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PubMedDate not supplied

Plasticity and functional recovery in neurology.

Experiments on patients with phantom limbs suggest that neural connections in the adult human brain are much more malleable than previously assumed. Three weeks after amputation of an arm, sensations from the ipsilateral face are referred to the phantom; this effect is caused by the sensory input from the face skin 'invading' and activating deafferented hand zones in the cortex and thalamus. Many phantom arms are 'paralysed' in a painful position. If a mirror is propped vertically in the sagittal plane and the patient looks at the reflection of his/her normal hand, this reflection appears superimposed on the 'felt' position of the phantom. Remarkably, if the real arm is moved, the phantom is felt to move as well and this sometimes relieves the painful cramps in the phantom. Mirror visual feedback (MVF) has shown promising results with chronic regional pain syndrome and hemiparesis following stroke. These results suggest two reasons for a paradigm shift in neurorehabilitation. First, there appears to be tremendous latent plasticity even in the adult brain. Second, the brain should be thought of, not as a hierarchy of organised autonomous modules, each of which delivers its output to the next level, but as a set of complex interacting networks that are in a state of dynamic equilibrium with the brain's environment. Both principles can be potentially exploited in a clinical context to facilitate recovery of function.

Brain↗
PubMed1998

Predictive value of 99Tcm-sestamibi gated SPET for long-term myocardial perfusion and functional recovery after an acute myocardial infarction.

We assessed the predictive value of 99Tcm-sestamibi gated single photon emission tomography (SPET) for changes in perfusion and functional outcome after an acute myocardial infarction and compared the findings on functional recovery with echocardiography using low-dose dobutamine. Gated 99Tcm-sestamibi SPET and radionuclide angiocardiography were performed in 17 patients 4-10 days after an acute myocardial infarction. Six months later, both isotopic studies and rest-dobutamine echocardiography were performed to assess outcome. Perfusion improved in six of seven severely hypoperfused segments (positive predictive value = 85.7%) that showed wall thickening but not in any of 28 segments (negative predictive value = 100%) without wall thickening. The mean ejection fraction improved from 47.7 to 52.3% (P = 0.018). Furthermore, there was a greater improvement in ejection fraction in the group of patients in whom wall thickening predicted a recovery in perfusion (9.0 vs 3.7%, P = 0.01). A comparison of the assessment of functional recovery between gated SPET and dobutamine echocardiography showed good agreement (81.4%). We conclude that the presence of wall thickening in severely hypoperfused segments on 99Tcm-sestamibi gated SPET is predictive of changes in perfusion and functional recovery after acute myocardial infarction, thus identifying the presence of viable myocardium. In contrast, segments showing hypoperfusion and dysfunction after an acute myocardial infarction probably contain scar tissue only.

Adult↗
PubMed1996

Dobutamine stress echocardiography early after myocardial infarction treated with thrombolysis. Identification of myocardial viability and ischemia and relation to spontaneous functional recovery.

The aim of the study was to assess the ability of dobutamine stress echocardiography to detect myocardial viability and ischemia in patients with acute myocardial infarction treated with thrombolysis and to correlate the acute response to dobutamine with late spontaneous functional recovery at follow-up. Forty-two consecutive patients with myocardial infarction treated with thrombolysis underwent low- (5 and 10 mcg/kg/min) and high-dose (20 to 40 mcg/kg/min) dobutamine stress echocardiography at a mean of 7 +/- 3 days of the acute phase. A follow-up 2D-echocardiogram was performed in all patients to evaluate the spontaneous recovery of function in the infarct area. On the basis of the response to the test, 3 groups of patients were identified: group 1 included 7 patients showing an improvement in left ventricular asynergy score index at low doses (from 1.5 +/- 0.3 to 1.3 +/- 0.2, p < 0.05) with no deterioration at high doses, indicative of myocardial viability without ischemia; group 2 (23 patients) showed a significant improvement in the asynergy index at low doses (from 1.58 +/- 0.3 to 1.32 +/- 0.32, p < 0.05) followed by a deterioration at high doses (1.68 +/- 0.4, p < 0.05 vs low-dose), suggestive of residual myocardial ischemia in the infarct zone; group 3 included 12 patients who showed no significant changes in the baseline asynergy score index (1.67 +/- 0.2) either at low or at high doses. The acute response to dobutamine stress echocardiography accurately predicted the spontaneous recovery of function in the infarct area at follow-up: both group 1 and group 2 patients showed a significant reduction in the asynergy score index (group 1: 1.16 +/- 0.3 vs 1.5 +/- 0.2, p < 0.001; group 2: 1.43 +/- 0.3 vs 1.58 +/- 0.3, p < 0.05), while group 3 had no recovery in the asynergy index (1.67 +/- 0.2 vs 1.67 +/- 0.2). Thus, in patients with acute myocardial infarction treated with thrombolysis dobutamine stress echocardiography can detect myocardial viability in 71% and ischemia in the infarct zone in 55% of patients; moreover, the response to the test during the acute phase is correlated with the degree of the late spontaneous recovery of function in the infarct area.

Adult↗
PubMed1983

Reversal of myocardial ischemic contracture and the relationship to functional recovery and tissue calcium.

We subjected isolated rat hearts to normothermic ischemia until contracture developed, then reperfused them for 30 min. Recovery of developed pressure, rate of change in left ventricular pressure (dP/dt), and changes in end-diastolic pressure measured after 30 min of reperfusion were compared with preischemic values for each heart. Values after untreated ischemic arrest were compared with those after potassium arrest, potassium reperfusion (both oxygenated and deoxygenated), and combined potassium arrest and potassium reperfusion. Potassium arrest lengthened the time to the onset of contracture and thus lengthened the total ischemic time. Functional recovery was not improved over that in the untreated hearts, most likely due to this additional ischemic time. The use of buffer with a high potassium content for the first 5 min of reperfusion, however, significantly improved functional recovery if the perfusate was oxygenated, but did not improve functional recovery if the perfusate was deliberately deoxygenated. Combined potassium arrest and reperfusion delayed the onset of contracture and thus increased total ischemic time, yet improved recovery. Tissue calcium was elevated in all hearts undergoing contracture and reperfusion. Our results suggest that contracture can be reversed and that functional recovery can be improved in spite of increased tissue calcium.

Animals↗
PubMed1993

[Correlation of myocardial temperature, intramyocardial pH, and myocardial electrical activity during hyperkalemic hypothermic cardioplegic arrest to functional recovery after reperfusion].

We estimated the correlation of myocardial temperature, intramyocardial pH, and myocardial electrical activity (MEA) during hyperkalemic hypothermic cardioplegic arrest to functional recovery after reperfusion to assess those parameters as intra-operative on-line assessment of myocardial preservation during cardiac operation. Twenty dogs underwent cardiopulmonary bypass at 30 degrees C. Cardiac function was evaluated before and after two hours ascending aortic cross-clamping. The dogs were divided into four groups according to cardiac preservation methods employed. Group I (n = 6): 4 degrees C hyperkalemic crystalloid cardioplegic solution was delivered antegradely through the aorta every 30 minutes without topical cooling. Group II (n = 4): total volume of cardioplegic solution same as Group I was delivered only once without topical cooling. Group III (n = 5): cardioplegic solution same as Group I with lidocaine (100 mg/l) was delivered every 30 minutes without topical cooling. Group IV (n = 5): cardioplegic solution same as Group I was delivered every 30 minutes with topical cooling. Hearts at less than 8 degrees C during aortic cross-clamping (Group I) revealed better functional recovery (72 +/- 21%) than those over 15 degrees C (Group II-IV, 28 +/- 30%). There was no significant correlation between intramyocardial pH changes during aortic cross-clamping and functional recovery after reperfusion (R = -.2257). During aortic cross-clamping, the occurrence of MEA which was obtained directly from the electrode inserted into left ventricular anterior free wall (direct MEA) was observed in all cases. However the myocardial activities which were identified by direct MEA were not necessarily observed visually or by routine electrocardiogram.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed2003

Regeneration and functional recovery in the upper extremity of rats after various types of nerve injuries.

The aim was to establish an accurate, reproducible, and simple method to evaluate functional recovery after different types of nerve injuries to the brachial plexus of rats. To that end, pawprints, measured as distance between the first and fourth and second and third digits, were used for evaluation of injuries including crush injury, transection/repair, or graft repair of the median, ulnar, and radial nerves. Immunocytochemistry of the C-terminal flanking peptide of neuropeptide Y (CPON) and neurofilaments was used to investigate the cell body response and axonal outgrowth, respectively. Functional recovery was dependent on the severity as well as on the level of the lesion. Neither a single injury to the median nerve nor an injury to the ulnar nerve affected the pawprint, while an injury to both these nerves or a single injury to the radial nerve caused impairment of pawprints. There was a rapid recovery after crush injury to these nerves compared to previous reports of a similar injury to the sciatic nerve. The pattern of axonal outgrowth was related to the severity of the lesion. A conditioning lesion, i.e., an initial lesion of the same nerve preceding a test injury by a few days, of both motor/sensory fibers led to a quicker functional recovery. Surprisingly, conditioning of only sensory fibers had nearly the same effect. The cell body response was dependent on the level of the nerve lesion. The upper extremity of rats might be useful to evaluate the effects of new repair methods after nerve injuries using functional evaluation with pawprints as a simple and accurate method.

Analysis of Variance↗
PubMed1982

Improved functional recovery of ischemic myocardium by suppression of adenosine catabolism.

Isolated working rat heart preparations were used to ascertain whether the addition of adenosine and prevention of its catabolism could aid in the functional recovery of hearts following global ischemia. Hearts were infused with either 80 micro M EHNA (an adenosine deaminase inhibitor) or 20 micro M adenosine and EHNA in either normal (2.4 mM) or low (0.05 mM) calcium-containing buffer prior to clamping of the aorta for 30 minutes. In one series of hearts, postischemic concentrations (mumoles/gram wet weight) of adenosine triphosphate (ATP), diphosphate (ADP), and monophosphate (AMP), adenosine, inosine, and hypoxanthine were measured; in another series, the recovery of aortic flow rate was used as a measure of functional recovery of ventricular muscle. With normal electrolyte balance, EHNA was unable to protect hearts against ATP loss and ventricular failure. Hearts with EHNA + adenosine recovered 14% of preischemic aortic output and ATP levels were slightly elevated at 0.93 mumole/gm. Those treated with either EHNA or EHNA + adenosine in low-calcium buffer recoverd 100% of their original aortic output. However, EHNA + adenosine maintained considerably higher ATP levels (1.57 mumoles/gm) than did EHNA alone (1.14 mumoles/gm) and was associated with faster initial recovery of aortic output. Thus the prevention of adenosine catabolism was insufficient for adequate ventricular recovery unless the tissue ATP was maintained above about 1.0 mumole/gm. EHNA + adenosine in a 0.05 mM Ca++ infusion solution conserved ATP, markedly improved the functional recovery of hearts, and thus may have a role to play in myocardial preservation during elective cardiac arrest.

Adenine↗
PubMed2003

5-HT1A receptors are involved in short- and long-term processes responsible for 5-HT-induced locomotor function recovery in chronic spinal rat.

After thoracic spinal cord transection, a paraplegic syndrome occurs. Previous data showed that an acute administration of a 5-HT2 agonist (quipazine) could promote motor function recovery in spinal rats. However, continuous subdural perfusion of quipazine via an osmotic pump over 1 month proved to be more effective. The present study was designed to investigate the possible involvement of 5-HT1A receptors in such recovery. Motor performances and locomotor parameters were analysed in spinal animals receiving daily, for 1 month, a dose of the 5-HT1A agonist 8-OHDPAT. The results were compared to those obtained in spinal rats receiving either a placebo or quipazine in the same conditions. Using daily injections instead of continuous perfusion of either receptor agonist to spinal animals allowed characterization of short- and long-term consequences of pharmacological stimulation of 5-HT1A and 5-HT2 receptors on motor function recovery. Our data demonstrate that daily injections of a 5-HT1A agonist induce long-term, cumulative, positive effects on motor function recovery, as assessed by the improvement in the walking parameters observed before the 'day-test' injection. This might involve use-dependent processes depending on a chronic and/or repetitive stimulation of the spinal network for locomotion in relation to 5-HT receptor activation. A further improvement in the motor parameters, transiently observed following the injection, suggests a more direct action of 5-HT1A and 5-HT2 receptor activation on spinal neurons involved in motor pattern generation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2007

Observation of locomotor functional recovery in adult complete spinal rats with BWSTT using semiquantitative and qualitative methods.

STUDY DESIGN: Experimental rat model of spinal cord transection . SETTING: China rehabilitation research center. OBJECTIVE: To investigate locomotor functional recovery in spinal rats with BWSTT using semiquantitative and qualitative methods. METHODS: Five-day postoperative (dpo), adult female complete spinal rats (at T(8) level) received 40 days of body weight-supported treadmill training (BWSTT). Signs of functional recovery were examined with average combined scores (ACOS) and Basso Beattie and Bresnahan (BBB) scales at different time points. RESULTS: At 1-dpo, none of the spinal rats exhibited hindlimb movements. The spinal rats displayed functional progress with time, but the rare could recover to full weight-bearing hindlimb at 45-dpo. BBB and ACOS scores in the BWSTT group obtained better scores than those in the spinal cord injury (SCI) group at 30- and 45-dpo. Furthermore, all BBB and ACOS scores of spinal rats reached statistical significance between 7- and 30-dpo, and between 15- and 30-dpo. However, only ACOS but not BBB scores in the SCI and BWSTT groups showed statistics differences between 15- and 45-dpo, and between 30- and 45-dpo. The Spearman correlation coefficients of BBB and ACOS scores were 0.913 and 0.972 for the SCI and BWSTT groups, respectively. CONCLUSIONS: The results confirmed the existence of partial spontaneous hindlimb functional recovery in adult chronically spinal cord-transected rats, and that BWSTT can improve motor performance. In addition, our study suggests that qualitative and semiquantiative methods are strongly correlated with locomotor recovery in spinal rats, and the latter may be more sensitive in reflecting minor variance at different time points.

Analysis of Variance↗
PubMed1997

Reperfusion adequacy and functional recovery.

Ischemic myocardium undergoes many physiologic changes, including alterations in contractile function, histologic condition, and oxygen utilization. Reperfusion of ischemic myocardium may reverse some of these changes; however, the level of reperfusion needed for adequate functional recovery, as opposed to myocyte salvage, remains controversial. This study examines the effects of varying levels of reperfusion following ischemia on functional parameters of recovery. Isolated rabbit hearts were subjected to global ischemia at 37 degrees C for 10, 20, or 45 min. The hearts were reperfused at either mean normal baseline pressure (80 mm Hg), one half baseline (40 mm Hg), or one fourth baseline (20 mm Hg). With reperfusion, although all hearts retained the compensatory metabolic ability to upregulate oxygen extraction, reduction of reperfusion pressure resulted in depression of contractility and myocardial oxygen consumption, especially with low-pressure reperfusion. These findings suggest that all levels of reperfusion are not equal for optimal myocardial functional recovery. As minimal reperfusion may result in persistent stunning of myocardium, other means of enhancing reperfusion, such as percutaneous transluminal coronary angioplasty or coronary artery bypass grafting, should be considered.

Angioplasty, Balloon, Coronary↗
PubMed2001

Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins.

Little axonal regeneration occurs after spinal cord injury in adult mammals. Regrowth of mature CNS axons can be induced, however, by altering the intrinsic capacity of the neurons for growth or by providing a permissive environment at the injury site. Fetal spinal cord transplants and neurotrophins were used to influence axonal regeneration in the adult rat after complete spinal cord transection at a midthoracic level. Transplants were placed into the lesion cavity either immediately after transection (acute injury) or after a 2-4 week delay (delayed or chronic transplants), and either vehicle or neurotrophic factors were administered exogenously via an implanted minipump. Host axons grew into the transplant in all groups. Surprisingly, regeneration from supraspinal pathways and recovery of motor function were dramatically increased when transplants and neurotrophins were delayed until 2-4 weeks after transection rather than applied acutely. Axonal growth back into the spinal cord below the lesion and transplants was seen only in the presence of neurotrophic factors. Furthermore, the restoration of anatomical connections across the injury site was associated with recovery of function with animals exhibiting plantar foot placement and weight-supported stepping. These findings suggest that the opportunity for intervention after spinal cord injury may be greater than originally envisioned and that CNS neurons with long-standing injuries can reinitiate growth, leading to improvement in motor function.

Animals↗
PubMedDate not supplied

Noradrenergic pharmacotherapy, intracerebral infusion and adrenal transplantation promote functional recovery after cortical damage.

The research described in this review briefly summarizes evidence that short term pharmacological enhancement of noradrenergic (NA) synaptic activity, combined with symptom relevant experience (SRE), promotes functional recovery of some symptoms of cortical damage in rat, cat and human beings even when treatment is initiated from days to weeks after injury. A summary is provided of the numerous drugs tested in rodent cortical injury models which have been proven useful for predicting beneficial or harmful effects on behavioral outcome in human stroke. The pattern of drug effects indicates a central role for NA in functional recovery. Additionally, studies of the effects of direct intraventricular infusion of monoamine neurotransmitters are reviewed and further support the hypothesized role of NA in recovery from some symptoms of cortical injury. The site of NA/SRE interaction to promote recovery from hemiplegia apparently involves the cerebellar hemisphere contralateral to the cortical injury. Microinfusions of NA into the contra- but not ipsilateral cerebellar hemisphere dramatically enhance recovery. Furthermore, like its systemic action, microinfusion of the alpha 1-NA receptor antagonist, phenoxybenzamine, reinstates hemiplegia. A "permanent" symptom of motor cortex injury in the cat is the complete loss of tactile placing contralateral to the injury which does not spontaneously recover for as long as seven years after ablation. This postural reflex is temporarily restored for 8-12 hours following amphetamine administration. However, this permanently lost reflex can be enduringly restored by transplanting catecholamine secreting adrenal tissue into the wound cavity. The experiment is reviewed in detail and involves chromaffin cell autografts into the frontal cortex ablation wound cavity producing a restoration of tactile placing for the 7-10 month duration of the study. This enduring restoration of tactile placing is considered a result of the release of catecholamines into the CNS from the grafted chromaffin cells found, by histochemical methods, surviving 7-10 months after transplant. Lastly, we attribute these delayed treatment effects to an attenuation of a diaschisis, or remote functional depression, in morphologically intact areas anatomically connected to the area of injury. The widespread reduction of glycolytic and oxidative metabolism, produced by focal cortical injury, is normalized by the same treatment which alleviates symptoms and is worsened by drugs which exacerbate deficits. These data support the hypothesis that providing SRE during a period of enhanced NA synaptic activity produces an enduring functional recovery after cortical injury by attenuating remote functional depression. This treatment for enhancing recovery is especially attractive since it is effective even when begun weeks after cortical damage.

Adrenal Glands↗
PubMedDate not supplied

Determinants of functional recovery in older adults surgically treated for cancer.

The purpose of this study was to examine the psychosocial and disease-specific factors that influence functional recovery in older adults newly diagnosed with cancer. Multivariate logistic regression models were estimated using panel data from a sample of community-residing adults older than 65 years surgically treated for lung, prostate, breast, or colorectal cancer (N = 172). Data were obtained between 1993 and 1997 during interviews 4 to 6 weeks after cancer surgery for Wave 1 and 14 to 16 weeks after hospital discharge for Wave 2. The outcome measure, functional recovery, was determined by comparing the physical function and physical role subscales of Medical Outcomes Study (MOS) SF-36 over time. Findings showed that prostatectomy patients were more likely to recover by Wave 2 when compared to individuals with lung, colon, or breast resections. Comorbidities and symptom severity were each significantly associated with a decreased probability of recovery. Pain and fatigue were the most common and most severe symptoms reported, regardless of primary site. Psychological well-being was a significant factor influencing functional recovery when age, comorbidities, site of disease, and symptom severity were controlled. The results clearly point to the need for psychological support following cancer surgery.

Activities of Daily Living↗
PubMed2000

Combined treatment with alphaMSH and methylprednisolone fails to improve functional recovery after spinal injury in the rat.

To date, relatively little progress has been made in the treatment of spinal cord injury (SCI)-related neurological impairments. Until now, methylprednisolone (MP) is the only agent with clinically proven beneficial effect on functional outcome after SCI. Although the mechanism of action is not completely clear, experimental data point to protection against membrane peroxidation and edema reduction. The melanocortin melanotropin is known to improve axonal regeneration following sciatic nerve injury, and to stimulate corticospinal outgrowth after partial spinal cord transection. Recently, we showed that intrathecally administered alphaMSH had beneficial effects on functional recovery after experimental SCI. Since both drugs have shown their value in intervention studies after (experimental) spinal cord injury (ESCI), we decided to study the effects of combined treatment. Our results again showed that alphaMSH enhances functional recovery after ESCI in the rat and that MP, although not affecting functional recovery adversely by itself, abolished the effects observed with alphaMSH when combined. Our data, thus, suggest that the mechanism of action of MP interferes with that of alphaMSH.

Action Potentials↗
PubMed2002

Functional recovery and neuroanatomical plasticity following middle cerebral artery occlusion and IN-1 antibody treatment in the adult rat.

Stroke is a prevalent and devastating disorder, and no treatment is currently available to restore lost neuronal function after stroke occurs. One unique therapy that may improve functional recovery after stroke is blockade of the neurite inhibitory protein Nogo-A with the monoclonal antibody IN-1, through enhancement of neuroanatomical plasticity from uninjured areas of the central nervous system. In the present study, we combined IN-1 treatment with an ischemic lesion (permanent middle cerebral artery occlusion) to determine the effect of Nogo-A neutralization on cortical plasticity and functional recovery. We report here that, following ischemic stroke and treatment with IN-1, adult rats demonstrated functional recovery on a forelimb-reaching task and new cortico-efferent projections from the opposite, unlesioned hemisphere. These results support the efficacy of Nogo-A blockade as a treatment for ischemic stroke and implicate plasticity from the unlesioned hemisphere as a mechanism for recovery.

Age Factors↗
PubMed2004

Contractile reserve, thallium-201 reverse redistribution and mismatch between perfusion and metabolism in reperfused infarct-related myocardium with delayed and incomplete functional recovery.

We investigated simultaneously the correlations between dobutamine-induced contractile reserve (CC), thallium-201 reverse redistribution (RR) and a mismatch between perfusion and metabolism (MM) to the magnitude of functional recovery. In 32 patients with coronary angioplasty early after infarction, echocardiography was performed at low-dose dobutamine stress within 1 week and at resting state at 1 month. Thallium-201/iodine-123 beta-methyl-iodophenyl pentadecanoic acid (BMIPP) dual-isotope single photon emission tomography was performed at 1 month. Wall motion and the uptake of each tracer were scored as 0 to 2 in the infarct-related segments, and CC, RR, and MM were evaluated in the infarct-related segments. In 71 akinetic or dyskinetic segments before reperfusion, the initial thallium-201 uptake and initial BMIPP uptake scores and the 4 hour redistribution thallium-201 uptake scores were less severe in the group with complete functional recovery (group A), followed by the group with incomplete recovery (group B) and then the group with no recovery (group C) (each P < 0.0001). CC was the greatest in group A, followed by group B, and then group C (76.2% in 16/21, 60% in 15/25, 36% in 9/25, P = 0.0212). RR and MM were greater in group B (52% in 13 and 64% in 16) than in groups A and C (19% in 4 and 8% in 2, 33.3% in 7 and 24% in 6, P = 0.0013 and P = 0.0113). The intensity of functional damage reflects perfusion and metabolism, but the delayed and incomplete functional recovery after reperfusion may be closely related to RR, MM, and CC.

Aged↗
PubMed2006

The effect of verapamil on the restoration of myocardial perfusion and functional recovery in patients with angiographic no-reflow after primary percutaneous coronary intervention.

OBJECTIVE: Angiographic thrombolysis in myocardial infarction (TIMI) flow grade < or = 2 after primary percutaneous coronary intervention (PCI), defined as angiographic no-reflow, predicts poor functional recovery in patients with acute myocardial infarction. We investigated the effect of verapamil on the restoration of myocardial perfusion and functional recovery in patients with angiographic no-reflow after PCI. METHODS: 99mTc tetrofosmin single photon emission computed tomographic (SPECT) imaging was performed (before, immediately after and 1 month after PCI) in 101 consecutive patients with acute myocardial infarction. The defect score was calculated as the sum of perfusion defect in a 13-segment model (scores of 3, complete defect to 0, normal perfusion). The asynergic score, defined as the number of asynergic segments, was assessed by echocardiography before and 1 month later. Multiple logistic regression analysis was performed to elucidate the effect of verapamil administration. RESULTS: Of 101 patients, 32 (31%) had angiographic no-reflow and were divided into two groups: 18 patients with verapamil (group 1) and 14 patients without verapamil (group 2). Sixty-nine patients had TIMI grade 3 reflow after PCI (group 3). The change in the defect score 1 month after PCI in group 1 was significantly larger than that in group 2 (P = 0.003). The asynergic score improved more at 1 month in group 1 compared to that in group 2 (P = 0.007). Moreover, logistic regression analysis revealed that TIMI grade reflow < or = 2 after PCI (P = 0.04, OR = 5.51), the defect score before PCI (P = 0.03, OR = 1.15), the asynergic score before PCI (P = 0.01, OR = 0.64) and the administration of verapamil (P = 0.002, OR = 22.4) were independently associated with successful myocardial reperfusion immediately after PCI. CONCLUSIONS: Intracoronary verapamil restored myocardial perfusion in patients with angiographic no-reflow after PCI and lead to better functional recovery after acute myocardial infarction.

Aged↗
PubMed2003

A novel dehydroepiandrosterone analog improves functional recovery in a rat traumatic brain injury model.

The purpose of this study was to investigate the efficacy of a novel steroid, fluasterone (DHEF, a dehydroepiandrosterone (DHEA) analog), at improving functional recovery in a rat model of traumatic brain injury (TBI). The lateral cortical impact model was utilized in two studies of efficacy and therapeutic window. DHEF was given (25 mg/kg, intraperitoneally) at the initial time point and once a day for 2 more days. Study A included four groups: sham injury, vehicle treated (n = 22); injured, vehicle treated (n = 30); injured, pretreated (5-10 min prior to injury, n = 24); and injured, posttreated (initial dose 30 min postinjury, n = 15). Study B (therapeutic window) included five groups: sham injury, vehicle treated (n = 17); injured, vehicle treated (n = 26); and three posttreatment groups: initial dose at 30 min (n = 18), 2 h (n = 23), or 12 h (n = 16) postinjury. Three criteria were used to grade functional recovery. In study A, DHEF improved beam walk performance both with pretreatment (79%) and 30-min posttreatment group (54%; p < 0.01, Dunnett vs. injured vehicle). In study B, the 12-h posttreatment group showed a 97% improvement in beam walk performance (p < 0.01, Dunnett). The 30-min and 12-h posttreatment groups showed a decreased incidence of falls from the beam, which reached statistical significance (p < 0.05, Dunnett). Tests of memory (Morris water maze) and neurological reflexes both revealed significant improvements in all DHEF treatment groups. In cultured rat mesangial cells, DHEF (and DHEA) potently inhibited interleukin-1beta-induced cyclooxygenase-2 (COX2) mRNA and prostaglandin (PGE2) production. In contrast, DHEF treatment did not alter injury-induced COX2 mRNA levels in the cortex or hippocampus. However, DHEF (and DHEA) relaxed ex vivo bovine middle cerebral artery preparations by about 30%, with an IC(50) approximately 40 microM. This was a direct effect on the vascular smooth muscle, independent of the endothelial cell layer. Fluasterone (DHEF) treatments improved functional recovery in a rat TBI model. Possible mechanisms of action for this novel DHEA analog are discussed. These findings suggest an exciting potential use for this agent in the clinical treatment of traumatic brain injury.

Animals↗