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Article ; Online: Extracellular Vesicles: A New Paradigm for Cellular Communication in Perioperative Medicine, Critical Care, and Pain Management.

Zhou, Yingqiu K / Patel, Hemal H / Roth, David M

2021 Volume 133, Issue 5, Page(s) 1162–1179

Abstract: Extracellular vesicles (EVs) play critical roles in many health and disease states, including ischemia, inflammation, and pain, which are major concerns in the perioperative period and in critically ill patients. EVs are functionally active, nanometer- ... ...

Abstract	Extracellular vesicles (EVs) play critical roles in many health and disease states, including ischemia, inflammation, and pain, which are major concerns in the perioperative period and in critically ill patients. EVs are functionally active, nanometer-sized, membrane-bound vesicles actively secreted by all cells. Cell signaling is essential to physiological and pathological processes, and EVs have recently emerged as key players in intercellular communication. Recent studies in EV biology have improved our mechanistic knowledge of the pathophysiological processes in perioperative and critical care patients. Studies also show promise in using EVs in novel diagnostic and therapeutic clinical applications. This review considers the current advances and gaps in knowledge of EVs in the areas of ischemia, inflammation, pain, and in organ systems that are most relevant to anesthesiology, perioperative medicine, critical care, and pain management. We expect the reader will better understand the relationship between EVs and perioperative and critical care pathophysiological states and their potential use as novel diagnostic and therapeutic modalities.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Cell Communication/drug effects ; Critical Care ; Disease ; Extracellular Vesicles/drug effects ; Extracellular Vesicles/metabolism ; Extracellular Vesicles/pathology ; Humans ; Pain Management ; Perioperative Care ; Perioperative Medicine ; Signal Transduction
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-07-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	80032-6
ISSN	1526-7598 ; 0003-2999
ISSN (online)	1526-7598
ISSN	0003-2999
DOI	10.1213/ANE.0000000000005655
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Article ; Online: No pain, no gain: balancing central versus peripheral benefits of analgesics in the age of the opioid crisis.

Patel, Hemal H / Roth, David M

British journal of pharmacology

2018 Volume 175, Issue 5, Page(s) 855–856

MeSH term(s)	Analgesics ; Analgesics, Opioid ; Animals ; Laparotomy ; Pain ; Rats ; Receptors, Opioid
Chemical Substances	Analgesics ; Analgesics, Opioid ; Receptors, Opioid
Language	English
Publishing date	2018-01-17
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.14130
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Article ; Online: 1 + 1 = 4? Balanced anaesthesia: A sum that is greater than its parts.

Zhou, Yingqiu / Roth, David M / Patel, Hemal H

British journal of pharmacology

2020 Volume 176, Issue 24, Page(s) 4785–4786

MeSH term(s)	Anesthetics, General ; Anesthetics, Intravenous ; Balanced Anesthesia ; Binding Sites ; Receptors, GABA-A
Chemical Substances	Anesthetics, General ; Anesthetics, Intravenous ; Receptors, GABA-A
Language	English
Publishing date	2020-01-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.14908
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Article ; Online: Modeling and Phenotyping Acute and Chronic Type 2 Diabetes Mellitus In Vitro in Rodent Heart and Skeletal Muscle Cells.

Kopp, Elena L / Deussen, Daniel N / Cuomo, Raphael / Lorenz, Reinhard / Roth, David M / Mahata, Sushil K / Patel, Hemal H

Cells

2023 Volume 12, Issue 24

Abstract: Type 2 diabetes (T2D) has a complex pathophysiology which makes modeling the disease difficult. We aimed to develop a novel model for simulating T2D in vitro, including hyperglycemia, hyperlipidemia, and variably elevated insulin levels targeting muscle ... ...

Abstract	Type 2 diabetes (T2D) has a complex pathophysiology which makes modeling the disease difficult. We aimed to develop a novel model for simulating T2D in vitro, including hyperglycemia, hyperlipidemia, and variably elevated insulin levels targeting muscle cells. We investigated insulin resistance (IR), cellular respiration, mitochondrial morphometry, and the associated function in different T2D-mimicking conditions in rodent skeletal (C2C12) and cardiac (H9C2) myotubes. The physiological controls included 5 mM of glucose with 20 mM of mannitol as osmotic controls. To mimic hyperglycemia, cells were exposed to 25 mM of glucose. Further treatments included insulin, palmitate, or both. After short-term (24 h) or long-term (96 h) exposure, we performed radioactive glucose uptake and mitochondrial function assays. The mitochondrial size and relative frequencies were assessed with morphometric analyses using electron micrographs. C2C12 and H9C2 cells that were treated short- or long-term with insulin and/or palmitate and HG showed IR. C2C12 myotubes exposed to T2D-mimicking conditions showed significantly decreased ATP-linked respiration and spare respiratory capacity and less cytoplasmic area occupied by mitochondria, implying mitochondrial dysfunction. In contrast, the H9C2 myotubes showed elevated ATP-linked and maximal respiration and increased cytoplasmic area occupied by mitochondria, indicating a better adaptation to stress and compensatory lipid oxidation in a T2D environment. Both cell lines displayed elevated fractions of swollen/vacuolated mitochondria after T2D-mimicking treatments. Our stable and reproducible in vitro model of T2D rapidly induced IR, changes in the ATP-linked respiration, shifts in energetic phenotypes, and mitochondrial morphology, which are comparable to the muscles of patients suffering from T2D. Thus, our model should allow for the study of disease mechanisms and potential new targets and allow for the screening of candidate therapeutic compounds.
MeSH term(s)	Animals ; Humans ; Diabetes Mellitus, Type 2/metabolism ; Rodentia/metabolism ; Muscle Fibers, Skeletal/metabolism ; Glucose/metabolism ; Insulin/metabolism ; Insulin Resistance ; Hyperglycemia/metabolism ; Palmitates/metabolism ; Adenosine Triphosphate/metabolism
Chemical Substances	Glucose (IY9XDZ35W2) ; Insulin ; Palmitates ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2023-12-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12242786
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Article ; Online: Dexmedetomidine and Cardiac "Postconditioning": Clearing the Dex for Clinical Application.

Satomi, Shiho / Patel, Hemal H / Roth, David M

Anesthesia and analgesia

2019 Volume 130, Issue 1, Page(s) 87–89

MeSH term(s)	Dexmedetomidine ; Heart ; Humans ; Myocardial Reperfusion Injury
Chemical Substances	Dexmedetomidine (67VB76HONO)
Language	English
Publishing date	2019-12-16
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	80032-6
ISSN	1526-7598 ; 0003-2999
ISSN (online)	1526-7598
ISSN	0003-2999
DOI	10.1213/ANE.0000000000004497
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Zs.MO 149: Show issues

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Article ; Online: Impact of blood factors on endothelial cell metabolism and function in two diverse heart failure models.

Song, Young / Leem, Joseph / Dhanani, Mehul / McKirnan, M Dan / Ichikawa, Yasuhiro / Braza, Julie / Harrington, Elizabeth O / Hammond, H Kirk / Roth, David M / Patel, Hemal H

PloS one

2023 Volume 18, Issue 2, Page(s) e0281550

Abstract: Role of blood-based factors in development and progression of heart failure (HF) is poorly characterized. Blood contains factors released during pathophysiological states that may impact cellular function and provide mechanistic insights to HF management. ...

Abstract	Role of blood-based factors in development and progression of heart failure (HF) is poorly characterized. Blood contains factors released during pathophysiological states that may impact cellular function and provide mechanistic insights to HF management. We tested effects of blood from two distinct HF models on cardiac metabolism and identified possible cellular targets of the effects. Blood plasma was obtained from daunorubicin- and myocardial infarction-induced HF rabbits (Dauno-HF and MI-HF) and their controls (Dauno-Control and MI-Control). Effects of plasma on bioenergetics of myocardial tissue from healthy mice and cellular cardiac components were assessed using high-resolution respirometry and Seahorse flux analyzer. Since endothelial cell respiration was profoundly affected by HF plasma, effects of plasma on endothelial cell barrier function and death were further evaluated. Western-blotting and electron microscopy were performed to evaluate mitochondrial proteins and morphology. Brief exposure to HF plasma decreased cardiac tissue respiration. Endothelial cell respiration was most impacted by exposure to HF plasma. Endothelial cell monolayer integrity was decreased by incubation with Dauno-HF plasma. Apoptosis and necrosis were increased in cells incubated with Dauno-HF plasma for 24 h. Down-regulation of voltage-dependent anion-selective channel (VDAC)-1, translocase of outer membrane 20 (Tom20), and mitochondrial fission factor (MFF) in cells exposed to Dauno-HF plasma and mitochondrial signal transducer and activator of transcription 3 (Stat3) and MFF in cells exposed to MI-HF plasma were observed. Mitochondrial structure was disrupted in cells exposed to HF plasma. These findings indicate that endothelial cells and mitochondrial structure and function may be primary target where HF pathology manifests and accelerates. High-throughput blood-based screening of HF may provide innovative ways to advance disease diagnosis and management.
MeSH term(s)	Mice ; Animals ; Rabbits ; Endothelial Cells/metabolism ; Mitochondria, Heart/metabolism ; Heart Failure ; Myocardium/metabolism ; Energy Metabolism
Language	English
Publishing date	2023-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0281550
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Article ; Online: An electroencephalogram microdisplay to visualize neuronal activity on the brain surface.

Tchoe, Youngbin / Wu, Tianhai / U, Hoi Sang / Roth, David M / Kim, Dongwoo / Lee, Jihwan / Cleary, Daniel R / Pizarro, Patricia / Tonsfeldt, Karen J / Lee, Keundong / Chen, Po Chun / Bourhis, Andrew M / Galton, Ian / Coughlin, Brian / Yang, Jimmy C / Paulk, Angelique C / Halgren, Eric / Cash, Sydney S / Dayeh, Shadi A

Science translational medicine

2024 Volume 16, Issue 744, Page(s) eadj7257

Abstract: Functional mapping during brain surgery is applied to define brain areas that control critical functions and cannot be removed. Currently, these procedures rely on verbal interactions between the neurosurgeon and electrophysiologist, which can be time- ... ...

Abstract	Functional mapping during brain surgery is applied to define brain areas that control critical functions and cannot be removed. Currently, these procedures rely on verbal interactions between the neurosurgeon and electrophysiologist, which can be time-consuming. In addition, the electrode grids that are used to measure brain activity and to identify the boundaries of pathological versus functional brain regions have low resolution and limited conformity to the brain surface. Here, we present the development of an intracranial electroencephalogram (iEEG)-microdisplay that consists of freestanding arrays of 2048 GaN light-emitting diodes laminated on the back of micro-electrocorticography electrode grids. With a series of proof-of-concept experiments in rats and pigs, we demonstrate that these iEEG-microdisplays allowed us to perform real-time iEEG recordings and display cortical activities by spatially corresponding light patterns on the surface of the brain in the surgical field. Furthermore, iEEG-microdisplays allowed us to identify and display cortical landmarks and pathological activities from rat and pig models. Using a dual-color iEEG-microdisplay, we demonstrated coregistration of the functional cortical boundaries with one color and displayed the evolution of electrical potentials associated with epileptiform activity with another color. The iEEG-microdisplay holds promise to facilitate monitoring of pathological brain activity in clinical settings.
MeSH term(s)	Animals ; Brain/physiology ; Electroencephalography/methods ; Swine ; Rats ; Neurons/physiology ; Brain Mapping/methods ; Rats, Sprague-Dawley ; Electrocorticography/methods ; Male
Language	English
Publishing date	2024-04-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.adj7257
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Article ; Online: Epigenetics: The Epicenter for Future Anesthesia Research?

Stary, Creed M / Patel, Hemal H / Roth, David M

Anesthesiology

2015 Volume 123, Issue 4, Page(s) 743–744

MeSH term(s)	Animals ; Isoflurane/administration & dosage ; Male ; MicroRNAs/physiology ; Mitochondrial Membrane Transport Proteins/metabolism ; Myocardial Reperfusion Injury/metabolism ; Nitric Oxide Synthase/metabolism ; Proto-Oncogene Proteins c-akt/metabolism
Chemical Substances	MicroRNAs ; Mitochondrial Membrane Transport Proteins ; Isoflurane (CYS9AKD70P) ; Nitric Oxide Synthase (EC 1.14.13.39) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2015-10
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	269-0
ISSN	1528-1175 ; 0003-3022
ISSN (online)	1528-1175
ISSN	0003-3022
DOI	10.1097/ALN.0000000000000808
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Zs.MO 199: Show issues

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Article ; Online: Caveolins in cardioprotection - translatability and mechanisms.

Schilling, Jan M / Roth, David M / Patel, Hemal H

British journal of pharmacology

2015 Volume 172, Issue 8, Page(s) 2114–2125

Abstract: Translation of preclinical treatments for ischaemia-reperfusion injury into clinical therapies has been limited by a number of factors. This review will focus on a single mode of cardiac protection related to a membrane scaffolding protein, caveolin, ... ...

Abstract	Translation of preclinical treatments for ischaemia-reperfusion injury into clinical therapies has been limited by a number of factors. This review will focus on a single mode of cardiac protection related to a membrane scaffolding protein, caveolin, which regulates protective signalling as well as myocyte ultrastructure in the setting of ischaemic stress. Factors that have limited the clinical translation of protection will be considered specifically in terms of signalling and structural defects. The potential of caveolin to overcome barriers to protection with the ultimate hope of clinical translation will be discussed.
MeSH term(s)	Aging/physiology ; Animals ; Cardiomyopathies/metabolism ; Caveolins/metabolism ; Diabetes Mellitus/metabolism ; Humans ; Ischemic Preconditioning, Myocardial ; Myocardium/metabolism
Chemical Substances	Caveolins
Language	English
Publishing date	2015-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.13009
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Article ; Online: Role of caveolae in cardiac protection.

Roth, David M / Patel, Hemal H

Pediatric cardiology

2011 Volume 32, Issue 3, Page(s) 329–333

Abstract: Myocardial ischemia/reperfusion injury is a major cause of morbidity and mortality. The molecular signaling pathways involved in cardiac protection from myocardial ischemia/reperfusion injury are complex. An emerging idea in signal transduction suggests ... ...

Abstract	Myocardial ischemia/reperfusion injury is a major cause of morbidity and mortality. The molecular signaling pathways involved in cardiac protection from myocardial ischemia/reperfusion injury are complex. An emerging idea in signal transduction suggests the existence of spatially organized complexes of signaling molecules in lipid-rich microdomains of the plasma membrane known as caveolae. Caveolins-proteins abundant in caveolae-provide a scaffold to organize, traffic, and regulate signaling molecules. Numerous signaling molecules involved in cardiac protection are known to exist within caveolae or interact directly with caveolins. Over the last 4 years, our laboratories have explored the hypothesis that caveolae are vitally important to cardiac protection from myocardial ischemia/reperfusion injury. We have provided evidence that (1) caveolae and the caveolin isoforms 1 and 3 are essential for cardiac protection from myocardial ischemia/reperfusion injury, (2) stimuli that produce preconditioning of cardiac myocytes, including brief periods of ischemia/reperfusion and exposure to volatile anesthetics, alter the number of membrane caveolae, and (3) cardiac myocyte-specific overexpression of caveolin-3 can produce innate cardiac protection from myocardial ischemia/reperfusion injury. The work demonstrates that caveolae and caveolins are critical elements of signaling pathways involved in cardiac protection and suggests that caveolins are unique targets for therapy in patients at risk of myocardial ischemia.
MeSH term(s)	Caveolae/metabolism ; Caveolins/metabolism ; Humans ; Myocardial Ischemia/metabolism ; Myocardial Reperfusion Injury/metabolism ; Signal Transduction
Chemical Substances	Caveolins
Language	English
Publishing date	2011-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	800857-7
ISSN	1432-1971 ; 0172-0643
ISSN (online)	1432-1971
ISSN	0172-0643
DOI	10.1007/s00246-010-9881-8
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