Neuroprotective role of melatonin in methamphetamine- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity.
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Biomedical subjects
M D Black
Publications and source records attributed to M D Black.
The role of neuronal nitric oxide synthase in cocaine-induced conditioned place preference.
Previous studies suggested the involvement of the neuronal nitric oxide synthase (nNOS) in the development of sensitization to psychostimulants. In the present study we investigated the role of nNOS in the rewarding properties of cocaine. Swiss Webster mice treated with cocaine (20 mg/kg) and saline every other day for 8 days (four drug and four saline sessions) developed conditioned place preference (CPP) for the drug-paired compartment of the cage. Pretreatment with the nNOS inhibitor, 7-nitroindazole (7-NI; 25 mg/kg), completely blocked cocaine-induced CPP. Mice deficient for the nNOS gene (homozygote nNOS(-/-) mice) were resistant to cocaine-induced CPP, while wild-type nNOS(+/+) mice developed a marked CPP following cocaine administration. Both, the pharmacological and genetic manipulations of nNOS suggest that nitric oxide (NO) is involved in the rewarding properties of cocaine.
Animals↗
Resistance of neuronal nitric oxide synthase-deficient mice to cocaine-induced locomotor sensitization.
In brain, nitric oxide (NO) is considered as a retrograde messenger involved in synaptic plasticity. The present study was undertaken to investigate whether mice lacking the neuronal nitric oxide synthase (nNOS) gene are protected from cocaine-induced behavioral sensitization. Mice were administered, IP. either saline or cocaine (15 mg/kg) for 5 days. Sensitization was determined as an increase in cocaine-induced locomotor activity on day 5 compared with day 1 and an amplified response of cocaine-experienced mice to a challenge cocaine injection given after a 10-day drug free period (e.g., on day 15). To investigate the development of a context-dependent locomotion (conditioning), the responses of cocaine- and saline-experienced mice to a saline injection were determined on day 17. Male homozygote nNOS(-/-) mice were sensitive to the acute effect of cocaine (15 mg/kg) on day 1; however, they developed neither a sensitized response to cocaine (on day 5 and 15) nor a conditioned locomotion. Female homozygote nNOS(-/-) mice neither were responsive to 15 mg/kg cocaine on day 1,5 and 15, nor did they develop a conditioned locomotion. In contrast, the same cocaine regimen delivered to male and female heterozygote nNOS(+/-) mice, and wild type mice (B6 J/sv129, C57BL/6 and sv129) resulted in sensitization to cocaine-induced locomotor activity and context-dependent locomotion. Investigation of [3H]cocaine disposition in the striatum and frontal cortex of the mice revealed neither gender nor strain differences in the drug disposition. Also, no major difference in striatal dopaminergic markers between homozygote nNOS(-/-) and wild type mice was observed. The most significant distinction, however, was the finding that nNOS(-/-) mice are completely deficient in striatal nNOS binding sites. Taken together, our results suggest that the resistance of homozygote nNOS(-/-) mice to cocaine-induced behavioral sensitization is primarily due to the deletion of the nNOS gene. Considering the role of NO in synaptic plasticity, it is conceivable that reduced brain NOS activity blunts the processes that underlie the development of sensitization to cocaine.
Animals↗
Should we address the course as well as the origin of a translocated anomalous coronary artery?
The identification of an anomalous left coronary artery arising from the pulmonary artery demands urgent surgical attention. Myocardial infarction and ongoing myocardial ischemia are a direct consequence with subsequent left ventricular dysfunction. A modification using a combination of autogenous aortic and pulmonary artery flaps is described, which addresses both the origin and the course of the anomalous coronary artery--until now, a feature not generally considered necessary of repairs involving anomalous left coronary artery arising from the left facing pulmonary sinus.
Coronary Vessel Anomalies↗
Obstructive rhabdomyoma and univentricular physiology: a rare combination.
We report the successful excision of a large left atrial rhabdomyoma producing complete obstruction of both inflow and outflow to the left ventricle. Systemic perfusion was dependent on anterograde ductual flow. The resultant univentricular physiology was initially managed medically, with spontaneous tumor regression contemplated as a means of possible long-term "cure." Failure to achieve hemodynamic stability compelled urgent surgical excision. This neonate was successfully discharged home with an in-series biventricular circulation.
Heart Neoplasms↗
Truncal valve repair: initial experience in neonates.
BACKGROUND: The identification of moderate to severe preoperative truncal valve regurgitation has been synonymous with significant postoperative mortality after neonatal repair of truncus arteriosus. Spurned by the deficiencies of current truncal valve substitutes surgeons are once again reexamining the option of truncal valve reparative techniques. METHODS: From May 1996 until June 1997, 8 children underwent correction of truncus arteriosus. A retrospective analysis was conducted. RESULTS: There was one in-hospital death secondary to a postoperative massive coronary air embolism. Moderate-to-severe truncal valve regurgitation was identified clinically and confirmed with cardiac ultrasound in 3 neonates with a mean age of 7 days (range, 4 to 12 days) all with quadracusp truncal valves. Successful truncal valve repair was accomplished in 2 infants, with a third neonate requiring homograft replacement with coronary reimplantation for failure in achieving valvular competence after attempted valvuloplasty. Postoperative echocardiograms in those neonates who underwent truncal valve repair confirmed a functional "tricuspid" valve with only mild to mild-plus regurgitation. CONCLUSIONS: We give further credence to the hypothesis that primary neonatal truncal valve repair is feasible and may be successful in the avoidance and delay of serial truncal valve replacements using either mechanical or allograft substitutes.
Aortic Valve↗
Cardiac rhabdomyomas and obstructive left heart disease: histologically but not functionally benign.
BACKGROUND: Cardiac rhabdomyoma is the most common primary heart tumor in infants. Spontaneous regression of such tumors is common, particularly with smaller lesions, followed by resolution of symptoms. Based on our data on spontaneous involution, our institutional philosophy has been one of expectant management in the absence of life-threatening symptoms. However, surgical intervention sometimes is required for the extirpation of a rhabdomyoma from the left ventricular outflow tract. METHODS: A retrospective review was conducted of 30 children in whom a rhabdomyoma was diagnosed over a 27-year period. RESULTS: Twenty-three percent (7/30) of the children required surgical extirpation of the tumor from within their left ventricular outflow tract, although a total of 94% had left ventricular involvement. There were no deaths. To date, no child has required reexcision of tumor. CONCLUSIONS: The natural history of rhabdomyoma is one of spontaneous regression (the 23 children who did not undergo surgical intervention are alive and continue to be followed up medically). We recommend surgical excision to alleviate acute outflow tract obstruction with reliance on the tumor's natural history of regression to achieve long-term freedom from reoperation. Although operation has been recognized as lifesaving, we were somewhat surprised to find that greater than 20% of our pediatric population required operative intervention.
Female↗
Effect of melatonin on methamphetamine- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity and methamphetamine-induced behavioral sensitization.
Methamphetamine (METH)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity is thought to be associated with the formation of free radicals. Since evidence suggests that melatonin may act as a free radical scavenger and antioxidant, the present study was undertaken to investigate the effect of melatonin on METH- and MPTP-induced neurotoxicity. In addition, the effect of melatonin on METH-induced locomotor sensitization was investigated. The administration of METH (5 mg kg(-1) x 3) or MPTP (20 mg kg(-1) x 3) to Swiss Webster mice resulted in 45-57% depletion in the content of striatal dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 57-59% depletion in dopamine transporter binding sites. The administration of melatonin (10 mg kg(-1)) before each of the three injections of the neurotoxic agents (on day 1), and thereafter for two additional days, afforded a full protection against METH-induced depletion of dopamine and its metabolites and dopamine transporter binding sites. In addition, melatonin significantly diminished METH-induced hyperthermia. However, the treatment with melatonin had no significant effect on MPTP-induced depletion of the dopaminergic markers tested. In the set of behavioral experiments, we found that the administration of 1 mg kg(-1) METH to Swiss Webster mice for 5 days resulted in marked locomotor sensitization to a subsequent challenge injection of METH, as well as context-dependent sensitization (conditioning). The pretreatment with melatonin (10 mg kg(-1)) prevented neither the sensitized response to METH nor the development of conditioned locomotion. Results of the present study indicate that melatonin has a differential effect on the dopaminergic neurotoxicity produced by METH and MPTP. Since it is postulated that METH-induced hyperthermia is related to its neurotoxic effect, while regulation of body temperature is unrelated to MPTP-induced neurotoxicity or METH-induced locomotor sensitization, the protective effect of melatonin observed in the present study may be due primarily to diminishing METH-induced hyperthermia.
Animals↗
Conversion of complex neonatal Ebstein's anomaly into functional tricuspid or pulmonary atresia.
BACKGROUND: Ebstein's anomaly, due to failure of delamination of one or more leaflets of the tricuspid valve (TV), is associated with varying degrees of tricuspid regurgitation (TR) and dysplasia of the right ventricle (RV). Although refinement of tricuspid valvuloplasty and plication techniques have opened the way to a satisfactory outlook for the majority of older children and adults, Ebstein's anomaly presenting at neonatal age, secondary to ineffective forward flow into the pulmonary and systemic circulation, has a reported mortality rate of as high as 75%. In order to improve the dismal outcome in neonatal Ebstein's anomaly, we have strived for early univentricular palliation. PATIENTS AND METHODS: Univentricular repair was performed in five neonates (median age 5 days; range 2-14 days) with Ebstein's anomaly, ductal dependent pulmonary blood flow, severe TR, absence of forward flow across the pulmonary valve, and small left ventricular (LV) area due to right-to-left bowing of the ventricular septum and ineffective LV loading (median indexed LV area 10.5 cm2/m2). In addition, two neonates had moderate pulmonary regurgitation (PR), one with additional pulmonary stenosis. In all patients, the indexed area of the combined right atrium and atrialized RV was greater than that of the combined functional RV, left atrium, and left ventricle (median 22.0 and 20.8 cm2/m2, respectively). The median preoperative systemic oxygen tension was 35 mmHg and the median pH 7.28. Repair consisted of TV closure with a pericardial patch (with the coronary sinus draining into the RV) (n = 3) or, in the presence of PR, resection of the dysplastic TV and division and oversewing of the main pulmonary artery (n = 2), as well as excision of the atrial septum, resection of redundant right atrial wall, and construction of an aortopulmonary shunt (n = 5). RESULTS: The median indexed LV area increased from 10.5 to 18.8 cm2/m2 as a result of more effective loading of the left ventricle. There was no intraoperative or late mortality. The patients were extubated at a median of 7 days postoperatively. At discharge, the median systemic oxygen tension was 46 mmHg. In all five patients, at 6, 7, 10, 12 and 16 weeks of age, a bidirectional cavopulmonary anastomosis has been constructed. CONCLUSIONS: In neonates with Ebstein's anomaly and ductal dependent pulmonary blood flow, rational palliation consists of the surgical creation of tricuspid atresia or, in the additional presence of PR or pulmonary stenosis, the creation of pulmonary atresia. These procedures may result in effective LV decompression and more effective volume loading of the left ventricle with increase of systemic output and improved clinical outcome.
Aorta↗
Extracardiac repair versus intracardiac baffle repair of complex unroofed coronary sinus.
Complex unroofed coronary sinus with a persistent left superior vena cava has as its commonest major associated intracardiac anomaly a partial or complete atrioventricular canal defect. In this clinical setting, biventricular repair with construction of a complex intra-atrial baffle from the pulmonary veins to the mitral valve has a reported mortality rate of as high as 50%. Looking for an improvement, we have carried out an extracardiac repair of the anomalous systemic venous component with atrial septation. In 2 infants (aged 7 and 12 weeks) with unroofed coronary sinus, bilateral superior venae cavae, right isomerism, and complete atrioventricular canal, in addition to patch closure of the ventricular component of the atrioventricular septal defect, a baffle was constructed between the pulmonary veins and the mitral valve. In four subsequent infants (aged 7,10,16, and 20 weeks) with unroofed coronary sinus, bilateral superior venae cavae, complete atrioventricular canal, right isomerism (n = 2), and mild infundibular stenosis (n = 1), repair consisted of end-to-side anastomosis of the left superior vena cava to the right superior vena cava and complete repair of the atrioventricular canal and associated conditions. There was no mortality. The early postoperative course in the two patients with intra-atrial baffle was characterized by increased left-atrial pressure (18 and 20 mm Hg), with varying degrees of pulmonary venous congestion, supraventricular tachycardias, and systemic hypotension. The pulmonary venous congestion increased, so that one patient was successfully converted 10 weeks postoperatively to an extracardiac repair with septation of the atria and the other will probably follow. In the 4 patients with a primary extracardiac repair, the hemodynamic result was excellent, with a median left-atrial pressure of 11 mm Hg on the first postoperative day. At a median follow-up of 12 months, all 5 patients with an extracardiac repair are clinically well with widely patent anastomoses between the left and right superior venae cavae. The extracardiac repair technique for complex unroofed coronary sinus, as opposed to the intra-atrial baffle repair, avoids creation of a small and low-compliance left-atrial compartment with the potential for development of pulmonary venous congestion.
Cardiac Surgical Procedures↗
Minimally invasive repair of atrial septal defects.
BACKGROUND: Minimally invasive pediatric cardiac surgical techniques continue to evolve and remain challenged by technologic advances in percutaneous devices developed to treat congenital heart disease exclusive of cardiopulmonary bypass. Public tenacity for "incisionless" operations, however, must remain balanced scrupulously against the collective safety of the surgical procedure. METHODS: Twenty-three pediatric patients underwent repair of atrial septal defects through a partial sternal split and a limited skin incision (5 to 7 cm) at our institution between July 1995 and October 1996. RESULTS: The average age of the patients was 6 years and 2 months (range, 19 months to 15 years) and the average weight was 23.3 kg (range, 11.3 to 61.7 kg). The average bypass time was 35 minutes (range, 19 to 81 minutes). Fourteen patients had a single dose of blood cardioplegia administered, whereas 9 had ventricular fibrillation electrically induced. Twenty-two patients had ostium secundum defects and 1 had a sinus venosus defect. The average length of the hospital stay was 3.6 days (range, 3 to 6 days). There were no operative or late deaths. CONCLUSIONS: Modifications of this technique continue to evolve as an effective cosmetic alternative to submammary and thoracotomy approaches. Advantages of this modification include excellent cosmetic results in all age groups and the concomitant security and familiarity of mediastinal access and full sternotomy when required.
Adolescent↗
Biventricular repair of hypoplastic left heart disease: a realistic goal?
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Endocardial Fibroelastosis↗
Azygos vein agenesis and PAPVR: a potential surgical hazard.
A 15-year-old boy underwent surgical correction of partial anomalous pulmonary venous return (right upper and middle lobe veins) into the high superior vena cava with an intact atrial septum using entirely autologous tissue. The rare association of azygos vein agenesis and partial anomalous pulmonary venous return should be emphasized to prevent the inadvertent inclusion of the anomalous systemic vein (hemiazygos vein) into the pulmonary venous circuit during the surgical repair.
Adolescent↗
Total anomalous systemic venous drainage to the coronary sinus in association with hypoplastic left heart disease: more than a mere coincidence.
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Coronary Angiography↗
Median sternotomy for prolonged resuscitation in neonatal tetralogy of Fallot with absent pulmonary valve.
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Cardiopulmonary Bypass↗
Coarctation repair using end-to-side anastomosis of descending aorta to proximal aortic arch.
BACKGROUND: Recurrent aortic coarctation after primary operative repair in the neonate and small infant is seen most commonly within the first year of life. Inadequate removal of ductal tissue, failure to address hypoplasia of the aortic arch, and suture line tension have been cited as important factors in early recurrence. METHODS: To address these issues, we have used a technique of coarctation resection and extended anastomosis of the descending aorta to the undersurface of the aortic arch. THe salient features of this approach include extensive mobilization of the aortic arch and neck vessels, careful trimming of all ductal tissue, ligation of the isthmus just beyond the left subclavian artery, and end-to-side anastomosis of the descending aorta to a separate incision in the undersurface of the aortic arch proximal to all tubular hypoplasia. Between July 1992 and January 1995, 19 consecutive neonates (median age, 13 days) and 4 consecutive infants under 3 months of age (median age, 69 days) with a mean peak systolic upper to lower extremity resting gradient of 27.9 +/- 16.9 mm Hg underwent repair of aortic coarctation and tubular hypoplasia of the arch. Other procedures performed at the time of repair included ligation of a patent ductus arteriosus (n = 19), pulmonary artery banding (n = 3), and closure of ventricular septal or atrial septal defect (n = 3). RESULTS: There were no perioperative deaths. Early postoperative complication included a recurrent laryngeal nerve injury and a transient focal tonic clonic seizure. There was one late death, after a subsequent intracardiac surgical procedure, at a median follow-up of 16 months (range, 1 to 29 months). Twenty-one of 22 late survivors were free of recurrent aortic coarctation by echocardiography findings and clinical examination, with a median upper to lower extremity gradient of 0 mm Hg. Reintervention for recurrent aortic coarctation was not required in any survivor. CONCLUSIONS: The technique described herein completely removes all potentially abnormal tissue from the aorta, including ductal tissue and all tubular hypoplastic tissue proximal to the coarctation site.
Anastomosis, Surgical↗
Trachea-innominate artery fistula and concomitant critical cerebrovascular disease.
To avoid the laborious task of investigating the cerebrovascular circulation in the midst of a trachea-innominate artery fistula, we strongly recommend preoperative cerebrovascular investigations in all patients about to undergo mediastinal tracheostomy. Paramount to this dictum remains the possibility of asymptomatic cerebrovascular disease. Inadequate preoperative cerebrovascular assessment may result in, as described in this report, the possibility of significant postoperative neurologic morbidity or mortality. Angiography should assist the surgeon in deciding which method of cerebral arterial reconstruction is best suited to the individual circumstance. We recommend the avoidance of innominate artery reconstruction even with the interposition of autologous tissues, as the operative field remains grossly infected.
Aged↗
Morphologic determinants favoring surgical aortic valvuloplasty versus pulmonary autograft aortic valve replacement in children.
UNLABELLED: The pulmonary autograft is being used with increasing frequency to replace the diseased aortic valve in the pediatric population. Attempted surgical aortic valvuloplasty with an unacceptable result and return to cardiopulmonary bypass for aortic valve replacement with a pulmonary autograft results in prolonged bypass time and increased potential for morbidity. Therefore, the ability to predict an unsuccessful outcome for valvuloplasty would be of significant clinical benefit. This issue is addressed in the present study. METHODS: Twenty-two patients (median age 5.7 years, range 3 weeks to 14 years) with bicuspid (n = 11), tricuspid (n = 9), or quadricuspid (n = 2) aortic valves underwent valvuloplasty for aortic stenosis (n = 9), aortic regurgitation (n = 7), or a combination (n = 6). Previous related procedures included balloon aortic valvuloplasty (n = 3) and open surgical valvotomy (n = 1). Median pressure gradient across the aortic valve was 80 mm Hg. Surgical valvuloplasty techniques included thinning of leaflets (n = 18), commissurotomy (n = 15), suspension of reconstructed leaflet to the aortic wall (n = 10), closure of leaflet fenestration (n = 5), shortening of free edge of prolapsed cusp (n = 4), repair of torn leaflets (n = 3), and augmentation of scarred leaflets with autologous pericardium (n = 3). Concomitant subvalvular and supravalvular stenosis were repaired in nine and four patients, respectively. In five patients, during the same hospital stay, a failed valvuloplasty was converted into a valve replacement with a pulmonary autograft because of residual or resultant stenosis (n = 3) or regurgitation (n = 2). RESULTS: No early or late deaths occurred. At a median follow-up of 16.3 months the median pressure gradient across the aortic valve in the 15 patients with preoperative stenosis or combined stenosis and regurgitation was 16 mm Hg (p < 0.01 versus preoperative gradient). Of the 22 patients, the aortic valve functioned normally (defined as < or = mild stenosis or regurgitation, or both) in 14 patients (including five patients with valve replacement); four patients had stenosis (gradients 40, 45, 60, and 60 mm Hg), two patients had regurgitation, and two patients had combined stenosis (gradients 40 and 50 mm Hg) and regurgitation. Three of the patients with recurrent stenosis underwent secondary surgical valvuloplasty without improvement. Outcome after valvuloplasty was examined according to valve structure: six of nine tricuspid valves functioned normally, whereas only three of 13 nontricuspid valves functioned normally (P = 0.07). Patients with a nontricuspid aortic valve and regurgitation had a high probability of requiring immediate valve replacement (P = 0.009). The actuarial freedom from significant native valve stenosis or regurgitation at 24 months was 82% for tricuspid valves and 36% for nontricuspid valves (P = 0.007). CONCLUSIONS: (1) Surgical aortic valvuloplasty should be the preferred approach when the aortic valve is tricuspid. (2) In contrast, aortic valve replacement with a pulmonary autograft should be the preferred strategy in the presence of a nontricuspid aortic valve (especially when the aortic valve is regurgitant) and after failed surgical valvuloplasty.
Adolescent↗