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

Company Logo

www.themegallery.com

Company Logo

www.themegallery.com

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).