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

This study tests the hypothesis that retrograde/antegrade cardioplegic delivery can overcome the limitations of poor cardioplegic distribution resulting from either technique alone and, potentially, may expand the safety of using internal mammary artery grafts in cardiac muscle in jeopardy of inadequate cardioplegic protection. Jeopardized myocardium was produced in 20 dogs by ligating the left anterior descending coronary artery for 15 minutes before starting cardiopulmonary bypass and by 1 hour of aortic clamping with multidose 6 degrees C cold blood cardioplegia. Five dogs received antegrade cardioplegia via the aortic root. Ten dogs received retrograde cardioplegia via the coronary sinus. Five additional dogs received retrograde/antegrade cardioplegia via both routes. The ligature on the left anterior descending coronary artery was removed after aortic unclamping, and regional myocardial temperature (thermistor probe), segmental shortening (ultrasonic crystals), and global left ventricular and right ventricular myocardial function were evaluated. Antegrade cardioplegia produced excellent right ventricular cooling (14 degrees C) and allowed complete right ventricular functional recovery. However, it failed to cool muscle supplied by the left anterior descending coronary artery (only 31 degrees versus 12 degrees C, p less than 0.05), postischemic global left ventricular function recovered only 38% (p less than 0.05), and segmental shortening in the region supplied by the left anterior descending coronary artery recovered only 22% (p less than 0.05). Retrograde cardioplegia produced homogeneous cooling (17 degrees C) and allowed near normal recovery of global and regional left ventricular function (99% and 86%), but right ventricular cooling was variable (19 degrees to 30 degrees C) and right ventricular function recovered inconstantly (range 64% to 100%, average 82%). The best myocardial protection occurred after retrograde/antegrade cardioplegia; myocardial cooling was homogeneous, left ventricular and right ventricular global function recovered completely (95% and 90%), and regional contractility in muscle supplied by the left anterior descending coronary artery returned to 84% of control. We conclude that retrograde/antegrade cardioplegia provides better myocardial protection than either technique alone, ensures good cardioplegic distribution to the left and right ventricles, and allows regional delivery of cardioplegic flow to segments supplied by occluded arteries.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Studies of retrograde cardioplegia. II. Advantages of antegrade/retrograde cardioplegia to optimize distribution in jeopardized myocardium. 292 65

Previous studies show that (1) hypoxemia depletes immature myocardium of amino acid substrates and their replenishment improves ischemic tolerance, (2) reoxygenation on cardiopulmonary bypass causes oxygen-mediated damage without added ischemia, and (3) this damage may be related to the nitric oxide-L-arginine pathway that is affected by amino acid metabolism. This study tests the hypothesis that priming the cardiopulmonary bypass circuit with glutamate and aspartate limits reoxygenation damage. Of 22 immature Duroc-Yorkshire piglets (< 3 weeks old), five were observed over a 5-hour period (control), and five others underwent 30 minutes of CPB without hypoxemia (cardiopulmonary bypass control). Twelve others became hypoxemic by reducing ventilator inspired oxygen fraction to 6% to 7% (oxygen tension about 25 mm Hg) before reoxygenation on cardiopulmonary bypass for 30 minutes. Of these five were untreated (no treatment), and the cardiopulmonary bypass circuit was primed with 5 mmol/L glutamate and aspartate in seven others (treatment). Left ventricular function before and after bypass was measured by inscribing pressure-volume loops (end-systolic elastance). Myocardial conjugated diene levels were measured to detect lipid peroxidation, and antioxidant reserve capacity was tested by incubating cardiac muscle with the oxidant t-butylhydroperoxide to determine the susceptibility to subsequent oxidant injury. CPB (no hypoxemia) allowed complete functional recovery without changing conjugated dienes and antioxidant reserve capacity, whereas reoxygenation injury developed in untreated hearts. This was characterized by reduced contractility (elastance end-systolic recovered only 37% +/- 8%*), increased conjugated diene levels (1.3 +/- 0.1 vs 0.7 +/- 0.1*), and decreased antioxidant reserve capacity (910 +/- 59 vs 471 +/- 30 malondialdehyde nmol/g protein at 2 mmol/L t-butylhydroperoxide*). In contrast, priming the cardiopulmonary bypass circuit with glutamate and aspartate resulted in significantly better left ventricular functional recovery (75% +/- 8% vs 37% +/- 8%*), minimal conjugated diene production (0.8 +/- 0.1 vs 1.3 +/- 0.1*), and improved antioxidant reserve capacity (726 +/- 27 vs 910 +/- 59 malondialdehyde nmol/g protein*) (*p < 0.05 vs cardiopulmonary bypass control). We conclude that reoxygenation of immature hypoxemic piglets by the initiation of cardiopulmonary bypass causes myocardial dysfunction, lipid peroxidation, and reduced tolerance to oxidant stress, which may increase vulnerability to subsequent ischemia (i.e., aortic crossclamping). These data suggest that supplementing the prime of cardiopulmonary bypass circuit with glutamate and aspartate may reduce these deleterious consequences of reoxygenation.
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PMID:Studies of hypoxemic/reoxygenation injury: without aortic clamping. VIII. Counteraction of oxidant damage by exogenous glutamate and aspartate. 747 74

The objective of the current editorial is to introduce a new concept ("maimed myocardium") that we believe describes more accurately the incomplete, delayed recovery of LV function that may occur late after reperfusion after AMI. It has been demonstrated previously that myocardium remains viable for a prolonged period in many patients with nonsustained coronary occlusion, despite the occurrence of myocardial necrosis; late reperfusion may result in myocardial salvage in reversibly ischemic (stunned) segments (complete recovery) and in intensely injured (maimed) segments that display partial return of LV function over time (incomplete recovery). Clinically, the basis for maimed myocardium is the observation that delayed, LV functional recovery may occur in partially infarcted segments where there has been an antecedent ischemic insult of sufficient duration to result in some degree of myocardial necrosis. Certain acute coronary syndromes characterized by nonsustained coronary occlusion followed by spontaneous reperfusion (e.g., non-Q-wave AMI) or drug-induced reperfusion induced by the exogenous administration of thrombolytic therapy are associated with incomplete, delayed recovery of LV function as detected clinically by partial improvement in serial radionuclide-ejection measurement, enhanced metabolic integrity of cardiac tissue by F-18 deoxyglucose myocardial imaging, and scintigraphic findings of reverse thallium redistribution--findings that support the presence of partially viable myocardium that has been incompletely salvaged during reperfusion late after AMI. Experimentally, delayed LV functional recovery has been reported in animal models in which prolonged coronary occlusion (hours to days) followed by reperfusion is associated with late recovery of regional LV function in myocardial segments subtending border (stunned) zones and central infarct (maimed) zones. In studies in animals and human beings, postextrasystolic potentiation and pharmacologic inotropic interventions may augment maimed and stunned segments, although the magnitude of regional contractile reserve that can be unmasked with these interventions is quantitatively less in the maimed than in stunned segments. In summary, the propensity of intensely injured or partially infarcted LV segments to display intermediate functional recovery followed by reperfusion late after coronary occlusion suggests that even severely depressed but residually viable cardiac muscle can be salvaged incompletely over time.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Incomplete, delayed functional recovery late after reperfusion following acute myocardial infarction: "maimed myocardium". 757 10

The objective was to relate the response of the HSP70 and P53 genes to the cessation and the recovery of cardiac muscle cell functions when submitted to ischemia-reperfusion. We have measured the electromechanical activity, the released enzymes and HSP70 RNA and protein levels in cultured neonatal rat cardiomyocytes (CM) in a substrate-free, hypoxia-reoxygenation model of ischemia-reperfusion. In parallel the expression of the two genes P53 (the key apoptosis regulator gene) and P21/Waf1 (the P53 target gene) has been evaluated. The functional recovery during post-'ischemic' reoxygenation was associated with an overexpression of HSP70 and P53 lasting until the functional parameters reverted back to the normal, prehypoxic values. In contrast, extending the substrate-free hypoxic treatment worsens the dysfunction of the cardiac muscle cell and, in these conditions, reoxygenation failed to restore cell functions and to activate HSP70. Finally, in the conditions of reversible 'ischemic' cell injury, an early and transitory activation of P53 was associated with the functional recovering process of the CM submitted to simulated ischemia. These observations are suggestive of a contributive role of both HSP70 and P53 to a cytoprotective program activated by reoxygenation in post-'ischemic' CM.
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PMID:Changes in HSP70 and P53 expression are related to the pattern of electromechanical alterations in rat cardiomyocytes during simulated ischemia. 1145 86

The objective of this study was to determine the effect of calcium on water homeostasis in cardiac muscle and whether cytotoxic edema is involved in ischemic-reperfusion injury. Cellular water was quantified by multinuclear nuclear magnetic resonance (NMR) spectroscopy in isolated rat hearts during 30 min of ischemia and reperfusion. An increase in extracellular calcium from 0.75 to 2.25 mM increased ischemic swelling twofold, with a marginal effect on functional recovery at reperfusion. Inhibition of Ca2+ channels with verapamil and bepridil reduced ischemic swelling by 58-66% and improved cardiac viability and functional recovery. Inhibition of the Na/Ca exchange with amiloride resulted in reperfusion swelling resulting from the inhibition of calcium efflux via the Na/Ca exchange. This was confirmed by inhibition with amiloride of 63% of cellular swelling induced by calcium overload via the Na/Ca exchange after calcium-free perfusion (calcium paradox). The volume-related activity of amiloride was attributed to the inhibition of Na/Ca exchange because the inhibition of the Na/H antiport resulted in low cellular volumes. The consistent changes in cellular volumes induced by the various agents used to alter calcium fluxes provide evidence of a pro-edematous effect of intracellular calcium accumulation during myocardial ischemia. The administration of toxic doses of bepridil to the perfused and ischemic heart resulted in the shrinkage of cellular volumes and in functional failure. The toxicity of bepridil was mediated by unrestricted release of calcium from the sarcoplasmic reticulum because magnesium cardioplegia, which limits calcium release, lowered ischemic swelling without cellular shrinkage and improved functional recovery. In all experimental groups, cellular edema subsided during the early stages of reperfusion, indicating efficient dissipation of intracellular hyperosmolarity. There was no evidence that cytotoxic edema develops during ischemia or reperfusion, or both. On the contrary, calcium-mediated cardiac toxicity was associated with cellular volume shrinkage as a result of the efflux of osmolytes through permeabilized sarcolemmal membranes. It is concluded that calcium ion is involved in the regulation of cellular volumes, and its intracellular accumulation promotes swelling in ischemic myocytes with intact membranes.
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PMID:Is cytotoxic cellular edema real? The effect of calcium ion on water homeostasis in the rat heart. 1221 94

Myocardial ischemia is the leading cause of all cardiovascular deaths in North America. Myocardial ischemia is accompanied by profound changes in metabolism including alterations in glucose and fatty acid metabolism, increased uncoupling of glucose oxidation from glycolysis and accumulation of protons within the myocardium. These changes can contribute to a poor functional recovery of the heart. One key player in the ischemia-induced alteration in fatty acid and glucose metabolism is 5'AMP-activated protein kinase (AMPK). Accumulating evidence suggest that activation of AMPK during myocardial ischemia both increases glucose uptake and glycolysis while also increasing fatty acid oxidation during reperfusion. Gain-of-function mutations of AMPK in cardiac muscle may also be causally related to the development of hypertrophic cardiomyopathies. Therefore, a better understanding of role of AMPK in cardiac metabolism is necessary to appropriately modulate its activity as a potential therapeutic target in treating ischemia reperfusion injuries. This review attempts to update some of the recent findings that delineate various pathways through which AMPK regulates glucose and fatty acid metabolism in the ischemic myocardium.
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PMID:AMP-activated protein kinase (AMPK) control of fatty acid and glucose metabolism in the ischemic heart. 1268 19

Identification of all three nitric oxide (NO) synthase (NOS) isoforms in cardiac myocytes and the recognition of the importance of their subcellular localization have greatly advanced the understanding of the critical role of NO signaling in myocardial function. Targeted deletion of endothelial NOS (NOS3) has revealed a fundamental role for this NOS isoform in the structural and functional responses of the heart to pressure and volume overload. The recent generation of transgenic models with overexpression of NOS3 restricted to the cardiac myocyte has enabled a unique appreciation of the ability of NO to modulate cardiac muscle, independent of changes in cardiac loading conditions. Consistent with the targeting of overexpressed NOS3 to caveolae in the vicinity of cholinergic and adrenergic receptors, these studies have highlighted the importance of NOS3-derived NO in the modulation of autonomic cardiac stimulation. In vivo models of myocardial infarction suggest that NOS3 overexpression can limit compensatory hypertrophy in the remote myocardium and preserve left ventricular performance. Development of therapeutic strategies designed to enhance NO signaling in cardiac myocytes may target maladaptive left ventricular remodeling and improve functional recovery after myocardial infarction.
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PMID:Cardiomyocyte-specific overexpression of nitric oxide synthase 3: impact on left ventricular function and myocardial infarction. 1622 79

We have previously shown that VEGF165 gene delivery into ischemic skeletal muscle exerts not only proangiogenic, but also remarkable antiapoptotic and proregenerative activity. The aim of this study was to determine whether recombinant adeno-associated virus (rAAV)-mediated gene delivery of VEGF165 into cardiac muscle, during acute myocardial infarction, exerts a protective effect to promote long-term functional recovery. Acute infarction of the anterior LV wall was induced in 12 chronically instrumented dogs by permanent occlusion of the LAD coronary artery. Four hours after occlusion, rAAV-VEGF165 or rAAV-LacZ (n=6 each; 5x10(12) viral particles per animal) was directly injected with an echo-guided needle into the dysfunctional cardiac wall. LV and arterial pressure, dP/dtmax, and ejection fraction were not significantly different between the two groups over time. In contrast, in the infarcted region, at four weeks after infarction, fractional shortening was 75+/-18% and -3+/-15% of baseline and length-pressure area was 54+/-15% and 0.8+/-15% of baseline in VEGF165 versus LacZ, respectively (P<0.05). Histological analysis of the border regions showed a marked increase in the number of alpha-SMA-positive arterioles (68+/-2.8 versus 100+/-3.8 vessels per microscopic field in LacZ and VEGF165 group, respectively; P<0.05). In both groups, the receptor VEGFR-2 was diffusely expressed on the surviving cardiomyocytes and, consistently, myocardial viability was significantly improved in the VEGF165-treated group, with several troponin T-expressing cardiomyocytes displaying nuclear positivity for the proliferation marker PCNA. Altogether, our results indicate that VEGF165 gene delivery exerts a marked beneficial action by enhancing both arteriologenesis and cardiomyocyte viability in infarcted myocardium.
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PMID:Adeno-associated virus-mediated transduction of VEGF165 improves cardiac tissue viability and functional recovery after permanent coronary occlusion in conscious dogs. 1733 32

Antisense-mediated exon skipping holds great potential for the treatment of DMD. In mdx mice, functional recovery of skeletal muscle has been obtained upon systemic delivery of "naked" oligonucleotides or viral vectors encoding for antisense snRNAs. However, amongst the studies reported so far, which used either neonatal or young adult animals--only one achieved dystrophin restoration in cardiac muscle, using an adeno-associated vector. Here we report the in vivo delivery of morpholino oligos in aged mdx mice, both in skeletal muscle, via intra-arterial injection, and in cardiac muscle, via intra-muscular injection. Localized intra-arterial delivery yielded high levels of dystrophin restoration and just two doses of 100 microg each resulted into detectable force recovery in the EDL muscles of treated limbs. On the other hand, upon intra-cardiac injections in the left ventricle wall the skipping effect was much lower than what obtained in tibialis anterior muscles injected with comparable amounts of oligos. This latter finding suggests that even upon direct delivery antisense-mediated dystrophin restoration in cardiac muscle might suffer from limitations that do not exist in skeletal muscle.
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PMID:In vivo delivery of naked antisense oligos in aged mdx mice: analysis of dystrophin restoration in skeletal and cardiac muscle. 1860 63

In vitro expanded beating cardiac myocytes derived from induced pluripotent stem cells (iPSC-CMs) are a promising source of therapy for cardiac regeneration. Meanwhile, the cell sheet method has been shown to potentially maximize survival, functionality, and integration of the transplanted cells into the heart. It is thus hypothesized that transplanted iPSC-CMs in a cell sheet manner may contribute to functional recovery via direct mechanical effects on the myocardial infarction (MI) heart. F344/NJcl-rnu/rnu rats were left coronary artery ligated (n = 30), followed by transplantation of Dsred-labeled iPSC-CM cell sheets of murine origin over the infarct heart surface. Effects of the treatment were assessed, including in vivo molecular/cellular evaluations using a synchrotron radiation scattering technique. Ejection fraction and activation recovery interval were significantly greater from day 3 onward after iPSC-CM transplantation compared to those after sham operation. A number of transplanted iPSC-CMs were present on the heart surface expressing cardiac myosin or connexin 43 over 2 weeks, assessed by immunoconfocal microscopy, while mitochondria in the transplanted iPSC-CMs gradually showed mature structure as assessed by electron microscopy. Of note, X-ray diffraction identified 1,0 and 1,1 equatorial reflections attributable to myosin and actin-myosin lattice planes typical of organized cardiac muscle fibers within the transplanted cell sheets at 4 weeks, suggesting cyclic systolic myosin mass transfer to actin filaments in the transplanted iPSC-CMs. Transplantation of iPSC-CM cell sheets into the heart yielded functional and electrical recovery with cyclic contraction of transplanted cells in the rat MI heart, indicating that this strategy may be a promising cardiac muscle replacement therapy.
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PMID:Functional and Electrical Integration of Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Myocardial Infarction Rat Heart. 2560 21


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