Bio

Clinical Focus


  • Anesthesia
  • Critical Care Medicine

Academic Appointments


Administrative Appointments


  • Division Chief, Critical Care Medicine, Dept. of Anesthesia, Stanford University (2013 - Present)
  • Critical Care Medicine Fellowship Director, Dept. of Anesthesia, Stanford University (2013 - Present)
  • Chair, Pharmacy and Therapeutics Committee, Stanford University Medical Center (2009 - 2013)

Honors & Awards


  • Fellow, American College of Critical Care Medicine (2011)
  • Excellence in Teaching Award, Stanford University School of Medicine (2008)
  • Presidential Citation, Society of Critical Care Medicine (2008-2013)
  • H. Barrie Fairley Excellence in Teaching Award, Stanford University (2001)

Boards, Advisory Committees, Professional Organizations


  • Board of Directors, American Board of Anesthesiology (2011 - Present)
  • Council (Board of Directors), Society of Critical Care Medicine (2014 - Present)
  • ACGME RRC Anesthesiology, Accreditation Council for Graduate Medical Education (2013 - Present)
  • Co-Chair, AMA PCPI Work Group for Anesthesiology and Critical Care, American Medical Association Physician Consortium for Performance Improvement (2011 - Present)
  • ASA Committee on Performance and Outcomes Measurement, American Society of Anesthesiologists (2013 - Present)
  • CSA Educational Programs Division, California Society of Anesthesiologists (2008 - Present)

Professional Education


  • Residency:Massachusetts General Hospital (1995) MA
  • Internship:Emory University School of Medicine (1992) GA
  • Board Recertification, Critical Care Medicine, American Board of Anesthesiology (2008)
  • Board Recertification, Anesthesia, American Board of Anesthesiology (2005)
  • Board Certification: Critical Care Medicine, American Board of Anesthesiology (1999)
  • Board Certification: Anesthesia, American Board of Anesthesiology (1996)
  • Fellowship:Massachusetts General Hospital (1996) MA
  • Chief Residency, Massachusetts General Hospital, MA (1995)
  • Residency, Massachusetts General Hospital, Anesthesiology (1995)
  • Internship, Emory University, Internal Medicine (1992)
  • Medical Education:Emory University School of Medicine (1991) GA
  • Ph.D., Stanford University, Neurosciences (2002)
  • B.S., University of Michigan, History & Chemistry (1987)

Community and International Work


  • Hospital de la Familia, Nuevo Progreso, Guatemala

    Topic

    Health Care for Underprivileged Children and Adults

    Populations Served

    Rural Guatemala

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • Medical Missions for Children, Gitwe Rwanda, Cusco Peru

    Topic

    Health Care for Underprivileged Children

    Populations Served

    Gitwe Rwanda, Cusco Peru

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • Interplast, La Ceiba Honduras, Loja Ecuador, Santa Cruz Bolivia

    Topic

    Health Care for Underprivileged Children and Adults

    Populations Served

    Honduras, Ecuador, Bolivia

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

Research & Scholarship

Current Research and Scholarly Interests


Critical Care Medicine,
Cardiovascular Pharmacology,
Adrenergic Receptors,
Congestive Heart Failure,
Vascular Biology,
Cardiopulmonary Physiology,
Sepsis

Teaching

2013-14 Courses


Graduate and Fellowship Programs


Publications

Journal Articles


  • Focused transthoracic echocardiography during critical care medicine training: curriculum implementation and evaluation of proficiency*. Critical care medicine Beraud, A., Rizk, N. W., Pearl, R. G., Liang, D. H., Patterson, A. J. 2013; 41 (8): e179-81

    Abstract

    OBJECTIVES:: We designed and implemented a focused transthoracic echocardiography curriculum for critical care medicine fellows participating in 1- and 2-year training programs. We quantitatively evaluated their proficiency in focused transthoracic echocardiography. DESIGN:: Prospective study evaluating curriculum implementation and objective assessment of focused transthoracic echocardiography proficiency. SETTING:: Medical and surgical ICUs at an academic teaching hospital. Simulation laboratory. SUBJECTS:: Eighteen critical care medicine fellows. INTERVENTIONS:: Training in focused transthoracic echocardiography followed by proficiency testing. MEASUREMENTS AND MAIN RESULTS:: We assessed the ability of critical care medicine fellows to obtain and interpret focused transthoracic echocardiography images from critically ill patients and a from transthoracic echocardiography simulator. Using a cognitive examination test, we also evaluated each fellow's knowledge with regard to focused transthoracic echocardiography and each fellow's ability to interpret prerecorded focused transthoracic echocardiography images. After training, critical care medicine fellows were able to rapidly obtain five essential focused transthoracic echocardiography views: parasternal long axis, parasternal short axis, apical four chamber, subcostal four chamber, and subcostal inferior vena cava. Fellows were also able to expeditiously identify four important abnormalities: asystole, left ventricular dysfunction, right ventricular dilation and dysfunction, and a large pericardial effusion. CONCLUSIONS:: A focused transthoracic echocardiography curriculum that includes quantitative measures of proficiency can be integrated into critical care medicine fellowship training programs.

    View details for DOI 10.1097/CCM.0b013e31828e9240

    View details for PubMedID 23760156

  • Vasopressin Compared with Norepinephrine Augments the Decline of Plasma Cytokine Levels in Septic Shock AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Russell, J. A., Fjell, C., Hsu, J. L., Lee, T., Boyd, J., Thair, S., Singer, J., Patterson, A. J., Walley, K. R. 2013; 188 (3): 356-364

    Abstract

    Changes in plasma cytokine levels may predict mortality and therapies (vasopressin versus norepinephrine) could change plasma cytokine levels in early septic shock.Our hypotheses were that changes in plasma cytokine levels over 24 hours differ between survivors and non-survivors and there are different effects of vasopressin vs. norepinephrine on plasma cytokine levels in septic shock.We studied 394 patients in a randomized, controlled trial of vasopressin vs. norepinephrine in septic shock. We used hierarchical clustering and principal components analysis (PCA) of the baseline cytokine concentrations to subgroup cytokines; we then compared survivors to non-survivors (28-day) and compared vasopressin- vs. norepinephrine-induced changes in cytokine levels over 24 hours.Thirty-nine plasma cytokines were measured at baseline and 24 hours. Hierarchical clustering and PCA grouped cytokines similarly. Survivors (vs. non-survivors) had greater decreases of overall cytokine levels (p < 0.001). Vasopressin decreased overall 24-hour cytokine concentration compared to norepinephrine (p = 0.037). In less severe septic shock, the difference in plasma cytokine reduction over 24 hours between survivors and non-survivors was less pronounced than seen in more severe septic shock. Furthermore, vasopressin decreased IP-10 and GCSF more than did norepinephrine in less severe septic shock, whereas vasopressin decreased GMCSF in patients who had more severe shock.Survivors of septic shock had greater decreases of cytokines, chemokines and growth factors in early septic shock. Vasopressin decreased 24-hour plasma cytokine levels more than did norepinephrine. The vasopressin-associated decrease of cytokines differed according to severity of shock.

    View details for DOI 10.1164/rccm.201302-0355OC

    View details for Web of Science ID 000322617800017

    View details for PubMedID 23796235

  • FXR agonist INT-747 upregulates DDAH expression and enhances insulin sensitivity in high-salt fed Dahl rats. PloS one Ghebremariam, Y. T., Yamada, K., Lee, J. C., Johnson, C. L., Atzler, D., Anderssohn, M., Agrawal, R., Higgins, J. P., Patterson, A. J., Böger, R. H., Cooke, J. P. 2013; 8 (4)

    Abstract

    Genetic and pharmacological studies have shown that impairment of the nitric oxide (NO) synthase (NOS) pathway is associated with hypertension and insulin-resistance (IR). In addition, inhibition of NOS by the endogenous inhibitor, asymmetric dimethylarginine (ADMA), may also result in hypertension and IR. On the other hand, overexpression of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that metabolizes ADMA, in mice is associated with lower ADMA, increased NO and enhanced insulin sensitivity. Since DDAH carries a farnesoid X receptor (FXR)-responsive element, we aimed to upregulate its expression by an FXR-agonist, INT-747, and evaluate its effect on blood pressure and insulin sensitivity.In this study, we evaluated the in vivo effect of INT-747 on tissue DDAH expression and insulin sensitivity in the Dahl rat model of salt-sensitive hypertension and IR (Dahl-SS). Our data indicates that high salt (HS) diet significantly increased systemic blood pressure. In addition, HS diet downregulated tissue DDAH expression while INT-747 protected the loss in DDAH expression and enhanced insulin sensitivity compared to vehicle controls.Our study may provide the basis for a new therapeutic approach for IR by modulating DDAH expression and/or activity using small molecules.

    View details for DOI 10.1371/journal.pone.0060653

    View details for PubMedID 23593273

  • Cardiovascular management of septic shock in 2012. Current infectious disease reports Guillamet, M. C., Rhee, C., Patterson, A. J. 2012; 14 (5): 493-502

    Abstract

    Septic shock is a major cause of morbidity and mortality throughout the world. Source control, antimicrobial therapy, early goal-directed fluid resuscitation, and infusion of vasoactive pharmaceuticals remain the cornerstones of treatment. However, the cardiovascular management of septic shock is evolving. Basic science and clinical researchers have identified novel drug targets and are testing the efficacy of new therapeutic agents. For example, prevention of microvascular leak during septic shock is the focus of active investigations and may soon provide considerable benefit to patients. Among the important topics that will be discussed in this review are the following: the role of vascular endothelial dysfunction in microvascular leak, the impact of cytokines upon structural and functional proteins within the endothelial barrier and within the heart, and the ability of selective vasopressin 1a receptor agonists to minimize tissue edema and improve hemodynamic status.

    View details for DOI 10.1007/s11908-012-0279-z

    View details for PubMedID 22941043

  • Potential for overuse of corticosteroids and vasopressin in septic shock. Critical care (London, England) Hsu, J. L., Liu, V., Patterson, A. J., Martin, G. S., Nicolls, M. R., Russell, J. A. 2012; 16 (5): 447

    View details for PubMedID 23102413

  • Mice Lacking the Beta 2 Adrenergic Receptor have a Unique Genetic Profile Before and After Focal Brain Ischemia ASN Neuro White RE, Palm CJ, Xu L, Ling EB, Ginsburg M, Daigle Jr BJ, Han R, Patterson AJ, Altman RB, Giffard RG 2012; Epub (Aug 6): XXX
  • Regulatory T Cells Limit Vascular Endothelial Injury and Prevent Pulmonary Hypertension CIRCULATION RESEARCH Tamosiuniene, R., Tian, W., Dhillon, G., Wang, L., Sung, Y. K., Gera, L., Patterson, A. J., Agrawal, R., Rabinovitch, M., Ambler, K., Long, C. S., Voelkel, N. F., Nicolls, M. R. 2011; 109 (8): 867-U120

    Abstract

    Pulmonary arterial hypertension (PAH) is an incurable disease associated with viral infections and connective tissue diseases. The relationship between inflammation and disease pathogenesis in these disorders remains poorly understood.To determine whether immune dysregulation due to absent T-cell populations directly contributes to the development of PAH.Vascular endothelial growth factor receptor 2 (VEGFR2) blockade induced significant pulmonary endothelial apoptosis in T-cell-deficient rats but not in immune-reconstituted (IR) rats. T cell-lymphopenia in association with VEGFR2 blockade resulted in periarteriolar inflammation with macrophages, and B cells even prior to vascular remodeling and elevated pulmonary pressures. IR prevented early inflammation and attenuated PAH development. IR with either CD8 T cells alone or with CD4-depleted spleen cells was ineffective in preventing PAH, whereas CD4-depleting immunocompetent euthymic animals increased PAH susceptibility. IR with either CD4(+)CD25(hi) or CD4(+)CD25(-) T cell subsets prior to vascular injury attenuated the development of PAH. IR limited perivascular inflammation and endothelial apoptosis in rat lungs in association with increased FoxP3(+), IL-10- and TGF-?-expressing CD4 cells, and upregulation of pulmonary bone morphogenetic protein receptor type 2 (BMPR2)-expressing cells, a receptor that activates endothelial cell survival pathways.PAH may arise when regulatory T-cell (Treg) activity fails to control endothelial injury. These studies suggest that regulatory T cells normally function to limit vascular injury and may protect against the development of PAH.

    View details for DOI 10.1161/CIRCRESAHA.110.236927

    View details for Web of Science ID 000295368300008

    View details for PubMedID 21868697

  • Genetic Polymorphisms in Sepsis CRITICAL CARE NURSING CLINICS OF NORTH AMERICA Namath, A., Patterson, A. J. 2011; 23 (1): 181-?
  • Genetic polymorphisms in sepsis. Critical care nursing clinics of North America Namath, A., Patterson, A. J. 2011; 23 (1): 181-202

    Abstract

    The number of genetic polymorphisms shown to play a role in sepsis continues to increase. At the same time, platforms for genetic sequencing and expression analysis are being refined, allowing unprecedented data generation. International databases may soon facilitate synchrony of genotypic and phenotypic data using enormous numbers of septic patients. If this occurs, 2 strategies for investigating polymorphisms in sepsis are likely to gain favor. In the first strategy, sepsis will continue to be viewed as a single entity. High-throughput genetic techniques will be used to evaluate numerous polymorphisms, each with fractional disease responsibility. Nongenetic variables, such as pathogen characteristics, underlying host medical conditions, and type and timing of resuscitation, will be considered cofactors. Using this approach, principal components that predict susceptibility to and outcomes during sepsis are likely to be identified. In the second strategy, sepsis will be divided into subtypes based on the concentration of specific variables. Categories will be based on features like the presence or absence of specific polymorphisms, gram-positive or gram-negative staining of causative organisms, age and comorbid conditions of the host, recent administration of chemotherapeutic agents, and hospital setting (ie, community vs teaching institution). Each category will be used to create homogenous sepsis subgroups for detailed evaluation. This approach will increase the odds of finding single dominant factors responsible for predilection and/or outcome within well-defined groups among those with sepsis. Several elements will be essential for the success of both these strategies. Firstly, databases that are extremely detailed will have to be generated. Secondly, better clinical information technology systems will be needed to facilitate large-scale phenotyping. Thirdly, standardization of protocols will need to take place to ensure uniformity of data sets. If the rapid advances in technology and informatics continue, they may catalyze paradigm shifts with regard to how clinicians address sepsis. Clinicians may change their focus from aggressive uniform treatment strategies to rapid stratification and subcategorization, with subsequent aggressive targeted therapeutic interventions. Advances in technology have the potential to change our primary goal in sepsis from rapid treatment to prevention for those most at risk. The cost savings to the US health care systems from such changes could be substantial.

    View details for DOI 10.1016/j.ccell.2010.12.011

    View details for PubMedID 21316575

  • Gene expression profiling: Classification of mice with left ventricle systolic dysfunction using micyoarray analysis CRITICAL CARE MEDICINE Wong, J., Chang, C., Agrawal, R., Walton, G. B., Chen, C., Murthy, A., Patterson, A. J. 2010; 38 (1): 25-31

    Abstract

    We tested the hypothesis that a set of differentially expressed genes could be used to classify mice according to cardiovascular phenotype after prolonged catecholamine stress.Prospective, randomized study.University-based research laboratory.One hundred seventy-three male mice were studied: wild-type (WT) C57, WT FVB, WT B6129SF2/J, and beta2 adrenergic receptor knockout.Mice of each genotype were randomly assigned to 14-day infusions of isoproterenol (120 microg/g/day) or no treatment. Approximately half of the animals underwent left ventricle pressure volume loop analysis. The remaining animals were killed for extraction of messenger RNA from whole heart preparations for microarray analysis.We observed that WT FVB and beta2 adrenergic receptor knockout mice developed systolic dysfunction in response to continuous catecholamine infusion, whereas WT C57 mice developed diastolic dysfunction. Using these mice as the derivation cohort, we identified a set of 83 genes whose differential expression correlated with left ventricle systolic dysfunction. The gene set was then used to accurately classify mice from a separate group (WT B6129SF2/J) into the cohort that developed left ventricle systolic dysfunction after catecholamine stress.The differential expression pattern of 83 genes can be used to accurately classify mice according to physiological phenotype after catecholamine stress.

    View details for DOI 10.1097/CCM.0b013e3181b427e8

    View details for Web of Science ID 000273224800005

    View details for PubMedID 19770745

  • Genetic Polymorphisms in Sepsis CRITICAL CARE CLINICS Namath, A., Patterson, A. J. 2009; 25 (4): 835-?

    Abstract

    This article is meant to serve as a summary of scientific advances from the past 5 years with regard to genetic polymorphisms in sepsis. It is also meant to highlight some of the discoveries that may improve our ability to identify vulnerable patients at earlier time points in sepsis, when interventions are more likely to have a positive effect. The article begins with an overview of polymorphism studies and a discussion of candidate gene versus genome-wide association studies. Next, an overview of polymorphisms associated with sepsis is presented. The overview includes detailed descriptions of E-selectin, apolipoprotein E, and C-reactive protein polymorphisms and a table in which numerous other sepsis-related polymorphisms are introduced. An examination of consortia-based projects that have the potential to catalyze sepsis research is included as is a preview of technological advancements that are likely to strongly influence sepsis studies in the near future. The article concludes with a brief consideration of ethical and social issues relevant to human genomic studies.

    View details for DOI 10.1016/j.ccc.2009.06.004

    View details for Web of Science ID 000272162800013

    View details for PubMedID 19892256

  • Postischemic Brain Injury Is Attenuated in Mice Lacking the beta(2)-Adrenergic Receptor ANESTHESIA AND ANALGESIA Han, R., Ouyang, Y., Xu, L., Agrawal, R., Patterson, A. J., Giffard, R. G. 2009; 108 (1): 280-287

    Abstract

    Several beta-adrenergic receptor (betaAR) antagonists have been shown to have neuroprotective effects against cerebral ischemia. However, clenbuterol, a beta(2)AR agonist, was shown to have neuroprotective activity by increasing nerve growth factor expression. We used beta(2)AR knockout mice and a beta(2) selective antagonist to test the effect of loss of beta(2)ARs on outcome from transient focal cerebral ischemia.Ischemia was induced by the intraluminal suture method, for 60 min of middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion. Neurological score was determined at 24 h reperfusion and infarct size was determined by cresyl violet or 2,3,5-triphenyltetrazolium chloride staining. beta(2)AR knockout mice and wild-type congenic FVB/N controls were studied, as well as 2 groups of wild type mice given either ICI 118,551 (0.2 mg/kg) or 0.9% saline intraperitoneally 30 min before MCAO (n = 10 per group). Changes in expression of heat shock protein (Hsp)72 after ischemia were examined by immunohistochemistry and western blots.Compared with wild type littermates, infarct volume was decreased by 22.3% in beta(2)AR knockout mice (39.7 +/- 10.7 mm(3) vs 51.0 +/- 11.4 mm(3), n = 10/group, P = 0.034) after 60 min of MCAO followed by 24 h reperfusion. Pretreatment with a beta(2)AR selective antagonist, ICI 118,551, also decreased infarct size significantly, by 25.1%, compared with the saline control (32.8 +/- 11.9 mm(3) vs 43.8 +/- 10.3 mm(3), n = 10/group, P = 0.041). Neurological scores were also significantly improved in mice lacking the beta(2)AR or pretreated with ICI 118,551. After cerebral ischemia, total levels of Hsp72 and the number of Hsp72 immunopositive cells were greater in mice lacking beta(2) AR.Brain injury is reduced and neurological outcome improved after MCAO in mice lacking the beta(2)AR, or in wild type mice pretreated with a selective beta(2)AR antagonist. This is consistent with a shift away from prosurvival signaling to prodeath signaling in the presence of beta(2)AR activation in cerebral ischemia. Protection is associated with higher levels of Hsp72, a known antideath protein. The effect of beta(2)AR signaling in the setting of cerebral ischemia is complex and warrants further study.

    View details for DOI 10.1213/ane.0b013e318187ba6b

    View details for Web of Science ID 000261963000043

    View details for PubMedID 19095863

  • Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis JOURNAL OF CLINICAL INVESTIGATION Chun, H. J., Ali, Z. A., Kojima, Y., Kundu, R. K., Sheikh, A. Y., Agrawal, R., Zheng, L., Leeper, N. J., Pearl, N. E., Patterson, A. J., Anderson, J. P., Tsao, P. S., Lenardo, M. J., Ashley, E. A., Quertermous, T. 2008; 118 (10): 3343-3354

    Abstract

    Apelin and its cognate G protein-coupled receptor APJ constitute a signaling pathway with a positive inotropic effect on cardiac function and a vasodepressor function in the systemic circulation. The apelin-APJ pathway appears to have opposing physiological roles to the renin-angiotensin system. Here we investigated whether the apelin-APJ pathway can directly antagonize vascular disease-related Ang II actions. In ApoE-KO mice, exogenous Ang II induced atherosclerosis and abdominal aortic aneurysm formation; we found that coinfusion of apelin abrogated these effects. Similarly, apelin treatment rescued Ang II-mediated increases in neointimal formation and vascular remodeling in a vein graft model. NO has previously been implicated in the vasodepressor function of apelin; we found that apelin treatment increased NO bioavailability in ApoE-KO mice. Furthermore, infusion of an NO synthase inhibitor blocked the apelin-mediated decrease in atherosclerosis and aneurysm formation. In rat primary aortic smooth muscle cells, apelin inhibited Ang II-mediated transcriptional regulation of multiple targets as measured by reporter assays. In addition, we demonstrated by coimmunoprecipitation and fluorescence resonance energy transfer analysis that the Ang II and apelin receptors interacted physically. Taken together, these findings indicate that apelin signaling can block Ang II actions in vascular disease by increasing NO production and inhibiting Ang II cellular signaling.

    View details for DOI 10.1172/JCI34871

    View details for Web of Science ID 000259828600016

    View details for PubMedID 18769630

  • Signaling from beta(1)- and beta(2)-adrenergic receptors is defined by differential interactions with PDE4 EMBO JOURNAL Richter, W., Day, P., Agrawal, R., Bruss, M. D., Granier, S., Wang, Y. L., Rasmussen, S. G., Horner, K., Wang, P., Lei, T., Patterson, A. J., Kobilka, B., Conti, M. 2008; 27 (2): 384-393

    Abstract

    Beta1- and beta2-adrenergic receptors (betaARs) are highly homologous, yet they play clearly distinct roles in cardiac physiology and pathology. Myocyte contraction, for instance, is readily stimulated by beta1AR but not beta2AR signaling, and chronic stimulation of the two receptors has opposing effects on myocyte apoptosis and cell survival. Differences in the assembly of macromolecular signaling complexes may explain the distinct biological outcomes. Here, we demonstrate that beta1AR forms a signaling complex with a cAMP-specific phosphodiesterase (PDE) in a manner inherently different from a beta2AR/beta-arrestin/PDE complex reported previously. The beta1AR binds a PDE variant, PDE4D8, in a direct manner, and occupancy of the receptor by an agonist causes dissociation of this complex. Conversely, agonist binding to the beta2AR is a prerequisite for the recruitment of a complex consisting of beta-arrestin and the PDE4D variant, PDE4D5, to the receptor. We propose that the distinct modes of interaction with PDEs result in divergent cAMP signals in the vicinity of the two receptors, thus, providing an additional layer of complexity to enforce the specificity of beta1- and beta2-adrenoceptor signaling.

    View details for DOI 10.1038/sj.emboj.7601968

    View details for Web of Science ID 000253408600009

    View details for PubMedID 18188154

  • beta1 and beta2 Adrenergic Receptor Polymorphisms: Their Impact on Cardiovascular Physiology, Disease States, and Response to Therapeutic Agents Seminars in Anesthesia, Perioperative Medicine, and Pain Namath A, Chen C, Agrawal R, Patterson AJ 2007; 26 (1): 2-9
  • Impact of Phosphodiesterase 4D on Cardiac beta2 Adrenergic Receptor Signaling Seminars in Anesthesia, Perioperative Medicine, and Pain Patterson AJ, Pearl N, Chang C 2007; 26 (1): 22-27
  • Ushering in the Era of Nuclear Terrorism Critical Care Medicine Patterson AJ 2007; 35 (3): 953-954
  • Fiberoptic light source-induced surgical fires - the contribution of forced-air warming blankets ACTA ANAESTHESIOLOGICA SCANDINAVICA Williams, D. M., Littwin, S., Patterson, A. J., Brock-Utne, J. G. 2006; 50 (4): 505-508

    Abstract

    Fiberoptic light sources have been identified as a fire ignition mechanism in the operating room. This study attempted to determine whether a forced-air warming blanket (FAWB) could affect the ignition or spread of fire caused by a fiberoptic light source.We exposed surgical drapes to a fiberoptic light source at close range. The results were categorized according to time to first smoke and damage resulting at 1 min. Data were analyzed using the Mann-Whitney rank-sum test.The sums of the rank values for the components of the drape indicated that there was a greater than 96.8-99.2% chance that the FAWB accelerated the time to first smoke. The FAWB appeared to protect the patient gown from damage during all trials. The presence of an FAWB under a surgical drape accelerated the time to first smoke when exposed to unprotected fiberoptic light sources, yet prevented damage to the underlying patient gown. In an actual surgical setting, it is likely that the FAWB would offer some protection to the patient's skin directly below the surgical drape.It is likely that the FAWB can offer some protection to the patient should an unprotected fiberoptic light source cause a fire.

    View details for DOI 10.1111/j.1399-6576.2006.00975.x

    View details for Web of Science ID 000236069900015

    View details for PubMedID 16548865

  • Overexpression of dimethylarginine dimethylaminohydrolase reduces tissue asymmetric dimethylarginine levels and enhances angiogenesis CIRCULATION Jacobi, J., Sydow, K., von Degenfeld, G., Zhang, Y., Dayoub, H., Wang, B. Y., Patterson, A. J., Kimoto, M., Blau, H. M., Cooke, J. P. 2005; 111 (11): 1431-1438

    Abstract

    This study was designed to determine whether overexpression of the enzyme dimethylarginine dimethylaminohydrolase (DDAH) could enhance angiogenesis by reducing levels of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA).In DDAH1 transgenic (TG) and wild-type mice (each n=42), the role of DDAH overexpression on angiogenesis was studied by use of the disk angiogenesis system and a murine model of hindlimb ischemia (each n=21). After surgery, animals were treated with either PBS or the NOS inhibitors ADMA or N(omega)-nitro-L-arginine methyl ester (L-NAME; each 250 micromol x kg(-1) x d(-1)) by use of osmotic minipumps (each n=7). L-NAME was chosen to study an inhibitor that is not degraded by DDAH. Neovascularization in the disk angiogenesis system was impaired by both NOS inhibitors; however, TG animals were resistant to the effects of ADMA on neovascularization. Similarly, TG mice were more resistant to the inhibitory effect of ADMA on angioadaptation (angiogenesis and arteriogenesis) after hindlimb ischemia, as assessed by fluorescent microsphere studies and postmortem microangiograms. Enhanced neovascularization and limb perfusion in TG mice were associated with reduced plasma and tissue ADMA levels and enhanced tissue NOS enzyme activity.We describe a novel mechanism by which DDAH regulates postnatal neovascularization. Therapeutic manipulation of DDAH expression or activity may represent a novel approach to restore tissue perfusion.

    View details for DOI 10.1161/01.CIR.0000158487.80483.09

    View details for Web of Science ID 000227805700012

    View details for PubMedID 15781754

  • The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo CARDIOVASCULAR RESEARCH Ashley, E. A., Powers, J., Chen, M., Kundu, R., Finsterbach, T., Caffarelli, A., Deng, A., Eichhorn, J., Mahajan, R., Agrawal, R., Greve, J., Robbins, R., Patterson, A. J., Bernstein, D., Quertermous, T. 2005; 65 (1): 73-82

    Abstract

    The endogenous peptide apelin is differentially regulated in cardiovascular disease but the nature of its role in cardiac function remains unclear.We investigated the functional relevance of this peptide using ECG and respiration gated magnetic resonance imaging, conductance catheter pressure-volume hemodynamic measurements, and echocardiography in vivo. In addition, we carried out histology and immunohistochemistry to assess cardiac hypertrophy and to localize apelin and APJ in the adult and embryonic mouse heart.Intraperitoneal injection of apelin (300 microg/kg) resulted in a decrease in left ventricular end diastolic area (pre: 0.122+/-0.007; post: 0.104+/-0.005 cm(2), p=0.006) and an increase in heart rate (pre: 537+/-20; post: 559+/-19 beats per minute, p=0.03). Hemodynamic measurements revealed a marked increase in ventricular elastance (pre: 3.7+/-0.9; post: 6.5+/-1.4 mm Hg/RVU, p=0.018) and preload recruitable stroke work (pre: 27.4+/-8.0; post: 51.8+/-3.1, p=0.059) with little change in diastolic parameters following acute infusion of apelin. Chronic infusion (2 mg/kg/day) resulted in significant increases in the velocity of circumferential shortening (baseline: 5.36+/-0.401; 14 days: 6.85+/-0.358 circ/s, p=0.049) and cardiac output (baseline: 0.142+/-0.019; 14 days: 0.25+/-0.019 l/min, p=0.001) as determined by 15 MHz echocardiography. Post-mortem corrected heart weights were not different between apelin and saline groups (p=0.5) and histology revealed no evidence of cellular hypertrophy in the apelin group (nuclei per unit area, p=0.9). Immunohistochemistry studies revealed APJ staining of myocardial cells in all regions of the adult mouse heart. Antibody staining, as well as quantitative real time polymerase chain reaction identified expression of both APJ and apelin in embryonic myocardium as early as embryonic day 13.5.Apelin reduces left ventricular preload and afterload and increases contractile reserve without evidence of hypertrophy. These results associate apelin with a positive hemodynamic profile and suggest it as an attractive target for pharmacotherapy in the setting of heart failure.

    View details for DOI 10.1016/j.cardiores.2004.08.018

    View details for Web of Science ID 000226477600011

    View details for PubMedID 15621035

  • Protecting the myocardium: A role for the beta 2 adrenergic receptor in the heart CRITICAL CARE MEDICINE Patterson, A. J., Zhu, W. Z., Chow, A., Agrawal, R., Kosek, J., Xiao, R. P., Kobilka, B. 2004; 32 (4): 1041-1048

    Abstract

    The sympathetic nervous system enhances cardiac muscle function by activating beta adrenergic receptors (betaARs). Recent studies suggest that chronic betaAR stimulation is detrimental, however, and that it may play a role in the clinical deterioration of patients with congestive heart failure. To examine the impact of chronic beta1AR and beta2AR subtype stimulation individually, we studied the cardiovascular effects of catecholamine infusions in betaAR subtype knockout mice (beta1KO, beta2KO).Prospective, randomized, experimental study.Animal research laboratory.beta1KO and beta2KO mice and wild-type controls.The animals were subjected to 2 wks of continuous infusion of the betaAR agonist isoproterenol. Analyses of cardiac function and structure were performed during and 3 days after completion of the infusions. Functional studies included graded exercise treadmill testing, in vivo assessments of left ventricular function using Mikro-Tip catheter transducers, right ventricular pressure measurements, and analyses of organ weight to body weight ratios. Structural studies included heart weight measurements, assessments of myocyte ultrastructure using electron microscopy, and in situ terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling staining to quantitate myocyte apoptosis.We found that isoproterenol-treated beta2KO mice experienced greater mortality rates (p =.001, chi-square test using Fisher's exact method) and increased myocyte apoptosis at 3- and 7-day time points (p =.04 and p =.0007, respectively, two-way analysis of variance).The results of this study suggest that in vivo beta2AR activation is antiapoptotic and contributes to myocardial protection.

    View details for DOI 10.1097/01.CCM.0000120049.43113.90

    View details for Web of Science ID 000220872700021

    View details for PubMedID 15071399

  • Thrombin activatable fibrinolysis inhibitor, a potential regulator of vascular inflammation JOURNAL OF BIOLOGICAL CHEMISTRY Myles, T., Nishimura, T., Yun, T. H., Nagashima, M., MORSER, J., Patterson, A. J., Pearl, R. G., Leung, L. L. 2003; 278 (51): 51059-51067

    Abstract

    The latent plasma carboxypeptidase thrombin-activable fibrinolysis inhibitor (TAFI) is activated by thrombin/thrombomodulin on the endothelial cell surface, and functions in dampening fibrinolysis. In this study, we examined the effect of activated TAFI (TAFIa) in modulating the proinflammatory functions of bradykinin, complement C5a, and thrombin-cleaved osteopontin. Hydrolysis of bradykinin and C5a and thrombin-cleaved osteopontin peptides by TAFIa was as efficient as that of plasmin-cleaved fibrin peptides, indicating that these are also good substrates for TAFIa. Plasma carboxypeptidase N, generally regarded as the physiological regulator of kinins, was much less efficient than TAFIa. TAFIa abrogated C5a-induced neutrophil activation in vitro. Jurkat cell adhesion to osteopontin was markedly enhanced by thrombin cleavage of osteopontin. This was abolished by TAFIa treatment due to the removal of the C-terminal Arg168 by TAFIa from the exposed SVVYGLR alpha 4 beta 1 integrin-binding site in thrombin-cleaved osteopontin. Thus, thrombin cleavage of osteopontin followed by TAFIa treatment may sequentially up- and down-modulate the pro-inflammatory properties of osteopontin. An engineered anticoagulant thrombin, E229K, was able to activate endogenous plasma TAFI in mice, and E229K thrombin infusion effectively blocked bradykinin-induced hypotension in wild-type, but not in TAFI-deficient, mice in vivo. Our data suggest that TAFIa may have a broad anti-inflammatory role, and its function is not restricted to fibrinolysis.

    View details for DOI 10.1074/jbc.M306977200

    View details for Web of Science ID 000187206300029

    View details for PubMedID 14525995

  • Dimethylarginine dimethylaminohydrolase regulates nitric oxide synthesis - Genetic and physiological evidence CIRCULATION Dayoub, H., Achan, V., Adimoolam, S., Jacobi, J., Stuehlinger, M. C., Wang, B. Y., Tsao, P. S., Kimoto, M., Vallance, P., Patterson, A. J., Cooke, J. P. 2003; 108 (24): 3042-3047

    Abstract

    NO is a major regulator of cardiovascular physiology that reduces vascular and cardiac contractility. Accumulating evidence indicates that endogenous inhibitors may regulate NOS. The NOS inhibitors asymmetric dimethylarginine (ADMA) and N-monomethylarginine are metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). This study was designed to determine if increased expression of DDAH could reduce tissue and plasma levels of the NOS inhibitors and thereby increase NO synthesis.We used gene transfer and transgenic approaches to overexpress human DDAH I in vitro and in vivo. The overexpression of DDAH in cultured endothelial cells in vitro induced a 2-fold increase in NOS activity and NO production. In the hDDAH-1 transgenic mice, we observed approximately 2-fold increases in tissue NOS activity and urinary nitrogen oxides, associated with a 2-fold reduction in plasma ADMA. The systolic blood pressure of transgenic mice was 13 mm Hg lower than that of wild-type controls (P<0.05). The systemic vascular resistance and cardiac contractility were decreased in response to the increase in NO production.DDAH I overexpression increases NOS activity in vitro and in vivo. The hDDAH-1 transgenic animal exhibits a reduced systolic blood pressure, systemic vascular resistance, and cardiac stroke volume. This study provides compelling evidence that the elaboration and metabolism of endogenous ADMA plays an important role in regulation of NOS activity.

    View details for DOI 10.1161/01.CIR.0000101924.04515.2E

    View details for Web of Science ID 000187286300018

    View details for PubMedID 14638548

  • Abnormal cardiac function associated with sympathetic nervous system hyperactivity in mice AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Brum, P. C., Kosek, J., Patterson, A., Bernstein, D., Kobilka, B. 2002; 283 (5): H1838-H1845

    Abstract

    alpha(2A)-Adrenergic receptors (ARs) in the midbrain regulate sympathetic nervous system activity, and both alpha(2A)-ARs and alpha(2C)-ARs regulate catecholamine release from sympathetic nerve terminals in cardiac tissue. Disruption of both alpha(2A)- and alpha(2C)-ARs in mice leads to chronically elevated sympathetic tone and decreased cardiac function by 4 mo of age. These knockout mice have increased mortality, reduced exercise capacity, decreased peak oxygen uptake, and decreased cardiac contractility relative to wild-type controls. Moreover, we observed significant abnormalities in the ultrastructure of cardiac myocytes from alpha(2A)/alpha(2C)-AR knockout mice by electron microscopy. Our results demonstrate that chronic elevation of sympathetic tone can lead to abnormal cardiac function in the absence of prior myocardial injury or genetically induced alterations in myocardial structural or functional proteins. These mice provide a physiologically relevant animal model for investigating the role of the sympathetic nervous system in the development and progression of heart failure.

    View details for DOI 10.1152/ajpheart.01063.2001

    View details for Web of Science ID 000178625800012

    View details for PubMedID 12384461

  • Vasoregulation at the molecular level: A role for the beta 1 subunit of the calcium-activated potassium (BK) channel TRENDS IN CARDIOVASCULAR MEDICINE Patterson, A. J., Henrie-Olson, J., Brenner, R. 2002; 12 (2): 78-82

    Abstract

    Essential hypertension is among the most common and most costly medical conditions in the United States. Multiple defects in the kidneys, the vasculature, and the neuro-endocrine system may contribute to the development of this disorder. Within the past decade investigators have identified several molecular components of the vasculature that control tone and influence blood pressure. For example, the large conductance BK type calcium-activated potassium channel has recently been shown to play an important role in maintaining the dynamic equilibrium between vasoconstriction and vasodilation of vascular smooth muscle. Activation of vascular smooth muscle BK channels leads to hyperpolarization of the cell membrane, which causes deactivation of voltage-dependent calcium channels and vasodilation. In this review, we will summarize recently published data focusing on the role of the BK channel's accessory beta1 subunit as well as other modulators of BK channel activation that influence vascular tone and blood pressure.

    View details for Web of Science ID 000173930400006

    View details for PubMedID 11852255

  • Abnormal Cardiac Function Associated with Sympathetic Nervous System Hyperactivity in Mice Am J Physiol Heart Circ Physiol Patrcia C. Brum, Jon Kosek, Andrew Patterson, Daniel Bernstein, Brian Kobilka 2002; 283: H1838-H1845
  • Vasoregulation by the beta 1 subunit of the calcium-activated potassium channel NATURE Brenner, R., Perez, G. J., Bonev, A. D., Eckman, D. M., Kosek, J. C., Wiler, S. W., Patterson, A. J., Nelson, M. T., Aldrich, R. W. 2000; 407 (6806): 870-876

    Abstract

    Small arteries exhibit tone, a partially contracted state that is an important determinant of blood pressure. In arterial smooth muscle cells, intracellular calcium paradoxically controls both contraction and relaxation. The mechanisms by which calcium can differentially regulate diverse physiological responses within a single cell remain unresolved. Calcium-dependent relaxation is mediated by local calcium release from the sarcoplasmic reticulum. These 'calcium sparks' activate calcium-dependent potassium (BK) channels comprised of alpha and beta1 subunits. Here we show that targeted deletion of the gene for the beta1 subunit leads to a decrease in the calcium sensitivity of BK channels, a reduction in functional coupling of calcium sparks to BK channel activation, and increases in arterial tone and blood pressure. The beta1 subunit of the BK channel, by tuning the channel's calcium sensitivity, is a key molecular component in translating calcium signals to the central physiological function of vasoregulation.

    View details for Web of Science ID 000089901900041

    View details for PubMedID 11057658

  • Nitrous oxide produces antinociceptive response via alpha(2B) and/or alpha(2C) adrenoceptor subtypes in mice ANESTHESIOLOGY Guo, T. Z., Davies, M. F., Kingery, W. S., Patterson, A. J., Limbird, L. E., Maze, M. 1999; 90 (2): 470-476

    Abstract

    Opiate receptors in the periaqueductal gray region and alpha2 adrenoceptors in the spinal cord of the rat mediate the antinociceptive properties of nitrous oxide (N2O). The availability of genetically altered mice facilitates the detection of the precise protein species involved in the transduction pathway. In this study, the authors establish the similarity between rats and mice in the antinociceptive action of N2O and investigate which alpha2 adrenoceptor subtypes mediate this response.After obtaining institutional approval, antinociceptive dose-response and time-course to N2O was measured in wild-type and transgenic mice (D79N), with a nonfunctional alpha2A adrenoceptor using tail-flick latency. The antinociceptive effect of N2O was tested after pretreatment systemically with yohimbine (nonselective alpha2 antagonist), naloxone (opiate antagonist), L659,066 (peripheral alpha2-antagonist) and prazosin (alpha2B- and alpha2C-selective antagonist). The tail-flick latency to dexmedetomidine (D-med), a nonselective alpha2 agonist, was tested in wild-type and transgenic mice.N2O produced antinociception in both D79N transgenic and wild-type litter mates, although the response was less pronounced in the transgenic mice. Antinociception from N2O decreased over time with continuing exposure, and the decrement was more pronounced in the transgenic mice. The antinociceptive response could be dose dependently antagonized by opiate receptor and selective alpha2B-/alpha2C-receptor antagonists but not by a central nervous system-impermeant alpha2 antagonist (L659,066). Whereas dexmedetomidine exhibited no antinociceptive response in the D79N mice, the robust antinociceptive response in the wild-type litter mates could not be blocked by a selective alpha2B-/alpha2C-receptor antagonist.These data confirm that the antinociceptive response to an exogenous alpha2-agonist is mediated by an alpha2A adrenoceptor and that there appears to be a role for the alpha2B- or alpha2C-adrenoceptor subtypes, or both, in the analgesic response to N2O.

    View details for Web of Science ID 000078326100021

    View details for PubMedID 9952154

  • Airway obstruction caused by an oleothorax JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Patterson, A. J., Leong, M. S., Brodsky, J. B., Mark, J. B. 1998; 12 (2): 189-191

    View details for Web of Science ID 000073194700015

    View details for PubMedID 9583553

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