RESUMO
Family physicians are frequently asked to complete disability certification forms for workers. The certification process can be contentious because of the number of stakeholders, the varying definitions of disability and the nature of the administrative systems. Insufficient training on disability during medical school and residency complicates this process. Disability systems discussed include workers' compensation, private disability insurance, the Americans with Disabilities Act and the Family and Medical Leave Act. Strategies that help the physician complete disability certification forms effectively include identification of disability type, ascertainment of the definition of disability being applied, evaluation of workplace demands and essential job functions, assessment of worker capacity, and accurate and timely completion of the forms in their entirety.
Assuntos
Avaliação da Deficiência , Pessoas com Deficiência/legislação & jurisprudência , Medicina de Família e Comunidade , Indenização aos Trabalhadores/organização & administração , Adulto , Algoritmos , Humanos , Estados UnidosRESUMO
The absence of stainable iron in a bone marrow aspirate is widely considered to be diagnostic of iron deficiency anemia (IDA). We re-evaluated this concept by studying a cohort of 108 consecutive bone marrow specimens from an unselected series of patients who were seen at a hematology clinic and in whom iron stores were reported as being absent. A review of the pathologic reports revealed 19 inadequate specimens and 15 with decreased, but not absent, iron stores. Thus, only 74 of the 108 cases had been accurately reported. In 37 of these cases, adequate clinical and laboratory data were available and allowed further analysis. In 18 patients, careful review of patient history, physical examination, results of endoscopic procedures, and follow-up information failed to suggest the presence of IDA (group A). The review process in the remaining 19 patients suggested the possibility of IDA (group B). Significant differences between groups A and B were observed in serum ferritin (P = 0.001) and red blood cell mean corpuscular volume (P = 0.004). In contrast, the two groups did not differ significantly in hemoglobin concentration, serum iron, total iron-binding capacity, transferrin saturation, or erythrocyte sedimentation rate. These observations suggest that a pathology report of absent bone marrow hemosiderin may be inaccurate in more than 30% of cases and, even when accurate, may not necessarily signify the presence of IDA. Measurement of the serum ferritin level is needed to confirm a clinical diagnosis.
Assuntos
Anemia Ferropriva/diagnóstico , Medula Óssea/metabolismo , Ferro/metabolismo , Idoso , Anemia Ferropriva/sangue , Exame de Medula Óssea , Feminino , Ferritinas/metabolismo , Hemossiderina/metabolismo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We evaluated parameters of cell differentiation and proliferation to improve prognostication of ovarian adult granulosa cell tumors. Recurrent tumors (n = 10, REC group) and nonrecurrent tumors (n = 30, NED group) were compared in terms of cellular atypia, nuclear area, p53 overexpression, ploidy, DNA index, mitosis count, S-phase fraction, and nucleolar organizer region number and area per cell. Cellular atypia was significantly more frequent in REC than NED tumors (50% versus 13%; P = .03). Mean nuclear area was significantly larger in the REC than in the NED group (44 microm2 versus 36 microm2; P = .006). Mitotic count was significantly higher in REC than NED tumors (mean of 4.8 versus 1.7; P = .004). S-phase fraction and ploidy did not predict outcome: neither did nucleolar organizer region numbers and area per cell, or p53 overexpression. Cellular atypia and mitotic count may help in determining the prognosis of adult granulosa tumors of the ovary. The histochemical parameters evaluated did not provide additional information.
Assuntos
Tumor de Células da Granulosa/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Adulto , Aneuploidia , Diferenciação Celular , Divisão Celular , Núcleo Celular/ultraestrutura , Feminino , Citometria de Fluxo , Tumor de Células da Granulosa/metabolismo , Tumor de Células da Granulosa/ultraestrutura , Humanos , Mitose , Região Organizadora do Nucléolo/ultraestrutura , Prognóstico , Fase S , Proteína Supressora de Tumor p53/metabolismoRESUMO
Although preproenkephalin mRNA is abundant in the heart, the myocardial synthesis and processing of proenkephalin is largely undefined. Isolated working rat hearts were perfused to determine the rate of myocardial proenkephalin synthesis, its processing into enkephalin-containing peptides, their subsequent release into the coronary arteries, and the influence of prior sympathectomy. Enkephalin-containing peptides were separated by gel filtration and quantified with antisera for specific COOH-terminal sequences. Proenkephalin, peptide B, and [Met(5)]enkephalin-Arg(6)-Phe(7) (MEAP) comprised 95% of the extracted myocardial enkephalins (35 pmol/g). Newly synthesized enkephalins, estimated during a 1-h perfusion with [(14)C]phenylalanine (4 pmol x h(-1) x g wet wt(-1)), were rapidly cleared from the heart during a second isotope-free hour. Despite a steady release of enkephalins into the coronary effluent (4 pmol x h(-1) x g wet wt(-1)), enkephalin replacement apparently exceeded its release, and tissue enkephalins actually accumulated during hour 2. In contrast to the tissue, methionine-enkephalin accounted for more than half of the released enkephalin. Chemical sympathectomy produced an increase in total enkephalin content similar to that observed after 2-h control perfusion. This observation suggested that the normal turnover of myocardial enkephalin may depend in part on continued sympathetic influences.
Assuntos
Vasos Coronários/metabolismo , Encefalina Metionina/análogos & derivados , Encefalinas/metabolismo , Miocárdio/metabolismo , Precursores de Proteínas/metabolismo , Animais , Encefalina Metionina/metabolismo , Técnicas In Vitro , Masculino , Perfusão , Ratos , Ratos Sprague-Dawley , Simpatectomia Química , Fatores de TempoRESUMO
Baroreflex gain and coronary sinus norepinephrine and epinephrine levels were measured before and immediately after radiofrequency ablation in the posteroseptal region in 9 patients with atrioventricular nodal reentrant tachycardia or posteroseptal accessory pathways. Arterial baroreflex gain was significantly reduced after radiofrequency ablation (p = 0.046), whereas coronary sinus epinephrine and norepinephrine levels did not change significantly compared with preablation levels.
Assuntos
Ablação por Cateter , Sistema de Condução Cardíaco/anormalidades , Parassimpatectomia , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Barorreflexo , Biomarcadores/sangue , Epinefrina/sangue , Feminino , Sistema de Condução Cardíaco/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Sistema Nervoso Parassimpático/metabolismo , Sistema Nervoso Parassimpático/fisiopatologia , Taquicardia por Reentrada no Nó Atrioventricular/sangue , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Resultado do TratamentoRESUMO
Opioid peptides have long been considered as neuropeptides or neurotransmitters. The more recent discovery of these same peptides in non-neuronal tissue suggests that the peptides may have autocrine, paracrine, or endocrine functions as well. The opioid peptides, enkephalins, dynorphins, and endorphins, have been found in isolated cardiac myocytes and heart tissue. This review will cover the recent literature on opioid peptides in respect to cardiac distribution, biochemistry, and function.
Assuntos
Peptídeos Opioides/metabolismo , Animais , Coração/fisiologia , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Miocárdio/metabolismo , Peptídeos Opioides/fisiologia , Especificidade de Órgãos , Receptores Opioides/fisiologiaRESUMO
The heart is a complex neuroendocrine (opioids, NPY, VIP) or mechanoendocrine (ANP) organ. Opioid peptides and receptors are present in the heart and nerves such that they can easily modulate cardiac function. Cardiac opioids may have autocrine, paracrine and endocrine function. The challenge is to find the signal that turns them on and then what they do in the face of an overwhelmingly redundant system making knock-out technology hard to interpret. Determining the cardiac release of opioids in an intact system still requires a larger animal model.
Assuntos
Miocárdio/metabolismo , Peptídeos Opioides/fisiologia , Receptores Opioides/metabolismo , Medula Suprarrenal/metabolismo , Animais , Gatos , Modelos Animais de Doenças , Cães , Cobaias , Antagonistas de Entorpecentes , Peptídeos Opioides/biossíntese , Ratos , SuínosRESUMO
Short-term morphine stimulates vagal bradycardia. This led us to propose the hypothesis that chronically administered morphine would down-regulate myocardial muscarinic receptor systems. Dogs received morphine continuously for 2 weeks through an s.c. catheter, and cellular aspects of parasympathetic control of the heart were examined. Contrary to expectations, morphine increased muscarinic receptor density in the right atrium and left ventricle by 17 and 34%, respectively, with no change in the apparent affinity of the receptor (K(D)). Morphine also increased the expression of the G protein G(ialpha) by 115 and 233%, respectively, in right atrial and left ventricular sarcolemmal membranes. Morphine increased ventricular and atrial G(salpha) to a much lesser degree (49 and 25%). Morphine failed to alter basal or maximally stimulated (forskolin plus MnCl(2)) adenylate cyclase activity. The maximum cyclase activation by isoproterenol and the maximum inhibition by carbachol were similarly unaltered by morphine. Morphine reduced the ventricular but not atrial norepinephrine. Both long- and short-term morphine lowered tissue epinephrine content, suggesting that short-term morphine reduces extraneuronal uptake. Potential systemic and cellular models for myocardial adaptation to morphine are proposed, including sequential sympathetic and parasympathetic compensations.
Assuntos
Adenilil Ciclases/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Coração/efeitos dos fármacos , Morfina/farmacologia , Receptores Muscarínicos/metabolismo , Animais , Função Atrial , Carbacol/farmacologia , Colforsina/farmacologia , Cães , Interações Medicamentosas , Epinefrina/farmacologia , Proteínas de Ligação ao GTP/classificação , Proteínas de Ligação ao GTP/genética , Coração/fisiologia , Átrios do Coração/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Isoproterenol/farmacologia , Morfina/sangue , Norepinefrina/farmacologia , Receptores Muscarínicos/efeitos dos fármacos , Fatores de Tempo , Função VentricularRESUMO
The vagotonic effect of chronic morphine on the parasympathetic control of the heart was examined in dogs treated with morphine for 2 wk. Because normal vagal function is critical to myocardial stability, the study was conducted to evaluate for potential impairments following chronic vagal stimulation. The hypothesis that persistent vagal outflow would result in a loss of vagal reserve and reduced vagal control of heart rate was tested. Heart rate and the high-frequency variation in heart rate (power spectral analysis) declined shortly after initiation of subcutaneous morphine infusion. A progressive bradycardia correlated well with the rising plasma morphine. The resting bradycardia (57 beats/min) was maintained through day 2 and was accompanied by a significant parallel increase in vagal effect and a decline in the intrinsic heart rate (160 vs. 182 beats/min). A compensatory increase in the ambient sympathetic control of heart rate was evident on day 2 and was supported by an increase in circulating catecholamines. The lowered intrinsic heart rate and elevated sympathetic activity were maintained through day 10 despite a return of the resting heart rate and plasma catecholamines to pretreatment values. These observations suggested that chronic morphine alters either the intrinsic function of the sinoatrial node or reduces the postvagal tachycardia normally attributed to nonadrenergic, noncholinergic agents. Both acute and chronic morphine depressed the rate of development of bradycardia during direct vagal nerve stimulation without altering the rate of recovery afterward. This last observation suggests that acute morphine reduces the rate of acetylcholine release. Results provide insight into the mechanisms that maintain vagal responsiveness. The results are also relevant clinically because opiates are increasingly prescribed for chronic pain and opiate abuse is currently in resurgence.
Assuntos
Sistema Nervoso Autônomo/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Morfina/administração & dosagem , Entorpecentes/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Cães , Estimulação Elétrica , Epinefrina/sangue , Morfina/sangue , Morfina/farmacologia , Entorpecentes/sangue , Entorpecentes/farmacologia , Norepinefrina/sangue , Fatores de Tempo , Nervo Vago/fisiologiaRESUMO
The present study compared cocaine-induced hyperlocomotion and cocaine i.v. self-administration in DBA/2J and C57BL/6J mice. In the locomotor activity experiment, these strains were tested for hyperlocomotion after i.p. cocaine injection (0-60.0 mg/kg), using a Digiscan Animal Activity Monitoring System. In the cocaine i.v. self-administration experiment, they were compared for their ability to acquire and maintain cocaine self-administration in operant chambers with levers as the manipulanda. Animals were first trained to respond for food as a reinforcer (condensed milk solution); they were then submitted to surgical i.v. insertion of an in-dwelling catheter, and required to respond for i.v. cocaine (0.25-4.0 mg/kg per injection) as a reinforcer. DBA/2J mice showed significantly higher maximal cocaine-induced hyperlocomotion, more rapid acquisition of cocaine self-administration, and significantly lower rates of cocaine self-administration. Cocaine concentration in the brains of DBA/2J and C57BL/6J mice failed to differ following i.p. injection, suggesting that distribution factors were not involved in the differential responses to cocaine. Although not conclusive, this pattern of effects may suggest that cocaine has greater reinforcing efficacy in DBA/2J mice, confirming genetic make-up as a determinant factor in cocaine taking behavior.
Assuntos
Encéfalo/metabolismo , Cocaína/farmacologia , Atividade Motora/efeitos dos fármacos , Entorpecentes/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Cocaína/metabolismo , Condicionamento Operante , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , AutoadministraçãoRESUMO
BACKGROUND: The role of chemoprophylaxis in aircrew transiting malaria endemic regions has been, and remains, a point of controversy. The recent emergence of multi-drug resistant parasites and pesticide-resistant mosquitoes have made malaria prevention and control even more challenging and complex. The primary purpose was to review the efficacy of chemoprophylaxis (as compared with no chemoprophylaxis) in U.S. Naval aircrew traveling to malaria endemic areas for short periods of time on a frequent, infrequent, or isolated basis. A secondary purpose was to generate chemoprophylaxis guidelines based on the outcomes of this review. METHODS: A comprehensive MEDLINE database search was performed for the interval from January 1966 to April 1997. Additional resources were obtained from references cited in relevant journal articles, monographs, textbooks, and U. S. government publications. Pertinent U. S. Navy publications were also reviewed. Selection criteria were developed and applied to the data. RESULTS: The investigation failed to identify any analytic studies that met selection criteria regarding the efficacy of chemoprophylaxis in U.S. Naval aircrew or aircrew surrogates transiting malaria endemic areas. The data were therefore used to qualitatively assess the risks/benefits of chemoprophylaxis and generate chemoprophylaxis guidelines. Based on the results of this review, the decision to prescribe chemoprophylaxis was strongly dependent on the following risk factors: a) geographic region; b) transmission risk; c) duration of nighttime exposure; and d) aircrew, aircraft, and mission profiles. CONCLUSIONS: Studies of adequate analytic design are needed to delineate the role of chemoprophylaxis in aircrew transiting malaria endemic areas and to validate the chemoprophylaxis guidelines suggested in this review.
Assuntos
Aviação , Quimioprevenção , Malária/prevenção & controle , Militares , Quimioprevenção/normas , Guias como Assunto , Humanos , Fatores de RiscoRESUMO
Chronic exercise changes cardiac function and responsiveness to autonomic control. Catecholamines and enkephalins are neuroendocrine transmitters involved in autonomic regulation and signaling. We hypothesized that intermittent increased sympathetic stimulation caused by exercise training would decrease cardiac catecholamine and enkephalin content. Dogs and miniswine were exercise trained and hearts extracted for catecholamine and enkephalin measurements. Atrial catecholamine content is greater than ventricular content in dog heart which is in keeping with the greater atrial neuronal density. In contrast, porcine epinephrine content was evenly distributed across heart sections and norepinephrine content was greater on the right side than the left. Changes in miniswine and dog heart catecholamine content after exercise training were different. Canine cardiac norepinephrine content decreased and porcine norepinephrine content increased. This indicates a difference in cardiac adrenergic control in miniswine versus canines. Methionine-enkephalin (met-enk) distribution across canine heart is uniform, unlike the miniswine, where the atria contain more than the ventricles. Proenkephalin processing produces four met-enk sequences and one met-enk-arg-phe; despite this, ventricles of both species contain more met-enk-arg-phe immunoreactivity than met-enk. Therefore, proenkephalin processing is incomplete in heart tissue. Exercise training in the dog resulted in decreased cardiac met-enk, decreased left atrial met-enk-arg-phe, and increased ventricular met-enk-arg-phe. Porcine cardiac enkephalin concentration was unchanged by training. The changes in the enkephalins may be explained by changes in proenkephalin processing and/or release. Met-enk-arg-phe is particularly good at modulating vagal stimulation of the canine heart. The changes in tissue content seen after exercise training may be a result of the exercise-induced change in autonomic tone to the heart. These data suggest species dependent changes in autonomic regulation.
Assuntos
Catecolaminas/metabolismo , Encefalinas/metabolismo , Miocárdio/metabolismo , Condicionamento Físico Animal , Análise de Variância , Animais , Vias Autônomas/fisiologia , Cromatografia Líquida de Alta Pressão , Cães , Frequência Cardíaca/efeitos dos fármacos , Radioimunoensaio , Suínos , Porco MiniaturaRESUMO
BACKGROUND: The clinical course of adult granulosa cell tumor of the ovary is characterized by indolent growth tending toward late recurrence. A variety of clinical and pathologic parameters have previously been evaluated for prognostication with inconclusive results. METHODS: The clinical records and tumor sections of 70 patients with adult granulosa cell tumors of the ovary were reviewed. Patients with recurrent tumors (REC) (n = 19) were compared with patients who remained without disease (NED) (n = 51). RESULTS: Significant differences in stage and tumor size were noted between the two groups; however, after logistic regression analysis, only stage remained statistically significant. Pathologic evaluation revealed that Call-Exner bodies occurred more frequently in tumors of the NED patients. Cellular atypia and high mitotic rates were more frequent in the REC group; however, after logistic regression analysis, only atypia remained statistically significant. When early (< 10 years) and late recurring tumors (> 10 years) were compared, statistically significant differences were again noted: early recurring tumors had fewer Call-Exner bodies, higher mitotic rates, and higher degrees of atypia; late recurring tumors were similar to tumors in the NED patients. CONCLUSIONS: Tumor stage and, to a lesser extent, tumor size are the only clinical parameters of prognostic importance in adult granulosa cell tumors. Cellular atypia and, to lesser extents, mitotic rate and the absence of Call-Exner bodies are the only significant pathologic prognosticators. It is difficult to predict early recurrences and impossible to predict late recurrences using these clinical and pathologic parameters.
Assuntos
Tumor de Células da Granulosa/patologia , Neoplasias Ovarianas/patologia , Adulto , Quimioterapia Adjuvante , Intervalo Livre de Doença , Tubas Uterinas/cirurgia , Feminino , Previsões , Tumor de Células da Granulosa/cirurgia , Humanos , Histerectomia , Corpos de Inclusão/ultraestrutura , Modelos Logísticos , Pessoa de Meia-Idade , Mitose , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/cirurgia , Ovariectomia , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de TempoRESUMO
AIMS: Possible risk factors were evaluated for herpes simplex virus (HSV) epithelial keratitis in patients with stromal keratouveitis. METHODS: The study population included 260 patients who had active stromal keratitis and/or iridocyclitis without epithelial disease and who were enrolled in one of three clinical trials of the Herpetic Eye Disease Study. Study treatment involved a 10 week course of topical placebo, topical prednisolone phosphate, or topical prednisolone phosphate with oral acyclovir. All groups received topical trifluridine four times daily for 3 weeks then twice daily for another 7 weeks. Patients were examined for HSV epithelial keratitis for 16 weeks. RESULTS: Dendritic or geographic epithelial keratitis occurred in 12 (4.6%) study patients. Adverse effects attributable to trifluridine prophylaxis were acute allergic blepharoconjunctivitis in 10 (3.8%) study patients and corneal epithelial erosions in 11 (4.2%) study patients. No significant difference in the occurrence of HSV epithelial keratitis was found among the study treatment groups: one (2.0%) of 49 topical placebo treated patients, nine (6.5%) of 138 patients treated with topical corticosteroids without acyclovir, and two (2.7%) of 73 patients treated with topical corticosteroids and oral acyclovir. Univariate exponential models suggested that patients with a history of previous HSV epithelial keratitis and non-white patients were more likely to develop HSV epithelial keratitis during treatment of stromal keratouveitis. CONCLUSION: Individuals with prior HSV epithelial keratitis and certain ethnic groups may have a higher rate of recurrent epithelial keratitis during the acute treatment of HSV stromal keratouveitis.
Assuntos
Endotélio Corneano/virologia , Iridociclite/tratamento farmacológico , Ceratite Herpética/tratamento farmacológico , Aciclovir/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Iridociclite/virologia , Ceratite Dendrítica/etiologia , Ceratite Herpética/patologia , Masculino , Prednisolona/uso terapêutico , Recidiva , Fatores de Risco , Trifluridina/efeitos adversos , Trifluridina/uso terapêuticoRESUMO
To determine whether endogenous cardiac catecholamines mediate ischemic preconditioning (PC) in the rabbit heart, myocardial catecholamines were depleted by reserpine (5 mg/kg, 18-24 h pre-PC) or surgical sympathectomy (2 wk pre-PC). In vivo hearts were subjected to 30 min of regional ischemia and 3 h of reperfusion. PC involved either one or four cycles of 5-min ischemia and 10-min reperfusion before the 30-min ischemic period. Right ventricular norepinephrine content (pmol/mg protein), 51.4 +/- 11.1 in untreated rabbits, was reduced to 0.6 +/- 0.2 and 1.8 +/- 0.5 by surgical sympathectomy and reserpine, respectively. Infarct size (IS) was measured by tetrazolium and expressed as percentage of the risk zone. In untreated animals exposed solely to 30 min of regional ischemia IS was 35.5 +/- 1.6% and was unchanged by reserpine (43.3 +/- 5.4%) or surgical sympathectomy (33.4 +/- 3.5%). compared with infarction in the respective non-PC controls, IS in untreated (7.4 +/- 1.5%, P < 0.0001) and surgically sympathectomized (11.2 +/- 1.5%, P < 0.0001) animals was significantly diminished by a single cycle of PC, but the latter exerted less protection in reserpinized animals (27.6 +/- 3.5%, P < 0.0025). Four cycles of PC, however, reduced IS to 10.3 +/- 1.2% in reserpinized animals. Therefore, despite comparable depression of myocardial norepinephrine content, surgical and chemical sympathectomy had different effects on the level of protection afforded by ischemic PC. These data demonstrate that endogenous myocardial catecholamines are not essential for protection from PC in the rabbit.
Assuntos
Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Norepinefrina/deficiência , Animais , Feminino , Coração/inervação , Masculino , Isquemia Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/patologia , Coelhos , SimpatectomiaRESUMO
Intrinsic cardiac enkephalins participate in circulatory regulation either through the modification of vagal control or vasomotor sympathetic control. We extracted, chromatographed, and assayed plasma and myocardial enkephalins from anesthetized dogs under control conditions and during hemorrhagic hypotension (2 h at 40 mmHg). Blood samples were collected at intervals during the experiment. Blood gases were stable, pH declined to 7.1, and heart rate rose. Plasma catecholamines increased and remained high throughout hypotension. Catecholamine and enkephalin immunoreactivities (ir) were unchanged in time controls. Plasma methionine-enkephalin (ME) and peptide F increased twofold and methionine-enkephalin-arginine-phenylalanine (MEAP) and peptide B increased 10- to 30-fold during hypotension. Plasma proenkephalin (ProEnk) and other large enkephalins were unchanged during hypotension. Myocardial norepinephrine was greater in the atria and both atrial and ventricular contents were decreased after hypotension. ProEnk and peptide B accounted for > 60% of the cardiac enkephalins, and their ventricular concentrations were three to four times atrial concentrations. Myocardial MEAP concentrations were 15-25 times the ME concentrations in the same tissue extracts. Hypotension increased myocardial peptide B and ProEnk, and ME, MEAP, and peptide F were unchanged. The data demonstrate a preferential processing to or retention of MEAP rather than ME-ir enkephalins in the heart. The data also indicate that myocardial MEAP-ir enkephalins respond to changes in the circulatory environment and appear in the plasma during hemorrhagic hypotension.
Assuntos
Encefalina Metionina/análogos & derivados , Encefalinas/sangue , Encefalinas/metabolismo , Hemorragia/metabolismo , Miocárdio/metabolismo , Animais , Catecolaminas/metabolismo , Cromatografia , Cães , Encefalina Metionina/sangue , Encefalina Metionina/metabolismo , Hemorragia/sangue , Hipotensão/metabolismo , Peptídeos/sangue , Peptídeos/metabolismo , Precursores de Proteínas/sangue , Precursores de Proteínas/metabolismoRESUMO
Decreased cardiac catecholamines were observed following incision and repair of the pericardium in sham-operated vs. unoperated control dogs. Animals were assigned to five groups: unoperated, sham-operated intact pericardia, open pericardia, sutured pericardia and complete ventricular sympathectomy. Hearts were collected four weeks after surgery. Sympathectomy decreased catecholamine content when compared to all other groups. Hearts with open/sutured pericardia contained significantly less catecholamines than controls. When the pericardium was intact or left open following incision, cardiac catecholamines were unchanged compared to unoperated controls. Since opioid peptides are colocalized with catecholamines, we measured met-enkephalin and met-enkephalin-arg-phe, proenkephalin A peptide products, in parallel samples. Similar to norepinephrine, met-enkephalin was decreased following both sympathectomy and pericardial repair. However, met-enkephalin-arg-phe, which may be more associated with the myocardium than its innervation, was not changed by any treatment. The sutured pericardium more than the stress of surgery apparently alters the tissue catecholamines and enkephalin. This may have resulted from the mechanical friction at the site of repair. Epinephrine and met-enkephalin contents in sympathectomized hearts were significantly lower than unoperated controls but were not significantly different from the intermediate values observed in the sutured group. The functional consequences of these changes on neuroendocrine status are unclear and will require further evaluation. The results also emphasize the need for careful attention to proper controls for surgical studies.
Assuntos
Catecolaminas/metabolismo , Encefalina Metionina/metabolismo , Miocárdio/metabolismo , Pericárdio/cirurgia , Animais , Cães , Encefalina Metionina/análogos & derivados , Epinefrina/metabolismo , Feminino , Ventrículos do Coração/inervação , Ventrículos do Coração/metabolismo , Masculino , Norepinefrina/metabolismo , SimpatectomiaRESUMO
Met-enkephalin-Arg-Phe (MEAP) has been identified in acid extracts of canine heart tissue. The effects of synthetic MEAP on the vagal control of heart rate were investigated in anesthetized dogs. The arterial infusion of MEAP (3 nmol.min-1.kg-1) inhibited the bradycardia observed during electrical stimulation of the right vagus nerve by 72%. After the infusion was stopped, the responsiveness to vagal stimulation returned to normal, with a half-time between 2 and 3 min. The inhibition by MEAP was reversed by the high-affinity opiate antagonist diprenorphine (100 micrograms/kg). MEAP did not alter the negative chronotropic effect of the direct-acting muscarinic agonist methacholine. This observation suggested that MEAP exerted its effect at a site in the efferent vagal tract proximal to nodal muscarinic receptors. Increasing MEAP infusions (0.09-3.00 nmol.min-1.kg-1) produced a graded suppression of vagal bradycardia, with a half-maximal effect near 0.3 nmol.min-1.kg-1. Met-enkephalin (ME) produced responses very similar to those obtained with MEAP. The effects of ME were also blocked by prior administration of diprenorphine. Dose responses to ME were shifted to the right of those for MEAP, and half-maximal responses for ME were obtained at two to four times the dose required for MEAP. The data suggest that the intrinsic cardiac enkephalin MEAP can regulate vagal control of heart rate at physiologically achievable concentrations and may serve as a local regulator of the parasympathetic-myocardial interface.
Assuntos
Bradicardia/prevenção & controle , Encefalina Metionina/análogos & derivados , Nervo Vago/fisiologia , Animais , Diprenorfina/farmacologia , Cães , Relação Dose-Resposta a Droga , Estimulação Elétrica , Encefalina Metionina/antagonistas & inibidores , Encefalina Metionina/metabolismo , Encefalina Metionina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Cloreto de Metacolina/farmacologia , Miocárdio/metabolismoRESUMO
Previous findings of enkephalins in cardiac tissue led us to investigate enkephalin distribution in animal models used for cardiovascular research. Canine cardiac methionine-enkephalin (ME) concentrations are low and evenly distributed between atria (4.2 +/- 0.6 fmol/mg protein, n = 30) and ventricles (4.4 +/- 0.5). In contrast, methionine-enkephalyl-arginyl-phenylalanine (MEAP) immunoreactivity (IR) is higher and preferentially concentrated in the ventricle (112 +/- 12) vs. the atria (23.2 +/- 2.6 fmol/mg protein). HPLC analysis suggests the atrial/ventricular difference is partly due to altered posttranslational processing. Nearly 90% of ventricular IR is comprised of MEAP (46%) and peptide B (40%) whereas these peptides represent less than half of the atrial content. A nonneuronal localization is indicated because the peptide distribution does not correspond to the catecholamine distribution. Canine left ventricular tissue sections were processed for immunohistochemistry with the MEAP antibody. Fluorescence was distributed throughout the myocytes and concentrated in ordered lines perpendicular to the myocyte longitudinal axis corresponding to the area of the intercalated disc. This suggests opioids may be important in communication between cardiomyocytes, and possibly the presence of a unique peptide secretory mechanism utilizing the intercalated disc. The relative peptide content in cat and pig hearts was similar to the dog; however, the distribution was different. Feline cardiac ME content was distributed 2:1 in favor of the ventricles and corresponded with a preferential ventricular norepinephrine distribution. The MEAP-IR pattern gave a ventricular/atrial ratio lower (3.5:1) in cat heart vs. dog (5:1). In contrast, pig heart ME and MEAP-IR ventricular/atrial ratios were reversed for both ME (1:10) and MEAP (1:2). HPLC of pig left ventricle showed that MEAP and peptide B represented 33% and 39% of the MEAP-IR, respectively. These species variations may correlate to the differences observed in cardiac function.