Publications by authors named "Christopher J Babbitt"

13 Publications

  • Page 1 of 1

Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome.

JAMA Neurol 2021 05;78(5):536-547

Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham.

Importance: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear.

Objective: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19.

Setting, Design, And Participants: Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features.

Exposures: Severe acute respiratory syndrome coronavirus 2.

Main Outcomes And Measures: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge.

Results: Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died.

Conclusions And Relevance: In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.
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http://dx.doi.org/10.1001/jamaneurol.2021.0504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936352PMC
May 2021

Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19.

JAMA 2021 03;325(11):1074-1087

Division of Hospital Medicine, Department of Pediatrics, Hackensack University Medical Center, Hackensack, New Jersey.

Importance: Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes.

Objective: To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19).

Setting, Design, And Participants: Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement.

Exposure: SARS-CoV-2.

Main Outcomes And Measures: Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19.

Results: Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days.

Conclusions And Relevance: This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.
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http://dx.doi.org/10.1001/jama.2021.2091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905703PMC
March 2021

Functional Brain Hyperactivations Are Linked to an Electrophysiological Measure of Slow Interhemispheric Transfer Time after Pediatric Moderate/Severe Traumatic Brain Injury.

J Neurotrauma 2020 01 25;37(2):397-409. Epub 2019 Sep 25.

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, California.

Increased task-related blood oxygen level dependent (BOLD) activation is commonly observed in functional magnetic resonance imaging (fMRI) studies of moderate/severe traumatic brain injury (msTBI), but the functional relevance of these hyperactivations and how they are linked to more direct measures of neuronal function remain largely unknown. Here, we investigated how working memory load (WML)-dependent BOLD activation was related to an electrophysiological measure of interhemispheric transfer time (IHTT) in a sample of 18 msTBI patients and 26 demographically matched controls from the UCLA RAPBI (Recovery after Pediatric Brain Injury) study. In the context of highly similar fMRI task performance, a subgroup of TBI patients with slow IHTT had greater BOLD activation with higher WML than both healthy control children and a subgroup of msTBI patients with normal IHTT. Slower IHTT treated as a continuous variable was also associated with BOLD hyperactivation in the full TBI sample and in controls. Higher WML-dependent BOLD activation was related to better performance on a clinical cognitive performance index, an association that was more pronounced within the patient group with slow IHTT. Our previous work has shown that a subgroup of children with slow IHTT after pediatric msTBI has increased risk for poor white matter organization, long-term neurodegeneration, and poor cognitive outcome. BOLD hyperactivations after msTBI may reflect neuronal compensatory processes supporting higher-order capacity demanding cognitive functions in the context of inefficient neuronal transfer of information. The link between BOLD hyperactivations and slow IHTT adds to the multi-modal validation of this electrophysiological measure as a promising biomarker.
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http://dx.doi.org/10.1089/neu.2019.6532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964811PMC
January 2020

Does an Antimicrobial Time-Out Impact the Duration of Therapy of Antimicrobials in the PICU?

Pediatr Crit Care Med 2019 06;20(6):560-567

Pediatric Critical Care, Miller Children's and Women's Hospital of Long Beach, Long Beach, CA.

Objectives: Our aim was to perform an antimicrobial time-out 48-72 hours after commencing therapy in order to achieve a decrease in days of therapy per 1,000 patient days for vancomycin, meropenem, and piperacillin/tazobactam in all PICU patients during an 8-month period.

Design: This is a pre- and postimplementation quality improvement study.

Settings: A 30-bed PICU at a tertiary children's hospital.

Patients: Patients less than 21 years old admitted to the PICU from July 1, 2015, until March 31, 2016, or from July 1, 2016, until March 31, 2017, who received antibiotics for greater than 48 hours were eligible for inclusion.

Intervention: An antimicrobial time-out was performed after 48-72 hours of antimicrobials for all patients in the PICU during postimplementation.

Measurements And Main Results: The primary outcome measure was days of therapy per 1,000 patient-days for three target antibiotics: vancomycin, meropenem, and piperacillin/tazobactam. Ninety-five patients meeting inclusion criteria were admitted to the PICU during the pre-time-out period and 95 patients during the post-time-out period. The cohort that underwent time-outs had lower days of therapy for vancomycin (81.3 vs 138.1; p = 0.037) and meropenem (34.7 vs 67.1; p = 0.045). Total acquisition cost was 31 % lower for piperacillin/tazobactam and vancomycin and 46% for meropenem post implementation. Time-outs led to antimicrobial duration being defined 63% of the time and deescalation or discontinuation of antimicrobials 29% of the time.

Conclusions: A 48-72-hour time-out process in rounds is associated with a reduction in days of therapy for antibiotics commonly used in the PICU and may lead to more appropriate usage. The time-outs are associated with discontinuation, deescalation, or duration being defined, which are key elements of Centers for Disease Control and Prevention-recommended antimicrobial stewardship programs.
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http://dx.doi.org/10.1097/PCC.0000000000001925DOI Listing
June 2019

The impact of early enteral nutrition on pediatric acute respiratory failure.

Clin Nutr ESPEN 2018 08 11;26:42-46. Epub 2018 May 11.

Pediatric Critical Care, Miller Children's Hospital, Long Beach CA 90806, USA. Electronic address:

Background And Aims: Children who are critically ill undergo metabolic stress and it is important that they receive adequate calories and protein in order to recover. Our objective was to investigate the impact of early enteral nutrition (EEN) on pediatric intensive care (PICU) patients with acute respiratory failure.

Methods: A retrospective cohort study was performed on all patients admitted to a 20 bed PICU at a tertiary children's hospital over a 30 month period. Inclusion criteria were: intubation on admission or within 24 h of admission, ventilation over 48 h and enteral nutrition initiated on ventilatory support. Baseline patient characteristics and nutritional, ventilatory and overall outcome data were collected. Subgroup analysis was performed comparing those that received EEN (goal in 72 h) and those that did not.

Results: Patients that received EEN had a shorter PICU and overall length of stay 8.7 vs 10.7 and 17.5 vs 22; p < 0.05 and received a higher percentage of goal Kcal and protein (71 vs 54, and 61 vs 51%, p < 0.002) in the PICU. After adjusting for age and severity of illness, EEN was still associated with decreased PICU and overall length of stay. More patients with feeding intolerance were on vasoactive agents (33 vs 9%, p = 0.02), but intolerance was not associated with use of motility agents or degree of respiratory failure. Feeds were interrupted in 19% of patients, most commonly for procedures.

Conclusions: In PICU patients with acute respiratory failure, EEN is associated with shorter PICU and overall length of stay and delivery of higher percentage of goal Kcal and protein by tube feeds. Feeds are commonly interrupted despite efforts to achieve EEN and patients receiving vasoactive agents have feeds held more commonly for perceived intolerance.
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http://dx.doi.org/10.1016/j.clnesp.2018.04.017DOI Listing
August 2018

The UCLA Study of Children with Moderate-to-Severe Traumatic Brain Injury: Event-Related Potential Measure of Interhemispheric Transfer Time.

J Neurotrauma 2016 06 8;33(11):990-6. Epub 2015 Oct 8.

1 Department of Psychiatry and Biobehavioral Sciences, University of California , Los Angeles, Los Angeles, California.

Traumatic brain injury (TBI) frequently results in diffuse axonal injury and other white matter damage. The corpus callosum (CC) is particularly vulnerable to injury following TBI. Damage to this white matter tract has been associated with impaired neurocognitive functioning in children with TBI. Event-related potentials can identify stimulus-locked neural activity with high temporal resolution. They were used in this study to measure interhemispheric transfer time (IHTT) as an indicator of CC integrity in 44 children with moderate/severe TBI at 3-5 months post-injury, compared with 39 healthy control children. Neurocognitive performance also was examined in these groups. Nearly half of the children with TBI had IHTTs that were outside the range of the healthy control group children. This subgroup of TBI children with slow IHTT also had significantly poorer neurocognitive functioning than healthy controls-even after correction for premorbid intellectual functioning. We discuss alternative models for the relationship between IHTT and neurocognitive functioning following TBI. Slow IHTT may be a biomarker that identifies children at risk for poor cognitive functioning following moderate/severe TBI.
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http://dx.doi.org/10.1089/neu.2015.4023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445177PMC
June 2016

White matter disruption in moderate/severe pediatric traumatic brain injury: advanced tract-based analyses.

Neuroimage Clin 2015 12;7:493-505. Epub 2015 Feb 12.

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, USA ; Department of Psychology, UCLA, Los Angeles, CA, USA.

Traumatic brain injury (TBI) is the leading cause of death and disability in children and can lead to a wide range of impairments. Brain imaging methods such as DTI (diffusion tensor imaging) are uniquely sensitive to the white matter (WM) damage that is common in TBI. However, higher-level analyses using tractography are complicated by the damage and decreased FA (fractional anisotropy) characteristic of TBI, which can result in premature tract endings. We used the newly developed autoMATE (automated multi-atlas tract extraction) method to identify differences in WM integrity. 63 pediatric patients aged 8-19 years with moderate/severe TBI were examined with cross sectional scanning at one or two time points after injury: a post-acute assessment 1-5 months post-injury and a chronic assessment 13-19 months post-injury. A battery of cognitive function tests was performed in the same time periods. 56 children were examined in the first phase, 28 TBI patients and 28 healthy controls. In the second phase 34 children were studied, 17 TBI patients and 17 controls (27 participants completed both post-acute and chronic phases). We did not find any significant group differences in the post-acute phase. Chronically, we found extensive group differences, mainly for mean and radial diffusivity (MD and RD). In the chronic phase, we found higher MD and RD across a wide range of WM. Additionally, we found correlations between these WM integrity measures and cognitive deficits. This suggests a distributed pattern of WM disruption that continues over the first year following a TBI in children.
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http://dx.doi.org/10.1016/j.nicl.2015.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338205PMC
September 2015

Use of dexmedetomidine as adjunctive therapy for anti-N-methyl-D-aspartate receptor encephalitis.

J Pediatr Intensive Care 2013 Sep;2(3):143-145

Pediatric Critical Care, Miller's Children Hospital, Long California, CA, USA.

Anti-N-methyl-D-aspartate receptor encephalitis is a recently discovered disease that is more commonly being diagnosed in children. Patients often require intensive care and assisted ventilation due to agitation, abnormal movements, hypoventilation, seizures and autonomic instability. There is no consensus on which medicines are best suited to acutely treat this constellation of central nervous system symptoms. We present the first case report of using dexmedetomidine to treat this condition.
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http://dx.doi.org/10.3233/PIC-13064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530728PMC
September 2013

Hyperglycemia is associated with intracranial injury in children younger than 3 years of age.

Pediatr Emerg Care 2013 Mar;29(3):279-82

Pediatric Critical Care, Miller Children's Hospital, Long Beach, CA 90806, USA.

Objectives: The objective was to see if hyperglycemia in the emergency department predicted traumatic intracranial hemorrhage (ICH) for infants and young children.

Methods: A 6-year retrospective chart review was performed on patients younger than 3 years. Patients identified from the pediatric intensive care unit (PICU) database with ICH on computer tomography were compared with those with a history of trauma without ICH identified from a radiology database. Subgroup analysis was performed on the ICH group comparing abusive head trauma (AHT) and accidental. Primary outcomes measured were initial serum glucose level, length of stay, length of ventilation, mortality, and disability on discharge.

Results: Fifty-three patients were admitted to the PICU with traumatic ICH with an overall mortality of 7.5%. The average initial glucose in the emergency department was significantly higher for the patients with ICH than those without (164 vs. 99 mg/dL, P < 0.0001). Combining elevated serum glucose with any abnormality in Glasgow Coma Scale score yielded sensitivity and specificity of 100%. The average presenting glucose was higher for AHT compared with accidental injury (190 vs. 133 mg/dL, P < 0.001). Patients with AHT had greater PICU and hospital length of stay and more severe disabilities on discharge (P < 0.001).

Conclusions: Elevated serum glucose is a good marker of ICH in children younger than 3 years. When correlated with an abnormal neurological examination, it is highly sensitive and specific. Patients with AHT have further elevation of serum glucose at presentation. Emergency department physicians should consider measuring the serum glucose in children younger than 3 years with abnormal neurological examinations and obtaining a head computer tomography if it is elevated.
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http://dx.doi.org/10.1097/PEC.0b013e3182850409DOI Listing
March 2013

High-frequency oscillatory ventilation in pediatric acute hypoxemic respiratory failure: disease-specific morbidity survival analysis.

Lung 2012 Dec 5;190(6):685-90. Epub 2012 Oct 5.

Pediatric Critical Care, Miller Children's Hospital, Long Beach, CA 90806, USA.

Background: Multiple ventilatory strategies for acute hypoxemic respiratory failure (AHRF) in children have been advocated, including high-frequency oscillatory ventilation (HFOV). Despite the frequent deployment of HFOV, randomized controlled trials remain elusive and currently there are no pediatric trials looking at its use. Our longitudinal study analyzed the predictive clinical outcome of HFOV in pediatric AHRF given disease-specific morbidity.

Methods: A retrospective 8-year review on pediatric intensive care unit admissions with AHRF ventilated by HFOV was performed. Primary outcomes included survival, morbidity, length of stay (LOS), and factors associated with survival or mortality.

Results: A total of 102 patients underwent HFOV with a 66 % overall survival rate. Survivors had a greater LOS than nonsurvivors (p = 0.001). Mortality odds ratio (OR) for patients without bronchiolitis was 8.19 (CI = 1.02, 65.43), and without pneumonia it was 3.07 (CI = 1.12, 8.39). A lower oxygenation index (OI) after HFOV commencement and at subsequent time points analyzed predicted survival. After 24 h, mortality was associated with an OI > 35 [OR = 31.11 (CI = 3.25, 297.98)]. Sepsis-related mortality was associated with a higher baseline FiO(2) (0.88 vs. 0.65), higher OI (42 vs. 22), and augmented metabolic acidosis (pH of 7.25 vs. 7.32) evaluated 4 h on HFOV (p < 0.05).

Conclusion: High-frequency oscillatory ventilation may be safely utilized. It has a 66 % overall survival rate in pediatric AHRF of various etiologies. Patients with morbidity limited to the respiratory system and optimized oxygenation indices are most likely to survive on HFOV.
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http://dx.doi.org/10.1007/s00408-012-9417-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101837PMC
December 2012

Modulation of integrins and integrin signaling molecules in the pressure-loaded murine ventricle.

Histochem Cell Biol 2002 Dec 22;118(6):431-9. Epub 2002 Nov 22.

Department of Physiology, and The Cardiovascular Research Laboratories, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Integrins are heterodimeric cell-surface receptors that link the extracellular matrix and the intracellular cytoskeleton and function as mechanotransducers. Signaling through integrins is important for cell growth, migration, and survival. Extracellular matrix is altered in the myocardium during hypertrophic induction and the transition to heart failure. The role of integrins in this process is poorly understood. Recently, integrin subunits have been identified that are dominantly expressed in striated muscle. We tested the hypothesis that since integrins are mechanotransducers, their expression and signaling would be modulated with murine left ventricular hemodynamic loading. The acute and chronic effects of pressure overload on changes in the expression of integrins, as well as related integrin-mediated signaling events were studied. Acute pressure loading increased phosphorylation of focal adhesion kinase, p42 and p44 extracellular signal-regulated kinase. Chronic loading: (1) increased expression of alpha1, alpha5, and beta1 integrin transcripts and (2) increased protein expression of integrin subunits which are dominantly expressed in striated muscle (alpha7 and beta1D) both by western blotting and immunofluorescent microscopy. These results show that adaptive responses of the myocardium to pressure overload include acute modulation of integrin-related signaling molecules and more chronic changes effect expression of integrin subunits, including ones dominantly expressed in muscle.
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http://dx.doi.org/10.1007/s00418-002-0476-1DOI Listing
December 2002

Cardiac myocyte-specific excision of the beta1 integrin gene results in myocardial fibrosis and cardiac failure.

Circ Res 2002 Mar;90(4):458-64

Department of Physiology, University of California-Los Angeles 90095, USA.

Integrins link the extracellular matrix to the cellular cytoskeleton and serve important roles in cell growth, differentiation, migration, and survival. Ablation of beta1 integrin in all murine tissues results in peri-implantation embryonic lethality. To investigate the role of beta1 integrin in the myocardium, we used Cre-LoxP technology to inactivate the beta1 integrin gene exclusively in ventricular cardiac myocytes. Animals with homozygous ventricular myocyte beta1 integrin gene excision were born in appropriate numbers and grew into adulthood. These animals had 18% of control levels of beta1D integrin protein in the heart and displayed myocardial fibrosis. High-fidelity micromanometer-tipped catheterization of the intact 5-week-old beta1 integrin knockout mice showed depressed left ventricular basal and dobutamine-stimulated contractility and relaxation (LV dP/dt(max) and LV dP/dt(min)) as compared with control groups (n=8 to 10 of each, P<0.01). Hemodynamic loading imposed by 7 days of transverse aortic constriction showed that the beta1 integrin knockout mice were intolerant of this stress as they had 53% survival versus 88% in controls (n=15 each). By 6 months of age, mice with depressed ventricular expression of beta1 integrin developed a dilated cardiomyopathy that was not evident in any control animals and had patchy decrease in glucose metabolism as determined by positron emission tomography. Myocyte membrane integrity as determined via Evan's blue dye staining was disrupted in the beta1 integrin knockout mice. This model provides strong evidence for the importance of beta1 integrin in cardiac form and function and indicates that integrins can be linked to development of cardiomyopathies.
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http://dx.doi.org/10.1161/hh0402.105790DOI Listing
March 2002