exert a cardioprotective effect by reducing endothelial postischemic functional alterations (vascular permeability) and reperfusion edema. The importance of fluid diffusion within the interstitium in the development of reperfusion damage is supported by better postischemic recovery in Group C, in which an interference on osmotic load was performed.
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PMID:[Ischemic preconditioning of the myocardium: the role of changes in the permeability of the coronary microcirculation]. 911 56

Heat shock protein 70 (HSP70) has been reported to be involved in the myocardial self-preservation system. To obtain the evidence that HSP70 plays a direct role in the protection from myocardial ischemia-reperfusion injury, rat hearts were transfected with human HSP70 gene by intracoronary infusion of hemagglutinating virus of Japan (HVJ)-liposome containing human HSP70 gene. The control hearts were infused with HVJ-liposome without the HSP70 gene. The hearts from whole-body heat-stressed or nontreated rats were also examined. Western blot and immunohistochemical analysis showed that apparent overexpression of HSP70 occurred in the gene transfected hearts and that gene transfection might be more effective for HSP70 induction than heat stress. In Langendorff perfusion, better functional recovery as well as less creatine phosphokinase leakage after ischemia were obtained in the gene transfected hearts with HSP70 than in the control or nontreated hearts. Furthermore, the gene transfected hearts showed better functional recovery than the heat-stressed hearts. These results indicated that overexpressed HSP70 plays a protective role in myocardial injury, suggesting the possibility that gene transfection with HSP70 may become a novel method for myocardial protection through enforcing the self-preservation systems.
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PMID:In vivo gene transfection with heat shock protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat. 912 8

The purposes of this study were to determine whether ischemic preconditioning (IPC) in human atrial trabeculae is mediated by alpha 1-adrenoceptors and protein kinase C (PKC) and whether the protection of IPC is replicated with alpha 1-adrenoceptor stimulation [alpha 1-adrenoceptor preconditioning (alpha 1-PC)]. Atrial trabeculae were obtained during coronary bypass surgery. The trabeculae were suspended in organ baths containing Tyrode solution and field stimulated at 1 Hz, and developed force was recorded. The trabeculae underwent 45 min of simulated ischemia (SI) and 120 min of reperfusion (I/R injury). IPC trabeculae received transient SI before I/R injury, alpha 1-Adrenoceptor blockade with BE-2254 and PKC inhibition with chelerythrine were independently combined with IPC before I/R injury. alpha 1-PC before I/R was examined with alpha 1-adrenergic agonist (phenylephrine) pre-treatment. Improved recovery of developed force and higher tissue creatine kinase activity were present in IPC trabeculae, and the protective effect of IPC was eliminated with either alpha 1-adrenoceptor blockade or PKC inhibition. alpha 1-PC trabeculae also exhibited enhanced functional recovery after I/R injury but lacked preservation of tissue creatine kinase activity. PKC inhibition eliminated the functional protection of alpha 1-PC. These results suggest that, in human atrial trabeculae, alpha 1-adrenoceptors and PKC mediate, in part, the functional and tissue CK preservation conferred by IPC, but alpha 1-PC does not replicate the protection of IPC.
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PMID:Ischemic preconditioning of human myocardium: protein kinase C mediates a permissive role for alpha 1-adrenoceptors. 927 9

The aim of this study was to evaluate whether assessment of ST-segment changes in the 12-lead electrocardiogram from admission to 30 minutes after successful direct coronary angioplasty can predict myocardial damage and functional outcome in patients with acute myocardial infarction (AMI). Of 158 consecutive patients, 117 (92 men, aged 61 +/- 11 years) were prospectively classified into 2 groups: group 1, <50% reduction in ST-segment elevation in a single selected lead (42 patients); group 2, > or =50% reduction in ST-segment elevation (75 patients). Baseline characteristics were similar except for anterior wall AMI and Killip class >2, which were more prevalent in group 1. Peak creatine kinase was significantly higher in group 1 (3,690 +/- 2,809 vs 2,592 +/- 1,960 U/L; p = 0.018). One-month echocardiograms were obtained in 102 patients (87%). Infarct zone wall motion score index decreased in both groups, but this reduction was higher in group 2 (p <0.001). Functional recovery (>0.22 decrease in infarct zone wall motion score index) was observed in 34% of group 1 and in 78% of group 2 patients (p <0.001). One-month left ventricular ejection fraction was higher in group 2 (p <0.001). At multivariate analysis, reduction of ST-segment elevation was the only independent predictor of functional recovery (p <0.001). In conclusion, ST-segment analysis provides rapid and inexpensive information allowing identification of patients who are likely to benefit the most from myocardial reperfusion as early as 30 minutes after the last balloon inflation.
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PMID:Rapid reduction of ST-segment elevation after successful direct angioplasty in acute myocardial infarction. 931 69

To explore the effects of heat stress (HS) in aged hypertrophied and nonhypertrophied rat hearts, postischemic recovery was investigated 15 mo after aortic constriction (AoB) or sham operation (Sham). Twenty-four hours after HS (42 degrees C; 15 min) or control treatment (normothermia), global ischemia was induced for 20 min in isolated AoB hearts and for 20 or 30 min in Sham hearts. After HS, postischemic recovery after 20-min ischemia in AoB hearts and 30-min ischemia in Sham hearts, respectively, was significantly better than in corresponding controls. In AoB hearts, cardiac output (CO), left ventricular developed pressure (LVDP), and the positive maximal first derivative of left ventricular pressure (+dP/dtmax) recovered to 33 +/- 26 (means +/- SD), 87 +/- 5, and 72 +/- 12%, respectively, after HS and to 5 +/- 8, 22 +/- 39, and 17 +/- 29% of preischemic values, respectively, in controls. Postischemic arrhythmias were significantly reduced in HS hypertrophied hearts, but creatine kinase (CK) loss was not reduced. In Sham hearts subjected to 30 min ischemia, CO, LVDP, and +dP/dtmax recovered to 20 +/- 20, 75 +/- 8, and 59 +/- 15%, respectively, after HS and to 3 +/- 8, 21 +/- 32, and 16 +/- 32% of preischemic values, respectively, in controls. Duration of arrhythmias and CK loss were not reduced in the heated hearts. When Sham hearts were subjected to only 20-min ischemia, functional recovery was not different in HS and control hearts, indicating that HS pretreatment extends the ischemic interval before irreversible injury occurs in the heart. In all HS Sham hearts, the myocardial 72-kDa HS protein (HSP 70) content was significantly increased. However, in HS AoB hearts, HSP 70 levels were not significantly different from the values in the control hearts. These results indicate that HS pretreatment induces cardioprotection in aged hypertrophied and nonhypertrophied rat hearts, which, however, cannot be unequivocally related to increased HSP 70 tissue contents.
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PMID:Heat stress protects aged hypertrophied and nonhypertrophied rat hearts against ischemic damage. 932 23

This study was designed to assess whether the protective effect of ischemic preconditioning can be adapted for myocardium undergoing 6 h of no-flow ischemia. Twelve isolated rat hearts were either perfused with oxygen-bicarbonated Krebs-Henseleit buffer in the Langendorff mode for 35 min (n=6), or perfused in the same way for 20 min, following 5 min of global normothermic ischemia and 100 min of buffer-perfusion (n=6). The 12 hearts were then preserved for 6 h in HTK solution at 4 degrees C, followed by 30 min of reperfusion. Recovery of cardiac function, metabolic activity and intracellular free calcium concentration were compared between the two groups. After 6 h ischemia, the hearts that underwent preconditioning showed better recovery of left ventricular developed pressure (P<0.01), a lower end-diastolic pressure level (P<0.05), less creatine kinase leakage and a lower calcium concentration. There was no statistical difference in the recovery rate of coronary flow and leakage rate of LDH between the two groups. In conclusion, this experiment demonstrates that ischemic preconditioning improved myocardial functional recovery after 6 h of hypothermic ischemic preservation in the isolated rat heart. Preconditioning might be a potential mechanism for preserving the heart against long-term ischemia/reperfusion injury.
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PMID:Cardioprotective efficacy of ischemic preconditioning on long-term myocardial ischemia. 946 84

Few results, and those controversial, have been published on ischemic preconditioning followed by low-flow ischemia. The aim of this study was to assess whether ischemic preconditioning: (1) confers protection against severe underperfusion; and (2) is mediated by mobilization of proglycogen, resulting in increased anaerobic glycolysis and reduced myocardial injury. Isolated rat hearts were retrogradely perfused and subjected to either 25 min low-flow ischemia (0.6 ml/min) followed by 30 min reperfusion (IC; n=5), or the same protocol preceded by two cycles of 5 min no-flow ischemia and 5 min reperfusion (PC; n=7). Additionally, hearts (n=52) were freeze-clamped at different time points throughout the protocol. Preconditioning improved functional recovery (developed force X heart rate in PC hearts: 54 v 21% in IC hearts; P<0.01) and reduced ischemic damage (cumulative release of creatine kinase during reperfusion: 93 v 215 micro/g dry weight; P<0.05). During ischemia and reperfusion, release of adenosine and the sum of purines was smaller in PC hearts (P<0.05), while lactate release was similar in the two groups. PC reduced both macroglycogen and proglycogen by c. 60% (P<0.01) resulting in constant glycogen levels during low-flow ischemia. In contrast, in IC hearts, both fractions decreased by c. 60% during underperfusion (P<0.01). These results demonstrate that: (1) ischemic preconditioning reduces injury due to severe flow reduction; and (2) preconditioning reduced glycogenolysis without affecting anaerobic glycolysis, suggesting increased glucose uptake.
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PMID:Carbohydrates and purines in underperfused hearts, protected by ischemic preconditioning. 951 44


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