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)

This study was designed to test the hypothesis that infusion of ATP-MgCl2 during reperfusion following a prolonged period of hypothermic global ischemia would result in enhanced functional recovery of cardiac function. Two groups of dogs (n = 6 each) were placed on cardiopulmonary bypass (CP) with systemic hypothermia to 28 degrees C and subjected to 150 min of aortic cross-clamping. Crystalloid cardioplegia was infused every 20 min during ischemia. Reperfusion and rewarming were carried out for 20 min before discontinuation of CP bypass. During reperfusion, the experimental group received ATP-MgCl2(1.0 mg/kg/min ATP, 0.33 mg/kg/min magnesium). At 15 and 45 min following bypass, hemodynamic assessment was carried out for each animal by constructing Starling curves over a range of filling pressures at constant heart rate and comparing each animal to its own prebypass control level. The results indicated that ATP-treated animals exhibited complete functional recovery whereas control animals showed marked reduction in hemodynamic performance and myocardial compliance and had a higher myocardial water content (P less than 0.05). We conclude that infusion of ATP-MgCl2 during reperfusion following hypothermic ischemia may help ameliorate reperfusion injury.
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PMID:Reperfusion with ATP-MgCl2 following prolonged ischemia improves myocardial performance. 349 93

Recovery from ischaemia in heart tissue can be accelerated by addition of precursors of ATP such as AMP to the coronary circulation. Endocytosis in capillary endothelia is also stimulated by AMP; therefore endocytosis may be important in the transport of AMP from the circulation into myocytes. Alternatively, the increase in endocytotic transport itself could be responsible for accelerated recovery, irrespective of the stimulating agent. The effects of sham, AMP, cytochalasin-D (an inhibitor of endocytosis), and cytochalasin-D + AMP infusates given prior to, during, and following a 15 min ischaemic episode, were examined. AMP accelerated biochemical and functional recovery after episodes of ischaemia and stimulated endocytosis in coronary capillaries. Cytochalasin-D strongly inhibited contractility before, during, and after ischaemia, and similarly depressed ATP and creatine phosphate levels. Cytochalasin-D also strongly inhibited endocytosis and caused swelling of the capillary endothelium. When cytochalasin-D and AMP were provided together, the beneficial effects of AMP were only partially inhibited by cytochalasin-D. In fact, AMP was able to reverse most of the effects of cytochalasin-D including the inhibition of endocytosis. This suggests accelerated recovery of ischaemic myocytes requires precursors of ATP such as AMP, and the stimulation of endocytosis may abet transport of these precursors, or may be a spurious phenomenon.
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PMID:Recovery of myocardial function after ischaemia: the effects of AMP and inhibition of endocytosis. 359 9

Addition of diltiazem (0.0, 0.95, 2.5 or 7.5 microM) to isolated working rat hearts before and during ischemia, produced a concentration-dependent increase in recovery of contractile function. Recovery of post-ischemic pressure-rate product showed a strong relationship with depression of pre-ischemic pressure-rate product, primarily from decreased heart rate before ischemia and increased pressure development following reperfusion. Increased recovery in treated hearts was associated with higher ATP and adenine nucleotide levels (ADN), but no relationship was observed between energy levels and degree of recovery of function or concentration of diltiazem. Hearts made ischemic for 20 min without reperfusion had increased ATP and decreased lactic acid accumulation when treated with 7.5 microM diltiazem. The results indicate contractile-dependent mechanisms of action of diltiazem in global ischemic hearts which can only be partly explained by preservation of ATP and ADN, but also are associated with reduced lactic acid accumulation.
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PMID:Effects of diltiazem upon globally ischemic rat hearts. 362 15

An isolated, working, rabbit heart has been developed for use with nuclear magnetic resonance (NMR) spectroscopy. This model is functionally stable over a 4-h period and displays classic hemodynamic responses to work-load changes. Control 31P spectra of this preparation (n = 5) were obtained with simultaneous recordings of left ventricular pressure (LVP), LVP differentiated with respect to time (dP/dt), heart rate (HR), and cardiac output (CO). ATP, phosphocreatine (PCr), and hemodynamics remained stable over a 90-min perfusion. Hearts were also subjected to 13.5 min of global ischemia (IS) at 37 degrees C followed by 60 min of reperfusion (RE, n = 7) or 45 min of chronic IS (n = 6). Contraction ceased within 60 s of IS. PCr loss was rapid, reaching undetectable limits by 11 min. ATP loss was gradual and bore no relationship to functional loss. ATP fell to 60 +/- 4% (means +/- SE) of pre-IS levels after 13.5 min of IS. With RE, PCr returned to control levels, whereas ATP values remained depressed for the entire 60 min. Functional activity resumed with RE, but dP/dt did not rise above 85 +/- 7% of preischemic values. No correlation between residual ATP at the end of IS and functional recovery during RE was evident.
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PMID:High-energy phosphates and function in isolated, working rabbit hearts. 368 61

The effects of exogenous inosine (IN) on high-energy phosphate metabolism and function in isolated, working rabbit hearts were monitored with 31P-nuclear magnetic resonance spectroscopy. Dynamic measurements of ATP and phosphocreatine (PCr) were made along with concomitant functional recordings during normal perfusion, global ischemia (IS), and reperfusion (RE). We found that 0.1 mM IN enhanced the rate of pressure development (dP/dt) within the left ventricle by 10 +/- 5% (n = 7). Although IN levels in treated hearts were elevated during normal perfusion, no effect was observed on ATP or PCr levels. However during IS, pretreatment with IN minimized ATP loss for the first 20 min relative to untreated controls (UNT, P less than 0.05). Both IN and UNT hearts that were ischemic for only 13.5 min regained function during a 60-min RE period. However, at the end of IS, IN hearts (n = 8) displayed 88 +/- 10% of the pre-IS ATP levels, whereas UNT hearts (n = 7) retained only 60 +/- 10%. With RE, ATP in IN hearts remained elevated over that of UNT hearts for the entire 60 min. IN treatment also increased the rate of recovery of dP/dt and maintained improved function over 60 min of RE. No correlation was found between post-IS ATP levels and dP/dt values during RE in either IN or UNT hearts. These data indicate that IN was protective against ATP loss during IS and improved functional recovery on RE.
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PMID:Inosine preserves ATP during ischemia and enhances recovery during reperfusion. 368 62

Magnesium-diltiazem cardioplegia was evaluated in the intact, perfused rat heart to determine whether the joint administration of these agents would adversely affect myocardial contractile and high-energy phosphate recovery following intermittent, normothermic global ischemic arrest. Sequential metabolic and functional analyses were performed on isolated perfused rat hearts during each phase of the experimental protocol: control (10 min), normoxic cardioplegia (10 min), intermittent global ischemic arrest (two 15-min periods separated by 2 min infusion of the normoxic cardioplegic perfusate), and normoxic postischemic control reperfusion (60 min). Four different cardioplegic solutions were evaluated: 30 mM KCl, 30 mM KCl with 2 mg diltiazem/liter, 20 mM MgCl2, and 20 mM MgCl2 with 2 mg diltiazem/liter. Myocardial phosphatic metabolite levels and intracellular pH were analyzed nondestructively in the intact hearts by phosphorus-31 NMR spectroscopy. Corresponding measurements of peak left intraventricular pressure, rate of peak pressure development (dP/dt), and contraction frequency were performed at the midpoint during each 5-min interval of 31P NMR signal averaging. Magnesium plus diltiazem-treated hearts were distinguished from all other groups by a marked delay in postischemic functional recovery consisting of a prolonged depression in contractility (34% of control, P less than 0.01) that persisted throughout the first 50 min of postischemic reperfusion. Diltiazem in combination with magnesium cardioplegia was detrimental to postischemic functional recovery, despite a rapid restoration of high-energy phosphate stores. The apparent adverse interactive effects of excess magnesium and diltiazem suggest that elective ischemic arrest with magnesium cardioplegia in combination with diltiazem may be contraindicated clinically. The mechanistic basis and drug specificity of this response require further clarification. The present findings appear to exclude ATP and PCr production, and structural causes as the basis for the observed aberrant functional recovery from global ischemia of magnesium plus diltiazem-arrested hearts.
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PMID:Sustained postischemic cardiodepression following magnesium-diltiazem cardioplegia. 371 20

Spontaneously beating isolated rat atria were subjected to 1 h of anoxia at 37 degrees C in various cardioplegic solutions. Contraction continued for different times upon initiation of anoxia, depending on the nature of the cardioplegic solution. Two hundred micromolar P1,P5-di(adenosine-5')pentaphosphate (Ap5A) stopped atrial function in less than 30 s of anoxia in contrast to 50 s in the case of Hearse's cardioplegic solution (16 mM MgCl2, 16 mM KCl, 1 mM Procaine), and 20 min in the case of controls. The stopping time was also prolonged from 30 to approximately 50-55 seconds if a lower concentration of Ap5A (100 microM) was used. Function, adenine nucleotides (AN), and phosphocreatine (PCr) were then measured 20 min after reoxygenation. The recovery of both function and AN was most rapid and complete with 200 microM Ap5A (97% recovery in ATP and 100% in function) and least complete in control (50% recovery in ATP and 78% in function). A positive correlation between recovery of ATP, or total adenine nucleotides, and recovery of function was observed in all cases. The higher the level of ATP remaining at the end of 1 h of anoxia and the more recovered after 20 min of reoxygenation, the more complete the recovery of function. The PCr returned to normal or even higher than normal values in all cases, even though function returned only in proportion to ATP. Since PCr is mitochondrial in origin, it appears that loss of a portion of the AN localized at the energy-utilizing sites occurred before serious mitochondrial damage and was responsible for the incomplete postanoxic functional recovery.
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PMID:Recovery of isolated rat atrial function related to ATP under different anoxic conditions. 372 10

The effect of diltiazem on post-ischemic metabolic and functional recovery was investigated in regionally ischemic dog hearts. The duration of ischemia was 60 min, followed by 60 min of reperfusion. Diltiazem (bolus injection of 0.1 mg X kg-1 body weight prior to ischemia, followed by a continuous infusion of 0.1 mg X kg-1 X h-1) had no effect on residual coronary flow in the centre of the ischemic area, but blunted the reactive hyperemia response after restoration of flow. The drug partially prevented the depletion of ATP and glycogen in the severely underperfused subendocardial layers, i.e. when residual flow was below 0.1 ml X min-1 X g-1. Reduction of the content of these substances in the subepicardial layers was moderate and not influenced by diltiazem. Segment shortening in the subepicardial layers disappeared whereas segment lengthening was observed in the subendocardial layers during the ischemic period. Diltiazem did not prevent the loss of contractile function. Despite an initial restoration of contractile function within 10 min after reperfusion, no significant beneficial effect of diltiazem treatment on mechanical function of the reperfused area was present thereafter.
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PMID:The effect of diltiazem on myocardial recovery after regional ischemia in dogs. 373 98

Provision of ATP precursors before, during, and after an episode of myocardial ischaemia accelerates repletion of ATP levels and functional recovery of the tissue. To investigate ultrastructural effects of such provision, canine hearts were perfused in situ with sham and AMP solutions. Perfusion was begun 15 min before induction of ischaemia and continued during the 15 min ischaemic and 15 min reperfusion period. Some hearts were then treated with LaOH to label endocytotic vesicles, and the hearts were fixed for electron microscopy. A dramatic and significant increase was found in the number and size of capillary endothelial and subsarcolemmal vesicles in hearts treated with AMP, but not in hearts treated with sham additives. Endocytosis and exocytosis across capillary endothelia, and endocytosis into myocytes is suggested as a mechanism for rapid transport of ATP precursors from the coronary circulation into myocytes.
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PMID:AMP stimulation of endocytotic transport from canine coronary circulation into myocytes. 374 33

Contractile dysfunction in stunned myocardium could result from a decrease in the intracellular free [Ca2+] transient during each beat, a decrease in maximal Ca2+-activated force, or a shift in myofilament Ca2+ sensitivity. We measured developed pressure (DP) at several [Ca]0 (0.5-7.5 mM) in isovolumic Langendorff-perfused ferret hearts at 37 degrees C after 15 min of global ischemia (stunned group, n = 13) or in a nonischemic control group (n = 6). At all [Ca]0, DP was depressed in the stunned group (P less than 0.001). Maximal Ca2+-activated pressure (MCAP), measured from tetani after exposure to ryanodine, was decreased after stunning (P less than 0.05). Normalization of the DP-[Ca]0 relationship by corresponding MCAP (Ca0 sensitivity) revealed a shift to higher [Ca]0 in stunned hearts. To test whether cellular Ca overload initiates stunning, we reperfused with low-[Ca]0 solution (0.1-0.5 mM; n = 8). DP and MCAP in the low-[Ca]0 group were comparable to control (P greater than 0.05), and higher than in the stunned group (P less than 0.05). Myocardial [ATP] observed by phosphorus NMR failed to correlate with functional recovery. In conclusion, contractile dysfunction in stunned myocardium is due to a decline in maximal force, and a shift in Ca0 sensitivity (which may reflect either decreased myofilament Ca2+ sensitivity or a decrease in the [Ca2+] transient). Our results also indicate that calcium entry upon reperfusion plays a major role in the pathogenesis of myocardial stunning.
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PMID:Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts. 381 56


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