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1.
Article in English | MEDLINE | ID: mdl-38888521

ABSTRACT

INTRODUCTION: We compare in-hospital complications in youth with isolated diabetic ketoacidosis (DKA) to youth with hyperosmolarity. METHOD: We reviewed medical records of youth (1-20 years) admitted over two years with DKA, hyperglycemic hyperosmolar state (HHS), and hyperosmolar DKA. We evaluated outcomes, including hospital length of stay, altered mental status (AMS), and acute kidney injury (AKI). RESULTS: Of 369 admissions, 334 had isolated DKA, 32 had hyperosmolar DKA, and three had isolated HHS. Hyperosmolar youth had longer length of stay, larger initial fluid boluses, more frequent pediatric intensive care unit admissions, and increased risk of AKI and AMS. The odds of AKI were positively associated with serum osmolality and negatively associated with new-onset diabetes mellitus (DM) compared with established DM. CONCLUSIONS: In youth with DM, hyperosmolarity increases acute complications compared with isolated DKA. Larger-scale studies are needed to identify ways to prevent acute complications in youth experiencing hyperglycemic emergencies.

2.
Paediatr Anaesth ; 31(11): 1234-1240, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34482581

ABSTRACT

BACKGROUND: Pediatric patients with a mediastinal mass can experience severe complications while undergoing anesthesia. Nearly, all published reviews involve either patients with an anterior mediastinal mass or patients with an oncologic disease. AIM: The identification of risk factors for anesthetic-related complications in pediatric patients with any type of mediastinal mass. METHODS: From January 1, 2008 to December 31, 2019, patients with a newly diagnosed mediastinal mass that underwent anesthesia were retrospectively identified. Each patient's medical record was reviewed for presenting symptoms, preprocedure imaging results, the type of anesthetic delivered, and the occurrence of any anesthetic-related complications. A complication was defined as severe hypoxia, severe hypotension, or loss of endtidal carbon dioxide. RESULTS: Eighty-six patients presented with a new mediastinal mass. Six of these patients (7%) had a complication. Complications were no more likely in patients with orthopnea than in patients without orthopnea (P = 1.00; relative risk (RR) = 0.95; 95% CI (0.1, 7.5). Complication rates in patients with anterior, middle, and posterior mediastinal masses were similar, as were complication rates in patients with large, medium, and small masses. Six of the 41 patients (15%) who had tracheal compression had a complication, while none of the 45 patients (0%) who did not have tracheal compression had a complication (p = .0096). Six of the 48 patients (13%) that were intubated had a complication, while none of the 38 patients (0%) who were not intubated had a complication (p = .032). Five of 36 patients (14%) who had mainstem bronchus compression had a complication, while one of 50 patients (2%) who did not have mainstem bronchus compression had a complication (p = .078; RR = 6.9l; 95% CI (0.8, 56.9)). CONCLUSIONS: Anesthetic-related complications were associated with airway compression and endotracheal intubation. The absence of preprocedure orthopnea did not ensure that the anesthetic would be uncomplicated. Complications occurred in similar frequencies in patients with a mediastinal mass of any location or size.


Subject(s)
Anesthesia , Mediastinal Neoplasms , Anesthesia/adverse effects , Child , Humans , Intubation, Intratracheal , Mediastinal Neoplasms/complications , Retrospective Studies , Risk Factors
3.
Pediatr Infect Dis J ; 36(3): 290-295, 2017 03.
Article in English | MEDLINE | ID: mdl-28187115

ABSTRACT

BACKGROUND: Enterovirus D68 (EV-D68) has been sporadically reported as a cause of respiratory tract infections. In 2014, an international outbreak of EV-D68 occurred and caused severe respiratory disease in the pediatric population. METHODS: A retrospective chart review was performed of children admitted to Children's Mercy Hospital from August 1, 2014, to September 15, 2014, with positive multiplex polymerase chain reaction testing for EV/rhinovirus (RV). Specimens were subsequently tested for EV-D68, and clinical data were obtained from the medical records. Patients with EV-D68 were compared with children presenting simultaneously with other EV/RV. RESULTS: Of 542 eligible specimens, children with EV-D68 were significantly older than children with other EV/RV (4.6 vs. 2.2 years, P < 0.001). Children with EV-D68 were more likely to have a history of asthma (38.6% vs. 30.0%, P = 0.04) or recurrent wheezing (22.1% vs. 14.8%, P = 0.04). EV-D68-positive children more commonly received supplemental oxygen (86.7% vs. 65.0%, P < 0.001), albuterol (91.2% vs. 65.5%, P < 0.001) and corticosteroids (82.9% vs. 58.6%, P < 0.001). Age ≥5 years was an independent risk factor for intensive care unit management in EV-D68-infected children. Children with a history of asthma or recurrent wheezing and EV-D68 received supplemental oxygen (92.7% vs. 82.4%, P = 0.007) and magnesium (42.7% vs. 29.7%, P = 0.03) at higher rates and more continuous albuterol (3 vs. 2 hours, P = 0.03) than those with other EV/RV. CONCLUSIONS: EV-D68 causes severe disease in the pediatric population, particularly in children with a history of asthma or recurrent wheezing. EV-D68-positive children are more likely to require therapy for refractory bronchospasm and may need intensive care unit- level care.


Subject(s)
Enterovirus D, Human , Enterovirus Infections/diagnosis , Enterovirus Infections/epidemiology , Child , Child, Preschool , Disease Outbreaks/statistics & numerical data , Enterovirus Infections/therapy , Enterovirus Infections/virology , Female , Hospitalization , Humans , Male , Retrospective Studies
4.
J Clin Virol ; 70: 77-82, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26305825

ABSTRACT

BACKGROUND: Enterovirus 68 (EV-D68) causes acute respiratory tract illness in epidemic cycles, most recently in Fall 2014, but clinical characteristics of severe disease are not well reported. OBJECTIVES: Children with EV-D68 severe respiratory disease requiring pediatric intensive care unit (PICU) management were compared with children with severe respiratory disease from other enteroviruses/rhinoviruses. STUDY DESIGN: A retrospective review was performed of all children admitted to Children's Mercy Hospital PICU from August 1-September 15, 2014 with positive PCR testing for enterovirus/rhinovirus. Specimens were subsequently tested for the presence of EV-D68. We evaluated baseline characteristics, symptomatology, lab values, therapeutics, and outcomes of children with EV-D68 viral infection compared with enterovirus/rhinovirus-positive, EV-D68-negative children. RESULTS: A total of 86 children with positive enterovirus/rhinovirus testing associated with respiratory symptoms were admitted to the PICU. Children with EV-D68 were older than their EV-D68-negative counterparts (7.1 vs. 3.5 years, P=0.01). They were more likely to have a history of asthma or recurrent wheeze (68% vs. 42%, P=0.03) and to present with cough (90% vs. 63%, P=0.009). EV-D68 children were significantly more likely to receive albuterol (95% vs. 79%, P=0.04), magnesium (75% vs. 42%, P=0.004), and aminophylline (25% vs. 4%, P=0.03). Other adjunctive medications used in EV-D68 children included corticosteroids, epinephrine, and heliox; 44% of EV-D68-positive children required non-invasive ventilatory support. CONCLUSIONS: EV-D68 causes severe disease in the pediatric population, particularly in children with asthma and recurrent wheeze; children may require multiple adjunctive respiratory therapies.


Subject(s)
Critical Care , Enterovirus D, Human/classification , Enterovirus D, Human/genetics , Enterovirus Infections/diagnosis , Enterovirus Infections/virology , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/virology , Age Factors , Biomarkers , Child , Child, Preschool , Disease Management , Enterovirus Infections/therapy , Female , Hospitalization , Humans , Infant , Male , Respiratory Tract Infections/therapy , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , Severity of Illness Index , Treatment Outcome
5.
Intensive Care Med ; 41(8): 1445-53, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26077052

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the association between early fluid accumulation and mortality in children with shock states. METHODS: We retrospectively reviewed children admitted in shock states to the pediatric intensive care unit (ICU) at a tertiary level children's hospital over a 7-month period. The study was designed as a matched case-control study. Children with early fluid overload, defined as fluid accumulation of ≥10% of admission body weight during the initial 3 days, were designated as the cases. They were compared with matched controls without early fluid accumulation. Cases and controls were matched for age, severity of illness at ICU admission and need for organ support. They were compared with respect to all-cause ICU mortality and other secondary outcomes. RESULTS: A total of 114 children (age range 0-17.4 years; N = 42 cases and 72 matched controls) met the study criteria. Mortality rate was 13% (15/114) in this cohort. Multivariable logistic regression analysis identified the presence of early fluid overload [adjusted odds ratio (OR) 9.17, 95% confidence interval (CI) 2.22-55.57], its severity (adjusted OR 1.11, 95% CI 1.05-1.19) and its duration (adjusted OR 1.61, 95% CI 1.21-2.28) as independent predictors of mortality. Cases had higher mortality than the controls (26 vs. 6 %; p 0.003), and this difference remained significant in the matched analysis (37 vs. 3%; p 0.002). CONCLUSION: The presence, severity and duration of early fluid are associated with increased ICU mortality in children admitted to the pediatric ICU in shock states.


Subject(s)
Hospital Mortality , Shock/complications , Water-Electrolyte Imbalance/epidemiology , Adolescent , Case-Control Studies , Child , Child, Preschool , Critical Illness , Female , Humans , Infant , Intensive Care Units, Pediatric , Male , Retrospective Studies , Shock/mortality , Tertiary Care Centers , Water-Electrolyte Imbalance/complications , Water-Electrolyte Imbalance/mortality
7.
Pediatr Crit Care Med ; 15(9): 861-9, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25251516

ABSTRACT

OBJECTIVES: Describe aspects of one center's experience extubating infants and children during extracorporeal membrane oxygenation. DESIGN: Retrospective review of medical records. SETTING: Seventy-one-bed critical care service (PICU and cardiovascular ICU) in a large urban tertiary children's hospital. PATIENTS: Pediatric and neonatal patients supported on extracorporeal membrane oxygenation between 1996 and 2013 who were either not intubated or extubated greater than 24 hours during their extracorporeal membrane oxygenation course. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixteen of 511 patients on extracorporeal membrane oxygenation were extubated for at least 24 hours during their extracorporeal membrane oxygenation courses. Fourteen had respiratory failure and two had cardiac disease. Five patients died while on extracorporeal membrane oxygenation, but the cause of death was not related to complications associated with extubation. Extubated patients were supported a median of 19.7 days on extracorporeal membrane oxygenation, with a median extubation latency (time between cannulation and first extubation) of 6.2 days and a median extubation duration of 5.5 days. Mean time extubated was 43% of the total time on extracorporeal membrane oxygenation. Two patients were reintubated briefly or had a laryngeal mask airway placed for decannulation (n = 1). The remaining patients were extubated within 5 days of decannulation, weeks afterward (n = 2), transferred to outside facilities (n = 2), or died during extracorporeal membrane oxygenation support (n = 5). We also observed no complications directly attributable to extubation and spontaneous reaeration of consolidated lungs in acute respiratory distress syndrome in extubated patients on extracorporeal membrane oxygenation. CONCLUSION: Extubation and discontinuation of mechanical ventilation appear feasible in patients requiring long-term extracorporeal membrane oxygenation. Emergency procedure planning may need to be modified in extubated patients on extracorporeal membrane oxygenation.


Subject(s)
Airway Extubation/methods , Extracorporeal Membrane Oxygenation/methods , Intensive Care Units, Pediatric , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective Studies , Tertiary Care Centers
8.
Crit Care Med ; 42(4): 943-53, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24231758

ABSTRACT

OBJECTIVES: Acute kidney injury and fluid overload frequently necessitate initiation of continuous renal replacement therapy in critically ill patients admitted to the ICU. In this study, our primary objective was to determine the effect of timing of initiation of continuous renal replacement therapy on ICU mortality in children requiring renal support for management of acute kidney injury and/or fluid overload. DESIGN: Retrospective cohort study. SETTING: Tertiary level, multidisciplinary PICU. PATIENTS: Children who received continuous renal replacement therapy for management of acute kidney injury and/or fluid overload from January 2000 through July 2009 were included in the study. Patients requiring extracorporeal life support and patients initiated on continuous renal replacement therapy for indications other than acute kidney injury and/or fluid overload were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Timing of initiation was defined chronologically as time from ICU admission to continuous renal replacement therapy initiation. Three hundred eighty treatments were performed during the study period, of which 190 were eligible and included in the study. Overall ICU mortality was 47% among the study population. Median timing of initiation was higher among nonsurvivors compared with survivors (3.4 vs 2.0 d, p = 0.001). Multivariable logistic regression analysis identified timing of initiation as an independent predictor of mortality with an adjusted odds ratio of 1.05 (95% CI, 1.01, 1.11). Fluid overload, indication for continuous renal replacement therapy initiation, severity of illness at ICU admission, and active oncologic diagnosis were the other independent predictors of mortality that were identified in the final regression model. In the survival analysis, late initiators (> 5 d) had higher mortality than early initiators (≤ 5 d) with a hazard ratio of 1.56 (95% CI, 1.02, 2.37). CONCLUSIONS: Earlier initiation of continuous renal replacement therapy was associated with lower mortality in this cohort of critically ill children. Future studies should focus on early identification of such children who may benefit from early continuous renal replacement therapy initiation.


Subject(s)
Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , Critical Illness/mortality , Critical Illness/therapy , Renal Replacement Therapy/mortality , Renal Replacement Therapy/methods , Adolescent , Child , Child, Preschool , Hospital Mortality , Humans , Infant , Infant, Newborn , Intensive Care Units, Pediatric/statistics & numerical data , Retrospective Studies , Severity of Illness Index , Time Factors
9.
Indian J Crit Care Med ; 16(4): 204-6, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23559727

ABSTRACT

Calcium channel blocker (CCB) toxicity is associated with refractory hypotension and can be fatal. A 13 year old young woman presented to the emergency department(ED) six hours after an intentional overdose of amlodipine, barbiturates, and alcohol. She remained extremely hypotensive despite the administration of normal saline and calcium chloride and despite infusions of norepinephrine, epinephrine, insulin, and dextrose. Due to increasing evidence of end organ dysfunction, Extracorporeal Life Support (ECLS) was initiated 9 hours after presentation to the ED. The patient's blood pressure and end organ function immediately improved after cannulation. She was successfully decannulated after 57 hours of ECLS and was neurologically intact. Patients with calcium channel blocker overdose who are resistant to medical interventions may respond favorably to early ECLS.

10.
Pediatr Crit Care Med ; 12(5): 504-11, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21076361

ABSTRACT

OBJECTIVES: To compare the efficacy of a low-dose methadone tapering schedule to a high-dose methadone tapering schedule in pediatric intensive care unit patients exposed to infusions of fentanyl, with or without infusions of midazolam, for ≥ 5 days. DESIGN: Prospective, double-blind, randomized trial. SETTING: Pediatric intensive care unit in a tertiary care children's hospital. PATIENTS: Seventy-eight patients, 74 of whom had been receiving infusions of both fentanyl and midazolam, were randomized. Forty-one patients were randomized to the low-dose methadone group and 37 were randomized to the high-dose methadone group. Sixty patients successfully completed the trial, 34 were in the low-dose methadone group, and 26 were in the high-dose methadone group. INTERVENTIONS: Patients were randomized to receive methadone either at a starting dose of 0.1 mg/kg/dose (low-dose methadone group) or at a starting dose based on both the patient's weight and the most recent fentanyl infusion rate (high-dose methadone group). In each group, methadone was administered every 6 hrs for the first 24 hrs and then every 12 hrs for the second 24 hrs. The methadone was then decreased to once daily and tapered off over the next 10 days. Patients were monitored for withdrawal symptoms using the Modified Narcotic Withdrawal Score. MEASUREMENTS AND MAIN RESULTS: The percentage of patients who successfully completed the 10-day methadone taper was the same in the low-dose methadone group as in the high-dose methadone group (56% vs. 62%; p = .79). Patients that failed to complete the assigned methadone taper had a greater total fentanyl dose and longer pediatric intensive care unit length of stay compared to patients who completed the assigned methadone taper. CONCLUSIONS: Patients who received infusions of fentanyl for at least 5 days were just as likely to complete a low-dose methadone taper as a high-dose methadone taper. Because of the risks of both withdrawal and oversedation with any fixed methadone schedule, the methadone dose must be adjusted according to each patient's response.


Subject(s)
Fentanyl/therapeutic use , Hypnotics and Sedatives/therapeutic use , Intensive Care Units, Pediatric , Methadone/administration & dosage , Midazolam/therapeutic use , Substance Withdrawal Syndrome/prevention & control , Child, Preschool , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Female , Fentanyl/administration & dosage , Humans , Hypnotics and Sedatives/administration & dosage , Infant , Male , Midazolam/administration & dosage , Prospective Studies , United States
11.
Pediatr Crit Care Med ; 11(3): 362-71, 2010 May.
Article in English | MEDLINE | ID: mdl-19924027

ABSTRACT

OBJECTIVES: Describe the use of extracorporeal cardiopulmonary resuscitation as rescue therapy in pediatric patients who experience cardiopulmonary arrest refractory to conventional resuscitation. We report on outcomes and factors associated with survival in children treated with extracorporeal cardiopulmonary resuscitation during cardiopulmonary arrest from the American Heart Association National Registry of CardioPulmonary Resuscitation. DESIGN: Multicentered, national registry of in-hospital cardiopulmonary resuscitation. SETTING: Two hundred eighty-five hospitals reporting to the registry from January 2000 to December 2007. PATIENTS: Pediatric patients <18 yrs of age who received extracorporeal membrane oxygenation during cardiopulmonary resuscitation for in-hospital cardiopulmonary arrest. INTERVENTIONS: None. MEASUREMENTS AND OUTCOMES: Prearrest and arrest variables were collected. The primary outcome variable was survival to hospital discharge. The secondary outcome was neurologic status after extracorporeal cardiopulmonary resuscitation at hospital discharge. Favorable neurologic outcome was defined as Pediatric Cerebral Performance Categories 1, 2, 3, or no change from admission Pediatric Cerebral Performance Category. RESULTS: Of 6288 pediatric cardiopulmonary arrest events reported, 199 (3.2%) index extracorporeal cardiopulmonary resuscitation events were identified; 87 (43.7%) survived to hospital discharge. Fifty-nine survivors had Pediatric Cerebral Performance Category outcomes recorded, and of those, 56 (94.9%) had favorable outcomes. In a multivariable model, the prearrest factor of renal insufficiency and arrest factors of metabolic or electrolyte abnormality and the pharmacologic intervention of sodium bicarbonate/tromethamine were associated with decreased survival. After adjusting for confounding factors, cardiac illness category was associated with an increased survival to hospital discharge. CONCLUSIONS: Forty-four percent of pediatric patients who failed conventional cardiopulmonary resuscitation from in-hospital cardiopulmonary arrest and who were reported to the National Registry of CardioPulmonary Resuscitation database as treated with extracorporeal cardiopulmonary resuscitation survived to hospital discharge. The majority of survivors with recorded neurologic outcomes were favorable. Patients with cardiac illness category were more likely to survive to hospital discharge after treatment with extracorporeal cardiopulmonary resuscitation. Extracorporeal cardiopulmonary resuscitation should be considered for select pediatric patients refractory to conventional in-hospital resuscitation measures.


Subject(s)
Cardiopulmonary Resuscitation/methods , Extracorporeal Membrane Oxygenation , Heart Arrest/therapy , Inpatients , Outcome Assessment, Health Care , Registries , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Survival Analysis
12.
Pediatr Crit Care Med ; 10(1): 56-9, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19057430

ABSTRACT

OBJECTIVE: Optimal cannula position is essential during extracorporeal membrane oxygenation (ECMO). We hypothesize that echocardiography is superior to chest radiography in diagnosing abnormal cannula position during ECMO. DESIGN: Retrospective. SETTING: Pediatric hospital. PATIENTS: 100 pediatric patients requiring ECMO. MEASUREMENTS AND MAIN RESULTS: We reviewed the medical records of all ECMO patients (n = 100), including reports of all echocardiograms (n = 326), during the years 2002-2004. Of the 91 patients who had echocardiograms while on ECMO, 33 had at least 1 echocardiogram for cannula-position evaluation. Of the remaining 58 patients with echocardiograms for reasons other than cannula-position evaluation, 4 (7%) were found to have abnormal cannula position. These included arterial cannula (AC) within 2-4 mm of the aortic valve (n = 2), AC across the aortic valve into the left ventricle (n = 1), and venous cannula (VC) abutting the atrial septum (n = 1). Of the 33 patients with echocardiograms for evaluation of cannula position, 8 (24%) required intervention. Of those 8 patients, 4 required cannula repositioning due to VC in the coronary sinus (n = 1), VC abutting atrial septum (n = 1), AC in left subclavian artery (n = 1), and AC within 3 mm of aortic valve (n = 1). The remaining 4 with normal cannula position required upsizing of the VC (n = 2), increased circuit flow (n = 1), or intravascular volume administration (n = 1). Overall, 12 of 91 patients (13%) required intervention based on echocardiographic findings. Chest radiography did not detect abnormalities of ECMO cannula position in any of the 8 patients with this problem, nor were any additional patients with abnormal cannula position identified by chest radiography. CONCLUSIONS: Echocardiography appears to be superior to chest radiography for assessing ECMO cannula position in our institution. A prospective study, including cost analysis, comparing chest radiography and echocardiography, is needed to definitely determine the preferred diagnostic test or sequence of tests to establish ECMO cannula position.


Subject(s)
Catheterization/methods , Echocardiography, Doppler/methods , Extracorporeal Membrane Oxygenation/methods , Radiography, Thoracic/methods , Adolescent , Catheterization/adverse effects , Child , Child, Preschool , Cohort Studies , Critical Care/methods , Critical Illness/therapy , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/instrumentation , Female , Foreign-Body Migration/diagnostic imaging , Humans , Infant , Infant, Newborn , Intensive Care Units, Pediatric , Male , Monitoring, Physiologic/methods , Retrospective Studies , Risk Factors , Sensitivity and Specificity , Young Adult
13.
Pediatr Blood Cancer ; 49(5): 751-4, 2007 Oct 15.
Article in English | MEDLINE | ID: mdl-16421913

ABSTRACT

We report the cases of two children presenting with severe airway compromise secondary to a mediastinal malignancy managed with extracorporeal membrane oxygenation without intubation. Results are presented on the use of ECMO as a primary means of stabilizing a pediatric patient with a critical mediastinal mass, thus providing another management strategy for this difficult situation.


Subject(s)
Extracorporeal Membrane Oxygenation , Mediastinal Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Child , Child, Preschool , Humans , Male , Mediastinal Neoplasms/diagnostic imaging , Radiography , Remission Induction , Respiratory Insufficiency/etiology
15.
Am J Physiol Heart Circ Physiol ; 285(4): H1616-25, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12738625

ABSTRACT

Whereas controversial, several studies have suggested that nitric oxide (NO) alters cardiac contractility via cGMP, peroxynitrite, or poly(ADP ribose) synthetase (PARS) activation. This study determined whether burn-related upregulation of myocardial inducible NO synthase (iNOS) and NO generation contributes to burn-mediated cardiac contractile dysfunction. Mice homozygous null for the iNOS gene (iNOS knockouts) were obtained from Jackson Laboratory. iNOS knockouts (KO) as well as wild-type mice were given a cutaneous burn over 40% of the total body surface area by the application of brass probes (1 x 2 x 0.3 cm) heated to 100 degrees C to the animals' sides and back for 5 s (iNOS/KO burn and wild-type burn). Additional groups of iNOS KO and wild-type mice served as appropriate sham burn groups (iNOS/KO sham and wild-type sham). Cardiac function was assessed 24 h postburn by perfusing hearts (n = 7-10 mice/group). Burn trauma in wild-type mice impaired cardiac function as indicated by the lower left ventricular pressure (LVP, 67 +/- 2 mmHg) compared with that measured in wild-type shams (94 +/- 2 mmHg, P < 0.001), a lower rate of LVP rise (+dP/dtmax, 1,620 +/- 94 vs. 2,240 +/- 58 mmHg/s, P < 0.001), and a lower rate of LVP fall (-dP/dtmax, 1,200 +/- 84 vs. 1,800 +/- 42 mmHg/s, P < 0.001). Ventricular function curves confirmed significant contractile dysfunction after burn trauma in wild-type mice. Burn trauma in iNOS KO mice produced fewer cardiac derangements compared with those observed in wild-type burns (LVP: 78 +/- 5 mmHg; +dP/dt: 1,889 +/- 160 mmHg/s; -dP/dt: 1,480 +/- 154 mmHg/s). The use of a pharmacological approach to inhibit iNOS (aminoguanidine, given ip) in additional wild-type shams and burns confirmed the iNOS KO data. Whereas the absence of iNOS attenuated burn-mediated cardiac contractile dysfunction, these experiments did not determine the contribution of cardiac-derived NO versus NO generated by immune cells. However, our data indicate a role for NO in cardiac dysfunction after major trauma.


Subject(s)
Burns/metabolism , Nitric Oxide/antagonists & inhibitors , Animals , Burns/physiopathology , Enzyme Inhibitors/pharmacology , Guanidines/pharmacology , Heart/physiopathology , In Vitro Techniques , Mice , Mice, Inbred C57BL , Mice, Knockout/genetics , Myocardial Contraction , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , Pressure , Ventricular Function, Left
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