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Background: Burn injuries remain one of the leading causes of injury and death in children. Studies have demonstrated a higher mortality for pediatric burns associated with non-accidental injury. Using data from a burn registry, our study aimed to discern potential factors associated with non-accidental burn injuries., Methods: We utilized the American Burn Association database from 2016 to 2018, which collects data from over one hundred burn centers across the United States, to evaluate a large pediatric burn population. Patients aged ≤14 years were analyzed. The population was then divided into suspected non-accidental versus accidental burn injuries. A multivariable logistic regression model was utilized to evaluate for predictors of burn injuries. Additional models were used to assess the relationship between suspected non-accidental burn injury and mortality, intensive care unit (ICU) stay, and hospital length of stay., Results: 16,671 pediatric patients were included. Of those, 1228 (7.4%) patients suffered non-accidental burn injury. A majority of children who sustained non-accidental burn injury were younger, non-white, and sustained scald burns. The regression model demonstrated predictors for non-accidental burn injuries included younger age, Black race, chemical/corrosion burns, government insurance, and increased total body surface area (TBSA) burn. Overall mortality for the population was 0.5%., Conclusion: This evaluation of a national burn registry reveals differences in pediatric patients sustaining non-accidental burns compared to accidental burns. The findings in this study identify pediatric populations at risk for suspected non-accidental burn injuries which may assist in preparing the families for expectations after admission for a burn injury., Level of Evidence: III., Competing Interests: Conflicts of interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Patients with pectus excavatum (PE) often undergo cross-sectional imaging (CSI) to quantify severity for insurance authorization before surgical repair. The modified percent depth (MPD), an external caliper-based metric, was previously validated to be similar to the pectus index and correction index. This study explored family perceptions of CSI and MPD with respect to value and costs., Methods: This is a cross-sectional survey study including families of patients enrolled in an ongoing prospective multicenter study evaluating the use of MPD as an alternative to CSI for quantifying PE severity. Families of PE patients who underwent both MPD and CSI completed a survey to determine their perceptions of MPD and costs of CSI. Responses were described and associations were evaluated using chi squared, Wilcoxon rank-sum test and logistic regression as appropriate. Statistical significance was set to 0.05., Results: There were 136 surveys completed for a response rate of 88%. Respondents were confident in MPD (86%) and confident in its similarity to CSI (76%). Families of females were less confident in the measurements than males (55% versus 80%, P = 0.02; odds ratio 0.30 (0.11, 0.83). Obtaining CSI required time off work/school in 90% and a copay in 60%. Nearly half (49%) of respondents reported CSI was a time/financial hardship. Increasing copay led to decreased reassurance in CSI (55%: copay > $100 versus 77%: lower copay/75%: no copay; P = 0.04)., Conclusions: From the family perspective, MPD is valuable in assessing the severity of PE. Obtaining CSI was financially burdensome, particularly for those with higher copays. MPD measurements provide high value at low cost in assessing the severity of PE., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Firearm injury is the leading cause of death in children. The recent rise has coincided with the COVID-19 pandemic. The purpose of this study was to evaluate the trends of pediatric firearm injury over a 6-y period, to include the COVID-19 pandemic, at our pediatric trauma center., Methods: A retrospective review of the trauma registry at a free-standing children's hospital from January 2018 to December 2023 was performed. The variables evaluated included year of injury, age of injury, race, gender, admission requirements, need for blood products, need for operation, mortality, insurance type, and reason for injury., Results: There were 397 firearm injury presentations identified over the 6-y period. The median age of injury was 13 y with an interquartile range of 6-15 y. Most were male (72.3%) and of Black race (74.6%). A majority of children who sustained a firearm injury had Medicaid (77.8%). During the years of 2018 and 2019, we evaluated 40 and 39 patients, respectively. Over the next 2 y, there was a dramatic increase in pediatric firearm injuries with an increase of 65% (N = 66) in 2020 and 102.5% (N = 81) in 2021. Although there was less of an increase above baseline in 2022, there was still an elevation of 82.5% (N = 73). By the end of 2023, there had been a 145% rise (N = 98) in pediatric firearm injuries above the baseline year of 2018. The mortality rate was 7.6% (N = 30), which is 2.5 times higher than the all-cause trauma mortality of 3.1% at our facility., Conclusions: The number of firearm injuries dramatically increased during the COVID-19 pandemic and these increases have been sustained. Most of the victims have been male, of Black race, and publicly insured. While the state population of Alabama is 26.4% Black race, Black children account for 74.6% of all firearm-injured pediatric patients in our trauma registry. The reason for this disparity is not well-understood. Through ongoing research, we hope to gain insight into the reasons behind pediatric firearm injury and the best ways to mitigate them through both the medical and public health arenas., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Neonatal renal replacement therapy (RRT) is a treatment modality used for severe kidney failure. Historically, its use has been limited in small infants due to circuits with large extra-corporeal volumes that require large double lumen vascular catheters. We sought to review our institution's experience with vascular access and overall survival in infants who receive RRT., Methods: A retrospective chart review of infants less than 5 kg (kg) was performed at our free-standing children's hospital from January 2016 to July 2023. We assessed the number of catheters used per patient, location of catheter placements, size of catheter, duration of treatment, reasons for line removal, and mortality., Results: A total of 93 neonatal patients were identified who underwent RRT. Thirty-two patients (34.4%) required more than one catheter, with a total of 145 catheters placed for this cohort. The median (IQR) weight at insertion was 3.3 kg (2.7-4.0). The most common location for placement was the right internal jugular vein (n = 114, 78.6%). Patients required catheters for RRT for a median (IQR) of 16 days (7-39). Six patients underwent catheter placement at a weight of less than 2 kg. Nineteen total patients went on to peritoneal dialysis (20.4%). Fifty-three patients died during their admission (57.0%)., Conclusion: To our knowledge this is the largest review of catheter use for RRT in infants within an intensive care unit and it reveals the success in treating renal failure in even the smallest infants., Level of Evidence: IV, Treatment Study., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Burn injuries are among the top ten leading causes of unintentional death in pediatric patients and are encountered by pediatric surgeons in all practice settings. There is a lack of literature evaluating mortality in pediatric burn injuries in regard to nonaccidental burns and potential disparities. Our study aims to determine the risk factors associated with mortality in pediatric burn injuries and highlight the characteristics of this patient population., Methods: We utilized the Trauma Quality Improvement Program database from 2017 to 2019 to identify primary burn injuries in children ≤14 y old. Physical abuse descriptors were used to identify patients with suspected nonaccidental injuries. Further demographics, including age, race, ethnicity, and insurance type, were evaluated. Descriptive statistics were generated and a multivariable logistic regression analysis was utilized to evaluate risk factors for mortality., Results: 13,472 pediatric burn patients (≤14 y old) were identified. The overall mortality was low (<1%). Children with burns to multiple body regions had the highest independent risk of mortality in this cohort. All older age groups had an independent risk of mortality compared to the youngest patients, but those from ages 5 to <10 y old had the highest risk of mortality (OR = 11.40; 95% confidence interval: 4.41-29.43, P < 0.001). Black children had a significantly higher mortality compared to White children. Nonaccidental burns carried a mortality that was twice that of accidental burns. Government insurance type was the primary insurance type for a majority of patients who died., Conclusions: Risk factors for mortality in pediatric burn include Black race, multiple affected body regions, and nonaccidental burns. This study identified an increased mortality risk in the older age groups in contrast to previous studies that showed increased mortality in younger patients suffering from burn injuries., (Published by Elsevier Inc.)

Introduction: Intestinal atresia is a common cause of neonatal bowel obstruction. Atresias are often associated with other congenital anomalies. The purpose of the study was to evaluate associated anomalies, operative management, and postoperative outcomes of infants with intestinal atresia., Methods: A review of patients presenting to a single free-standing children's hospital from March 2012 through February 2022 was performed. The variables examined were type of atresia, additional congenital anomalies, type of operative intervention, and postoperative outcomes. Standard statistical methods were utilized., Results: A total of 75 patients with intestinal atresia were identified and several of these patients had multiple atresias. Isolated duodenal atresia patients were the most common (49.3%), followed by jejunal (32%) and ileal (12%). Mixed atresias were rare at 4%, with isolated pyloric and colonic also rare at 1.3% each. Malrotation was associated with 13% of patients and equally associated with duodenal and jejunoileal atresias. A low percentage (3%) of intestinal atresias was seen in conjunction with gastroschisis and concomitant malrotation. A majority of infants with duodenal atresia underwent standard duodenoduodenostomy (19% laparoscopic, 81% open). In infants with jejunoileal atresia, most underwent resection with primary anastomosis. A tapering enteroplasty was performed primarily in 13% of atresias. There were no significant differences noted in time to first feed or length of stay between those with and without tapering enteroplasty. Eleven percent of patients required subsequent intervention for stricture or small bowel obstruction. There was one death in this series., Conclusions: Consistent with other literature, duodenal atresia was the most common type of intestinal atresia. However, we demonstrated that malrotation was equally associated with duodenal and jejunoileal atresias while prior reports had shown a higher association with duodenal atresia. In our patient population, the use of tapering enteroplasty did not appear to be associated with outcomes. Overall, these infants have a low morbidity and mortality rate with a rare need for reoperation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Introduction: Current guidelines recommend nonoperative management (NOM) of low-grade (American Association for the Surgery of Trauma-Organ Injury Scale Grade I-II) pancreatic injuries (LGPIs), and drainage rather than resection for those undergoing operative management, but they are based on low-quality evidence. The purpose of this study was to review the contemporary management and outcomes of LGPIs and identify risk factors for morbidity., Methods: Multicenter retrospective review of diagnosis, management, and outcomes of adult pancreatic injuries from 2010 to 2018. The primary outcome was pancreas-related complications (PRCs). Predictors of PRCs were analyzed using multivariate logistic regression., Results: Twenty-nine centers submitted data on 728 patients with LGPI (76% men; mean age, 38 years; 37% penetrating; 51% Grade I; median Injury Severity Score, 24). Among 24-hour survivors, definitive management was NOM in 31%, surgical drainage alone in 54%, resection in 10%, and pancreatic debridement or suturing in 5%. The incidence of PRCs was 21% overall and was 42% after resection, 26% after drainage, and 4% after NOM. On multivariate analysis, independent risk factors for PRC were other intra-abdominal injury (odds ratio [OR], 2.30; 95% confidence interval [95% CI], 1.16-15.28), low volume (OR, 2.88; 1.65, 5.06), and penetrating injury (OR, 3.42; 95% CI, 1.80-6.58). Resection was very close to significance (OR, 2.06; 95% CI, 0.97-4.34) (p = 0.0584)., Conclusion: The incidence of PRCs is significant after LGPIs. Patients who undergo pancreatic resection have PRC rates equivalent to patients resected for high-grade pancreatic injuries. Those who underwent surgical drainage had slightly lower PRC rate, but only 4% of those who underwent NOM had PRCs. In patients with LGPIs, resection should be avoided. The NOM strategy should be used whenever possible and studied prospectively, particularly in penetrating trauma., Level of Evidence: Therapeutic Study, level IV., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Airway inflammation is a key pathological feature of asthma which underlies its clinical presentation., Objectives: To examine whether adding a leukotriene modifier to an inhaled corticosteroid produces further clinical and/or anti-inflammatory benefits in patients symptomatic on short-acting beta(2)-agonists., Methods: Patients uncontrolled on short-acting beta(2)-agonists were treated for 12 weeks with either fluticasone propionate (100mcg BD) or fluticasone propionate (100mcg BD) and montelukast (10mg QD) in a randomized, double-blind, parallel group study. Bronchoscopy with endobronchial biopsy and bronchoalveolar lavage (BAL) was performed before and after treatment to compare effects on airway inflammation., Results: Of 103 subjects enrolled, 89 subjects completed treatment and 82 subjects had matched pair biopsy samples. Submucosal eosinophil counts, the primary endpoint, and asthma control improved to similar extents after both treatments (p

In this study, 647 subjects stable on fluticasone propionate/salmeterol Diskus 100/50 mcg BID (FSC) were randomized to continue FSC 100/50 mcg BID or "step down" to either fluticasone propionate (FP) 100 mcg BID, salmeterol (SAL) 50 mcg BID, or montelukast (MON) 10 mg once daily for 16 weeks. Overall asthma control significantly improved in the FSC group; whereas, "stepping down" to FP, SAL, or MON resulted in deterioration in asthma control, as determined by decreased measures of lung function and clinical features. This study provides support that treatment of both inflammation and smooth muscle dysfunction may be necessary to achieve and maintain asthma control in patients uncontrolled on ICS.

Rationale: Little is known about the use of biomarkers in guiding treatment decisions in routine asthma management. The objective of this study was to determine whether adding a LABA to an ICS would control bronchial hyperresponsiveness (BHR) at an overall lower dose of ICS when titration of medication was based upon the assessment of routine clinical measures with or without the measurement of BHR., Methods: After a 2-week run-in period, subjects (> or = 12 years) were randomized to one of three treatment groups. Two groups followed a BHR treatment strategy (based on clinical parameters [lung function, asthma symptoms, and bronchodilator use] and BHR) and were treated with either fluticasone propionate/salmeterol (FSC(BHR) group) or fluticasone propionate (FP(BHR) group) (n=156 each). The third group followed a clinical treatment algorithm (based on clinical parameters alone) and were treated with fluticasone propionate (FP(REF) group; n=154). All treatments were administered via Diskus. Treatment doses were adjusted as needed every 8 weeks for 40 weeks according to the subject's derived severity class, which was based on clinical measures of asthma control with or without BHR., Results: The mean total daily inhaled corticosteroids (ICS) dose during the double-blind treatment period was lower, although not statistically significant, in the FSC(BHR) group compared with the FP(BHR) group (a difference of -42.9 mcg; p=0.07). Compared with the FP(REF) group, the mean total daily ICS dose was higher in the FSC(BHR) group (a difference of 85.2 mcg) and was significantly higher in the FP(BHR) group (a difference of 131.2 mcg, p=0.037)., Conclusion: This study demonstrated that for most subjects, control of BHR was maintained when treatment was directed toward control of clinical parameters. In addition, there was a trend towards control of BHR and clinical measures at a lower dose of ICS when used concurrently with salmeterol.

While critically ill patients experience a life-threatening illness, they commonly contract ventilator-associated pneumonia. This nosocomial infection increases morbidity and likely mortality as well as the cost of health care. This article reviews the literature with regard to diagnosis, treatment, and prevention. It provides conclusions that can be implemented in practice as well as an algorithm for the bedside clinician and also focuses on the controversies with regard to diagnostic tools and approaches, treatment plans, and prevention strategies.

Background: Inhaled corticosteroids (ICSs) have been shown to reverse epithelial damage and decrease lamina reticularis thickness in patients with asthma., Objective: This study investigated whether clinical asthma control and airway inflammation could be maintained after switching therapy from medium-dose fluticasone propionate (FP) to low-dose FP administered with the long-acting beta2-agonist (LABA) salmeterol., Methods: Eighty-eight subjects (age, > or =18 years) who, during open-label screening, demonstrated improved asthma control after an increase from 100 microg of FP twice daily to 250 microg of FP twice daily were randomized to receive 100/50 microg of FP/salmeterol through a Diskus inhaler (GlaxoSmithKline, Research Triangle Park, NC) twice daily or continue 250 microg of FP twice daily through a Diskus inhaler for 24 weeks. Clinical outcomes were monitored, and bronchial biopsy specimens and bronchoalveolar lavage fluid were obtained before and after 24 weeks of treatment., Results: There were no significant differences between treatments with respect to eosinophils in the bronchial mucosa and bronchoalveolar lavage fluid; mucosal mast cells, neutrophils, or CD3+, CD4+, CD8+, or CD25+ T lymphocytes; or concentration of mediators (GM-CSF, IL-8, and eosinophil cationic protein). The 2 treatments were not different with respect to lamina reticularis thickness. Consistent with the airway inflammatory measures, clinical and physiologic measures of asthma control were also similar., Conclusion: This study demonstrates that control of asthma and airway inflammation is maintained over the 24-week treatment period when patients requiring a medium-dose ICS are switched to a lower-dose ICS with a LABA., Clinical Implications: A lower-dose ICS with a LABA is effective in controlling inflammation and providing clinical asthma control, confirming current guideline recommendations.

For the athlete, not only can pulmonary disorders cause significant alterations in training schedules or even prolonged stoppages, they can be life-threatening. Infectious diseases such as acute bronchitis, influenza, and pneumonia conspire to disrupt exercise regimens. Pneumothorax, vocal cord dysfunction, and exercise-induced asthma may present diagnostic and treatment challenges. Obstructive sleep apnea not only causes disruptive symptoms but can be associated with significant cardiovascular morbidity and even mortality. This article addresses the most common pulmonary conditions athletes face and provides a framework for the diagnosis and treatment of these conditions.

Obstructive sleep disordered breathing (OSDB) is a spectrum of disease resulting from changes in the upper airway. It affects a large proportion of the adult population, and in its most severe form, obstructive sleep apnea syndrome (OSAS), patients suffer the adverse effects of sleep disturbance and oxygen desaturation. Daytime somnolence leads to a significantly higher incidence of automobile and work-related accidents, while nocturnal hypoxia is associated with multiple physiological derangements. Patients with OSAS have higher incidences of hypertension, coronary artery disease, congestive heart failure, and arrhythmias. Noninvasive testing is used to confirm the diagnosis, and treatment may be conservative, medical, or surgical. Treatment is designed to improve daytime somnolence and has been shown to improve morbidity and mortality among patients with OSDB.

Background: Concurrent use of an inhaled corticosteroid (ICS) and an inhaled long-acting beta2-agonist provides better overall asthma control than the use of higher doses of ICS alone., Objective: The purpose of this investigation was to determine whether fluticasone propionate (FP) combined with salmeterol in the Diskus device can be used to reduce the dose of ICS in patients currently stable on medium-dose ICS while maintaining asthma control., Methods: This was a randomized, double-blind, parallel-group, 12- to 24-week trial consisting of a 3-part run-in period. The run-in period was designed to first establish FP 250 microg administered twice a day (bid) via Diskus as the minimum effective dose. During run-in period 1, patients received FP 220 microg bid or the equivalent for 10 to 14 days. Controlled patients moved to run-in period 2 (5-28 days), which assessed asthma stability on FP 100 microg bid administered via Diskus. Only patients who became unstable on FP 100 microg bid were eligible to enter run-in period 3 (26-30 days), during which they were placed on FP 250 microg bid and those regaining asthma control were eligible for randomization. The primary efficacy endpoint was the proportion of patients who remained in the study with no evidence of worsening asthma. Secondary efficacy measures included FEV1, morning peak expiratory flow, percent of symptom-free days, and daily albuterol use., Results: Only 5% of patients treated with FP100/salmeterol withdrew because of worsening asthma in the first 12 weeks; this compared with 7% in the FP250 group. All patients from a subset of sites continued in the study for an additional 12 weeks; only an additional 1% of patients treated with either FP100/salmeterol or FP250 withdrew because of worsening asthma. Secondary efficacy measures confirmed primary efficacy results., Conclusion: In patients requiring FP250 bid for asthma stability, FP100/salmeterol bid was steroid-sparing, allowing a 60% reduction in the FP dose while maintaining overall asthma control.

Obesity can profoundly alter pulmonary function and diminish exercise capacity by its adverse effects on respiratory mechanics, resistance within the respiratory system, respiratory muscle function, lung volumes, work and energy cost of breathing, control of breathing, and gas exchange. Weight loss can reverse many of the alterations of pulmonary function produced by obesity. Obesity places the patient at risk of aspiration pneumonia, pulmonary thromboembolism, and respiratory failure. It is the most common precipitating factor for obstructive sleep apnea and is a requirement for the obesity hypoventilation syndrome, both of which are associated with substantial morbidity and increased mortality. There are numerous medical and surgical therapies for obstructive sleep apnea and obesity hypoventilation. Weight reduction in the obese is among the most effective of these measures.

CSA is a heterogeneous disorder with numerous causes and associations. It is much more common than previously believed, and is easily overlooked if not carefully sought. If undiagnosed, it may be associated with significant morbidity and even mortality. It is easily and noninvasively diagnosed, and therapy is often effective and can favorably impact the course of disease. Consequently, it would behoove all physicians to at least consider the diagnosis of CSA in any patient who has any predisposing condition, sign or symptom associated with this disease entity.

We studied the effect of pertussis toxin (PT) and partial muscarinic antagonism using pirenzepine (PIR) on beta-adrenergic relaxation of muscarinic contraction in 188 tracheal smooth muscle (TSM) preparations from 25 dogs in vitro. Strips of TSM were incubated for 4 h at 37 degrees C in Krebs-Henseleit (K-H) perfusate with or without 10 micrograms/ml of PT. In tissues contracted to target tension (TT; 50% of maximal response to 127 mM potassium-substituted K-H [KCl]) with acetylcholine (ACh), pretreatment with PT decreased the concentration of isoproterenol (ISO) causing 30% relaxation from TT (RC30) from 1.3 +/- 0.8 x 10(-7) M (control) to 2.8 +/- 0.7 x 10(-8) M (p = 0.013). Pretreatment with PT also augmented the maximal relaxation elicited by 10(-5) M ISO. In separate studies, strips of TSM were contracted with ACh; pretreatment with 10(-7) M PIR decreased the concentration of ISO causing 50% relaxation (RC50) from 3.4 +/- 0.6 x 10(-7) to 9.6 +/- 1.5 x 10(-8) M (p = 0.042). Pretreatment with PIR did not affect relaxation elicited by ISO for strips contracted equivalently with KCl. In addition, PIR increased both the potency and efficacy of ISO in relaxing muscarinic contraction in sham-incubated strips of TSM but had no effect after incubation with PT. Neither PT nor PIR affected beta-adrenergic relaxation of TSM contracted with KCl. Our data demonstrate that beta-adrenergic receptor relaxation of muscarinic contraction is augmented by (1) incubation with PT and (2) partial blockade of muscarinic receptors.

The phenomenon of contractile agonist-dependent relaxation by isoproterenol (ISO) of active tension elicited by acetylcholine (ACh), histamine (HIS), serotonin (5-HT), and potassium chloride-substituted Krebs-Henseleit solution (KCl) was studied in 210 tracheal smooth muscle (TSM) strips from 28 mongrel dogs in vitro. All TSM strips were contracted to similar active tensions [target tension (TT) = 50% of the maximal active tension elicited by 127 mM KCl] with ACh, HIS, 5-HT, or KCl and relaxed with either ISO, forskolin (FSK), N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (db-cAMP), or 3-isobutyl-1-methylxanthine (IMX). The concentrations of ISO causing 50% relaxation from TT (RC50) were ACh (2.9 +/- 1.1 x 10(-6) M) greater than 5-HT (8.4 +/- 1.5 x 10(-8) M) approximately KCl (8.1 +/- 2.1 x 10(-8) M) greater than HIS (1.6 +/- 0.2 x 10(-8) M). FSK and IMX relaxed TSM in the same rank order of potency as ISO. In contrast to the contractile agonist-dependent relaxation elicited by ISO, FSK, and IMX, db-cAMP was nearly equipotent in relaxing similarly contracted strips. These results are consistent with contractile agonist-specific interaction with cAMP production by ISO and FSK. These data demonstrate that the phenomenon of contractile agonist-dependent relaxation by ISO is not related specifically to the beta-adrenoceptor.

We compared isotonic shortening with isometric force generation as a function of external Ca2+ in 166 tracheal smooth muscle (TSM) strips from 27 mongrel dogs in vitro. Concentration-response curves were generated with muscarinic stimulation (acetylcholine, ACh), alpha-adrenergic receptor activation (norepinephrine after beta-adrenoceptor blockade, NE), serotonin (5-HT), and KCl-substituted Krebs-Henseleit solution. The concentrations of 5-HT causing half-maximal shortening (ECS50, 1.54 +/- 0.14 X 10(-7) M) and half-maximal active isometric tension (ECT50, 1.72 +/- 0.30 X 10(-7) M) were similar (P = NS). Likewise, ECS50 (21.9 +/- 0.7 mM) and ECT50, (22.0 +/- 0.9 mM) were similar for KCl. In contrast, facilitated isotonic shortening (i.e., greater isotonic shortening for comparable degrees of force generation) was elicited with ACh and NE for all levels of force generation between 15 and 85% of maximum and for all concentrations of ACh from 3 X 10(-8) to 3 X 10(-5) M (P less than 0.05 for all points). Facilitated isotonic shortening also was elicited for all concentrations of NE from 10(-8) to 10(-6) M (P less than 0.05 for all points). Removal of Ca2+ from the perfusate substantially reduced the potency of ACh (P less than 0.001) and abolished differences between ECS50 (2.23 +/- 0.28 X 10(-5) M) and ECT50 (2.50 +/- 0.46 X 10(-5) M, P = NS). We demonstrate that for comparable degrees of force generation, muscarinic and alpha-adrenergic receptor activation cause greater isotonic shortening than KCl or 5-HT and that this facilitated shortening is associated with the concentration of external Ca2+.

The interaction of contractile agonists on the relaxation elicited with isoproterenol (ISO) was studied in 112 tracheal smooth muscle (TSM) strips from 20 dogs in vitro. Strips were contracted to the same active target tension (TT) with acetylcholine (ACh), histamine (HIS), serotonin (5-hydroxytryptamine, 5-HT), potassium chloride (KCl), or the combinations of ACh + HIS, ACh + 5-HT, HIS + KCl, HIS + 5-HT (50% TT from each agonist). Although a less potent agonist, adding HIS to cause 50% of the TT reduced the concentration of ACh to elicit the remaining 50% TT and substantially altered relaxation by ISO compared with HIS alone [concentration required to achieve 50% relaxation (RC50) = 9.2 +/- 2.4 X 10(-8) vs. 9.0 +/- 4.4 X 10(-9) M to HIS alone; P less than 0.003]. Relaxation for TSM strips contracted with ACh + HIS was comparable to that elicited from the same TT with ACh alone, although concentrations required in combination were lower than for either agonist alone. Trachealis strips contracted equivalently with KCl + HIS also had augmented contraction and attenuated relaxation (RC50 = 3.7 +/- 0.8 X 10(-8) M; P less than 0.015 vs. HIS alone). However, combinations of 5-HT + ACh and 5-HT + HIS did not alter relaxation to ISO from that elicited by the weaker agonist alone. We demonstrate that TSM relaxation depends on the combination of agonists eliciting contraction and may be inhibited substantially by interactions among contractile agonists.