Fisiologia CoronariaDr 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
Isquemia Coronaria
Factores que determina flujo sanguineo miocardico
• Sano• Enfermo
Vasos Coronarios
Grandes Vasos Conduccion
Pequeños 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
externalelastic 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 TranscelularAnatomia 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 α subunit (Gα). The activated α
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 TranscelularAnatomia y Fisiologia Coronaria
Receptor B Estimula Gs → ↑AMPc
Receptor muscarinico Activa Gi → ↓AMPc
Vasopresina Activa fosfolipasa C → ↑IP3 : ↑Ca
→ ↑DAG: Activa PKCApertura canales ionicos, contraccion o
relajacion musculo liso, actividad secretora, division celular
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011
EndotelioAnatomia y Fisiologia Coronaria
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011
Factores Relajantes EndotelioAnatomia 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,
1990The production of endothelium-derived
vasodilator substances.
Factores Relajantes EndotelioAnatomia 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 GMPcCausan relajacion de musculo liso e
inhiben la agregacion plaquetariaEdward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011
Factores Relajantes EndotelioAnatomia 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 EndotelioAnatomia 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 gene–related peptide; ET, endothelin; NA, norepinephrine; PAF, platelet-activating factor; SP, substance P; VIP, vasoactive intestinal polypeptide; VP, vasopressin.
Factores Constrictores EndotelioAnatomia y Fisiologia Coronaria
Prostaglandina H2Tromboxano 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 EndotelioAnatomia 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 EndotelioAnatomia 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 CoronarioAnatomia y Fisiologia Coronaria
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011
PP y Compresion MiocardicaDeterminantes 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 PFZDeterminantes 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 MiocardicoDeterminantes 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 - HormonalDeterminantes 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 ParasimpaticoDeterminantes 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
↓MvO2
Control NeuralDeterminantes del Flujo Coronario
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011
Dilatacion Beta adrenergica Pequeños y grandes vasos B1 y B2
• B1 predomina en vasos de conductancia• B2 en vasos de resistencia
Constriccion Alfa adrenergica
Control HumoralDeterminantes del Flujo Coronario
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011
VasopresinaPeptido natriuretico auricularPeptido intestinal vasoactivoNeuropeptido YPeptido relacionado con el gen de la
CalcitoninaPGI2
TxA2
Relacion Presion-Flujo CoronariaFisiologia 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 CoronariaFisiologia 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 CoronariaFisiologia 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 acompaña de incremento marcado en el flujo coronario
5 a 6 veces el flujo en reposo• Hiperemia reactiva
Reserva CoronariaFisiologia 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 TransmuralFisiologia 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
10%-20%
Flujo Sanguineo TransmuralFisiologia 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 pressuredependent 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 TransmuralFisiologia 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
AteroesclerosisPAtofisiologia
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
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Evaluacion US IntravascularAteroesclerosis
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 PlacaPatofisiologia del Flujo Coronario
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011
Mayor estenosis, mayor riesgo? mayor oclusion?
Estenosis Coronaria Ruptura PlacaPatofisiologia del Flujo Coronario
Circulation 1988, 78:1157-1166
Our study indicates that thelesion 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.
HemodinamiaFlujo 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.
75%
HemodinamiaFlujo Coronario - Estenosis Coronaria
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011
Estenosis CriticaFlujo 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 SignificativaFlujo 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 CoronariasFlujo Coronario - Estenosis Coronaria
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011
En el corazon humano sano son pequeñas y tienen poco o ningun rol funcional.
En pacientes con EAC pueden prevenir la muerte – IAM Variabilidad interespecies
Patogenesis Isquemia MiocardicaFlujo Coronario - Estenosis Coronaria
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011
Isquemia: Deprivacion de oxigeno acompañado por
remocion inadecuada de metabolitos consecuente a perfusion reducida.
- Miocardica: Disminucion del radio aporte/demanda (A/D)
con alteracion de la funcion
Determinante A/DFlujo 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/DFlujo 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. MVO2Flujo 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 isquemiaIndice presion-tiempo diastolico/presion
tiempo sistolico Estima perfusion subendocardica
PAM/FC Correlaciona con isquemia miocardica
Estenosis DinamicaFlujo 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 CoronarioFlujo 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 presión) es disminuido por vasodilatacion en un lecho vascular paralelo Ambos lechos usualmente son distales a la
estenosis
Raul Fernando Vasquez
HemodinamiaFlujo Coronario - Estenosis Coronaria
Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011
Equation relating stenosis geometry to hemodynamic. where ΔP 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 π 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 ρ 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).