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Fisiologia Coronaria

Dr Raul Fernando Vasquez


Enfermedad Coronaria
Cuando se manejan pacientes con
enfermedad coronaria el anestesiologo
debe
Prevenir
Minimizar


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Factores que determina flujo
sanguineo miocardico
Sano
Enfermo
Vasos Coronarios
Grandes Vasos
Conduccion
Pequeos vasos de
resistencia
Venas
Angiografia coronaria 10-250 um de diametro
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Anatomia y Fisiologia
En condiciones de
reposos cerca de
45% a 50% de la
resistencia vascular
coronaria total reside
en vasos mayores
de 100 um de
diametro
Pared Arterial Normal
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Anatomia y Fisiologia Coronaria
Endotelio - intima - lamina elastica interna media
lamina elastica externa adventicia vasa
vasorum
Normal human coronary artery of a 32-
year-old woman. The intima (i) and
media (m) are composed of smooth
muscle cells. The adventitia (a) consists
of a loose collection of adipocytes,
fibroblasts, vasa vasorum, and nerves.
The media is separated from the intima
by the internal elastic lamina (open
arrow) and the adventitia by the external
elastic lamina (closed arrow). (Movat's
pentachrome-stained slide, original
magnification, 6.6.)
Pared Arterial Normal
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Anatomia y Fisiologia Coronaria
Intima
Tradicionalmente considerada la capa mas
importante de la pared arterial
Endotelio sencillo neointima
Radio intima/media 0.1 a 1
Dos capas distintas
Interna: proteoglicanos, musculo liso aislado,
macrofagos
Externa o musculoelastica: musculo liso y fibras
elasticas
Pared Arterial Normal
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Anatomia y Fisiologia Coronaria
Media
Varias subpoblaciones especiales
Homeostasis pared arterial
Relajacion constriccion


Adventicia
Fibroblastos, microvasos, nervios y unas
pocas celulas inflamatorias

Comunicacion Transcelular
Anatomia y Fisiologia Coronaria

Brown AM, Birnbaumer L: Ionic
channels and their regulation by G-
protein subunits. Annu Rev Physiol
52:197, 1990
Steps in the process whereby hormone-receptor binding results in a change in
cell behavior. In this example, the final result is the opening of an ion channel.
A, A hormone or ligand (L) binds to a receptor (R) embedded in the cell
membrane. The receptor-ligand complex interacts with G protein (G) floating
in the membrane, resulting in activation of the subunit (G). The activated
subunit can then follow different pathways (B). Effector enzymes in the
membrane (E), such as adenylyl cyclase, cyclic guanosine monophosphate
(cGMP), phospholipase C, or phospholipase A2, change the cytoplasmic
concentration of their messengers: cyclic adenosine monophosphate
(cAMP), cGMP, diacylglycerol (DAG), and inositol 1,4,5-triphosphate (IP3).
These soluble molecules activate protein kinase A or C (PKA or PKC), or
release Ca++ from sarcoplasmic reticulum (SR). Subsequently, cell behavior
is changed by phosphorylation of an ionic channel on the cell membrane
(CHAN) or by release of Ca++ from SR. B, Several pathways coupling
receptor activation to final effect are illustrated. It is likely that multiple
pathways are activated concomitantly, both facilitatory and inhibitory. In this
way, the final response can be determined by the sum of the effects of several
stimuli.
Comunicacion Transcelular
Anatomia y Fisiologia Coronaria
Receptor B
Estimula Gs AMPc
Receptor muscarinico
Activa Gi AMPc
Vasopresina
Activa fosfolipasa C IP3 : Ca
DAG: Activa PKC
Apertura canales ionicos, contraccion o
relajacion musculo liso, actividad
secretora, division celular
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Endotelio
Anatomia y Fisiologia Coronaria

Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Factores Relajantes Endotelio
Anatomia y Fisiologia Coronaria

Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Rubanyi GM: Endothelium, platelets, and
coronary vasospasm. Coron Artery Dis 1:645,
1990
The production of endothelium-derived
vasodilator substances.
Factores Relajantes Endotelio
Anatomia y Fisiologia Coronaria
PGI2
Primera substancia endotelial vasoactiva
descubierta
NO
Molecula no prostanoide lipofilica
Vida media menor de 5 segundos
Se une con el grupo heme de guanilato
ciclasa aumentando 50 a 200 veces GMPc
Causan relajacion de musculo liso e
inhiben la agregacion plaquetaria

Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Factores Relajantes Endotelio
Anatomia y Fisiologia Coronaria
NO
Controla antetodo tono vascular en venas y
arterias. No asi en arteriolas
Ejercicio dilatacion microcirculacion flujo
coronario epicardico tension en la pared NO
flujo vasos de conductancia
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Factores Relajantes Endotelio
Anatomia y Fisiologia Coronaria

Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Role of endothelium in the control of coronary tone.
Intact endothelium has an important modulatory role in the
effect of numerous factors on vascular smooth muscle. In
the absence of a functional endothelium (mechanical
trauma, atherosclerosis), many factors act directly on
smooth muscle to cause constriction (left). Under normal
conditions (right), the release of nitric oxide (NO;
endothelium-derived relaxing factor [EDRF]) and
prostacyclin (PGI2) stimulated by these same factors can
attenuate constriction or cause dilation. PGI2 release is
predominantly into the lumen, whereas EDRF release is
similar on both the luminal and abluminal sides. Substances
in parentheses elicit only vasodilation. 5-HT, serotonin; A,
adenosine; ACh, acetylcholine; ADP, adenosine
monophosphate; AII, angiotensin II; ATP, adenosine
triphosphate; Bk, bradykinin; CGRP, calcitonin generelated
peptide; ET, endothelin; NA, norepinephrine; PAF, platelet-
activating factor; SP, substance P; VIP, vasoactive intestinal
polypeptide; VP, vasopressin.
Factores Constrictores Endotelio
Anatomia y Fisiologia Coronaria
Prostaglandina H2
Tromboxano A2 (via ciclooxigenasa=
Peptido endotelina
100 veces mas potente que NE
Tres clases relacionadas de 21 a.a
Endotelina-1 (ET-1), ET-2, y ET-3.

Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Endothelin (ET) released
abluminally interacts with
ETA and ETB receptors on
vascular smooth muscle to
cause contraction.
Activators of ETB receptors
on endothelial cells cause
vasodilation. cAMP, cyclic
Adenosine monophosphate
cGMP, cyclic guanosine
monophosphate; ECE,
endothelin-converting
enzyme; NO, nitric oxide;
PGI2, prostacyclin.
Inhibicion Plaquetaria X Endotelio
Anatomia y Fisiologia Coronaria
La funcion primaria del endotelio es
mantener la fluidez sanguinea
Sintesis y liberacion
Anticoagulantes (trombomodulina, proteina C)
Fibrinoliticos (activador tisular plasminogeno)
Inhibidores plaquetarios (PGI, NO)
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Inhibicion Plaquetaria X Endotelio
Anatomia y Fisiologia Coronaria

Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Inhibition of platelet adhesion and
aggregation by intact endothelium.
Aggregating platelets release adenosine
diphosphate (ADP) and serotonin (5-HT),
which stimulate the synthesis and release
of prostacyclin (PGI2) and endothelium-
derived relaxing factor (EDRF; nitric oxide
[NO]), which diffuse back to the platelets
and inhibit further adhesion and
aggregation, and can cause
disaggregation. PGI2 and EDRF act
synergistically by increasing platelet cyclic
adenosine monophosphate (cAMP) and
cyclic guanosine monophosphate
(cGMP), respectively. By inhibiting
platelets and also increasing blood flow
by causing vasodilation, PGI2 and EDRF
can flush away microthrombi and prevent
thrombosis of intact vessels. P2y,
purinergic receptor.
Determinantes del Flujo Coronario
Anatomia y Fisiologia Coronaria
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

PP y Compresion Miocardica
Determinantes del Flujo Coronario PP: Presion de Perfusion
El flujo sanguineo es
proporcional al gradiente de
presion a traves de la
circulacion coronaria
Presion coronaria
(downstream) presion en la
raiz de la aorta
Compresion extravascular
sistole, 10%-25% Resistencia
Mayor en subendocardio
Con presion sanguinea, FC,
contractilidad y precarga


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Presion de Cierre Critico PFZ
Determinantes del Flujo Coronario


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Presion a la cual el flujo coronario se
detiene
Excede por mucho la presion a nivel del seno
coronario
Discutida


Metabolismo Miocardico
Determinantes del Flujo Coronario


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

El flujo sanguineo esta apareado con los
requerimientos metabolicos
Tension de oxigeno venoso coronario es 15 a
20mmHg
MvO2 solo puede ocurrir si se aumenta la
entrega aumentando el flujo sanguineo
coronario



Control Neural - Hormonal
Determinantes del Flujo Coronario


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Neural
Dificil cuantificar debido a que la actividad
simpatica parasimpatica causa cambios en
PA, FC y contractilidad
Inervacion coronaria



Simpatico Parasimpatico
Terminaciones neurales a nivel de
musculo liso
Arterias y venas
Ganglio simpatico sup, med, inf y
los primeros 4 ganglios toracicos
Terminaciones neurales en la
adventicia de vasos coronarios
Arterias y venas
Nervio vago X PC
Control Parasimpatico
Determinantes del Flujo Coronario Control Neural


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Estimulo vagal
Bradicardia
Contractilidad
Presion sanguinea



Vasoconstriccion Coronaria
Mediada por metabolismo

Control Neural
Determinantes del Flujo Coronario


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Dilatacion Beta adrenergica
Pequeos y grandes vasos
B1 y B2
B1 predomina en vasos de conductancia
B2 en vasos de resistencia


Constriccion Alfa adrenergica

Control Humoral
Determinantes del Flujo Coronario


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Vasopresina
Peptido natriuretico auricular
Peptido intestinal vasoactivo
Neuropeptido Y
Peptido relacionado con el gen de la
Calcitonina
PGI2
TxA2
Relacion Presion-Flujo Coronaria
Fisiologia Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Autoregulacion PAM 60 140 mmHg
Flujo constante a pesar de cambios en
presion de perfusion arterial
Autoregulation at two levels of myocardial oxygen
consumption. Pressure in the cannulated left
circumflex artery was varied independently of aortic
pressure. When pressures were suddenly increased or
decreased from 40 mm Hg, flow instantaneously
increased with pressure (steep line, green triangles).
With time, flow decreases to the steady-state level
determined by oxygen consumption (purple and red
circles). The vertical distance from the steady-state
(autoregulating) line to the instantaneous pressure-flow
line is the autoregulatory flow reserve.
Relacion Presion-Flujo Coronaria
Fisiologia Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Autoregulacion PAM 60 140 mmHg
Tres teorias
Hipotesis de presion tisular
Cambios en PP altera permeabilidad capilar llevando a
resistencia extravascular que se opone a cambios flujo
Teoria miogenica
El musculo liso se contrae en respuesta al aumento de la
presion intraluminal
Teoria metabolica
Balance de aporte y consumo de O2
Reserva Coronaria
Fisiologia Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Isquemia coronaria causa vasodilatacion
intensa
Despues de 10 30 segundos de oclusion
restauramiento presion de perfusion se
acompaa de incremento marcado en el flujo
coronario
5 a 6 veces el flujo en reposo
Hiperemia reactiva
Reserva Coronaria
Fisiologia Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

No hay sobrepago de la deuda de oxigeno
ya que la tasa de extraccion declina
durante la hiperemia
La diferencia entre el flujo sanguineo
coronario en reposo y el flujo pico durante
la hiperemia reactiva representa el flujo de
reserva autoregulatorio
Capacidad del lecho arteriolar para dilatarse
en respuesta a la isquemia
Flujo Sanguineo Transmural
Fisiologia Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Distribucion transmural de consumo de oxigeno, uso de
substancias oxidables, actividad de enzimas glicoliticas
y mitocondriales, contenido endogeno de sustratos,
fosfatos de alta energia, lactato, isoformas de proteinas
contractiles y estres y acortmaiento de fibra cardiaca
Flujo Sanguineo Transmural
Fisiologia Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011


Pressure-flow relations of the
subepicardial and
subendocardial thirds of the
left ventricle in anesthetized
dogs. In the subendocardium,
autoregulation is exhausted
and flow becomes pressure
dependent when pressure
distal to a stenosis declines to
less than 70 mm Hg. In the
subepicardium,autoregulation
persists until perfusion
pressure declines to less than
40 mm Hg. Autoregulatory
coronary reserve is less in the
subendocardium.
Normal subendocardial/subepicardial
or inner/outer (I/O) blood flow ratio is 1.10
Flujo Sanguineo Transmural
Fisiologia Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Tres mecanismos se han propuesto para
explicar la reserva coronaria en el
subendocardio
Presion sistolica intramiocardica diferencial
Presion diastolica intramiocardica diferencial
Interaccion sistole - diastole
Ateroesclerosis
PAtofisiologia


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011


Atherosclerotic human coronary
artery of an 80-yearold
man. There is severe narrowing
of the central arterial lumen (L).
The intima consists of a
complex collection of cells,
extracellular matrix (M), and a
necrotic core with cholesterol
(C) deposits. Rupture of plaque
microvessels has resulted in
intraplaque hemorrhage (arrow)
at the base of the necrotic core

Company Logo
www.themegallery.com

Company Logo
www.themegallery.com
Evaluacion US Intravascular
Ateroesclerosis


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Angiografia coronaria estandar
Representacion bidimensional del lumen
Enfermedad coronaria
Invasion luminal
Remodelacion
Estenosis Coronaria Ruptura Placa
Patofisiologia del Flujo Coronario


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011







Mayor estenosis, mayor riesgo? mayor
oclusion?

Estenosis Coronaria Ruptura Placa
Patofisiologia del Flujo Coronario


Circulation 1988, 78:1157-1166
Our study indicates that the
lesion that will be the site of
the thrombotic occlusion
frequently is not severe when
evaluated by coronary
angiography weeks to years
before the infarct in patients
with mild-to-modern artery
disease; thus, coronary
angiography was not able to
accurately predict the time or
subsequent myocardial
infarction.
Hemodinamia
Flujo Coronario - Estenosis Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011





Sources of energy loss across a stenosis. Equations that (accurately) predict the pressure gradient
across a stenosis usually ignore entrance effects. Frictional losses are proportional to blood velocity but
are usually not important except in very long stenoses. Separation losses, caused by turbulence as blood
exits the stenosis, increase with the square of blood velocity and account for more than 75% of energy loss.
F, friction coefficient (Poiseuille); S, separation coefficient; V, blood velocity.
Hemodinamia
Flujo Coronario - Estenosis Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011





Estenosis Critica
Flujo Coronario - Estenosis Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Constriccion coronaria suficiente para
prevenir un incremento en el flujo sobre
los valores en reposo en respuesta a
aumento en la demanda de oxigeno
miocardico
Bloqueo de la respuesta hiperemia reactiva

Estenosis Significativa
Flujo Coronario - Estenosis Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Angiograficamente se define como
reduccion en area transversa de 75% lo
cual equivale a una disminucion del 50%
en el diametro de una lesion concentrica
Colaterales Coronarias
Flujo Coronario - Estenosis Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

En el corazon humano sano son
pequeas y tienen poco o ningun rol
funcional.
En pacientes con EAC pueden prevenir la
muerte IAM
Variabilidad interespecies
Patogenesis Isquemia Miocardica
Flujo Coronario - Estenosis Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Isquemia:
Deprivacion de oxigeno acompaado por
remocion inadecuada de metabolitos
consecuente a perfusion reducida.
- Miocardica:
Disminucion del radio aporte/demanda (A/D)
con alteracion de la funcion
Determinante A/D
Flujo Coronario - Estenosis Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011


Relative importance of variables
that determine myocardial oxygen
consumption (Mvo2). Each line
roughly approximates the effect of
manipulating one variable without
changing the others. Most
interventions cause changes in
several of the variables at the
same time. The importance of
contractility, which is difficult to
monitor in practice, is apparent.
Determinante A/D
Flujo Coronario - Estenosis Coronaria. PFDVI Presion de fin de diastole VI


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

FC
Acorta diastole
PA o PFDVI
Presion de perfusion coronaria
Isquemia
Retarda relajacion ventricular (tiempo de
perfusion subendocardica) y compliance
diastolica (PFDVI)
Indices A/D Miocardica. MVO2
Flujo Coronario - Estenosis Coronaria. PFDVI Presion de fin de diastole VI


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Doble producto FCxPAS
mmHg segundo por latido/100gr
Buen estimador de MVO2 pero no
correlaciona bien en isquemia
Indice presion-tiempo diastolico/presion
tiempo sistolico
Estima perfusion subendocardica
PAM/FC
Correlaciona con isquemia miocardica


Estenosis Dinamica
Flujo Coronario - Estenosis Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

EAC tolerancia variable al ejercicio en el
dia y entre dias
Excentrica 74%
Un acortamiento modesto del musculo en la
region compliante del vaso puede causar
cambios dramaticos en el calibre del lumen
Robo Coronario
Flujo Coronario - Estenosis Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

Ocurre cuando la presion de perfusion de
un lecho vascular vasodilatado (flujo
dependiente de presin) es disminuido por
vasodilatacion en un lecho vascular
paralelo
Ambos lechos usualmente son distales a la
estenosis

Raul Fernando Vasquez
Hemodinamia
Flujo Coronario - Estenosis Coronaria


Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011





Equation relating stenosis geometry to
hemodynamic. where P is the pressure
decline across the stenosis, Q is the volume flow
of blood, f is a factor counting for frictional
effects, and s accounts for separation effects.

Based on the Poiseuille law for laminar flow:
where is the blood viscosity, L is stenosis
length, An is the cross-sectional area of the
normal vessel, and As is the cross- sectional
area of the stenosis.


The separation or turbulence factor is:
where is blood density, and k is an
experimentally determined coefficient. Thus,
frictional losses are directly proportional to the
first power of stenosis length but are inversely
proportional to the square of the area (or fourth
power of diameter).