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)

Isolated working rat hearts were exposed to 25 min ischemia, and functional recovery was assessed by aortic flow (AoF) and rate-pressure product (RPP) to evaluate the beneficial effects of potassium (20 mM) induced arrest (K-arrest) prior to ischemia. K-arrest improved the recovery of function after 30 min of reperfusion compared with the control group (%AoF: 68 +/- 6 vs 0%, %RPP: 90 +/- 3% vs 60 +/- 3%, p less than 0.01). The accumulation of Ca++ at the end of reperfusion was less in hearts with K-arrest (2.2 +/- 0.1 vs 4.5 +/- 0.3 mumol/g dry, p less than 0.01). There was no difference between the two groups in high energy phosphate content at the end of ischemia. The increase in intracellular Na+ (Nai) during ischemia was reduced in hearts with K-arrest (delta: 19 vs 46 mumol/g dry), and the level of intracellular K+ (Ki) was higher at the end of ischemia in hearts with K-arrest (341 +/- 4 vs 318 +/- 2 mumol/g dry, p less than 0.01). During the first 5 min of reperfusion, the level of Ki in K-arrested hearts jumped to a higher level than in the control group (delta: 15 vs 2 mumol/g dry, p less than 0.01). The level of Nai was lower in hearts with K-arrest after 5 min of reperfusion. These data suggested that K-arrest might preserve the activity of Na+/K+ ATPase during ischemia and early reperfusion, and that it attenuated the increase in Nai during ischemia and reperfusion, which resulted in less Ca++ overload during reperfusion via the Na+/Ca++ exchange mechanism and led to improved recovery.
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PMID:[Mechanism of myocardial protection with potassium arrest in isolated ischemic rat hearts]. 166 47

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.
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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.
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PMID:Effect of inosine in the normal and reperfused rat heart. 169 7

During 10 mins of reperfusion after 25 mins global ischemia, subtoxic doses of ouabain (50, 100 microM) were used and followed by 20 mins reperfusion with standard buffer. At these doses ouabain had no harmful effects with 29% and 45% increase in developed pressure in aerobic hearts. Intracellular Na+ (Nai), 45Ca2+ uptake and recovery of ventricular function were measured. Nai increased from 15 to 64 mumol/g dw with no increase in 45Ca2+ uptake during ischemia. Upon reperfusion with standard buffer, additional gain in Nai at 2 mins (73 mumol/g dw) was followed by a rapid decline (at 10 mins: 48 mumol/g dw). 45Ca2+ uptake increased from 0.8 to 7.5 mumol/g dw after 30 mins reperfusion with decreased recovery of function (45%) and increased LVEDP (29 mmHg). Reperfusion with ouabain accelerated initial rise in Nai (2 mins: 79 and 83 mumol/g dw) and decline of Nai was retarded (10 mins: 65 and 83 mumol/g dw). Consequently, 45Ca2+ uptake and depression of function were augmented (Ca: 10.0, 11.5 mumol/g dw; function: 27%, 18%; LVEDP: 47, 48 mmHg) even when hearts were switched back to standard buffer. Combination of high K+ (20mM) reversed the effect of ouabain. The results suggested increased susceptibility to ouabain was caused by inhibited outward Na+ transport resulting in enhanced Ca2+ influx through Na+/Ca2+ exchange.
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PMID:[Enhancement of susceptibility to ouabain in ischemic rat heart]. 170 9

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)
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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.
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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.
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PMID:Enhanced myocardial protection during global ischemia with 5'-nucleotidase inhibitors. 836 Dec 3

Cardiopulmonary bypass is known to cause neutrophil activation, and activated neutrophils appear to be of importance in myocardial reperfusion injury. This study examined the effect of a preischemic infusion of activated neutrophils on the recovery of myocardial function after 40 minutes of hypothermic global ischemia. Studies were carried out in three groups of Langendorff-perfused rabbit hearts: control, control (unactivated) neutrophil infusion, and phorbol myristate acetate-activated neutrophil infusion. The activated neutrophil group showed significant deterioration in function during the activated neutrophil infusion. All three groups demonstrated significant depression of function initially after reperfusion, but the two control groups subsequently recovered to baseline levels. The activated neutrophil group, however, showed a persistent significant depression in ventricular force, rate of ventricular tension development, and rate of ventricular relaxation as well as a significant increase in coronary vascular resistance. It is concluded that activated neutrophils depress myocardial function and contribute to impaired recovery of function after global hypothermic ischemia.
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PMID:Activated neutrophils impair rabbit heart recovery after hypothermic global ischemia. 173 63

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.
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PMID:Cardiac 5'-nucleotidase activity increases with age and inversely relates to recovery from ischemia. 173 85

Triglyceride turnover in reperfused/ischemic rat hearts was investigated. Hearts were initially perfused under aerobic conditions for a 1-h "pulse" perfusion with 1.2 mM [1-14C]palmitate to label the endogenous lipid pools, followed by a 30-min period of no-flow ischemia or a 10-min period of retrograde perfusion (control). Hearts were then reperfused under aerobic conditions with buffer containing 1.2 mM [9,10-3H]palmitate. All buffers contained 11 mM glucose and 500 microunits/ml insulin. Rates of endogenous triglyceride lipolysis and synthesis were measured during reperfusion, whereas rates of exogenous palmitate oxidation were measured both prior to ischemia and during reperfusion following ischemia. During reperfusion of ischemic hearts, a 20% increase in exogenous fatty acid oxidation rates was seen compared with pre-ischemic rates. Despite an initial burst of endogenous fatty acid oxidation, no acceleration of steady state endogenous triglyceride lipolysis was seen compared with their nonischemic hearts. In contrast, a significant increase in triglyceride synthesis was observed. Triglyceride turnover was also measured in a series of hearts reperfused following ischemia in the absence of exogenous fatty acids. A significant enhancement of functional recovery was seen compared with hearts reperfused with 1.2 mM palmitate. In addition, a significant increase in fatty acid oxidation from endogenous triglyceride lipolysis was observed. We conclude that the heart quickly recovers its ability to oxidize exogenous fatty acids during reperfusion and that although triglyceride lipolysis is not accelerated during reperfusion of ischemic hearts in the presence of 1.2 mM palmitate, a significant increase in triglyceride synthesis does occur.
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PMID:Myocardial triglyceride turnover during reperfusion of isolated rat hearts subjected to a transient period of global ischemia. 174 Apr 30


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