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The Forgotten Driving Forces in Right Heart Failure: New Concept and Device

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Right heart failure is a frequent hemodynamic disturbance in pediatric cardiac patients. Besides inotropic and chronotropic drugs, fluid administration and inhaled nitric oxide, right ventricular mechanical assistance remains difficult to perform. A circulatory assist device adapted for the right heart biophysics and physiology might be more efficient. We are developing a prototype of a non-invasive cardiac assist device (CAD) for neonates and pediatrics. It is based on a pulsatile suit device covering and affecting all territories of the right heart circuit. It will be tested in a neonatal animal model of right ventricular (RV) failure. Experimental models will be matched and compared with control and sham groups. Expected results would be immediate hemodynamic improvement due to synchronized diastolic reduction of stagnant venous capacitance, increasing preload and contractility. On long term, increased shear stress with changing intrathoracic pressure in a phasic way would improve and remodel the pulmonary circulation. Future studies will be focused on: hemodynamic, biochemistry, endothelium function test, and angiogenesis. A non-invasive CAD guarantees better hemodynamics and endothelial function preservation with low morbidity and mortality. This is a physiological approach, cost-effective method, and particularly interesting in neonates and pediatrics with RV failure.
Shows 4 schematic figures (A,B,C and D) of the pulsatile suit cardiac assist device (CAD): (A), represents a whole figure of the pulsatile suit in 3 units compartments (jacket, belt and trouser), reassembled together and detailed as following: 1 ¼ Zipper and straps, are conceived to keep the suit tightly fit to the body. 2 ¼ Holes, to allow body access for medical management. 3 ¼ Security air release valve, to avoid over inflation accidents in case of mechanical failure. 4 ¼ Airport connectors, adapted to pneumatic rhythmic driving force. 5 ¼ Inner layer in direct contact with the skin, made of elastic material (e.g. neoprene). 6 ¼ Sandwiched, middle layer, contains gelatinous fluid, allowing mitigation of pulsed shocks, and facilitating impulses propagation. 7 ¼ Air receiving external space, connected directly to pneumatic driving force, through airports (4), and security valves (3), to allow air delivery inward-towards the body in safe manner. 8 ¼ Non-inflatable parts at the posterior parts of the suit to avoid spinal injury. (B) ¼ Represents the supra-diaphragmatic compartment of the suit, means a Jacket, composed of vest and 2 sleeves, that could be reassembled together through zippers and straps to fit the patient body tightly and securely to be used as circulatory as well as respiratory assist. (C) ¼ Trouser and waist Belt, representing the infra-diaphragmatic compartment of the suit. (D) ¼ Shows the 3 suit layers: (5–7) arranged inward-outward respectively, with air release security valve 3 attached to the external layer 7 .
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REVIEW PAPER
The Forgotten Driving Forces in Right Heart
Failure: New Concept and Device*
Sayed Nour
1
, Guifu Wu
2
, Zheng Zhensheng
2
, Juan C Chachques
1
,
Alain Carpentier
1
, Didier Payen
3
1
Laboratory of Biosurgical Research, Pompidou Hospital, University of Paris, France
2
Cardiovascular Research Center, The First Affiliated Hospital Sun Yat-sen University, Guangzhou, China
3
Department of Anesthesiology, Critical Care and SAMU, Lariboisiere Hospital, Paris, France
ABSTRACT
Background: Right heart failure is a frequent hemodynamic disturbance in pediatric
cardiac patients. Besides inotropic and chronotropic drugs, fluid administration and
inhaled nitric oxide, right ventricular mechanical assistance remains difficult to
perform. A circulatory assist device adapted for the right heart biophysics and
physiology might be more efficient. Materials and Methods: We are developing a
prototype of a non-invasive cardiac assist device (CAD) for neonates and pediatrics.
It is based on a pulsatile suit device covering and affecting all territories of the right
heart circuit. It will be tested in a neonatal animal model of right ventricular (RV)
failure. Experimental models will be matched and compared with control and sham
groups. Expected results would be immediate hemodynamic improvement due to
synchronized diastolic reduction of stagnant venous capacitance, increasing preload
and contractility. On long term, increased shear stress with changing intrathoracic
pressure in a phasic way would improve and remodel the pulmonary circulation.
Future studies will be focused on: hemodynamic, biochemistry, endothelium function
test, and angiogenesis. Comments: A non-invasive CAD guarantees better hemody-
namics and endothelial function preservation with low morbidity and mortality. This is
a physiological approach, cost-effective method, and particularly interesting in
neonates and pediatrics with RV failure.
(Asian Cardiovasc Thorac Ann 2009;17:525–30)
KEYWORDS:Pulsatile suit, Right heart failure, Shear stress, Pediatric circulatory
assist device
INTRODUCTION
Pressurized flow and shear rates are two constant endo-
thelial stimulants that continue to regulate the closed
hydraulic cardiovascular circuit since intrauterine life.
1
Our heart and peristaltic arteries represent the main
circulatory driving forces, otherwise accessory forces are
necessary to move up the steady blood flow at the right
heart side.
2
Surprisingly the right heart could adjust blood
volume and shear rates at 5 different anatomical
zones according to its physiological demands.
In antenatal period, the right heart receives and
pumps in equal rates more volume than the left,
but keeps low remodeling due to pressure release
through physiological shunts.
3
After birth and shunts
closure, both right and left ventricles share equal
volume and rate inducing equal pulmonary and
systemic cardiac output (CO), but remodeling
remains inferior at the right heart side most probably
due to venous steady flow and ventricular wall
trabeculae.
Sayed Nour Tel: þ0033140907615 Fax: þ0033145405049 E-mail: nourmd@mac.com
Laboratory of Biosurgical Research, 96 rue Didot, 75014 Paris, France.
*This paper was presented at the 4th International Cardiac Bio-Assist Association Congress, 12–13 March 2008, Singapore.
doi: 10.1177/0218492309348638
ßSAGE Publications 2009 Los Angeles, London, New Delhi and Singapore
2009, VOL. 17, NO.5 ASIAN CARDIOVASCULAR &THORACIC ANNALS
525
According to Guyton concept,
4,5
the venous side blood
volume can be considered containing two volumes; first
the ‘‘unstressed volume’’ that fills the venous circuit
without generation of driving flow forces; second, the
stress volume that is mobilizing blood towards the right
ventricle. Change in partition between these 2 compo-
nents is physiologically obtained by sympathetic over-
flow or by fluid loading.
6
The consequence of this
partition modification is a change in right heart filling
and performance. According to the net effect, this may
improve physical performance in healthy persons or
cardiac congestion with nitrates in cardiac failure.
Although professional scuba divers and astronauts are
subjected to totally opposite superficial surrounding
pressures, they share almost the same circulatory
disorders.
7,8
This may result from a trend to reduce the
driving pressure for venous blood, since forward and
backward pressures tend to equalize.
9
In general right ventricular (RV) hemodynamic dis-
orders could be improved by intravenous fluids and
chronotropic and inotropic drugs with or without pace-
maker.
10
This improvement has potential negative
impact such as right side congestion (liver and kidney
congestion) and/or reduced right ventricle coronary
perfusion during pacing.
Conversely to adult context, right heart failure occurs
more frequently in pediatric patients with more endothe-
lium dysfunction than atherosclerosis.
11
As a conse-
quence, left heart cardiac assist devices as intra-aortic
balloon pump cannot be efficient because of the large
vessel compliance in pediatric patients.
The aim of this work is to develop a non-invasive cardiac
assist device (CAD) to improve or replace accessory dri-
ving forces, adjust the requested volume and rates in each
zone of the right heart circuit in regular synchronized
pulsations. Leading to a better hemodynamic as well as
remodeling specially in the very young populations.
CONCEPT AND DEVICE
Understanding volume and rate interdependency mech-
anism is the main concept of this study for building up
the best device adapted to the right heart physiology and
biophysics. As shown in (Table 1) and (Figure 1) we
could distinguish 5 different anatomical zones:
Zone1: low remodeling systemic venous zone, where
blood is driven from extremities helped by the afore-
mentioned accessory driving forces in a low pressure,
steady stream flow.
Zone 2: mild remodeling atrio-ventricular cavity zone,
where the tangential frictions wall stress is induced by
contractions are tamed and alleviated by trabeculae in
order to keep the right ventricular mass almost the 1/6
th
of the left one.
12
Zone 3: normal remodeling zone, represented by the
interventricular septum.
13
Zone 4: high remodeling infudibular zone.
Zone 5: low remodeling zone of the pulmonary arterial
tributaries, with low resistance and pressure as shear
forces are already alleviated due to trabeculae, rotation
and squeezing axis of the RV, infudibulum, the pulmo-
nary artery compliance capacity, competent valves and
less developed Valsalva.
Device design: A 3 layers, pulsatile suit composed of
detachable parts: a. trouser, b. waist belt, c. chest jacket.
The three parts will be reassembled together in one unit
and wrapped tightly around the patient body through
straps and zippers, as shown in (Figure 2) and as patent
descriptions (WO/2008/000111).
The suit would be connected to a generator of rhythmic
driving force, through specific connectors. Regular
pulsations would be obtained via a currently used
pneumatic driving forces, or a specific either pneumatic
or low voltage-electric system.
The suit must be suitable for the postoperative situations
and provided with security features as following:
1. Inner layer made of elastic material (e.g. neoprene)
to insure smooth tight massage like pulsed surge at
the baby’s delicate skin.
2. Middle sandwiched layer filled with gelatinous
fluid, to alleviate the vigorous inflation/deflation,
power induced by the driving force.
3. External layer made from tougher materials to keep
the pulsed wave inwards toward the body. This part
is equipped by security air releasing valve to prevent
over inflation accident in case of mechanic defect.
4. Holes are previewed in the suit body, in order to
facilitate medical administrations and prevent
bedsores.
5. Layers thickness and design are modified according
to age, body weight and indication of the patient.
6. The back portion of the trunk part of the suit (vest
and belt) must not be inflatable in order to avoid any
spinal, or back injuries.
7. Blood must be pulsed back from periphery towards
the heart in a sloping progressive wave in longitu-
dinal axis. Except at the chest part, pulsations must
be started backward - forward towards the front, in a
horizontal axis in such a manner to increase venous
return within respect of the respiratory movement.
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8. Device manipulation including pulse rate, inflation
volume ...etc must be adapted to each clinical
situations to insure a harmonic, homogenous venous
return waveform, in continuity with each part.
9. The chest jacket and sleeves must be synchronized
together in a manner to avoid respiratory distress or
vascular incidents at the armpit, e.g. thrombosis,
edema.
10. Each suit component has its own inflation/deflation
control security valve. This allows different pres-
sure application according to different parts of the
delicate pediatric body.
Models: a neonatal animal model of right ventricular
(RV) failure. Future studies will be focused on: hemo-
dynamic, biochemistry, endothelium function test, and
angiogenesis. Experimental models will be matched and
compared with control and sham groups.
Patients: The suit could be applied in clinical trials, in
patients with chronic RV failure after right heart bypass
operations as secured non-invasive device.
Expected results: would be immediate hemodynamic
improvement due to synchronized diastolic reduction of
stagnant venous capacitance, increasing RV preload and
contractility. On long term increased shear stress with
changing intrathoracic pressure in a phasic way would
improve and remodel the pulmonary circulation.
DISCUSSION
The pulsatile suit could assist or replace some of the
troubled accessory driving forces and factors (Table 2),
that affect the right heart circuit.
14
A tight elastic suit
driven by regular external synchronized pulsations could
induce a continuous harmonic compressive waveform
movement over the body. This blood movement is
obtained by squeezing stagnant venous capacitance
which is usually accumulated at the superficial venous
- lymphatic vessels and visceral area in infants. The
consequence for right heart would be a better filling
inducing a better function to push blood towards
pulmonary circulation. In addition, this principle could
increase vascular shear stress in pulmonary circulation
which has been described as an important controller of
the downstream vascular resistances.
15
The potential effect of the device on the different defined
anatomical zones can be viewed as follows (Table 3):
Increased volume in zone ‘‘1’’ induces venous circuit
hemodynamic disorders with a venous congestion,
reduction of such a congestion is a major goal for
treatment. To achieve it, one can use diuretics, increase
in venous capacitance by nitrates and improve in right
ventricular pumping by inotropic-chronotropic drugs.
This strategy may have side effects such as a non
adapted reduction of preload, increase myocardial
oxygen consumption related to tachycardia, and arterial
blood pressure fall.
The proposed device would improve the mobilization of
the venous congestive blood towards the pulmonary
Z1
Z2
Z5
Z4
Z3
Figure 1. Represents the 5 different remodeling zones of the
right heart circuit as following: Zone 1 (Z1) represents the
superior vena cava (SVC) and inferior vena cava (IVC) low
remodeling zone. Zone 2 (Z2) represents a mild
remodeling zone of the right atrio-ventricular cavity (A-V
cavity). Zone 3 (Z3) represents a normal remodeling
interventricular septum zone. Zone 4 (Z4) represents high
remodeling infundibular zone. Zone 5 (Z5) represents a
pulmonary artery low remodeling zone.
Table 1. Right heart postnatal remodeling zones
Zones Anatomical site Remodeling Main Factors
Z1 SVC, IVC Low Accessory Driving forces !Steady flow
Z2 A-V cavity Mild Trabeculae
Z3 Septum Normal
Z4 Infundibulum High "Coronary supply
Z5 PA tributary Low #Pressure, Pulmonary Valve þInfundibulum
Z¼zone, SVC ¼superior vena cava, IVC ¼inferior vena cava, A-V ¼atrio-ventricular cavity; RV ¼right
ventricle; PA ¼pulmonary artery.
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circulation synchronized or not with the right heart
rhythm, in a more physiological way. It keeps the
optimal preload, does not increase the heart rate, and
reduced the venous congestion.
In addition, for the zone 2 and 3 for which the diastole is
essential, the device may help to oxygenate the
trabeculated crypts and the ventricular septum coronary
circulation particularly in complex congenital heart
disease.
20
In zone 4 and 5, both volume and rate
are needed to keep pulmonary resistance as low as
possible in acute situation. A sustained better volume
put the pulmonary circulation in a condition of
remodeling. If such a remodeling is over efficient in
absence of endothelial function, it might induce pulmo-
nary vascular hypertrophy leading at maximum to an
Eisenmenger syndrome.
16
The proposed device might
overcome such inconvenience by decreasing pulmonary
afterload through endogenous nitric oxide process and
enhancement of ventricular mass remodeling, particu-
larly in patients of sub-acute and chronic pulmonary
hypertension.
AB
C
D
6
37
5
8
1
247
5
1
82
1
4
(1)
(3)
(4)
(2)
Figure 2. Shows 4 schematic figures (A,B,C and D) of the pulsatile suit cardiac assist device (CAD): (A), represents a whole
figure of the pulsatile suit in 3 units compartments (jacket, belt and trouser), reassembled together and detailed as following: 1
¼Zipper and straps, are conceived to keep the suit tightly fit to the body. 2 ¼Holes, to allow body access for medical
management. 3 ¼Security air release valve, to avoid over inflation accidents in case of mechanical failure. 4 ¼Airport
connectors, adapted to pneumatic rhythmic driving force. 5 ¼Inner layer in direct contact with the skin, made of elastic
material (e.g. neoprene). 6 ¼Sandwiched, middle layer, contains gelatinous fluid, allowing mitigation of pulsed shocks, and
facilitating impulses propagation. 7 ¼Air receiving external space, connected directly to pneumatic driving force, through
airports (4), and security valves (3), to allow air delivery inward-towards the body in safe manner. 8 ¼Non-inflatable parts at
the posterior parts of the suit to avoid spinal injury. (B)¼Represents the supra-diaphragmatic compartment of the suit,
means a Jacket, composed of vest and 2 sleeves, that could be reassembled together through zippers and straps to fit the
patient body tightly and securely to be used as circulatory as well as respiratory assist. (C)¼Trouser and waist Belt,
representing the infra-diaphragmatic compartment of the suit. (D)¼Shows the 3 suit layers: (5–7) arranged inward-outward
respectively, with air release security valve
3
attached to the external layer
7
.
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The previous systems used for management circulatory
disorders such as anti-G suit
17
cannot be used in pediatric
context. Cardiomyoplasty as bioassist device,
18
which was used in RV failure by increasing shearing
rate only in volume dependent zone 2 and 3, might not be
efficient for right heart bypassed patients. The other
devices (Table 4), such as enhanced external counter-
pulsation (EECP)
19
are mostly indicated and usable for
adults and do not fit well with pediatric patients. They
induce strong and vigorous compression forces on deep
arteries and on thoracic cage, which may have side
effects in the pediatric patients.
Concerning clinical application of this concept
and device, it is important to remark that this is the
first described ‘‘non-invasive cardiac assist device’’
for neonates and pediatrics. It will be equipped with
security features facilitating clinical use, e.g.: in cases
of failed Fontan procedure with no issues except heart
transplant.
It is important to consider the right heart compliance in
physiological conditions (represented by Z1 in our
concept). Since the right heart circuit contains almost
64% of blood volume, i.e. venous compliance is 10–20
times greater than systemic arterial compliance, there-
fore the right heart represents a compliant chamber and a
good candidate for positive remodeling.
21
A decreased
pulmonary vascular resistance is the mean target in any
case of right heart hemodynamic disturbances, which is
shear stress-mediated endothelial nitric oxide synthesis
(NOS) dependent. Clinically in acute RV failure, the
improvement of hemodynamics with chronotropic drugs
or pacemaker is directly related to increased pulmonary
shear rates. Except our proposed pulsate suit, nothing is
currently available for the chronic phase of RV failure
management.
Proven clinical evidences show that the RV is a preload
dependent ventricle, necessitating both systolic and
diastolic phases for its oxygenation. RV is seriously
jeopardized in cases of decreased venous return, for this
reason is highly recommended to avoid nitrates in RV
ischemia. Recently it was shown improved Norwood’s
operation results with the Sano’s shunt, due to increased
RV diastolic filling. Maintained RV volume by IV fluids
Table 3. Pulsatile suit expected beneficial patients groups
Zones Mechanism Patients groups*
Z1 #venous capacitance, "shear rates RV bypass, Fontan operation,
Orthostatic intolerance syndrome,
ED syndrome, Divers, Astronauts, ...
Z2 "Preload, "shear rates, "angiogenesis TOF, Norwood
Z3 "Preload, "angiogenesis RV coronary dependent
Z4 #afterload, "angiogenesis RVPA transannular patch
Z5 #afterload, "angiogenesis Acute, chronic PHT
*Symbolic Categories, Z ¼zone, RV: right ventricle, TOF: Tetralogy of Fallot, RVPA: right ventricle-
pulmonary artery; PHT: pulmonary hypertension, ED: erectile dysfunction.
Table 4. Pneumatic Circulatory Assist Devices
Device Functions Patent n
Pneumatic Vest Cardiopulmonary resuscitation WO 96/28129
1
Pneumatic Vest Respiratory assist US6676614B1
2
Pulsatile cuffs Circulatory assist US19970955421
3
1
Mark G, George GK, Henry H. Improved vest design for cardiopulmonary resuscitation system.
University Johns Hopkins (US), Card Systems INC (US). 1996-09-19.
2
Craig H, Lonnie H. Vest for
body pulsating method and apparatus. Electromed INC (US); 2004-01-13.
3
Zhensheng Zh, Zhili H,
Shifang Y. High efficiency external counterpulsation apparatus and method for controlling same.
Vasomedical INC (US) 1999-12-07.
Table 2. Postnatal accessory driving forces and factors
Venous driving pump
Muscle pump
Thoracic pump (Respiratory muscles, Diaphragm)
Gravity
Atmospheric pressure
Pericardium
Venous valves
Oncotic pressure
Skin Baroreceptors
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is mandatory in cases of RV failure. Otherwise it is true
that vigorous abrupt squeezing forces could deteriorate
the overloaded RV, for this reason the device is
equipped with security features, as been detailed, to
insure sloping smooth regularly synchronized pulsed
waves at the level of the superficial venous system.
We believe that this concept is a cornerstone approach in
RH failure management. Currently we are testing
prototypes in neonate piglet’s models with acute pul-
monary hypertension (Z5) and acute RV failure (Z2).
Future studies will include application of this concept in
chronic or sub-acute phase of right heart failure models,
which are usually affecting (Z1).
CONCLUSION
A pulsatile suit is a physiological, non invasive thera-
peutic method to manipulate the right heart side natural
blood reservoir containing almost 64% the total blood
volume and endothelium stores. Such a reservoir serves
as a physiological therapeutic backup in case of
hemodynamic disturbances and circulatory disorders
particularly in pediatrics.
ACKNOWLEDGEMENTS
We would like to express our gratitude to the following
Doctors: Claude Planche, MD, Yves Lecarpentier, MD,
Guy Mazmmanian, MD, Pierre Chastanier, MD, Daniel
Carbognani, MD, Gerard Dine, MD, from Paris
(France), and Marc Deleval, MD from London (UK).
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... Right ventricular (RV) failure is an endothelial dysfunction disease caused by disturbed flow dynamics due to pump failure and/or elevated pulmonary vascular resistance. 1 Clinically, RV failure in an acute or acute-on-chronic presentation may predispose to hemodynamic shock and multiple organ failure, with high mortality. 2 Current strategies for management of RV failure can be summarized as based on three principles: reduction of afterload with pulmonary vasodilators, increasing preload with intravenous fluids, and increasing contractility with chronotropic drugs or a pacemaker. ...
... Alternatively, following our previous study, we have investigated a pulsatile suit for therapy in an acute RV failure animal model. 1 In this study, a prototype of pulsatile trousers and belt was tested in piglets with acute RV failure, and the results were compared to those of a control group managed with traditional pharmacological therapies. The expected hemodynamic improvement should occur due to shear stress-mediated enhancement of endothelial function, stimulated by trouser pulsations on the stagnant infradiaphragmatic venous capacitance. ...
... As described previously, the pulsatile suit is a noninvasive CAD composed of three layered compartments: an inner elastic layer (neoprene), an intermediate layer that contains gelatinous fluid (glycerin), and an external air chamber layer connected to a pneumatic rhythmic generator. 1 The suit is designed to cover a portion of the human body, and the therapist (doctor, nurse, or even patient) can put in place without effort. The suit may be connected directly to an external pump, as shown in Figure 1A. ...
Full-text available
Article
Background: Cardiac-assist devices for right ventricular failure remain controversial with poor results. This study evaluated a pulsatile cardiac-assist device in an acute right ventricular failure model vs. current therapies. Materials and methods: Pulmonary regurgitation was created in 12 piglets by valve avulsion and external transfixation of 2 pulmonary artery cusps suspended to the pulmonary arterial wall. The piglets were divided into 2 treatment groups: a pulsatile group P and a non-pulsatile group NP. Management started when severe right ventricular failure was observed (48.1 ± 24.5 min). In group P, pulsatile trousers driven by a pneumatic generator were pulsated intermittently at 40 beats min(-1). Group NP was treated with oral tadalafil 1 mg kg(-1), intravenous fluids, and adrenaline 0.3 μg kg(-1). After 1 h of therapy, cardiac output was significantly better in group P than group NP (1 ± 0.2 vs. 0.7 ± 0.2 L min(-1)). Mean right ventricular pressure (16 ± 6 vs. 24 ± 2 mm Hg) and pulmonary arterial pressure (22 ± 1 vs. 31 ± 2 mm Hg) were lower in group P. Vascular resistances indices were lower in group P than group NP: pulmonary resistance index was 174 ± 60 vs. 352 ± 118 dyne sec cm(-5)kg(-1); systemic resistance index was 611 ± 70 vs. 1215 ± 315 dyne sec cm(-5)kg(-1). Western-blot analysis showed higher endogenous NO synthase expression in group P pulmonary arteries. Conclusions: The pulsatile suit can be used safely as a noninvasive cardiac-assist device in acute right ventricular failure. This represents a cost-effective nearly physiological method, suitable for adults and children.
... It squeezes the pulmonary parenchyma in an accordion-like manner, to release plenty of endothelial mediators to drop the pulmonary vascular resistances (PVR), to improve hemodynamics as well as tissue oxygenation with first breath after birth. By controlling the pulmonary afterload, the respiratory pump controls RV preload and cardiac output (Frank-Starling law), helped with other influential forces, like the muscle pumps, gravity, and atmospheric pressure [10]. Functionally, the respiratory pump can redress hemodynamics and remedy the side effects of endothelial dysfunction caused by conventional circulatory assist devices (CAD), which may explain long-term survival of continuous flow artificial-hearts transplants [11]. ...
... Fig. 1Biophysics of cardiopulmonary circulatory driving forces. I Right-heart circuit main remodeling zones: Z1, systemic veins; Z2, right ventricle; Z3, septum; Z4, infundibulum; Z5, pulmonary artery[10]. II Respiratory pump, a low-pressure, momentarily hydraulic circuit that compresses two types of fluids: Newtonian (air) and non-Newtonian (blood), in an accordion-like manner, creating ESS. ...
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Most critically ill Covid-19 patients succumb to multiple organ failure and/or sudden cardiac arrest (SCA) as a result of comorbid endothelial dysfunction disorders which had probably aggravated by conventional mechanical assist devices. Even worse, mechanical ventilators prevent the respiratory pump from performing its crucial function as a potential generator of endothelial shear stress (ESS) which controls microcirculation and hemodynamics since birth. The purpose of this work is to bring our experience with ESS enhancement and pulmonary vascular resistance (PVR) management as a potential therapeutic solution in acute respiratory distress syndrome (ARDS). We propose a non-invasive device composed of thoracic and infradiaphragmatic compartments that will be pulsated in an alternating frequency (20/40 bpm) with low-pressure pneumatic generator (0.1–0.5 bar). Oxygen supply, nasogastric with, or without endotracheal tubes are considered.
... It squeezes the pulmonary parenchyma in an accordion-like manner, releasing plenty of endothelial mediators to drop the pulmonary vascular resistances (PVR), to improve hemodynamic as well as tissue oxygenation with first breath after birth. By controlling the pulmonary afterload, the respiratory pump controls RV preload and cardiac output (Frank-Starling law), helped with other influential forces like the muscle pumps, gravity, atmospheric pressure… [6]. ...
... It squeezes the pulmonary parenchyma in an accordionlike manner, releasing plenty of endothelial mediators to drop the pulmonary vascular resistance (PVR), to improve hemodynamics as well as tissue oxygenation with first breath after birth. By controlling the pulmonary afterload, the respiratory pump controls RV preload and cardiac output (Frank-Starling law), helped with other influential forces like the muscle pumps, gravity, atmospheric pressure [6]. ...
... It squeezes the pulmonary parenchyma in an accordionlike manner, releasing plenty of endothelial mediators to drop the pulmonary vascular resistance (PVR), to improve hemodynamics as well as tissue oxygenation with first breath after birth. By controlling the pulmonary afterload, the respiratory pump controls RV preload and cardiac output (Frank-Starling law), helped with other influential forces like the muscle pumps, gravity, atmospheric pressure [6]. ...
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Reviewing the Covid-19 literature over the past six months we can identify pervasive endothelial dysfunction disorders, whether in the form of comorbid conditions e.g. arterial hypertension, mediated by pathogens, e.g., thromboembolic syndrome and/or iatrogenic due to inadequate therapies, e.g., ventilators, vasopressors. The conclusion is unless you are young and slim and Caucasian, we cannot cure you! Indeed, it is unacceptable in the twenty-first century to involve racial or ethnic assumptions in science without providing substantial evidence, especially in renowned journals. The question is, do we realize the extent of the psychological damage we are causing to individuals belonging to these ethnic minorities, to their wives, children, and friends? We aim through the present work to correct this erroneous thought, as well as to expose our visions concerning the management of Covid-19, which unfortunately became a politico-mediatic subject and remains without an effective solution.
... Pressurized flow and shear rates are two constant endothelial stimulants that continue to regulate the closed hydraulic cardiovascular circuit since intrauterine life [10] As shown in (Figure 1), the left ventricle (LV) and peristaltic arteries represent the main circulatory driving forces, at the left-heart side that contains less than 10% of blood volume [11], otherwise accessory forces are necessary to move up the massif volume (≥70%) of steady blood flow at the right-heart side such as the gravitational effect, the respiratory and muscle pumps [12], which become severely disturbed in bedridden ventilated patients. ...
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Rationale: Most critically ill Covid-19 patients succumb to multiple organ failure and / or cardiac arrest as a result of comorbid endothelial dysfunction disorders which had probably aggravated by conventional mechanical assist devices. Even worse, mechanical ventilators prevent the respiratory pump from performing its crucial function as a potential generator of endothelial shear stress (ESS) which controls microcirculation and hemodynamics since birth. The purpose of this work is to bring our experience with ESS enhancement and pulmonary vascular resistance (PVR) management as a potential therapeutic solution in acute respiratory distress syndrome (ARDS). We propose a noninvasive device composed of thoracic and infradiaphragmatic compartments that will be pulsated in an alternating frequency (20/40 bpm) with low-pressure pneumatic generator (0.1-0.5 bar). Oxygen supply, nasogastric ± endotracheal tubes are considered. Proof-of-concept: prototypes were tested in pediatric models of refractory cardiac arrest (≥20min), showed restoration of hemodynamics (BP≥100 mm Hg) and urine output, regardless of heartbeats, pharmacological supports and mechanical ventilation. Conclusions ESS enhancement represents a more effective treatment to increase tissue oxygenation and improve hemodynamic in ARDS. A cost-effective method which could be induced with a non-invasive pulsatile device adaptable to cardiopulmonary-circulatory biophysics to maintain a fully functional respiratory pump and avoid confrontation of the opposite hydraulic circuits.
... Contrarily to the left heart side, the right heart side can adjust blood volume and shear rates at five different anatomical zones according to its physiological demands [45]. The PA represents a low-level remodeling zone, similar to systemic veins. ...
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Cardiac assist devices (CAD) cause endothelial dysfunction with considerable morbidity. Employment of pulsatile CAD remains controversial due to inadequate perfusion curves and costs. Alternatively, we are proposing a new concept of pulsatile CAD based on a fundamental revision of the entire circulatory system in correspondence with the physiopathology and law of physics. It concerns a double lumen disposable tube device that could be adapted to conventional cardiopulmonary bypass (CPB) and/or CAD, for inducing a homogenous, downstream pulsatile perfusion mode with lower energy losses. In this study, the device's prototypes were tested in a simulated conventional pediatric CPB circuit for energy losses and as a left ventricular assist device (LVAD) in ischemic piglets model for endothelial shear stress (ESS) evaluations. In conclusion and according to the study results the pulsatile tube was successfully capable of transforming a conventional CPB and/or CAD steady flow into a pulsatile perfusion mode, with nearly physiologic pulse pressure and lower energy losses. This represents a cost-effective promising method with low mortality and morbidity, especially in fragile cardiac patients.
... In our study the intrapulmonary pulsatile catheter was applied successfully as a shear stress-mediated endothelial function enhancement device. For this application we have designed a small balloon catheter prototype to cope with diameters and types of wall vessels, particularly in a high compliant pulmonary artery zone [33]. The purpose of the pulsatile catheter prototype was to induce rapid shear rates at stagnant blood boundaries layers of the PA, according to the Bernoulli's principles of shear stress, and to avoid volume distension (pulse pressure) at the right heart circuit, according to Newton's law [34]. ...
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Ischemic heart disease (IHD) is a leading cause of mortality with insufficient results of current therapies, most probably due to maintained endothelial dysfunction conditions. Alternatively, we propose a new treatment that promotes endothelial shear stress (ESS) enhancement using an intrapulmonary pulsatile catheter. Twelve piglets, divided in equal groups of 6: pulsatile (P) and non-pulsatile (NP), underwent permanent left anterior descending coronary artery ligation through sternotomy. After 1h of ischemia and heparin injection (150IU/kg): in P group, a pulsatile catheter was introduced into the pulmonary trunk and pulsated intermittently over 1h, and irrespective of heart rate (110bpm). In NP group, nitrates were given (7±2mg/kg/min) for 1h. In P group all 6 animals survived ischemia for 120min, but in NP group only 2 animals survived. The 4 animals that died during the experiment in NP group survived for 93±14min. Hemodynamics and cardiac output (CO) were significantly improved in P group compared with NP group: CO was 0.92±0.15 vs. 0.52±0.08 in NP group (L/min; p<0.05), respectively. Vascular resistances (dynes.s.cm(-5)/kg) were significantly (p<0.05) lower in P group versus NP group: pulmonary resistance was 119±13 vs. 400±42 and systemic resistance was 319±43 vs. 1857±326, respectively. Myocardial apoptosis was significantly (p<0.01) lower in P group (0.66±0.07) vs. (4.18±0.27) in NP group. Myocardial endothelial NO synthase mRNA expression was significantly (p<0.01) greater in P group (0.90±0.09) vs. (0.25±0.04) in NP group. Intrapulmonary pulsatile catheter could improve hemodynamics and myocardial contractility in acute myocardial ischemia. This represents a cost-effective method, suitable for emergency setting as a first priority, regardless of classical coronary reperfusion.
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Introduction Sudden cardiac arrest (SCA) remains a major health issue worldwide with gloomy outcomes due to poor perfusion of cardiopulmonary resuscitation (CPR), deemed unsuitable for hemostatic conditions, cardiotorsal anatomy, electrophysiology and thoracic biomechanics. Alternatively, we propose a new management, implementing rational mobilization of stagnant blood: manually with a novel technique of cardiac massage and mechanically with a circulatory flow restoration (CFR) device. Methods Simulated chest compressions were performed through the 5th intercostal space in professional Lifeguards volunteers, placed in the left lateral decubitus position with raised legs and abdominal compression. Expected results Compared to CPR, bypassing the sternal barrier, refilling the heart and then compressing the chest with a recoil-rebound maneuver (3R / CPR) can significantly promote ROSC. Results of CFR device were previously demonstrated. Conclusion 3R/CPR adapts human morphology promoting adequate perfusion and ROSC safely, under all circumstances. Preclinical computational models can confirm the effectiveness of 3R/CPR versus CPR.
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The “Heart” is still considered as the main organ to be dealt with, in case ofcardiovascular disease. Nevertheless, the heart is not the only driving force in ourcirculatory system. In fact, the heart and blood vessels are the direct issues of theendothelium and depend on its function. Moreover, almost all current therapeuticstrategies are still focusing on the heart and neglecting the entire circulatoryendothelialsystem. For example, development of cardiac assist devices (CAD) is stillrestrained by the heart, designed to follow, obey and must be synchronized with adiseased organ.Many "signals" of different nature are capable of activating endothelial cells: the shearforces created by the blood flow parallel to the surface of the vessel wall, but alsoforces caused by stretching perpendicular to the artery wall by the cyclic pressuregradient and the quality of these forces. The activation of endothelial cells is due tothat pressurized flow dynamic forces, but also to the action of vasoactive substancesand inflammatory mediators.In this thesis we are proposing a new therapeutic approach, based on a fundamentalrevision of the entire systems: exposing those defects of current management ofcardiovascular diseases (CVD). A concept that focuses on flow dynamics to stimulate,restore and maintain endothelial function including the heart itself. This includespreliminary results of new generations of pulsatile CAD that promote endothelial shearstress (ESS) enhancement. Devices prototypes were tested.During this thesis, pulsatile devices prototypes were tested in vivo, in vitro as well aswith pre-clinical volunteers as follow:1. A pulsatile catheter prototype was tested in 2 pediatric animal models (piglets) of:acute myocardial ischemia; and acute pulmonary arterial hypertension.2. A pulstile tube prototype was tested in vitro (mock circuit) and in vivo (piglets) as aleft ventricular assist device (ongoing).3. Pulsatile suit prototypes were tested: in vivo (piglets) for acute right ventricularfailure treatment. Prototypes of pulsatile mask and trousers are currently in plannedfor pre-clinical studies.9Conclusion, Think endothelial instead of cardiac is our policy for better management ofCVD.
Chapter
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