Cardiovascular microphysiological systems (CVMPS) for safety studies – a pharma perspective

Lab on a Chip ◽  
2021 ◽  
Vol 21 (3) ◽  
pp. 458-472
Author(s):  
Amy Pointon ◽  
Jonathan Maher ◽  
Myrtle Davis ◽  
Thomas Baker ◽  
Joseph Cichocki ◽  
...  
Keyword(s):  
Blood Flow ◽  
Entire Body ◽  
Microphysiological Systems ◽  
Safety Studies ◽  
Waste Removal

The integrative responses of the cardiovascular (CV) system are essential for maintaining blood flow to provide oxygenation, nutrients, and waste removal for the entire body.

MODELING REDISTRIBUTION CEREBRAL CIRCULATION

2021 ◽  
Vol 1 (4) ◽  
pp. 13-18
Author(s):  
Vladislav Nikolaevich Nikitin ◽  
◽  
Ekaterina Valerevna Kozhemyakina ◽  
Keyword(s):  
Blood Flow ◽  
Internal Carotid ◽  
Cerebral Arteries ◽  
Circle Of Willis ◽  
Entire Body ◽  
Compensatory Mechanisms ◽  
Vertebral Arteries ◽  
The Central Nervous System ◽  
Flow Through ◽  
The Brain

The brain is one of the most important organs responsible for the health and functioning of the entire body. The blood supply to the brain is carried out through 2 internal carotid and 2 vertebral arteries in norm. The brain, like other body systems, has protective (compensatory) mechanisms aimed at maintaining the necessary blood flow, one of which is the circle of Willis. The article proposes a mechanism for how blood flow is redistributed through the arteries feeding the brain, which is based on the assumption that the central nervous system controls in such a way that it minimizes flows through the connective arteries of the circle of Willis, the flows along which are normal (with symmetry of the left and right sides) practically equal to zero. Сase of the structure of the circle of Willis is considered in norm. The indicated redistribution mechanism is still only the first step towards an attempt to predict cases of changes in blood flow through the cerebral arteries, especially in stroke. In further works, it is planned to consider the inverse problem, i.e. determine the flows through the internal carotid and vertebral arteries, provided that the flows through the cerebral arteries extending from the circle of Willis have normal flow values.

Levamisole-Adulterated Cocaine Leading to Fatal Vasculitis: A Case Report

2017 ◽  
Vol 37 (4) ◽  
pp. 49-57 ◽  
Author(s):  
Belinda B. Hammond ◽  
Jordan Craven
Keyword(s):  
Blood Flow ◽  
Case Report ◽  
Severe Neutropenia ◽  
Peripheral Blood Flow ◽  
Entire Body ◽  
Tissue Necrosis ◽  
Cutaneous Lesions ◽  
Cocaine Use ◽  
Hands And Feet ◽  
Parasitic Worms

Cocaine is often “cut” with various additives to increase the profitability of the drug. One of the most common additives on today’s market is levamisole, an anthelmintic medication used to destroy and expel parasitic worms in animals. The use of levamisole-contaminated cocaine can result in agranulocytosis and vasculitis (inflammation and constriction of small blood vessels). The resulting clotting and decrease in peripheral blood flow lead to cutaneous lesions, particularly on the ears, face, hands, and feet, and in severe cases can cause generalized tissue necrosis throughout the entire body. Treatment is generally supportive, and symptoms typically abate with complete cessation of cocaine use. However, symptoms may recur with subsequent cocaine use and, as this case illustrates, severe neutropenia and extensive vasculitis may lead to overwhelming sepsis and death.

Reflex control of active cutaneous vasodilation by skin temperature in humans

1994 ◽  
Vol 266 (5) ◽  
pp. H1979-H1984 ◽  
Author(s):  
P. E. Pergola ◽  
D. L. Kellogg ◽  
J. M. Johnson ◽  
W. A. Kosiba
Keyword(s):  
Blood Flow ◽  
Skin Temperature ◽  
Control Site ◽  
Whole Body ◽  
Entire Body ◽  
Internal Temperature ◽  
Doppler Flowmetry ◽  
Vasodilator Activity ◽  
Forearm Skin ◽  
Reflex Control

The purpose of this study was to examine whether reflex effects of changes in whole body skin temperature (Tsk) on cutaneous vasculature are mediated through the vasoconstrictor or the active vasodilator arm of the sympathetic nervous system. In six subjects, reflex responses in forearm skin blood flow (SkBF) to changes in Tsk were monitored by laser-Doppler flowmetry. SkBF was monitored at a control site and at a 0.6-cm2 site where bretylium (BT) had been iontophoretically applied to abolish sympathetic vasoconstrictor control. Reflex control of SkBF at BT-treated sites is solely through active vasodilator activity. An index of cutaneous vascular conductance (CVC) was calculated from the blood flow signal and mean arterial pressure, measured noninvasively. Data are expressed relative to maximum CVC (CVCmax) achieved by local warming of measurement sites to 42 degrees C at the end of each study. Tsk was controlled with a water-perfused suit covering the entire body except for the head and arms. Esophageal temperature (Tes) was measured as an index of internal temperature. In part A (rest), raising Tsk at rest from 31.9 +/- 0.3 to 36.7 +/- 0.2 degrees C increased CVC at control sites from 3 +/- 0.2 to 5 +/- 0.6% of CVCmax. CVC did not change at BT-treated sites, suggesting that at rest, with a normal internal temperature, reflex effects of raising Tsk on SkBF are mediated through vasoconstrictor withdrawal. In part B (exercise), exercise at a low Tsk increased Tes to 37.49 +/- 0.1 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

50 Years of Computer Simulation of the Human Thermoregulatory System

2013 ◽  
Vol 135 (2) ◽  
Author(s):  
Daniel W. Hensley ◽  
Andrew E. Mark ◽  
Jayvee R. Abella ◽  
George M. Netscher ◽  
Eugene H. Wissler ◽  
...  
Keyword(s):  
Heat Transfer ◽  
Blood Flow ◽  
Skin Blood Flow ◽  
Blood Perfusion ◽  
High Rate ◽  
Glabrous Skin ◽  
Entire Body ◽  
Dynamic Regulation ◽  
Therapeutic Procedures ◽  
Hands And Feet

This paper presents an updated and augmented version of the Wissler human thermoregulation model that has been developed continuously over the past 50 years. The existing Fortran code is translated into C with extensive embedded commentary. A graphical user interface (GUI) has been developed in Python to facilitate convenient user designation of input and output variables and formatting of data presentation. Use of the code with the GUI is described and demonstrated. New physiological elements were added to the model to represent the hands and feet, including the unique vascular structures adapted for heat transfer associated with glabrous skin. The heat transfer function and efficacy of glabrous skin is unique within the entire body based on the capacity for a very high rate of blood perfusion and the novel capability for dynamic regulation of blood flow. The model was applied to quantify the absolute and relative contributions of glabrous skin flow to thermoregulation for varying levels of blood perfusion. The model also was used to demonstrate how the unique features of glabrous skin blood flow may be recruited to implement thermal therapeutic procedures. We have developed proprietary methods to manipulate the control of glabrous skin blood flow in conjunction with therapeutic devices and simulated the effect of these methods with the model.

Innervation of endoneurial microvessels in human sural nerve

1992 ◽  
Vol 50 (1) ◽  
pp. 920-921
Author(s):  
John L. Beggs ◽  
Peter C. Johnson ◽  
Astrid G. Olafsen ◽  
C. Jane Watkins
Keyword(s):  
Blood Flow ◽  
Blood Vessels ◽  
Blood Supply ◽  
Peripheral Nerves ◽  
Sural Nerve ◽  
Nerve Fibers ◽  
Arterial Supply ◽  
Autonomic Nerve ◽  
Vasa Nervorum ◽  
Endoneurial Blood Flow

The blood supply (vasa nervorum) to peripheral nerves is composed of an interconnected dual circulation. The endoneurium of nerve fascicles is maintained by the intrinsic circulation which is composed of microvessels primarily of capillary caliber. Transperineurial arterioles link the intrinsic circulation with the extrinsic arterial supply located in the epineurium. Blood flow in the vasa nervorum is neurogenically influenced (1,2). Although a recent hypothesis proposes that endoneurial blood flow is controlled by the action of autonomic nerve fibers associated with epineurial arterioles (2), our recent studies (3) show that in addition to epineurial arterioles other segments of the vasa nervorum are also innervated. In this study, we examine blood vessels of the endoneurium for possible innervation.

Correlation of γ-radioactivity and Scanning Electron Microscopy in measurement of retention of 111Indium-labeled canine endothelial cells on synthetic vascular grafts

1989 ◽  
Vol 47 ◽  
pp. 886-887
Author(s):  
E.J. Prendiville ◽  
S. Laliberté Verdon ◽  
K. E. Gould ◽  
K. Ramberg ◽  
R. J. Connolly ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ex Vivo ◽  
Vascular Grafts ◽  
Retention Data ◽  
Vascular Prostheses ◽  
Group 4 ◽  
Human Fibronectin ◽  
Insufficient Time ◽  
Group 3 ◽  
Group 2

Endothelial cell (EC) seeding is postulated as a mechanism of improving patency in small caliber vascular grafts. However the majority of seeded EC are lost within 24 hours of restoration of blood flow in previous canine studies . We postulate that the cells have insufficient time to fully develop their attachment to the graft surface prior to exposure to hemodynamic stress. We allowed EC to incubate on fibronectin-coated ePTFE grafts for four different time periods after seeding and measured EC retention after perfusion in a canine ex vivo shunt circuit.Autologous canine EC, were enzymatically harvested, grown to confluence, and labeled with 30 μCi 111 Indium-oxine/80 cm 2 flask. Four groups of 5 cm x 4 mm ID ePTFE vascular prostheses were coated with 1.5 μg/cm.2 human fibronectin, and seeded with 1.5 x 105 EC/ cm.2. After seeding grafts in Group 1 were incubated in complete growth medium for 90 minutes, Group 2 were incubated for 24 hours, Group 3 for 72 hours and Group 4 for 6 days. Grafts were then placed in the canine ex vivo circuit, constructed between femoral artery and vein, and subjected to blood flow of 75 ml per minute for 6 hours. Continuous counting of γ-activity was made possible by placing the seeded graft inside the γ-counter detection crystal for the duration of perfusion. EC retention data after 30 minutes, 2 hours and 6 hours of flow are shown in the table.

Microvascular features that suggest effectors of blood-flow regulation in the brain: Evidence by SEM of corrosion casts of intracerebral vessels

1990 ◽  
Vol 48 (3) ◽  
pp. 274-275
Author(s):  
Enrico D.F. Motti ◽  
Hans-Georg Imhof ◽  
Gazi M. Yasargil
Keyword(s):  
Blood Flow ◽  
Perfusion Pressure ◽  
Corrosion Casts ◽  
Cerebral Microcirculation ◽  
Pial Arteries ◽  
Random Occurrence ◽  
Brain Arteries ◽  
Homogeneous Network ◽  
The Brain

Physiologists have devoted most attention in the cerebrovascular tree to the arterial side of the circulation which has been subdivided in three levels: 1) major brain arteries which keep microcirculation constant despite changes in perfusion pressure; 2) pial arteries supposed to be effectors regulating microcirculation; 3) intracerebral arteries supposed to be deprived of active cerebral blood flow regulating devices.The morphological search for microvascular effectors in the cerebrovascular bed has been elusive. The opaque substance of the brain confines in vivo investigation to the superficial pial arteries. Most morphologists had to limit their observation to the random occurrence of a favorable site in the practically two-dimensional thickness of diaphanized histological sections. It is then not surprising most investigators of the cerebral microcirculation refer to an homogeneous network of microvessels interposed between arterioles and venules.We have taken advantage of the excellent depth of focus afforded by the scanning electron microscope (SEM) to investigate corrosion casts obtained injecting a range of experimental animals with a modified Batson's acrylic mixture.

Maximum Output Intensity of the Audiokinetron

1996 ◽  
Vol 5 (2) ◽  
pp. 68-72 ◽  
Author(s):  
Christine M. Rankovic ◽  
William M. Rabinowitz ◽  
Gregory L. Lof
Keyword(s):  
Developmental Disabilities ◽  
Maximum Output ◽  
Output Intensity ◽  
Safety Studies ◽  
Auditory Integration Training ◽  
Auditory Integration

The Audiokinetron is a device that processes music for earphone presentation to patients undergoing auditory integration training, a treatment for individuals with autism and other developmental disabilities. Intensity levels produced by the Audiokinetron were measured under realistic listening conditions with a KEMAR manikin substituted for a patient. Average levels at the eardrum were 110 dB SPL when the device was adjusted to the highest setting employed by a local, trained AIT practitioner and 118 dB SPL at the maximum setting of the device. These levels are potentially harmful to hearing and warrant further safety studies of AIT instruments and protocols.

Functional Magnetic Resonance Imaging Measures of Blood Flow Patterns in the Human Auditory Cortex in Response to Sound

1998 ◽  
Vol 41 (3) ◽  
pp. 538-548 ◽  
Author(s):  
Sean C. Huckins ◽  
Christopher W. Turner ◽  
Karen A. Doherty ◽  
Michael M. Fonte ◽  
Nikolaus M. Szeverenyi
Keyword(s):  
Magnetic Resonance Imaging ◽  
Blood Flow ◽  
Magnetic Resonance ◽  
Functional Magnetic Resonance Imaging ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Speech Stimuli ◽  
Complex Stimuli ◽  
Scanning Session ◽  
Auditory Research

Functional Magnetic Resonance Imaging (fMRI) holds exciting potential as a research and clinical tool for exploring the human auditory system. This noninvasive technique allows the measurement of discrete changes in cerebral cortical blood flow in response to sensory stimuli, allowing determination of precise neuroanatomical locations of the underlying brain parenchymal activity. Application of fMRI in auditory research, however, has been limited. One problem is that fMRI utilizing echo-planar imaging technology (EPI) generates intense noise that could potentially affect the results of auditory experiments. Also, issues relating to the reliability of fMRI for listeners with normal hearing need to be resolved before this technique can be used to study listeners with hearing loss. This preliminary study examines the feasibility of using fMRI in auditory research by performing a simple set of experiments to test the reliability of scanning parameters that use a high resolution and high signal-to-noise ratio unlike that presently reported in the literature. We used consonant-vowel (CV) speech stimuli to investigate whether or not we could observe reproducible and consistent changes in cortical blood flow in listeners during a single scanning session, across more than one scanning session, and in more than one listener. In addition, we wanted to determine if there were differences between CV speech and nonspeech complex stimuli across listeners. Our study shows reproducibility within and across listeners for CV speech stimuli. Results were reproducible for CV speech stimuli within fMRI scanning sessions for 5 out of 9 listeners and were reproducible for 6 out of 8 listeners across fMRI scanning sessions. Results of nonspeech complex stimuli across listeners showed activity in 4 out of 9 individuals tested.

Fit Vs Faint: Assessing Work Causation in “Idiopathic Fall” Cases

2014 ◽  
Vol 19 (5) ◽  
pp. 3-12
Author(s):  
Lorne Direnfeld ◽  
David B. Torrey ◽  
Jim Black ◽  
LuAnn Haley ◽  
Christopher R. Brigham
Keyword(s):  
Blood Flow ◽  
Electrical Activity ◽  
Loss Of Consciousness ◽  
Brain Electrical Activity ◽  
Medical Terminology ◽  
Scientific Analysis ◽  
Medical Causation ◽  
The Individual ◽  
The Brain ◽  
Current Science

Abstract When an individual falls due to a nonwork-related episode of dizziness, hits their head and sustains injury, do workers’ compensation laws consider such injuries to be compensable? Bearing in mind that each state makes its own laws, the answer depends on what caused the loss of consciousness, and the second asks specifically what happened in the fall that caused the injury? The first question speaks to medical causation, which applies scientific analysis to determine the cause of the problem. The second question addresses legal causation: Under what factual circumstances are injuries of this type potentially covered under the law? Much nuance attends this analysis. The authors discuss idiopathic falls, which in this context means “unique to the individual” as opposed to “of unknown cause,” which is the familiar medical terminology. The article presents three detailed case studies that describe falls that had their genesis in episodes of loss of consciousness, followed by analyses by lawyer or judge authors who address the issue of compensability, including three scenarios from Arizona, California, and Pennsylvania. A medical (scientific) analysis must be thorough and must determine the facts regarding the fall and what occurred: Was the fall due to a fit (eg, a seizure with loss of consciousness attributable to anormal brain electrical activity) or a faint (eg, loss of consciousness attributable to a decrease in blood flow to the brain? The evaluator should be able to fully explain the basis for the conclusions, including references to current science.

Sign in / Sign up

Export Citation Format

Share Document