Ca - Fapesp

MULTIDISCIPLINARY INVESTIGATION
AT THE CENTER FOR BIOMEDICAL
ENGINEERING OF UNICAMP
ROSANA A. BASSANI
Center for Biomedical Engineering (CEB)
University of Campinas (UNICAMP)
Campinas, SP, Brazil
[email protected]
Center for Biomedical Engineering (CEB/UNICAMP)
HUMAN RESOURCE
TRAINING
Technicians
Undegrad students
Graduate students
SUPPORT TO UNICAMP´S
HEALTH AREA
Medical Physics
CEB
UNICAMP
Radioprotection
Radiodiagnosis
Radiotherapy
Nuclear medicine
Clinical Engineering
RESEARCH AND
DEVELOPMENT
Basic investigation
Methods
Equipment
(Medical Technology)
Assessment
Specification
Maintenance
Management
INVESTIGATION IN CLINICAL ENGINEERING
METHODS FOR MEDICAL TECHNOLOGY MANAGEMENT
MEDICAL EQUIPMENT CLASSIFICATION
Oshiyama, Bassani, D´Ottaviano & Bassani. Medical equipment classification: method
and decision-making support based on paraconsistent annotated logic. Med Biol Eng
Comput 2012; 50:395-402.
(disbelief)
false
unknown
inconsistent
true
(belief)
INVESTIGATION IN CLINICAL ENGINEERING MANAGEMENT
GETS (Health Technology Management System): a web-based system to interconnect Clinical Engineering nuclei in hospitals in Brazil and other countries for
procedure standardization, information exchange and technical training.
CAISM
Information Central
CIEC
HD
HC
GETS
GETS
Intranet
HEMOT
Regional
NEC
MS/SUS
Agencies
P & D (IES)
Companies
NEC-CEB
(Clinical Engineering Nucleus)
Internet
Privilege
GETS
GETS
HD
Intranet
HD
Regional
Regional
NEC
HD
(Health Division)
HD
NEC
HD
HD: Health division
NEC: Clinical Engineering Nucleus
CIEC: Information Central
P&D: Research Institutions
RESEARCH AND DEVELOPMENT
Ultrasound-based Equipments for Diagnosis
and Therapy
Rehabilitation Engineering
Cardiac Physiology (Bioengineering)
Electrocardiogram (ECG) in the
gecko (Hemidactylus mabouia)
(Germer, Tomaz, Carvalho, Bassani & Bassani., J Comp Physiol, in press)
RESEARCH AND DEVELOPMENT
Microfluorimeters for measuring and imaging intracellular
calcium concentration
(Soriano, Bassani & Bassani, Braz J Biomed Engin, 2007)
(Zoccoler & Oliveira, unpublished)
RESEARCH AND DEVELOPMENT
Methods for tachyarrhythmia induction and analysis
of electrical propagation in isolated rat atria
20 M pinacidil
sinus rhythm
40
-200
-100
100
-100
Potential difference (µV)
200
Potential difference (µV)
Potential difference (µV)
100
-20
20
-40
Potential difference (µV)
TRANSLATIONAL RELEVANCE
APPLICATION: RESEARCH AND
PHARMACEUTICAL INDUSTRY
(Zafalon, Bassani & Bassani, J Mol Cell Cardiol 2004; Physiol Meas, 2009;
Zafalon, Oshiyama, Bassani & Bassani, J Mol Cell Cardiol, 2013)
RESEARCH AND DEVELOPMENT
Calcium Transport in Cardiac Cells
Membrane: ELECTRICAL EXCITATION
Myofibrils: CONTRACTION
EXCITATION
WAVE
CONTRACTION
(Candasamy et al., J Biol Chem, 2014)
RESEARCH AND DEVELOPMENT
Basic Investigation
Calcium Transport in Cardiac Cells during Postnatal Development
SARCOPLASMIC
RETICULUM (SR)
is major source
of Ca2+ for
contraction in the adult
electrical excitation
(Bers, Nature, 2002)
RESEARCH AND DEVELOPMENT
Calcium Transport in Cardiac Cells during Postnatal Development
NEONATAL
RAT
ADULT
RAT
Cardiac myocytes
20 m
transients
neonate
0.75
0.50
0.25
0.00
1.00
[Ca2+]i (M)
Ca2+
[Ca2+]i (M)
1.00
500 ms
adult
0.75
0.50
0.25
0.00
500 ms
Ca2+ fluxes
(Bassani & Bassani,
Am J Physiol, 2002)
RESEARCH AND DEVELOPMENT
Calcium Transport in Cardiac Cells during Postnatal Development
(Bassani & Bassani,
Am J Physiol, 2002)
Ca
Ca
Ca
Ca
SERCA
SERCA
DANGER!
X
Ca
Ca
T-Tubule
Ca
Ca
NCX
3Na
Ca
Ca
NCX
3Na
RESEARCH AND DEVELOPMENT
Calcium Transport in Cardiac Cells during Postnatal Development
1.25
neonate
1.25
(Bassani & Bassani, unpublished)
basal
30 nM ISO
0.75
1.00
[Ca2+]i (M)
-adrenoceptor stimulation
(e.g., adrenaline)
[Ca2+]i (M)
1.00
0.50
basal
30 nM ISO
0.75
0.50
0.25
0.25
0.00
0.00
adult
500 ms
500 ms
Catecholamines can RECRUIT the SR function in neonatal myocardium
Ca
Ca
Ca
Ca
SERCA
SERCA
Ca
Ca
Ca
Ca
Ca
Ca
NCX
NCX
3Na
3Na
RESEARCH AND DEVELOPMENT
Cardiac Electrical Stimulation
-
+
External electrical field (E)
RESEARCH AND DEVELOPMENT
Cardiac Electrical Stimulation: excitation and E orientation
6
20
Vmax (mV)
ET (V/cm)
5
4
3
2
1
p< 0.001
15
10
(Bassani, Lima, Gomes & Bassani,
Physiol Meas, 2006)
5
0
0
0
60
120
180
240
angle (degrees)
300
360
0
60
120
180
240
300
360
angle (degrees)
The extent of membrane
polarization depends on
the direction of the
electrical field
Cardiac Electrical Stimulation: excitation with multidirectional
E stimulation
Excitatory cell recruitment (%)
Greater efficiency!
100
***
80
60
40
20
0
1 direction
3 directions
(Fonseca, Bassani, Oliveira & Bassani, IEE Trans Biomed Engin, 2013)
Cardiac Defibrillation
Ventricular fibrillation (VF)
Cardiac arrest: 17 per 100,000 inhabitants,
only ~21% out-of-hospital survival
(Nolan et al, Resuscitation, 2010)
High-intensity electrical fields
Electrical Defibrillation
VF
+
Still, in out-of-hospital electrical defibrillation,
the first shock may fail in 50% of the cases
(Walker et al., Resuscitation, 2009)
Halliday, Resnick & Walker, 1997
Cardiac Defibrillation
DEFIBRILLATION: high E intensity may damage cell membrane
(ELECTROPORATION)
Sublethal E
~30 V/cm
0.9
[Ca2+]i ( M)
2+
[Ca ]i (M)
1.2
Lethal E
0.6
0.3
0.0
20x
1
10s
0
15 s
(Oliveira, Bassani & Bassani., Biophys J , 2005)
(Oliveira, Bassani & Bassani., EEE Trans Biomed Engin , 2008)
Cardiac Defibrillation
Cell damage depends on the electrical field orientation
Lethality (%)
100
LONGIT
TRANSV
75
50
25
12
5.
9
15
8.
5
19
9.
5
10
0
79
.4
63
.1
50
.1
39
.8
0
E (V/cm)
(Oliveira, Bassani & Bassani., IEEE Trans Biomed Engin , 2008)
Cardiac Defibrillation
RAPIDLY-SWITCHING MULTIDIRECTIONAL DEFIBRILLATOR
A
R
R
P
60 ms
Intl Patent: 1102055-5
(Viana, Bassani, Petrucci, Marques & Bassani,
J Cardiovasc Thor Surg , in press)
In vivo test in swine
R
P
Cardiac Defibrillation
6
1.00
0.75
*
0.50
0.25
1 direction
3 directions
0.00
Shock energy (J)
Probability of defibrillation
RAPIDLY-SWITCHING MULTIDIRECTIONAL DEFIBRILLATOR
5
3
2
1
3
1
2
3
4
5
energy (J)
6
1
3
1
3
1
0
0.50
0
*
*
4
*
0.75
0.90
probability of defibrillation
7
(Viana, Bassani, Petrucci, Marques & Bassani,
J Cardiovasc Thor Surg , in press)
MULTIDISCIPLINARY APPROACH:
- cell physiology
- mathematical modeling
- product development
- preclinical tests
Support
Thank you!
Fernando de Noronha
Brasil