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)

Impaired coronary flow during postischemic reperfusion may limit functional recovery. In the present studies we used the heterotopically transplanted rat heart and the isolated working rat heart to assess whether adenosine, given during reperfusion, could improve either the rate or the extent of postischemic recovery. Hearts were arrested (2 minutes at 4 degrees C) with the St. Thomas' Hospital cardioplegic solution and stored by immersion in the same solution for 8 hours at 4 degrees C. Hearts were then transplanted into the abdomen of homozygous recipients. Immediately before reperfusion, adenosine (0.5 ml of a 1 mumol/L solution, equivalent to 0.13 micrograms) was injected into the left ventricle (control rats received an equivalent amount of saline). Hearts were reperfused in vivo for 30 minutes or 24 hours, after which they were excised and perfused (Langendorff) for 20 minutes for the assessment of function. They were then freeze clamped and taken for metabolic analysis. After 50 minutes of reperfusion, left ventricular developed pressure was 75 +/- 5 mm Hg (4 mm Hg end-diastolic pressure) in the adenosine group versus 61 +/- 4 mm Hg in the control group (p less than 0.05); however, after 24 hours function was identical in the two groups (52 +/- 4 versus 52 +/- 3 mm Hg). After 50 minutes of reperfusion coronary flow was greater in the adenosine group (11.0 +/- 0.4 versus 9.7 +/- 0.4 ml/min in control rats; p less than 0.05), a difference that was sustained for 24 hours (12.8 +/- 0.3 versus 11.4 +/- 0.4 ml/min in control rats; p less than 0.05). Adenosine triphosphate and creatine phosphate contents recovered to similar extents in control and adenosine groups after both 50 minutes and 24 hours of reperfusion. In further studies with an identical storage protocol (8 hours at 4 degrees C), hearts were not transplanted but were reperfused with crystalloid medium in the Langendorff mode for 15 minutes (creatine kinase leakage measured) and in the working mode for 180 minutes. In an attempt to mimic the heterotopic transplant protocol, adenosine (1 mumol/L) was included in the perfusion fluid for the first 2 minutes of reperfusion. Similar results to those of the transplant studies were obtained, with coronary flow being consistently improved in the adenosine group; however, this benefit was lost after only 2 hours of reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)
J Thorac Cardiovasc Surg 1992 Jul
PMID:Exogenous adenosine accelerates recovery of cardiac function and improves coronary flow after long-term hypothermic storage and transplantation. 161 1

Impaired contractile performance at rest is not necessarily due to irreversible tissue damage but may relate to the "hibernating" myocardium. Hibernating myocardium has been defined as potentially reversible, chronic contractile dysfunction during prolonged, painless ischemia. The extent and time course of functional recovery after restoration of flow is of major importance for clinical decision making. The existence of hibernating myocardium was first documented in patients following bypass surgery. Angiographic studies in patients undergoing coronary angioplasty revealed immediate recovery of global and regional systolic, as well as diastolic, function after revascularization. Subgroup analysis showed an improvement in patients without previous myocardial infarctions and in those with non-Q-wave infarctions, but a benefit was not consistently seen in patients with transmural infarctions. A further improvement of systolic function after 15 weeks suggests a biphasic course of recovery. Prospective studies must clarify whether the potential for improvement in function constitutes an indication for revascularization independent of clinical symptoms.
Cardiovasc Drugs Ther 1992 Jun
PMID:Recovery of myocardial function in the hibernating heart. 163 34

U74006F, a novel 21-amino steroid is a potent inhibitor of iron-mediated lipid peroxidation and has been shown to be of therapeutic benefit in central nervous system ischemia. As oxygen radicals have been implicated in the development of postischemic myocardial dysfunction, we examined the efficacy of U74006F to enhance the recovery of function in a canine model of stunned, reperfused myocardium. Twenty-six dogs were randomized to either a vehicle (n = 11), U74006F (n = 10), or U74006F-paced group (n = 5). U74006F (6 mg/kg i.v.) was administered 15 min prior to coronary artery occlusion. Myocardial blood flows were measured by the microsphere technique, and function data were obtained by sonomicrometry. Both U74006F-treated groups demonstrated a significant increase in posterior wall thickening as compared to the vehicle treatment (U74006F-paced, 27.0 +/- 12.8%; U74006F, 22.4 +/- 11%; vehicle, -13.5 +/- 9.9%, p less than 0.001 following 3 h of reperfusion). Enhanced function recovery was accompanied by lower heart rates in the U74006F-treated group following reperfusion (treated versus vehicle, 109 +/- 6.7 versus 131 +/- 8.8 beats/min, p = 0.004). The U74006F-paced group was maintained at the same rate as the vehicle group, with no diminution in function recovery compared to the unpaced group. No effects in systemic hemodynamics or nutrient blood flow were evident as a function of drug treatment. We conclude that pretreatment with U74006F enhances the recovery of function in stunned canine myocardium via the inhibition of oxygen radicals and lipid peroxidation products. This activity suggests that this compound represents a new therapeutic adjunct in reperfusion and recanalization therapies.
J Cardiovasc Pharmacol 1990 Feb
PMID:Effects of U74006F, a novel inhibitor of lipid peroxidation, in stunned reperfused canine myocardium. 168 19

Inosine is a positive inotropic agent and dilates coronary blood vessels. During ischemia, inosine infusion increases blood flow, resulting in decreased myocardial damage. We wished (a) to determine inosine's effect in isolated rat hearts and (b) to determine if inosine attenuates myocardial dysfunction after transient global ischemia. Developed left ventricular pressure (LVP), LV dP/dt, and coronary perfusion pressure were monitored in hearts receiving Krebs-Henseleit buffer (KHB) (n = 10) or KHB + 2 mM inosine (n = 4). KHB + 2 mM inosine significantly reduced coronary perfusion pressure by 21% but had no effect on developed LVP or LV dP/dt. Hearts receiving KHB (n = 6) or KHB + 2 mM inosine (n = 5) were subjected to 15-min global ischemia followed by 30-min reperfusion with KHB. Recovery of LVP, LV dP/dt, the incidence of arrhythmias, and the time to peak recovery of developed LVP was not different between groups. In two additional hearts, KHB + 2 mM inosine administered during reperfusion had no effect on developed LVP, LV dP/dt, or coronary perfusion pressure. Thus, unlike other preparations, inosine pretreatment did not significantly affect the time course of postischemic functional recovery of rat myocardium.
J Cardiovasc Pharmacol 1990 Jun
PMID:Effect of inosine in the normal and reperfused rat heart. 169 7

The purpose of this study was to examine the protective activity of a low concentration of nifedipine (3 x 10(-8) M) against global myocardial ischemic injury in isolated perfused hearts from streptozotocin (STZ) diabetic rats (DR) as compared with control rats (CR). Hearts were subjected to 45-min global ischemia followed by 45-min reperfusion. During ischemia, the period of time until onset of the ischemic contracture was significantly longer in hearts from DR than in hearts from CR (20.3 +/- 1.0 and 15.5 +/- 0.5 min, p less than 0.05). The degree of the ischemic contracture was similar in both types of hearts. During reperfusion, a significantly smaller recovery of left ventricular pressure (LVP) was observed as was a tendency for postischemic coronary flow (CF) to be lower in hearts from DR than in those from CR. After pretreatment with nifedipine, the time of onset of the ischemic contracture was significantly more delayed in hearts from DR than in those from CR: from 20.3 +/- 1.0 to 28.1 +/- 1.2 min (p less than 0.05) and from 15.5 +/- 0.6 to 18.1 +/- 0.9 min (p less than 0.05), respectively. In addition, the degree of the ischemic contracture was reduced (45.3%) in hearts from DR but not in those from CR. During reperfusion, the CF was increased only in hearts from DR. No beneficial effects on functional recovery of LVP were observed in either type of hearts, although recovery tended to be better in diabetic hearts. Nifedipine in a low concentration appears to be more effective against myocardial ischemic injury in diabetes, resulting in an improvement in postischemic CF.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1991 Oct
PMID:Effects of nifedipine on global myocardial ischemic injury in hearts from diabetic and age-matched control rats. 172 31

Six young, sexually mature sheep and seven senescent sheep (aged 0.75 +/- 0.11 years and 7.1 +/- 0.45 years) were instrumented with sonomicrometric crystals and micromanometers to assess global left ventricular mechanics while preload was varied during right heart bypass both before and 30 minutes after 15 minutes of global normothermic ischemia. Left ventricular weight and end-diastolic volume were not significantly different between age groups when indexed to body weight. Contractility was quantitated by the slope of the linear preload-recruitable stroke work relationship and diastolic mechanics by an exponential end-diastolic pressure versus volume function generated over physiologic cardiac workloads. Postischemic systolic functional recovery was markedly worse in the older group (22.7% +/- 10.7% versus 54.2% +/- 9.5%, old versus young, p less than 0.05). However, diastolic stiffness was not changed in either group postischemically. These data demonstrate that the senescent myocardium is less tolerant of ischemia and may require specific intraoperative myocardial management strategies to preserve global pump function.
J Thorac Cardiovasc Surg 1992 Jan
PMID:Age-dependent sensitivity to unprotected cardiac ischemia: the senescent myocardium. 172 15

Depletion of adenosine triphosphate precursors, such as myocardial adenosine, during global ischemia results in poor postischemic adenosine triphosphate repletion and functional recovery. Neonatal hearts may be more resistant to this deleterious effect of ischemia, because they are characterized by low 5'-nucleotidase activity, which may result in higher sustained endogenous myocardial adenosine triphosphate precursor levels during ischemia. Adult hearts, however, have high levels of 5'-nucleotidase activity leading to depleted precursors during ischemia and poor postischemic functional recovery. Augmenting myocardial adenosine exogenously during ischemia in adult hearts has a beneficial effect on recovery. The present study tested if preservation of nucleotide precursors, better adenosine triphosphate repletion, and enhanced postischemic myocardial recovery in adult hearts could be achieved with a "neonatal" strategy. Therefore 5'-nucleotidase inhibitors were administered to isolated, perfused adult rabbit hearts subjected to 120 minutes of ischemia (at 34 degrees C) to determine if this improved functional recovery. Hearts received St. Thomas' Hospital cardioplegic solution (control hearts) or cardioplegic solution containing 5'-nucleotidase inhibitors: pentoxifylline, thioinosine, [s-(p-nitrophenyl)-4-thioinosine], or thioinosine's dimethyl sulfoxide vehicle alone. After ischemia and reperfusion, recovery of systolic function, diastolic function, and myocardial oxygen consumption was significantly better with 5'-nucleotidase inhibition. No changes in coronary flow were noted. We speculate and are pursuing the theory that the mechanism of 5'-nucleotidase inhibition's favorable action is due to preventing the catabolism, transport, and loss of nucleotide precursors during ischemia, maintaining adenosine triphosphate precursor availability.
J Thorac Cardiovasc Surg 1992 Jan
PMID:Enhanced myocardial protection during global ischemia with 5'-nucleotidase inhibitors. 836 Dec 3

The metabolic basis for the enhanced tolerance of immature hearts to ischemia remains to be elucidated. Loss of high-energy phosphate nucleotides occurs during ischemia/reperfusion in mature (adult) hearts through the breakdown of adenosine triphosphate, diphosphate, and monophosphate (nondiffusible) to adenosine (freely diffusible). However, previous work has shown that after ischemia nondiffusible nucleotides are better retained by immature (neonatal) hearts than by mature hearts. The enzyme responsible for the conversion of adenosine monophosphate to adenosine is 5'-nucleotidase. We therefore hypothesized lower activity of this enzyme in neonatal than in adult myocardium. The purposes of this study were (1) to document 5'-nucleotidase activities in neonatal and adult rabbit myocardium and (2) to correlate differences of 5'-nucleotidase activity with functional recovery from ischemia. Neonatal (5- to 10-day-old) and adult (4- to 6-month-old) rabbit hearts were isolated and perfused (retrograde Langendorff). A left ventricular balloon measured functional parameters. Hearts were subjected to 20 minutes of global 37 degrees C ischemia and 10 minutes of reperfusion followed by freeze clamping. Tissue homogenates were assayed for 5'-nucleotidase by the linked formation of nicotinamide-adenine dinucleotide at 340 nm (Arkesteijn method). Postischemic recovery of developed pressure was 86% +/- 3% in neonates (n = 5) versus 38% +/- 3% in adults (n = 8) (mean +/- standard deviation) (p less than 0.01). 5'-Nucleotidase activity was 4400 +/- 1208 nmol/min/gm in neonates (n = 5) versus 13,938 +/- 830 nmol/min/gm in adults (n = 8) (mean +/- standard deviation) (p less than 0.01). We conclude that (1) 5'-nucleotidase activity is 68% lower in neonatal than in adult myocardium and (2) functional recovery after ischemia inversely relates to 5'-nucleotidase activity.
J Thorac Cardiovasc Surg 1992 Feb
PMID:Cardiac 5'-nucleotidase activity increases with age and inversely relates to recovery from ischemia. 173 85

We tested the effects of glucose and oxygen in cardioplegic solutions on myocardial protection in the isolated perfused working rat heart. Recovery from 2 hours' hypothermic (8 degrees C) cardioplegic arrest was examined in 93 hearts. Cardioplegic solution, which was delivered every 15 minutes, was supplemented with glucose 28 mmol/L as a substrate or sucrose 28 mmol/L as a nonmetabolizable osmotic control; it was equilibrated with either 98% oxygen or 98% nitrogen, both with 2% carbon dioxide. Four combinations of hyperkalemic cardioplegic solution were studied: nitrogen-sucrose, nitrogen-glucose, oxygen-sucrose, and oxygen-glucose. During hypothermic arrest, oxygenation of cardioplegic solution greatly reduced myocardial lactate production and prevented ischemic contracture as indicated by coronary vascular resistance. Glucose increased lactate production modestly but significantly only when the cardioplegic solution was nitrogenated. Although end-arrest myocardial adenosine triphosphate and creatine phosphate were greatly increased by oxygenation of cardioplegic solution (p less than 0.005), we could not detect improved preservation of these high-energy phosphates by glucose. Averaged over reperfusion, percent recovery of cardiac output for the nitrogen-sucrose, nitrogen-glucose, oxygen-sucrose, and oxygen-glucose solutions was 32.3% +/- 6.1%, 45.9% +/- 4.6%, 44.5% +/- 4.6%, and 62.2% +/- 4.5%, respectively. Oxygenation of the glucose solution or addition of glucose to the oxygenated solution significantly improved recovery of cardiac output. The benefits of glucose and oxygen were additive, so that the oxygen-glucose cardioplegic solution provided the best functional recovery. We conclude that the addition of glucose to the fully oxygenated multidose cold cardioplegic solution improves functional recovery without increasing lactate production during arrest.
J Thorac Cardiovasc Surg 1992 Feb
PMID:Benefits of glucose and oxygen in multidose cold cardioplegia. 173 87

Experimental evidence indicates that calcium antagonists enhance the recovery of contractile function in canine myocardium stunned by a brief, 15-minute episode of transient coronary artery occlusion. In fact, both nifedipine and verapamil have been shown to improve systolic contraction, even when treatment was delayed, that is, when the agents were administered 30 minutes after reperfusion. The beneficial effects of delayed treatment were not a consequence of myocardial high-energy phosphate preservation. Furthermore, as low-dose intracoronary nifedipine enhanced the recovery of function in the absence of systemic hemodynamic or coronary vasodilatory effects, the improved function associated with delayed administration of calcium antagonists could not be attributed solely to afterload reduction or increased coronary blood flow. These data suggest that calcium-channel blockers exert a direct effect on the previously ischemic tissue, perhaps by subtle modulation of calcium transport or flux within the stunned myocytes. Although the precise mechanism of action of these agents remain unresolved, these intriguing experimental results raise the possibility that calcium antagonists may provide a clinically useful means of attenuating postischemic dysfunction of viable myocardium salvaged by thrombolysis, angioplasty, or cardiopulmonary bypass. The potential role of calcium-channel blockers in these clinical instances of stunned myocardium awaits further evaluation.
Cardiovasc Drugs Ther 1991 Oct
PMID:Calcium antagonists and stunned myocardium: importance for clinicians? 175 42


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