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

Thirty-three canine hearts were isolated after initial cardioplegia and preserved for 6 hours in 4 degrees C saline solution with intermittent infusion of cardioprotective solution every hour. Reperfusion was observed for 2 hours under normothermic cross-circulation. Hearts were divided into five groups depending on the agent(s) added to the K(+)-Mg2+ cardioplegic solution (K(+)-Mg(2+)-CP) infused. Control hearts (n = 6) received K(+)-Mg(2+)-CP solution alone; group I (n = 7) received lidocaine, 200 mg/L, added to the K(+)-Mg(2+)-CP solution; group II (n = 7) received betamethasone (250 mg/L) added to the formula for group I; group III (n = 6) received diltiazem (200 micrograms/L) added to the formula for group II; group IV (n = 7) received aprotinin (150 KIU/L) added to the formula of group III. Coronary sinus MB fraction of creatine kinase level was significantly decreased at 60 and 120 minutes of reperfusion in group II, as was mitochondrial aspartate aminotransferase level at 2 hours of reperfusion. Lysosomal enzyme release decreased in group IV. Myocardial adenosine triphosphate levels and total adenine nucleotides showed no significant difference among the groups at the end of reperfusion; however, myocardial adenosine diphosphate and adenosine monophosphate levels during reperfusion increased significantly in group I, and myocardial adenosine diphosphate and adenosine monophosphate levels at the end of reperfusion in groups I and IV were significantly higher than those of the control. Calcium overload, which was lowest in group II, was not completely prevented during reperfusion in any group. Left ventricular end-systolic pressure volume relationship in group II showed the "best" functional recovery. In addition, the ultrastructure of the left ventricular myocardium was well preserved in all groups. These results suggest that membrane stabilization with lidocaine and betamethasone affords beneficial effects on myocardial biochemical and functional viability. Diltiazem appears to be less effective in preventing calcium overload during ischemia-reperfusion, and protease inhibition with aprotinin (150 KIU/ml) seems to be highly effective in suppressing lysosomal enzyme activation-release and maintaining myocardial adenosine diphosphate and adenosine monophosphate levels.
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PMID:Heart preservation: analysis of cardioprotective infusate characteristics. Membrane stabilization, calcium antagonism, and protease inhibition on myocardial viability: a biochemical, ultrastructural, functional study. 137 28

Several biochemical and functional characteristics of immature myocardium suggest a diminished capacity to regulate intracellular Ca2+ during stress. In particular, cellular calcium overload has been postulated as an important pathogenetic mechanism accounting for suboptimal functional recovery following cardioplegia in immature myocardium. Using intracellular Fura-2 fluorescence as Ca2+ indicator, we measured cytosolic free calcium ([Cai]) in single myocytes and cell suspensions derived from both juvenile (4 weeks post-partum) and mature (6-12 months post-partum) New Zealand white rabbits. Resting [Cai] in juvenile heart cells (26 +/- 3 nM) were approximately 50% of that found in adult myocytes (55 +/- 5 nM). In addition, on exposure to increasing concentrations of extracellular potassium ([Kex]), adult but not juvenile myocytes exhibited increases in [Cai]. These two observations underscore developmental differences in intracellular Ca2+ homeostasis. Of particular clinical relevance is the [Cai] response to cardioplegia containing 16 mM [Kex]: neither group demonstrated the expected [Cai] increase in response to potassium depolarization. The lack of [Cai] response to cardioplegia was most likely due to the high levels of Mg2+ (32 mM) contained in cardioplegic solutions. We conclude that cellular calcium overload does not occur following exposure to cardioplegia alone. Accordingly, these findings do not account for recognized developmental differences in functional recovery from "myocardial protection".
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PMID:Developmental differences in the response of cytosolic free calcium to potassium depolarization and cardioplegia in cardiac myocytes. 147 17

The relationship between myocardial preservation and cardioplegic solution pH was assessed in isolated, perfused rat hearts. A base solution without calcium or magnesium and the same solution containing 0.2 mmol/L ionized calcium or 16 mmol/L magnesium or both ions were studied at several values of pH between 6.8 and 8.7. Hearts were arrested at 8 degrees C by multidose infusions of these bicarbonate-buffered solutions bubbled with oxygen and a varying percentage of carbon dioxide to control pH. Diastolic tone (left ventricular balloon) and adenosine triphosphate (ATP) depletion during arrest both increased as the cardioplegic solution became more alkaline. Calcium increased these effects of pH. Magnesium weakened the effect of pH on diastolic tone, maintained ATP at all pH levels, and inhibited the effects of calcium on the relationships of pH to diastolic tone and ATP. When data from all solutions were considered together, ATP depletion was shown to be linearly related to diastolic tone. Calcium depressed functional recovery (left ventricular developed pressure during reperfusion expressed as a percentage of its prearrest value) at all pH levels. With the other solutions, recovery was similar and best within a broad and relatively alkaline pH range. With the solution containing calcium and magnesium, at pH levels of 8.28 +/- 0.02, 7.87 +/- 0.03, 7.58 +/- 0.02, 7.41 +/- 0.01, 7.06 +/- 0.02, and 6.80 +/- 0.01, recovery at 5 minutes of reperfusion was 101.4% +/- 3.7%, 102.9% +/- 2.8%, 107.3% +/- 3.7%, 102.8% +/- 2.9%, 91.8% +/- 3.6%, and 94.3% +/- 3.5%, respectively. This effect of alkalinity was short-lived. Extreme alkalinity of the base, acalcemic solution produced the calcium paradox, as reported previously. Good preservation of ATP by the most acid solutions did not predict good functional recovery. Magnesium increased the persistence of frequent extrasystoles during early reperfusion, but the effect was attenuated by calcium. The data support the inclusion of magnesium in cardioplegic solutions, particularly when they contain calcium, show that cardioplegic solution pH can have major effects on the arrested heart, and suggest that a relatively alkaline pH may modestly benefit functional recovery.
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PMID:Relation of myocardial protection to cardioplegic solution pH: modulation by calcium and magnesium. 192 61

After 10-60 min of normothermic complete ischemia, hippocampal slices were prepared and allowed to recover for 60 min. The presence or absence of an evoked transsynaptic response was measured in CA1, CA3, and dentate gyrus. A selective vulnerability of the field excitatory postsynaptic potential to ischemia was found (CA1 greater than CA3 greater than dentate gyrus). Recovery of synaptic transmission in CA1 and CA3 was significantly improved by decreasing extracellular Ca2+ and increasing Mg2+ after ischemia. Addition of an N-methyl-D-aspartate antagonist further improved functional recovery. Postischemic reduction in extracellular Cl- increased recovery in CA1 and CA3, whilst reduction in Na+ was deleterious.
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PMID:Selective vulnerability of synaptic transmission in hippocampus to ex-vivo ischemia: effects of extracellular ionic substitution in the postischemic period. 254 84

Actually the maximum preservation time for donor hearts is limited to 4 hours. The aim of this experimental study in dogs was to develop techniques allowing an extension of this period up to 24 hours. In the first part of the study the influence of diastolic arrest on the preservation of high energy phosphates was studied: The following methods of cardioplegic arrest were used: 1. hyperkalemic arrest 2. hyperkalemic arrest plus high magnesium 3. low sodium and calcium-free cardioplegia. In all experiments cardioplegic arrest was followed by cold storage (0.5 degrees C). Single dose K+ plus Mg2+ cardioplegia offered the least protection. The other two types of cardioplegia were better but the ATP content was still below 50% after 24 hrs preservation. Reperfusion after cardiac transplantation induced irreversible injury and function did not recover after transplantation. In the second part of the study continuous hypothermic perfusion with low sodium and calcium-free cardioplegia was studied. With this technique HEP content, myocardial structure and functional recovery were 100% after transplantation.
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PMID:[Long-term preservation of the heart in view of its transplantation. An experimental study]. 263 87

Sustained left ventricular pressure development during each infusion of a cold calcium-containing hyperkalemic cardioplegic solution has been observed in rat hearts. The present study was undertaken to relate such contraction (i.e., increase in resting pressure) to myocardial preservation and to the calcium and magnesium contents of a crystalloid hyperkalemic cardioplegic solution. Isolated perfused rat hearts with a left ventricular isovolumic balloon were arrested at 8 degrees C by the fully oxygenated cardioplegic solution infused every 15 minutes for 2 hours. Cardioplegic solutions containing ionized calcium in concentrations of 0, 0.1, or 1.2 mmol/L were each studied with (groups 2, 4, and 6) and without (groups 1, 3, and 5) the addition of magnesium (16 mmol/L). Hearts arrested by the cardioplegic solution with no calcium or magnesium (group 1) developed a pressure (averaged over the second to eighth infusion and expressed as percent prearrest left ventricular pressure) of 6.0% +/- 0.4% during cardioplegic infusions. This solution maintained end-arrest myocardial adenosine triphosphate (13.1 +/- 1.0 nmol/mg dry weight) and phosphocreatine (21.7 +/- 2.8 nmol/mg dry weight) contents near the prearrest contents and preserved left ventricular function at 95% +/- 3% of prearrest developed left ventricular pressure at 15 minutes of reperfusion at 37 degrees C. Calcium (groups 3 and 5) increased pressure development during cardioplegic infusions (10.4% +/- 0.5% and 15.1% +/- 0.9%), depleted adenosine triphosphate (7.2 +/- 1.0 and 7.4 +/- 0.9) and phosphocreatine (13.3 +/- 1.8 and 10.7 +/- 1.5), and depressed left ventricular functional recovery (71% +/- 1% and 73% +/- 3%). Magnesium alone (group 2) decreased pressure development during cardioplegic infusions (3.0% +/- 0.3%), maintained adenosine triphosphate (15.6 +/- 0.9), augmented phosphocreatine (38.3 +/- 1.2), and preserved left ventricular function (99% +/- 4%). Magnesium added to calcium (groups 4 and 6) prevented the calcium-induced increased pressure development during cardioplegic infusions (4.0% +/- 0.5% and 6.7% +/- 0.6%), maintained adenosine triphosphate (13.6 +/- 1.4 and 14.9 +/- 0.7), augmented phosphocreatine (31.3 +/- 1.6 and 32.2 +/- 2.4), and ameliorated the depression of functional recovery (82% +/- 2% and 86% +/- 2%). These data suggest that left ventricular pressure development during arrest contributed to calcium-induced energy depletion and impairment of functional recovery and that these deleterious effects were inhibited by magnesium. The inhibitory effects of magnesium on left ventricular pressure development were rapidly reversed on reperfusion. The data support the addition
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PMID:The effects of calcium and magnesium in hyperkalemic cardioplegic solutions on myocardial preservation. 275 59

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

The protection afforded by cardioplegia during elective ischemic arrest can be partly compromised by a reperfusion injury, which may impede the recovery of cardiac function. We previously showed experimentally that this postischemic damage could be largely avoided by an appropriate crystalloid reperfusate. The present study was thus undertaken to assess the effects of this "reperfusion solution" clinically. One hundred twelve patients undergoing valve replacement with the aid of hypothermic cardioplegia (K+ 12 mEq, Mg2+ 26 mEq) were prospectively divided in two groups: Group I (n = 49) received an unmodified blood reperfusate. In Group II (n = 63), 1 L of the reperfusion solution was delivered just prior to removal of the aortic clamp. The formulation of the reperfusion solution adhered to the following principles: (1) maintenance of cardioplegia (K+ = 15 mEq), (2) replenishment of Ca2+ stores (Ca2+ = 2.5 mEq), (3) substrate provision (glutamate = 2,942 gm), (4) buffering (pH = 7.70 at 28 degrees C), and (5) hyperosmolarity (370 mOsm). The two groups were matched for preoperative data except for a higher incidence of isolated aortic valve replacement (p = 0.01) in Group II. Also, the cross-clamp time (mean +/- standard error of the mean) was longer in Group II (94 +/- 4 minutes versus 63 +/- 4 minutes, p less than 10(-6]. The reperfusion solution was found to increase both the rate and extent of postischemic functional recovery, as evidenced by (1) a lower proportion of catecholamine-supported patients 48 hours after operation (9/63 [14.28%] versus 16/49 [32.6%] in the control group [p less than 0.03]) and (2) a lower amount (gamma/kg/min) of dobutamine required to achieve stable hemodynamics (11 +/- 1 versus 26 +/- 6 in the control group [p less than 0.03]). A similar recovery pattern was noted in the high-risk subgroup of patients with mitral valve disease. Further, serial postoperative hemodynamic measurements were performed in 31 randomly selected patients (10 control and 21 reperfused). Although the reperfused patients were found to be at higher risk because of lower preoperative cardiac indices and longer cross-clamp times, they consistently achieved better postoperative hemodynamics with a lower incidence of catecholamine support. This hemodynamic improvement was particularly reflected by a higher left ventricular stroke work index throughout the postoperative course, the difference being significant 6 hours and 12 hours postoperatively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:An asanguineous reperfusion solution. An effective adjunct to cardioplegic protection in high-risk valve operations. 674 22

Cold K+ cardioplegia is commonly used to preserve the myocardium during surgical ischemia. Since the K+-induced membrane depolarization could cause a Ca2+-mediated breakdown of adenosine triphosphate, this study compared the influence of different electrolytes on high-energy phosphate metabolism during cardioplegic arrest phosphate metabolism during cardioplegic arrest and subsequent recovery of mechanical function. An isolated working heart was subjected to hypothermic ischemia for one hour. Metabolic studies were assessed on phosphorus 31 nuclear magnetic resonance (NMR). Results show that (1) K+ cardioplegia is harmful when the Ca2+ content is equal to 2 mEq/I; (2) deleterious effects of K+ are markedly reduced by lowering the Ca2+ content; (3) the most adequate preservation is provided by a Mg2+-rich-Ca2+-poor perfusate; (4) this protection is not enhanced by addition of K+. Finally, 31P NMR appears particularly appropriate for evaluating myocardial protection techniques since it allows noninvasive serial monitoring of high-energy phosphate content and subsequent correlation with functional recovery after ischemia.
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PMID:Limitations of potassium cardioplegia during cardiac ischemic arrest: a phosphorus 31 nuclear magnetic resonance study. 731 88

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


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