Stony Brook University Department of Anesthesiology

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ASA 2009

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Research Mission

  The Department has reaffirmed its strong commitment to its academic mission. Research in both basic sciences and clinical applications is well covered with world renowned, productive faculty. The department has active grants from the National Institutes of Health, the National Science Foundation and the Department of Energy. The department also receives substantial funding from industry for clinical research. At present there are active clinical protocols ranging from analgesics and gender to anticoagulants, to new forms of central nervous system monitoring. A new system of mentoring and career development has also been established for both residents and junior staff. Residents are welcome to attend the monthly research meetings.
   
  Residents participate in human studies in such areas as clinical pharmacodynamics and kinetics, neurophysiology, patient monitoring, critical care and outcomes research. They may also be involved in animal experimentation pertaining to anesthetic agents and their adjuvants. Electives and Research years are offered as allowed by the American Board of Anesthesiology.

  To promote these efforts, the department has several Ph.D. faculty members, post-doctoral fellows, research nurses and technicians.
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Benveniste Lab: Translational and Applied Research: High Resolution MRI, Addiction, Autism
Helene Benveniste, MD, PhD

  Research in Dr. Benveniste’s laboratory  focuses on applying microMRI and other imaging modalities (optics, microCT, PET) in translational neuroscience studies.
•    Developing methodologies to capture neuronal and astroglia activity at high spatial and temporal resolution
•    Understanding how anesthetics and analgesic interfere with brain activity
•    Understanding mechanisms underlying development of addiction to drugs of abuse
•    Informatics and high resolution MRI for anatomical and functional phenotyping of transgenic mouse models of human disease (Alzheimer’s disease, Attention Deficit Hyperactivity Disorder, Stroke).
  
  Experimental methodologies and projects associated with our laboratory include microMRI, optical imaging, in vivo and in vitro techniques for imaging and engineering and instrumentation development in collaboration with Division of Instrumentation and Central Shops at Brookhaven National Laboratory. Our long-term goal is to apply our new technologies and knowledge towards understanding the mechanisms underlying the action of anesthetics and mind altering drugs.


Surface renderings of the mouse brain based on MRI. [details]
Ma et al. Neuroscience. 2005;135(4):1203-15.

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Du Lab: Optical and fMRI Studies of Cocaine in the Rat Brain
Congwu Du, PhD

The broad goal of the research in Dr. Du's laboratory is to develop a fluorescence technique that permit tracking the intracellular calcium transients from a beating heart surface in ex-vivo or in vivo, along with the simultaneous measurement of cardiac contraction. This instrument can be used to understand the mechanisms of the cellular effects of the anesthetic drugs on the cardiac function. She are interested in studying drug-induced abnormalities of the heart function by measuring the intracellular calcium transient and the development pressure changes of the heart in response to the administration of cocaine or lidocine. Cocaine is chosen as one of the preliminary drug for the application of this project because cocaine has multiple pharmacological effects on cardiovascular function: One is its local anesthetic effect, and another is its inhibition of neuronal reuptake of catecholamines. Many studies have shown that the inhibition by cocaine of catecholamine reuptake is a key locus for the cardiovascular effects of this drug. More recently, it has become apparent that the local anesthetic actions of cocaine may also play an important role in its effects on the heart. However, the details how the local anesthetic effect of cocaine on the vasculature and heart function have not fully explored, and still needed to be further investigated.


Changes in cerebral blood volume, mean arterial blood pressure and cortical ADCs in response to an acute cocaine injection.
Du et al. J Neurosci. 2006 Nov 8;26(45):11522-31

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Dilger Lab: Potentiation of Glycine Receptor Channels by General Anesthetics

James P. Dilger, PhD

The current research in Dr. Dilger’s laboratory is focused on mechanisms of action of general anesthetics on synaptic ion channels. General anesthetics such as propofol and isoflurane potentiate inhibitory synaptic channels such as the strychnine-sensitive glycine receptor. Dr. Dilger uses patch clamp electrophysiological techniques to record the currents that flow through ion channels in the cell membrane. His lab pioneered the development of methods for rapid (less than 1 millisecond) concentration jumps that mimic conditions at a fast synapse. Both macroscopic and single channel currents are used in these investigations. The overall goals are a) to understand how the binding of glycine to the receptor causes the channel gate to open and b) to understand how general anesthetics cause this gating to be more efficient. He also uses computational techniques to simulate the actions of glycine and anesthetics at a realistic synapse.

A recently completed project from the Dilger Lab examined how different muscle relaxants bind to each of the two distinct ligand binding sites on the muscle acetylcholine receptor. Most benzylisoquinolines, such as (+)-tubocurarine have higher affinity for the site at the α-ε subunit interface while most aminosteroids, such as pancuronium, have higher affinity for the site at the α-δ subunit interface. See figure at right.


Cartoon illustrating the binding of curare (left) and pancuronium (right) to different interfacial binding sites on the adult muscle acetylcholine receptor. This may be part of the reason why some combinations of muscle relaxants are synergistic.
Liu & Dilger, Anesth Analg. 2008 Aug;107(2):525

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Liu Lab: Cardioprotection by Volatile Anesthetics in the Aging Heart
Lixin Liu, MD, PhD
  The current research interest is to study mechanisms of age-associated change in cardioprotection following anesthetic preconditioning. Preconditioning confers a remarkable cardioprotection in a variety of species, including humans. The majority of research into cardioprotective measurements involves models using young or early adult animals. However, cardioprotective strategies would most benefit the elderly patients. Indeed, recent studies in the isolated perfused rat heart model have shown that ischemia preconditioning (IPC) and anesthetic preconditioning (APC) failed to induce cardioprotection in the senescent myocardium. Clinically, it has been suggested that the benefit of “preinfarction angina” in elderly patients is substantially less than in younger patients. We have recently established an ischemia/reperfusion intact rat model that permits us to study anesthetic preconditioning. Our results have demonstrated a reduction in the cardioprotective effects of isoflurane and an attenuation of ROS in the aged myocardium. Our work should provide an avenue for new approaches to myocardial protection in the elderly population.

Long Nguyen, MD (Stony Brook Resident 2004-2006) receives second place award in the 2006 American Society of Anesthesiologists Resident Research Essay Competition from Dr. James Eisenach, Editor-in-Chief of AnesthesiologyChicago, Oct 2006
Dr. Nguyen's essay "Attenuation of Anesthetic Preconditioning and Reactive Oxygen Species Production in the Aged Heart" was based on research done in Dr. Liu's lab.
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Pentyala Lab: Translational Research, Cell Signaling Mechanisms
 
Srinivas Pentyala, PhD

  Research interests are to bridge the gap between basic and clinical research. Projects to develop diagnostic tests for detecting cerebrospinal fluid leaks and prostate cancer are in progress. A bioinformatics project on lead drug discovery using specific algorithms to identify bioactive peptides is also in progress. Basic research projects involve molecular actions of intravenous and inhalational anesthetics with regard to their effect on signal transduction pathways. Particularly, the effect of intravenous drugs on calcium flux and the effect of inhalational drugs on G-protein signaling mechanisms are being studied. Signaling mechanisms involving calcium-mobilizing enzymes in relation to cancer and cell death are also being studied.


Diagnostic test for detecting cerebrospinal fluid leaks. [US Patent App. No: 10/409,758]

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Rampil Lab: Molecular Mechanisms of Amnesia

Ira S. Rampil, MSEE, MD

Dr. Rampil, MD Professor of Anesthesiology and Neurological Surgery has been active in anesthesia research for more than twenty years and is the department’s Director of Clinical Research, Course Director for the Resident Research Course and the Director of the Department of Anesthesia’s  Journal Club. He has been a pioneer in developing clinically relevant neurophysiologic monitoring systems and in computer-based data acquisition and signal processing systems.

  Dr. Rampil has conducted a number of highly cited clinical trials involving inhaled anesthetic agents and was the principal investigator for the FDA phase one trial of desflurane. Dr. Rampil’s current interest involves the mechanisms and sites of general anesthetic action. He made the seminal observation that surgical immobility (lack of movement response to surgical incision) was mediated by spinal sites, not in the cerebrum. He was a member of a multicenter NIH program project investigating the molecular mechanisms of anesthesia which has discovered specific sites in ligand-gated ionophores which selectively block anesthetic effect. His most recent work involves the molecular mechanisms by which volatile anesthetics create surgical amnesia. This project uses proteomic and DNA microarray technology to examine how anesthetics act within the amygdala and other limbic areas to block the protein synthesis required for long term memory. Dr. Rampil is a Principal Investigator of a $5 million federal grant to design, build and test new imaging technologies which will work on awake, unrestrained animals. He has leadership roles in several national and international anesthesia societies and has served on the editorial boards of several major journals.

Cartoon illustration of the hypothesized functional/anatomic distribution of isoflurane-effected genes within a neural synapse.

Rampil IJ, Moller DH, Bell AH.
    Isoflurane modulates genomic expression in rat amygdala.
Anesth Analg. 2006 May;102(5):1431-8.

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Rebecchi Lab: Gene Regulation by Phosphoinositides, Ischemia and Reperfusion, Opiate Tolerance

Mario J. Rebecchi, PhD

Ever since the sequencing of the human genome, it has been realized how little we understand of gene regulation. The three levels of chromatin organization: the linear sequence, the histone-supported nucleosomal structures, and the larger chromosomal interaction domains give rise to highly complex molecular machines, that regulate the onset and completion of DNA replication, as well as the synthesis, maturation and export of messenger RNA, yet many of the control elements remain to be defined. All of human biology and much of human disease may trace their origins to the temporal and spatial control of this apparatus.

  Our work revolves around the functions of rare lipids, the phosphoinositides, and a class of enzymes that hydrolyze them, phospholipase C.   They and their metabolites are well known second messengers involved in a wide range of biological processes. Using small interfering RNA approaches, our studies reveal an essential role for these lipids in growth control and stress responses.  The various techniques employed include of fluorescence microscopy, FACS, RT-PCR, and protein mass spectrometry.  

  Other projects underway: a) a study of the mechanisms that underlie the responses of glia to injury; b) the role of phosphoinositides in anesthetic preconditioning in the heart; and c) mechanisms of opiate tolerance.
Detergent-resistant fraction of nuclear PIP2 and its localization with PLC1H356AEGFP in NIH-3T3 cells. [details]
Stallings et al.  J Biol Chem. 2005 Jun 10;280(23):22060-9

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Clinical Projects

Current clinical studies include:

Analgesic efficacy and safety of acetaminophen for pain following vaginal hysterectomy

Clevelox vs nitroglycerin for treatment of hypertension

Validation of spectral entropy in predicting awareness

Transdermal scopolamine patch plus ondansetron for prevention of postoperative nausea and vomiting in the outpatient setting

Comparison of anesthetic requirement at BIS40 and BIS60 for sevoflurane and propofol

Gender differences in resource utilization in patients undergoing aortic valve surgery



Relation Between Post Operative Length of Stay
and Number of Units of RBCs Received
Blood Transfusion in Cardiac Surgery:
Impact on Hospital Length of Stay and Mortality
Bharathi H. Scott, Frank C. Seifert, Roger Grimson
ASA 2006





Soto RG, Chu LF, Goldman JM, Rampil IJ, Ruskin KJ.
    Communication in critical care environments: mobile telephones improve patient care.
Anesth Analg. 2006 Feb;102(2):535-41.

Relationship between loss of responsiveness to an automated responsiveness monitor and other measures of level of consciousness during forced dose titration of propofol

Study to determine if Zofran ODT is as effective as Compazine in preventing postoperative nausea and vomiting

Study of granisetron + dexamethasone vs ondansetron + dexamethasone in the prevention of postoperative nausea and vomiting

Safety and efficacy of intravenous ondansetron with intravenous dexamethasone for the prevention of postoperative nausea and vomiting in female subjects

Comparison of Clevelox vs sodium nitroprusside for the treatment of hypertension as clinically required perioperatively

Phase III trial to assess efficacy & safety of Org 25969

Angelgesic efficacy & safety of acetaminophen injection for pain following primary total hip arthroplasty

Prospective study on the long-term effects of surgery on C-reactive protein level

A retrospective study comparing methohexital to pentothal for ECT

A survey study of surgeons and anesthesiologists regarding why they order preop lab tests

Preemptive use of the nicotine patch for postoperative pain relief after open abdominal wall surgery




Relation between intra-operative bispectral index scores (BIS) and end-tidal sevoflurane and halothane concentrations.
Edwards et al.  Acta Anaesthesiol Scand. 2005 Sep;49(8):1084-7




Regression of Entropy vs. Amnesia
State and Response Entropy Predict Amnesia during Propofol Sedation
Ira J. Rampil, M.D., Daryn Moller, M.D.
ASA 2006

Treatment of chronic pelvic pain

The influence of gender on recovery from general anesthesia with isoflurane and fentanyl

The impact of prenatal obstetric anesthesia consults on birth outcomes

Loss of resistance of air vs saline: Which is the safer technique to identify the epidural space?

Assessment of caudal anesthesia onset using temperature and tumescent measurements

Use of dexmedetomidine as an anesthetic adjunct in adolescent posterior spinal fusion surgery

The efficacy of perioperative intervention in smoking cessation

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