RESUMO
BACKGROUND: Late preterm infants are at high risk for medical complications and represent a growing NICU population. While 34-weeks' gestation infants are generally admitted to the NICU and 36-weeks'gestation infants stay in mother-baby, there is wide practice variation for 35-weeks'gestation infants. The objective of this study was to compare short-term outcomes of 35-weeks' gestation infants born at two hospitals within the same health system (DUHS), where one (DRH) admits all 35-weeks' gestation infants to their level II NICU and the other (DUH) admits all 35-weeks' gestation infants to mother-baby, unless clinical concern. METHODS: We conducted a retrospective cohort analysis of 35-weeks' gestation infants born at DUHS from 2014-2019. Infant specific data were collected for birth, demographics, medications, medical therapies, LOS, ED visits and readmissions. 35-weeks' gestation infants at each hospital (DRH vs DUH) that met inclusion criteria were compared, regardless of unit(s) of care. RESULTS: 726 infants of 35-weeks' gestation were identified, 591 met our inclusion criteria (DUH -462, DRH -129). Infants discharged from DRH were more likely to receive medical therapies (caffeine, antibiotics, blood culture, phototherapy, NGT), had a 4 day longer LOS, but were more likely to feed exclusively MBM at discharge. There were no differences in ED visits; however, more infants from DUH were readmitted within 30 days of discharge. CONCLUSIONS: Our findings suggest admitting 35-weeks' gestation infants directly to the NICU increases medical interventions and LOS, but might reduce hospital readmissions.
Assuntos
Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Mães , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: Evaluate spontaneous intestinal perforation (SIP)/death among extremely low birthweight (ELBW) infants before, during and after initiation of an antenatal magnesium for neuroprotection protocol (MgPro). STUDY DESIGN: We tested associations between SIP/death and magnesium exposure, gestational age (GA) and interactions with GA and magnesium exposure in a cohort of inborn ELBW infants before, during and after MgPro. RESULT: One hundred and fifty-five ELBW infants were included, 81 before, 23 during and 51 after MgPro. ELBW infants (78.3%) were exposed to Mg during MgPro compared with 50.6% and 60.8% before and after, respectively. Incidence of SIP on protocol was 30.4% vs 12.9% off protocol (P=0.03). GA was strongly associated with SIP (P<0.01). Antenatal Mg dose was also associated with SIP/death regardless of epoch (odds ratio 9.3 (1.04-104.6)), but increased SIP/death was limited to those <25 weeks gestation. CONCLUSION: Higher Mg dose was associated with higher SIP and death risk among infants with the lowest birthweights. Validation of this observation in larger populations is warranted.
Assuntos
Doenças do Prematuro/induzido quimicamente , Perfuração Intestinal/induzido quimicamente , Sulfato de Magnésio/efeitos adversos , Fármacos Neuroprotetores/efeitos adversos , Tocolíticos/efeitos adversos , Adulto , Feminino , Idade Gestacional , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Sulfato de Magnésio/uso terapêutico , Análise Multivariada , Fármacos Neuroprotetores/uso terapêutico , Tocolíticos/uso terapêuticoRESUMO
INTRODUCTION: We examined whether the bedside SensiCath Blood Gas Monitoring System could reduce both blood loss and the time needed to make ventilator-setting changes in a population of very low birth weight (VLBW; <1,500 g) infants. MATERIAL AND METHODS: A prospective, group sample trial was conducted on ventilator-dependent newly born VLBW infants. The trial was unblinded due to the nature of the device and parental consent was obtained before study enrollment. A total of 44 patients were studied. RESULTS: There was no difference (mean +/- SD) between the SensiCath group and controls with respect to birth weight, gestational age, pH, PCO(2), PO(2) or Apgar at 5 min (median 6, both groups). The amount of blood loss for arterial blood gas (ABG) measurement alone was less in the SensiCath group compared to the control group (1.2 +/- 0 ml vs. 6.7 +/- 2.4 ml, p < 0.001) and the total blood loss was also less in the SensiCath group (8.1 +/- 5 ml vs. 10.5 +/- 6.3 ml, p < 0.001), but there was no significant difference between each group in the amount of blood transfused. The time to obtain ABG results and to make a ventilator change was shorter in the SensiCath group compared to control (2 +/- 0 vs. 26 +/- 21 min, p < 0.001). DISCUSSION: Use of the modified SensiCath monitoring system permits near zero blood loss for ABG assessment and greatly reduces the time needed to make ventilator management decisions.
Assuntos
Anemia/prevenção & controle , Gasometria/instrumentação , Recém-Nascido de muito Baixo Peso , Sistemas Automatizados de Assistência Junto ao Leito , Respiração Artificial/métodos , Artérias , Feminino , Idade Gestacional , Hematócrito , Humanos , Doença Iatrogênica/prevenção & controle , Recém-Nascido , Masculino , Estudos ProspectivosRESUMO
Inflammation may contribute to lung injury and impaired alveolar development in bronchopulmonary dysplasia. We treated hyperoxia-exposed newborn rats with antibodies to the neutrophil chemokine cytokine-induced neutrophil chemoattractant-1 (CINC-1) during 95% O2 exposure to reduce adverse effects of hyperoxia-induced inflammation on lung development. Rats were exposed at birth to air, 95% O2, or 95% O2 + anti-CINC-1 (injected on days 3 and 4). Bromodeoxyuridine (BrdU) was injected 6 h before death. Anti-CINC-1 treatment improved weight gain but not survival at day 8. Anti-CINC-1 reduced bronchoalveolar lavage neutrophils at day 8 to levels equal to air controls. Total detectable lung CINC-1 was reduced to air control levels. Lung compliance was improved by anti-CINC-1, achieving air control levels in the 10-microg anti-CINC-1 group. Anti-CINC-1 preserved proliferating cell nuclear antigen expression in airway epithelium despite 95% O2 exposure. BrdU incorporation was depressed by hyperoxia but preserved by anti-CINC-1 to levels similar to air control. Alveolar volume and surface density were decreased by hyperoxia but preserved by anti-CINC-1 to levels equal to air control. Blockade of neutrophil influx in newborns may avert early lung injury and avoid alveolar developmental arrest that contributes to bronchopulmonary dysplasia.
Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Anticorpos/farmacologia , Quimiocinas CXC , Fatores Quimiotáticos/imunologia , Substâncias de Crescimento/imunologia , Hiperóxia/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/crescimento & desenvolvimento , Animais , Bromodesoxiuridina/metabolismo , Líquido da Lavagem Broncoalveolar/citologia , Divisão Celular , Quimiocina CXCL1 , Quimiocinas/análise , DNA/metabolismo , Hiperóxia/patologia , Contagem de Leucócitos , Pulmão/metabolismo , Pulmão/patologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Alvéolos Pulmonares/patologia , Ratos , Análise de Sobrevida , Aumento de PesoRESUMO
Two-week-old rabbit tracheal smooth muscle (TSM) and bronchial smooth muscle (BSM) segments were placed in organ baths, and isometric contractions to substance P (SP) were obtained. In the presence of phosphoramidon (PHOS), a neutral endopeptidase inhibitor, BSM segments were significantly more reactive and sensitive to SP than TSM segments. Neither neostigmine (NEO) nor atropine (ATR) eliminated these regional differences. Airway contractile responses to: 1) Senktide (NK-3 agonist); 2) neurokinin A (NKA, a NK-2 agonist); and 3) Septide (a highly selective NK-1 agonist) were separately obtained. In the presence of PHOS and NEO, Senktide was virtually inactive in both BSM and TSM. In the presence of PHOS, NEO, and ATR, NKA was equipotent in all airway segments; in contrast, the Septide response was significantly more reactive in BSM than in TSM segments. After inhibition of NK-1 activity with GR 82334, a competitive NK-1 receptor antagonist, the regional differences in SP reactivity were greatly diminished. This latter indication of a NK-1 contribution was confirmed using Septide-mediated inactivation of NK-1 receptors whereby the regional differences in airway sensitivity to SP were eliminated. These findings indicate that both endogenous neutral endopeptidase activity as well as NK-1 and NK-2 receptor influences may modulate the contractile responses to SP in immature rabbit airways.
Assuntos
Brônquios/efeitos dos fármacos , Contração Isométrica/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Receptores da Neurocinina-1/metabolismo , Receptores da Neurocinina-2/metabolismo , Substância P/metabolismo , Traqueia/efeitos dos fármacos , Animais , Atropina/farmacologia , Brônquios/metabolismo , Glicopeptídeos/farmacologia , Músculo Liso/metabolismo , Neostigmina/farmacologia , Neurocinina A/farmacologia , Fragmentos de Peptídeos/farmacologia , Ácido Pirrolidonocarboxílico/análogos & derivados , Coelhos , Substância P/análogos & derivados , Substância P/farmacologia , Traqueia/metabolismoRESUMO
The neuromodulatory actions of Septide, a selective neurokinin-1 (NK-1) agonist, and substance P (SP) were investigated in isolated rabbit tracheal smooth muscle (TSM) segments. The tissues were placed in organ baths containing modified Krebs-Ringer solution and contracted with either the agonists or electrical field stimulation (ES) with frequencies ranging from 1 to 50 Hz. The neutral endopeptidase (NEP) inhibitor, phosphoramidon (10(-6) M), had no significant effect on Septide-mediated contractions. Septide-mediated contractions were augmented in the presence of neostigmine, eliminated in the presence of atropine, and diminished in the presence of tetrodotoxin. Both SP and Septide increased ES-induced contractions in a dose-dependent manner. On the other hand, the presence of both Septide and SP did not further augment this neuromodulatory action. After NK-1 desensitization, Septide-mediated contractions were also virtually eliminated; however, the peptide's neuromodulatory action was unaffected. In contrast, the presence of GR-82334, a selective NK-1 antagonist, eliminated Septide's neuromodulatory activity. These findings provide evidence that 1) NK-1 receptors facilitate both the direct release of ACh as well as augment the release of ACh by ES and 2) the cholinergic pathways involved with these two processes may represent different mechanisms.
Assuntos
Receptores da Neurocinina-1/fisiologia , Traqueia/metabolismo , Acetilcolina/farmacologia , Animais , Estimulação Elétrica , Técnicas In Vitro , Contração Muscular , Músculo Liso/efeitos dos fármacos , Fenômenos Fisiológicos do Sistema Nervoso , Sistema Nervoso Parassimpático/efeitos dos fármacos , Sistema Nervoso Parassimpático/fisiologia , Fragmentos de Peptídeos/farmacologia , Fisalemina/análogos & derivados , Fisalemina/farmacologia , Ácido Pirrolidonocarboxílico/análogos & derivados , Coelhos , Substância P/análogos & derivados , Substância P/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Tetrodotoxina/farmacologia , Traqueia/inervaçãoRESUMO
The neuromodulatory action of chlorothiazide (CTZ) was investigated in isolated rabbit bronchial smooth muscle (BSM) segments contracted with electrical field stimulation (ES). The tissues were placed in organ baths and stimulated with ES frequencies ranging from 1 to 75 Hz. CTZ (10(-4) to 10(-3) M) produced dose-dependent increases in ES-induced contractions. In the presence of 10(-3) M CTZ, the mean +/- SEM maximal tension (Tmax) induced by ES increased significantly (p less than 0.03) from 292.8 +/- 39.5 to 363.0 +/- 58.5 g/g tissue. BSM sensitivity to ES, expressed as the log ES frequency producing 50% of Tmax (i.e., log ES50) was also increased (p less than 0.001) in the presence of CTZ as indicated by a fall in the mean +/- SEM log ES50 from 1.05 +/- 0.05 to 0.804 +/- 0.09 Hz. The potentiating effect of CTZ on ES-induced contractions was independently blocked by either the neurotoxin, tetrodotoxin (4 x 10(-6) M), or the cholinergic antagonist, atropine (10(-5) M). In the presence of CTZ, the mean Tmax response to acetylcholine (ACh) was unaffected, whereas BSM sensitivity to the agonist increased significantly (p less than 0.001). On the other hand, the dose-response relationship to carbachol, a cholinergic agonist resistant to cholinesterase degradation, was unaffected by CTZ. In tissues pretreated with 10(-5) M neostigmine, an acetylcholinesterase (AChase) inhibitor, CTZ did not further augment either ES- or ACh-induced contractions. Taken together, these findings suggested that CTZ might be acting as an AChase inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Brônquios/efeitos dos fármacos , Clorotiazida/farmacologia , Contração Muscular/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Animais , Atropina/farmacologia , Brônquios/enzimologia , Brônquios/inervação , Brônquios/fisiologia , Carbacol/farmacologia , Inibidores da Colinesterase/farmacologia , Relação Dose-Resposta a Droga , Estimulação Elétrica , Técnicas In Vitro , Músculo Liso/efeitos dos fármacos , Músculo Liso/enzimologia , Músculo Liso/inervação , Músculo Liso/fisiologia , Coelhos , Tetrodotoxina/farmacologiaRESUMO
The present study examines the effects of aerosolized ragweed antigen (RAg) on tracheal (TSM) and bronchial (BSM) smooth muscle contraction in rabbits actively immunized with RAg. Airway segments were isolated 48 h after aerosol challenge with either saline or RAg, and airway contractile responses to histamine were measured. Histamine remained a weak agonist in TSM segments after RAg challenge. In contrast, BSM responsivity to histamine was significantly increased after RAg challenge as evidenced by a parallel shift to the left (i.e., Fslope = 3.2; degrees of freedom (df) = 1,224; p = NS and Felev = 19.4; df = 1,225; p less than 0.001) of the mean dose-response relationship. In sham-immunized rabbits, the BSM contractile responses to histamine were similar after aerosol challenge with either RAg or normal saline. After the BSM segments were treated with 10(-6) M atropine, there was no significant difference in histamine reactivity between the RAg- and saline-challenged groups. The augmented BSM contractile response to histamine was only partially inhibited in the presence of either tetrodotoxin or hexamethonium. We conclude that 48 h after a single in vivo exposure to antigen in immune rabbits, the airway contractile responses to histamine in vitro are increased in BSM but not in TSM and that the mechanism of the augmented contractile responses in BSM likely involves the facilitated neural release of acetylcholine from both preganglionic and postganglionic sites.
Assuntos
Acetilcolina/fisiologia , Antígenos/imunologia , Brônquios/fisiopatologia , Histamina/farmacologia , Pólen/imunologia , Hipersensibilidade Respiratória/fisiopatologia , Traqueia/fisiopatologia , Animais , Atropina/farmacologia , Brônquios/efeitos dos fármacos , Brônquios/inervação , Bloqueadores Ganglionares/farmacologia , Hemicolínio 3/farmacologia , Hexametônio , Compostos de Hexametônio/farmacologia , Imunização , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiopatologia , Coelhos , Tetrodotoxina/farmacologia , Traqueia/efeitos dos fármacos , Traqueia/inervaçãoRESUMO
Airway cooling causes bronchoconstriction in many persons who have asthma. To determine the direct effect of cooling on the response of tracheal muscle to parasympathetic and muscarinic stimuli in situ, the temperature of a segment of canine cervical trachea was adjusted to 37 degrees, 30 degrees, or 25 degrees C by superfusing temperature-controlled saline over its epithelial surface. The contractile response of the tracheal muscle to electrical stimulation of the vagus nerves and to intra-arterial acetylcholine was then determined. Cooling the segment to 25 degrees C decreased the contraction induced by parasympathetic stimulation. However, cooling did not alter the contraction induced by intra-arterial acetylcholine. Parallel studies were conducted in vitro using nine excised tracheal muscle strips taken from the same section of trachea in three additional dogs. Cooling the tracheal muscle to 25 degrees C in vitro increased the maximal contraction induced by both electrical field stimulation and by acetylcholine. Thus, cooling in situ does not alter the response of tracheal muscle to muscarinic stimuli and inhibits the response to parasympathetic stimuli. These data indicate that augmentation of the tracheal muscle response elicited by cooling in vitro does not reflect the response in situ. They suggest that a direct effect of cooling on airway smooth muscle response to parasympathetic and muscarinic stimuli does not account for cooling-induced bronchoconstriction in vivo.
Assuntos
Broncoconstrição/fisiologia , Temperatura Baixa , Músculo Liso/fisiologia , Traqueia/fisiologia , Acetilcolina/farmacologia , Animais , Cães , Estimulação Elétrica , Feminino , Técnicas In Vitro , Masculino , Contração Muscular/fisiologia , Estimulação Química , Nervo Vago/fisiologiaRESUMO
Airway contractile responses to substance P (SP) were examined in isolated adult rabbit bronchial (BSM) and tracheal smooth muscle (TSM) segments. The tissues were placed in organ baths containing modified Krebs-Ringer solution, and isometric contractions to SP were monitored in the presence of phosphoramidon, an inhibitor of neutral endopeptidase (NEP). Under these conditions, BSM segments were significantly more reactive and more sensitive to SP than TSM segments. Removal of SPs cholinergic component with atropine (ATP) eliminated these regional differences in reactivity without affecting sensitivity. In considering the basis for these observations, it has been suggested that SP activates up to three different neurokinin (NK) subset receptors. Accordingly, we examined the regional airway contractile responses to Senktide, a selective NK-3 receptor agonist, and Septide, a selective NK-1 receptor agonist. In the presence of ATR, Senktide was inactive in both BSM and TSM, whereas Septide produced significantly greater contractions in BSM than in TSM. Subsequent desensitization of NK-1 receptors with Septide virtually eliminated the regional differences in airway sensitivity to SP. These findings indicate that 1) endogenous NEP activity can mask significant regional airway differences in SP-mediated contraction; and 2) these latter differences are the result of cholinergic, NK-1, and NK-2 receptor influences.
Assuntos
Brônquios/fisiologia , Contração Isométrica/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiologia , Receptores de Neurotransmissores/fisiologia , Substância P/farmacologia , Traqueia/fisiologia , Animais , Atropina/farmacologia , Brônquios/efeitos dos fármacos , Glicopeptídeos/farmacologia , Técnicas In Vitro , Cinética , Músculo Liso/efeitos dos fármacos , Neostigmina/farmacologia , Neurocinina A/fisiologia , Coelhos , Receptores da Neurocinina-2 , Receptores de Neurotransmissores/efeitos dos fármacos , Traqueia/efeitos dos fármacosRESUMO
The maturation of the neuromodulatory action of substance P (SP) was investigated in tracheal smooth muscle (TSM) segments isolated from rabbits aged 2-24 wk. The tissues were placed in baths containing Krebs-Ringer solution and contracted with electrical field stimulation (ES) with ES frequencies ranging from 1 to 75 Hz. In tissues greater than 1 mo of age, the ES frequency-response relationships were progressively shifted in the presence of a maximally effective neuromodulatory SP dose (10(-7) M) such that by 24 wk of age the mean (+/- SEM) maximal tension (Tmax) significantly increased from 380.4 (+/- 41.9) to 502.3 (+/- 64.2) g/g TSM, and the corresponding mean (+/- SEM) log ES frequency producing 50% of Tmax (log ES50) significantly decreased from 1.209 (+/- 0.069) to 1.055 (+/- 0.046) Hz. By contrast, relative to methacholine, the direct contractile effects of SP did not significantly vary with age. In further analyzing the basis for the above age-related difference in the neuromodulatory action of SP, we found that the magnitude of SP-induced neuromodulation was highly correlated to the tissue's intrinsic sensitivity to ES. Indeed, after accounting for the tissue's sensitivity to ES, the effect of age alone on the magnitude of SP-induced neuromodulation was not statistically significant. These findings provide new evidence that: (a) SP-induced neuromodulation of acetylcholine release at the airway neuromuscular junction is significantly enhanced during postnatal development; and (b) that the latter age-dependent action of SP is based on a close coupling of the magnitude of SP-induced neuromodulation to the tissue's intrinsic sensitivity to neurally mediated contraction.
Assuntos
Neurotransmissores/farmacologia , Substância P/farmacologia , Traqueia/efeitos dos fármacos , Fatores Etários , Animais , Estimulação Elétrica , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Coelhos , Substância P/antagonistas & inibidores , Tetrodotoxina/farmacologia , Traqueia/fisiologiaRESUMO
To elucidate the mechanism underlying temperature-induced changes in airway cholinergic contractility, the effects of organ bath cooling were evaluated in isolated rabbit airway smooth muscle (ASM) segments isometrically contracted with methacholine (METH) (10(-8)-10(-3) M) and electrical field stimulation (ES), wherein the ES stimulus frequency was varied between 1 and 100 Hz. Cooling from 37 to 25 degrees C produced systematic increases (P less than 0.01) in isometric tension at various administered doses of METH and at different levels of ES. Since the potentiated contractions to ES significantly exceeded (P less than 0.001) the corresponding increases in METH-induced contractility, we evaluated whether the latter was attributed to temperature-mediated changes in intrinsic airway neuronal acetylcholine (ACh) release. Accordingly, the effects of ASM cooling were independently determined before and after inhibition of the Na+-K+ electrogenic pump with ouabain (10(-5) M), and depletion of intrinsic neuronal ACh stores with hemicholinium-3 (HC-3) (10(-3) M). In the presence of either ouabain or HC-3 the above responses to temperature reduction were reversed, and airway cooling was associated with abrupt relaxation of ASM segments precontracted with METH. In contrast, neither inhibition of cyclooxygenase products with indomethacin (10(-6) M) nor cholinesterase inhibition with neostigmine (10(-3) M) notably influenced the ASM responses to organ bath cooling. Thus these findings demonstrate that 1) both METH-induced and neurally mediated cholinergic contractility are augmented during airway cooling; 2) the potentiated cholinergic responses are attributed to enhanced presynaptic release of ACh at the airway neuromuscular junction.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Resistência das Vias Respiratórias , Sistema Nervoso Parassimpático/fisiologia , Temperatura , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Brônquios/efeitos dos fármacos , Estimulação Elétrica , Técnicas In Vitro , Indometacina/farmacologia , Cloreto de Metacolina , Compostos de Metacolina/farmacologia , Neostigmina/farmacologia , Ouabaína/farmacologia , Coelhos , Traqueia/efeitos dos fármacosRESUMO
The neuromodulatory action of substance P (SP) was investigated in isolated rabbit tracheal smooth muscle (TSM) segments contracted with electrical field stimulation (ES). The tissues were placed in organ baths containing modified Krebs-Ringer solution and stimulated at a constant voltage (8 V; 24.5 mA) and pulse duration (2 ms) with ES frequencies ranging from 1 to 100 Hz. In the presence of SP, there occurred a dose-dependent augmentation of the TSM contractile response to any given ES, with the maximal effect of SP obtained at a dose of 10(-7) M. Accordingly, with the administration of 10(-7) M SP, the ES frequency-response relationship was altered so that 1) the mean (+/- SE) maximal tension (Tmax) induced by ES significantly increased (P less than 0.02) from a base-line value of 273 +/- 53 to 402 +/- 45 g/g TSM; and 2) the mean (+/- SE) log ES frequency producing 50% of Tmax (ES50) significantly decreased from a base-line value of 1.278 +/- 0.069 to 1.102 +/- 0.070 Hz (P less than 0.01). In contrast to these effects on ES-induced contraction, SP administration did not affect the TSM contractile response to administered methacholine chloride (10(-8) to 10(-3) M). On the other hand, the effects of SP on ES-induced contraction were independently blocked by the cholinergic antagonist, atropine (10(-6) M); the neurotoxin, tetrodotoxin (10(-6) g/ml); and the SP antagonist, D-Arg1,D-Pro2,D-Trp7,9,Leu11-SP (10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Contração Muscular/efeitos dos fármacos , Substância P/farmacologia , Traqueia/efeitos dos fármacos , Acetilcolina/metabolismo , Animais , Atropina/farmacologia , Estimulação Elétrica , Técnicas In Vitro , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Junção Neuromuscular/efeitos dos fármacos , Junção Neuromuscular/fisiologia , Coelhos , Receptores Colinérgicos/efeitos dos fármacos , Receptores Colinérgicos/fisiologia , Tetrodotoxina/farmacologia , Traqueia/inervação , Traqueia/fisiologiaRESUMO
Maturation of the respiratory pattern and the active and passive mechanical properties of the respiratory system were assessed in 19 tracheotomized rabbits (postnatal age range: 1-26 days) placed in a body plethysmograph. With maturation both minute ventilation and tidal volume significantly increased, whereas respiratory frequency decreased. When normalized for body weight (kg) both the passive (Rrs X kg) and active (R'rs X kg) resistances of the respiratory system significantly increased with age, whereas the corresponding passive (Crs X kg-1) and active (C'rs X kg-1) compliances significantly decreased. At any given age R'rs X kg only slightly exceeded Rrs X kg, whereas C'rs X kg-1 was significantly lower than Crs X kg-1. Moreover, the maturational increases in Rrs X kg and R'rs X kg exceeded the corresponding decreases in Crs X kg-1 and C'rs X kg-1, resulting in significant age-related increases in both the passive (tau rs) and active (tau'rs) time constants of the respiratory system. Due to the age-related increases in tau'rs, producing a delayed volume response to any given inspiratory driving pressure, the relative volume loss obtained at any time during inspiration was greater in the maturing rabbit. On the other hand, because of concomitant compensatory changes in respiratory pattern, evidenced by increases in inspiratory duration with age, the end-inspiratory tidal volume loss in the maturing animal was maintained generally less than 10% at all postnatal ages. Thus maturational changes in respiratory pattern appear coupled to changes in the active mechanical properties of the respiratory system. The latter coupling serves to optimize the transduction of inspiratory pressure into volume change in a manner consistent with establishing the minimum inspiratory work of breathing during postnatal development.
Assuntos
Animais Recém-Nascidos/fisiologia , Respiração , Fatores Etários , Resistência das Vias Respiratórias , Animais , Capacidade Inspiratória , Complacência Pulmonar , Coelhos , Volume de Ventilação PulmonarRESUMO
Substance P is a peptide implicated in the control of a variety of physiological processes. Although substance P-containing neurons impinge on the pulmonary vasculature, the effects of substance P on the pulmonary circulation have not been systematically investigated. Rabbits were anesthetized with methohexital sodium and paralyzed with pancuronium bromide. Injection of substance P (0.002-0.10 microgram/kg) in the vena cava produced dose-dependent pulmonary vasoconstriction and systemic vasodilation. Pulmonary arterial pressure reached a peak within 15-20 s and declined toward base line over 10 min. Aortic pressure fell rapidly, reaching minimum at 5-10 s. At higher doses cardiac output fell transiently, resulting in a 65% fall in pulmonary vascular conductance. If repeat substance P dosages were administered 15 min apart, there was no tachyphylaxis. Pulmonary vasoconstriction was inhibited by the cyclooxygenase blocker meclofenamate (10 mg/kg) and the thromboxane synthase inhibitor Dazmegrel (UK-38,485) (2 mg/kg). In contrast, vasoconstriction was enhanced by atropine (2 mg/kg). In Dazmegrel-treated animals in whom pulmonary vasoconstriction was established by epinephrine infusion, low doses of substance P produced vasodilation. Our findings indicate that substance P produces pulmonary vasoconstriction via prostaglandin (particularly thromboxane) generation and pulmonary vasodilation via activation of cholinergic pathways.
Assuntos
Pulmão/irrigação sanguínea , Substância P/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Imidazóis/farmacologia , Masculino , Ácido Meclofenâmico/farmacologia , Antagonistas de Prostaglandina/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Veias Pulmonares/efeitos dos fármacos , Coelhos , Tromboxano-A Sintase/antagonistas & inibidores , Vasodilatação/efeitos dos fármacosRESUMO
The vasoactive properties of substance P (SP) were studied in isolated rabbit pulmonary artery (PA) segments in vitro. In the absence of active base-line tone, noncumulative administration of SP (10(-11) to 10(-4) M) produced dose-dependent increases in PA tension. The peak isometric tension (Tmax) with SP was similar to the Tmax response to epinephrine; however, the doses of the agonist producing a threshold contraction and 25% of Tmax (ED25) were significantly lower for SP. In the presence of active base-line tone, induced by epinephrine or 5-hydroxytryptamine, SP produced transient PA relaxation which was directly related to the magnitude of the precontracted PA tension. Blockade of neurotransmission with tetrodotoxin (1 microgram/ml) and antagonists to alpha 1-adrenergic and histamine receptor binding had no effect on the contractile response to SP. On the other hand, PA contraction to an ED50 dose of SP was 1) inhibited by a mean of 33 +/- 10% (SE) following pretreatment with the cholinesterase inhibitor, neostigmine (10(-6) M) and 2) augmented by 52 +/- 21% with the cholinergic antagonist, atropine (10(-4) M). The latter also completely blocked the relaxation response to SP in precontracted PA. Similarly, removal of the PA endothelium also abolished the relaxation response to SP. In contrast, SP-induced contraction was markedly inhibited by the cyclooxygenase inhibitor, meclofenamate (1 microgram/ml), as well as the SP antagonist, D-Pro2, D-Trp7,9-SP.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Artéria Pulmonar/efeitos dos fármacos , Substância P/farmacologia , Animais , Atropina/farmacologia , Fenômenos Biomecânicos , Clorfeniramina/farmacologia , Cimetidina/farmacologia , Relação Dose-Resposta a Droga , Epinefrina/farmacologia , Técnicas In Vitro , Contração Isométrica/efeitos dos fármacos , Ácido Meclofenâmico/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Neostigmina/farmacologia , Fentolamina/farmacologia , Coelhos , Serotonina/farmacologia , Tetrodotoxina/farmacologiaRESUMO
The contractile effects of substance P (SP) were studied in isolated rabbit tracheal smooth muscle (TSM) segments in vitro. Noncumulative administration of SP produced dose-dependent increases in TSM tension. The mean (+/- SE) peak isometric tension (Tmax) with SP was 35.7 (+/- 6.2%) of the corresponding Tmax response to methacholine. The dose of agonist producing 50% of Tmax (ED50) was significantly lower for SP, averaging 1.8 (+/- 0.4) X 10(-7) M, vs. 1.7 (+/- 0.32) X 10(-6) M for methacholine. Blockade of both parasympathetic ganglia with hexamethonium (10(-4) M) and neural transmission with tetrodotoxin (1 microgram/ml) had no effect on the TSM response to SP. On the other hand, TSM contraction to an ED50 dose of SP was 1) augmented by a mean (+/- SE) of 470 (+/- 110%) following pretreatment with the cholinesterase inhibitor, neostigmine (10(-6) M);2) inhibited by a mean (+/- SE) of 35 (+/- 15%) with the cholinergic antagonist, atropine (10(-4) M); and 3) also inhibited by a mean (+/- SE) of 45 (+/- 11%) following inhibition of acetylcholine synthesis with hemicholinium-3 (10(-4) M). Antagonists to 5-hydroxytryptamine, alpha 1-adrenergic, and histamine receptor binding had no effect on TSM contraction with SP. In contrast, the SP antagonist, D-Pro2,D-Trp7,9-SP, markedly inhibited TSM contraction to SP. Our findings indicate that rabbit TSM is sensitive to SP and its contraction is in part mediated by a peripheral cholinergic action, likely involving the accelerated release of acetylcholine at the airway neuromuscular junction.
Assuntos
Contração Muscular , Músculo Liso/efeitos dos fármacos , Substância P/farmacologia , Traqueia/efeitos dos fármacos , Animais , Atropina/farmacologia , Fenômenos Biomecânicos , Relação Dose-Resposta a Droga , Gânglios Parassimpáticos/efeitos dos fármacos , Hemicolínio 3/farmacologia , Hexametônio , Compostos de Hexametônio/farmacologia , Cloreto de Metacolina , Compostos de Metacolina/farmacologia , Neostigmina/farmacologia , Bloqueio Nervoso , Inibição Neural , Coelhos , Transmissão Sináptica/efeitos dos fármacos , Tetrodotoxina/farmacologiaRESUMO
The maturational effects of substance P (SP) on airway function were quantitatively assessed in 30 anesthetized tracheotomized rabbits ranging in age from 2 to 29 days. Following paralysis, during mechanical ventilation with 100% O2 in a body plethysmograph, respiratory resistance (Rrs) and dynamic compliance (Cdyn) were continuously monitored. Noncumulative systemic infusions of SP (0.001-5.0 micrograms/g) produced dose-dependent decreases in pulmonary conductance (Grs), i.e., 1/Rrs, and Cdyn. The dose of SP producing a 50% decrease in Cdyn (PD50-Cdyn) significantly increased as a function of age indicating a diminution in airway sensitivity to SP. Bilateral cervical vagotomy and ganglionic blockade with hexamethonium had no effect on the airway response to SP. On the other hand, the response was significantly reduced following atropine sulfate infusion (2 mg/kg), suggesting a peripheral cholinergic contribution located distal to the airway parasympathetic ganglia. The magnitude of this cholinergic contribution increased as a function of age. Unlike atropine, antagonists to histamine and 5-hydroxytryptamine had no effect on the airway response to SP, however, the response was inhibited following infusion of the SP antagonist, D-Pro2,D-Trp7,9-SP. These findings indicate that the airway response to SP is age-related and mediated by binding of the agonist to airway smooth muscle coupled with an accelerated release of acetylcholine at the airway neuromuscular junction.