Dr Raul Fernando Vasquez

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1 Dr Raul Fernando Vasquez
Fisiologia Coronaria Dr Raul Fernando Vasquez

2 Factores que determina flujo sanguineo miocardico
Enfermedad Coronaria Cuando se manejan pacientes con enfermedad coronaria el anestesiologo debe Prevenir Minimizar Isquemia Coronaria Factores que determina flujo sanguineo miocardico Sano Enfermo Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

3 Grandes Vasos Conduccion Pequeños vasos de resistencia
Vasos Coronarios Anatomia y Fisiologia Grandes Vasos Conduccion Pequeños vasos de resistencia Venas Angiografia coronaria um de diametro En condiciones de reposos cerca de 45% a 50% de la resistencia vascular coronaria total reside en vasos mayores de 100 um de diametro One of the early changes in CAD is a diminished ability of the endothelium of epicardial coronary arteries to dilate in response to increased flow Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

4 Pared Arterial Normal Anatomia y Fisiologia Coronaria 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.) One of the early changes in CAD is a diminished ability of the endothelium of epicardial coronary arteries to dilate in response to increased flow Endotelio - intima - lamina elastica interna – media – lamina elastica externa – adventicia – vasa vasorum Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

5 Pared Arterial Normal Intima
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 more complex structure of an endothelium overlying a patchwork of extracellular matrix and vascular smooth muscle cells Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

6 Pared Arterial Normal Media Adventicia
Anatomia y Fisiologia Coronaria Media Varias subpoblaciones especiales Homeostasis pared arterial Relajacion – constriccion Adventicia Fibroblastos, microvasos, nervios y unas pocas celulas inflamatorias the role of the adventitia as not only a source of inflammatory cells in the development of atherosclerosis, but a hub for paracrine signaling that can maintain vascular homeostasis in a variety of vascular diseases. Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

7 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 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.

8 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

9 Endotelio Anatomia y Fisiologia Coronaria Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

10 Factores Relajantes Endotelio
Anatomia y Fisiologia Coronaria Prostacyclin (PGI2) is produced via the cyclooxygenase pathway of arachidonic acid (AA) metabolism, which can be blocked by indomethacin (Indo) and aspirin. PGI2 stimulates smooth muscle adenylyl cyclase and increases cyclic adenosine monophosphate (cAMP) production, which cause relaxation. Endothelium-derived relaxing factor (EDRF), now known to be nitric oxide (NO), is produced by the action of NO synthase on l-arginine in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH), oxygen (O2), and calcium and calmodulin. This process can be blocked by arginine analogs like NGmonomethyl- l-arginine (l-NMMA). NO combines with guanylate cyclase in the smooth muscle cell to stimulate production of cyclic guanosine monophosphate (cGMP), which results in relaxation. Less well characterized is an endothelium-derived factor, which hyperpolarizes the smooth muscle membrane (EDHF) and probably acts via activation of potassium (K+) channels. 5-HT, serotonin; ACh, acetylcholine; ADP, adenosine diphosphate; M, muscarinic receptor; P, purinergic receptor; T, thrombin receptor. PGI2 cause relaxation of the underlying smooth muscle or to inhibit platelet aggregation Rubanyi GM: Endothelium, platelets, and coronary vasospasm. Coron Artery Dis 1:645, 1990 The production of endothelium-derived vasodilator substances. Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

11 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 PGI2 cause relaxation of the underlying smooth muscle or to inhibit platelet aggregation Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

12 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

13 Factores Relajantes Endotelio
Anatomia y Fisiologia Coronaria 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. Both epoxyeicosatrienoic acid (a metabolite of cytochrome P450) and H2O2 have been suggested as possible endothelium-derived hyperpolarizing factors (EDHFs). Smooth muscle relaxation is a result of hyperpolarization of the myocyte, which leads to decreased intracellular calcium concentration. EDHF-mediated vasodilation can be blocked by inhibition of calcium-dependent potassium channels. EDHF may have an important vasodilator role in the human coronary microcirculation.24 Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

14 Factores Constrictores Endotelio
Anatomia y Fisiologia Coronaria 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. 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. Both epoxyeicosatrienoic acid (a metabolite of cytochrome P450) and H2O2 have been suggested as possible endothelium-derived hyperpolarizing factors (EDHFs). Smooth muscle relaxation is a result of hyperpolarization of the myocyte, which leads to decreased intracellular calcium concentration. EDHF-mediated vasodilation can be blocked by inhibition of calcium-dependent potassium channels. EDHF may have an important vasodilator role in the human coronary microcirculation.24 Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

15 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) Both epoxyeicosatrienoic acid (a metabolite of cytochrome P450) and H2O2 have been suggested as possible endothelium-derived hyperpolarizing factors (EDHFs). Smooth muscle relaxation is a result of hyperpolarization of the myocyte, which leads to decreased intracellular calcium concentration. EDHF-mediated vasodilation can be blocked by inhibition of calcium-dependent potassium channels. EDHF may have an important vasodilator role in the human coronary microcirculation.24 Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

16 Inhibicion Plaquetaria X Endotelio
Anatomia y Fisiologia Coronaria 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. Both epoxyeicosatrienoic acid (a metabolite of cytochrome P450) and H2O2 have been suggested as possible endothelium-derived hyperpolarizing factors (EDHFs). Smooth muscle relaxation is a result of hyperpolarization of the myocyte, which leads to decreased intracellular calcium concentration. EDHF-mediated vasodilation can be blocked by inhibition of calcium-dependent potassium channels. EDHF may have an important vasodilator role in the human coronary microcirculation.24 Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

17 Determinantes del Flujo Coronario
Anatomia y Fisiologia Coronaria Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

18 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 Blood flow in the left and right coronary arteries. The right ventricle is perfused throughout the cardiac cycle. Flow to the left ventricle is largely confined to diastole In pathologic conditions associated with pulmonary hypertension, right coronary flow assumes a phasic pattern similar to left coronary flow. Under normal conditions, extravascular compression contributes only a small component (10% to 25%) to total coronary vascular resistance. Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

19 Presion de Cierre Critico PFZ
Determinantes del Flujo Coronario Presion a la cual el flujo coronario se detiene Excede por mucho la presion a nivel del seno coronario Discutida Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

20 Metabolismo Miocardico
Determinantes del Flujo Coronario 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 Feigl43 has proposed six criteria for a chemical transmitter between the cardiac myocyte and the coronary vascular smooth muscle cell: 1. The transmitter is released under appropriate conditions and can be recovered from the tissue under those conditions. 2. Transmitter substance infused into the target tissue should faithfully mimic physiologic activation. 3. The biochemical apparatus for production of the proposed transmitter is present in the tissue in an appropriate location. 4. A mechanism for inactivation and/or uptake of the transmitter is present at an appropriate location in the tissue. 5. The action of various inhibitors and blocking agents on synthesis, release, target-organ receptor function, or transmitter inactivation should have effects consistent with the hypothesis. Blocking agents should give the same effect whether the transmitter is released physiologically or artificially applied. 6. Quantitative studies should indicate that the amount and time course of transmitter release under physiologic conditions are appropriate to give the indicated effect. Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

21 Control Neural - Hormonal
Determinantes del Flujo Coronario 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 Nervio vago X PC Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

22 Control Parasimpatico
Determinantes del Flujo Coronario Control Neural Estimulo vagal Bradicardia ↓Contractilidad ↓Presion sanguinea Vasoconstriccion Coronaria Mediada por metabolismo ↓MvO2 Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

23 Dilatacion Beta adrenergica
Control Neural Determinantes del Flujo Coronario Dilatacion Beta adrenergica Pequeños y grandes vasos B1 y B2 B1 predomina en vasos de conductancia B2 en vasos de resistencia Constriccion Alfa adrenergica Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

24 Peptido natriuretico auricular Peptido intestinal vasoactivo
Control Humoral Determinantes del Flujo Coronario Vasopresina Peptido natriuretico auricular Peptido intestinal vasoactivo Neuropeptido Y Peptido relacionado con el gen de la Calcitonina PGI2 TxA2 Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

25 Relacion Presion-Flujo Coronaria
Fisiologia Coronaria 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. myocardial contractility and metabolism increase when coronary pressure is increased to more than the normal autoperfused level. This phenomenon is known as the Gregg effect and may be explained by the “garden hose” hypothesis of Lochner, whereby engorgement of the coronary vasculature elongates the myocardial sarcomere length during diastole and contractile strength is increased because of the Frank–Starling mechanism Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

26 Relacion Presion-Flujo Coronaria
Fisiologia Coronaria 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 myocardial contractility and metabolism increase when coronary pressure is increased to more than the normal autoperfused level. This phenomenon is known as the Gregg effect and may be explained by the “garden hose” hypothesis of Lochner, whereby engorgement of the coronary vasculature elongates the myocardial sarcomere length during diastole and contractile strength is increased because of the Frank–Starling mechanism Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

27 Isquemia coronaria causa vasodilatacion intensa
Reserva Coronaria Fisiologia Coronaria 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 Schematic diagram of the reactive hyperemic response to a 10-second coronary occlusion. (From Marcus ML: Metabolic regulation of coronary blood flow. In Marcus ML [ed]: The coronary circulation in health and disease. New York: McGraw-Hill, 1983, pp 65–92. Reproduced by permission of McGraw-Hill Companies.) Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

28 Reserva Coronaria Fisiologia Coronaria 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 Schematic diagram of the reactive hyperemic response to a 10-second coronary occlusion. (From Marcus ML: Metabolic regulation of coronary blood flow. In Marcus ML [ed]: The coronary circulation in health and disease. New York: McGraw-Hill, 1983, pp 65–92. Reproduced by permission of McGraw-Hill Companies.) Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

29 Flujo Sanguineo Transmural
Fisiologia Coronaria 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 Cuando la presion de pesfusion coronaria es inadecuada 1/3 a ¼ a de la pared ventricular interna izquierda es la primera region en hacerse isquemica - necrotica 10%-20% Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

30 Flujo Sanguineo Transmural
Fisiologia Coronaria 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 Subendocardial blood flow is found using this technique to be about 10% greater than subepicardial blood flow under normal circumstances. This gives a normal subendocardial/subepicardial or inner/ outer (I/O) blood flow ratio of This ratio is maintained at normal perfusing pressures even at heart rates greater than 200 beats/min. If coronary pressure is gradually reduced, autoregulation is exhausted and flow decreases in the inner layers of the left ventricle before it begins to decrease in the outer layers (Figure 6-11). This indicates that there is less flow reserve in the subendocardium than in the subepicardium. In conscious dogs, the mean coronary pressure at which evidence of subendocardial ischemia appeared was 38 mm Hg at a heart rate of 100 beats/min, and increased to 61 mm Hg at 200 beats/min. Subepicardial flow during tachycardia did not decline even at pressures as low as 33 mm Hg.126 Because subepicardial flow is rarely inadequate, a subendocardial/subepicardial blood flow ratio close to 1.0 indicates adequate subendocardial flow and an appropriate matching of myocardial oxygen supply to oxygen demand. For this reason, the I/O ratio is often used as a measure of the adequacy of myocardial blood flow. Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

31 Flujo Sanguineo Transmural
Fisiologia Coronaria Tres mecanismos se han propuesto para explicar la reserva coronaria en el subendocardio Presion sistolica intramiocardica diferencial Presion diastolica intramiocardica diferencial Interaccion sistole - diastole Because the force of systolic myocardial compression is greatest in the inner layers of the ventricle and is low at the subepicardium, it was believed that the outer layers of the heart were perfused throughout the cardiac cycle, whereas the subendocardium was perfused only during diastole. The subendocardium would have to obtain its entire flow during only a portion of the cycle and, therefore, would have to have a lower resistance. Recent studies, suggesting that there may be little systolic flow even to the outer layers, argue against this explanation.127 The second mechanism is based on the high coronary pressures observed when coronary flow has ceased during a long diastole, Pzf (see Perfusion Pressure and Myocardial Compression earlier in this chapter).39 The shape of the pressure-flow relation during a long diastole suggests that Pzf is higher in the subendocardium. This would mean that perfusion pressure for the subendocardium is lower in diastole compared with the outer layers of myocardium. Available evidence suggests that Pzf is not high in any layer and is unlikely to be more than 2 to 3 mm Hg greater in the subendocardium than in the subepicardium.127 Hoffman109,127 proposed an interaction between systole and diastole as the explanation for the increased vulnerability of the subendocardium to ischemia. During systole, intramyocardial pressure is high enough throughout most of the ventricular wall to squeeze blood out of the intramural vessels and into the extramural coronary veins and arteries. Because the compressive force is greatest in the subendocardium, vessels here are the narrowest at end systole. At the beginning of diastole, blood will be directed first to vessels with the lowest resistance, the larger vessels in the subepicardium, and last to the most narrowed vessels in the subendocardium. In this way, should the duration of diastole or the diastolic perfusion pressure be reduced, the subendocardial muscle would receive the least flow. Spaan36 presents an interesting analysis of the interaction between arterial pressure and force of contraction as an intramyocardial pump. Although this theory is compatible with existing evidence, support for it will remain indirect until it becomes possible to measure phasic pressures and flows in separate layers of myocardium. Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

32 Atherosclerotic human coronary artery of an 80-yearold
Ateroesclerosis PAtofisiologia 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 Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

33 The dominant cell type in atherosclerotic lesions is the smooth muscle
The dominant cell type in atherosclerotic lesions is the smooth muscle cell, and as lesions progress, the number of smooth muscle cells in the artery wall tends to increase. Company Logo

34 Company Logo

35 Evaluacion US Intravascular
Ateroesclerosis Angiografia coronaria estandar Representacion bidimensional del lumen Enfermedad coronaria Invasion luminal Remodelacion IVUS images demonstrate remarkable fidelity to cross-sectional histologic specimens and permit accurate visualization and measurement Arterial remodeling with significant intimal hyperplasia but relatively intact lumen diameter can thus identify occult disease not otherwise appreciated on standard angiography. However, IVUS is not limited to simply documenting and quantifying atherosclerotic burden. Plaque composition also can be assessed qualitatively and classified based on acoustic impedance, allowing differentiation among fibromuscular “soft” lesions, dense “fibrous” lesions, and “calcified” hyperechoic lesions Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

36 Estenosis Coronaria Ruptura Placa
Patofisiologia del Flujo Coronario Mayor estenosis, mayor riesgo? mayor oclusion? Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

37 Estenosis Coronaria Ruptura Placa
Patofisiologia del Flujo Coronario 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. 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 angiogra able to accurately predict the time or lo subsequent myocardial infarction. Circulation 1988, 78:

38 Hemodinamia Flujo Coronario - Estenosis Coronaria 75% 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. Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

39 Hemodinamia Thus, the amount of energy loss or
Flujo Coronario - Estenosis Coronaria Thus, the amount of energy loss or pressure decline across the obstruction increases exponentially as flow rate increases. For this reason, exercise, anemia, and arteriolar vasodilator drugs (e.g., dipyridamole) are poorly tolerated in the presence of a severe stenosis. Figure 6-17 illustrates that, although resting flow is unaffected until coronary diameter is reduced by more than 80%, maximal flow begins to decline when diameter is reduced by 50%. Effect of increasing stenosis severity at resting and maximal coronary flows. At rest, lumen diameter must be reduced by more than 80% before flow decreases (green line). Because pressure drop across a stenosis increases exponentially with blood velocity, maximal coronary flow is restricted by a 50% diameter reduction ( purple line). (From Gould KL, Lipscomb K: Effect of coronary stenoses on coronary flow reserve and resistance. Am J Cardiol 34:48, 1974.) Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

40 Estenosis Critica Flujo Coronario - Estenosis Coronaria 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 Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

41 Estenosis Significativa
Flujo Coronario - Estenosis Coronaria 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 Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

42 Colaterales Coronarias
Flujo Coronario - Estenosis Coronaria 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 Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

43 Patogenesis Isquemia Miocardica
Flujo Coronario - Estenosis Coronaria 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 Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

44 Determinante A/D Flujo Coronario - Estenosis Coronaria 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. An increase in heart rate can reduce subendocardial perfusion by shortening diastole. Coronary perfusion pressure may decline because of reduced systemic pressure or increased left ventricular end-diastolic pressure Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

45 Determinante A/D FC ↓PA o ↑PFDVI Isquemia Acorta diastole
Flujo Coronario - Estenosis Coronaria. PFDVI Presion de fin de diastole VI FC Acorta diastole ↓PA o ↑PFDVI ↓Presion de perfusion coronaria Isquemia Retarda relajacion ventricular (↓tiempo de perfusion subendocardica) y ↓compliance diastolica (↑PFDVI) An increase in heart rate can reduce subendocardial perfusion by shortening diastole. Coronary perfusion pressure may decline because of reduced systemic pressure or increased left ventricular end-diastolic pressure Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

46 Indices A/D Miocardica. MVO2
Flujo Coronario - Estenosis Coronaria. PFDVI Presion de fin de diastole VI 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 patient with a systolic pressure of 160 and heart rate of 70 has a much lower likelihood of ischemia than a patient with a pressure of 70 and rate of 160, although both have a rate-pressure product of 11,200. Three indices, proposed to predict the adequacy of subendocardial perfusion in normal dogs, illustrate the variables determining myocardial oxygen supply and demand. The systolic pressure-time index (SPTI) relates to oxygen demand. The diastolic pressure-time index (DPTI) relates to the supply of coronary blood flow (CBF) to the inner layers of the left ventricle. Arterial oxygen content (O2 content) is important when there are large changes in hematocrit. Ao, aortic pressure; ENDO, subendocardial layer of left ventricle; EPI, subepicardial layer of the left ventricle; LV, left ventricular pressure. (From Hoffman JIE, Buckberg GD: Transmural variations in myocardial perfusion. In Yu PN, Goodwin JF [eds]: Progress in cardiology. Philadelphia: Lea & Febiger, 1976, p 37.) Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

47 EAC tolerancia variable al ejercicio en el dia y entre dias
Estenosis Dinamica Flujo Coronario - Estenosis Coronaria 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 Drawings and incidence of the various types of structure of stenoses observed in human coronary artery specimens. In almost three quarters of vessels with greater than 50% narrowing, the residual arterial lumen was eccentric and partially circumscribed by an arc of normal arterial wall. In such lesions, a decline in intraluminal pressure or an increase in vasomotor tone can cause lumen diameter to decrease further and sufficiently to precipitate myocardial ischemia. (From Brown BG, Bolson EL, Dodge HT: Dynamic mechanisms in human coronary stenosis. Circulation 70:917, 1984; redrawn from Freudenberg H, Lichtlen PR: The normal wall segment in coronary stenoses-a postmortem study. Z Kardiol 70:863, 1981.) Although the term hardening of the arteries suggests rigid, narrowed vessels, in fact, most stenoses are eccentric and have a remaining arc of compliant tissue (Figure 6-20). A modest amount (10%) of shortening of the muscle in the compliant region of the vessel can cause dramatic changes in lumen caliber.209 This was part of Prinzmetal’s original proposal to explain coronary spasm. Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

48 Robo Coronario Flujo Coronario - Estenosis Coronaria 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 Collateral steal in which one vascular bed (R3), distal to an occluded vessel, is dependent on collateral flow from a vascular bed (R2) supplied by a stenotic artery is shown (see Fig 6-21A). Because collateral resistance is high, the R3 arterioles are dilated to maintain flow in the resting condition (autoregulation). Dilation of the R2 arterioles will increase flow across the stenosis, R1, and decrease pressure, P2. If R3 resistance cannot further decrease sufficiently, flow there will decline, producing or worsening ischemia in the collateral-dependent bed. The values of all the resistances, including collaterals, and the baseline myocardial metabolic state will determine how powerful the vasodilator stimulus must be to produce ischemia in the collateral bed. Failure to recognize this has confounded studies of vasodilator drugs. If collateral vessels are very well developed or Mvo2 is low, sufficient autoregulatory reserve may remain in the collateral-dependent bed to maintain adequate myocardial blood flow even with the administration of a moderately powerful vasodilator. Transmural steal is also illustrated (see Figure 6-21B). Normally, vasodilator reserve is less in the subendocardium (see Transmural Blood Flow section earlier in this chapter). In the presence of a stenosis, flow may become pressure dependent in the subendocardium, whereas autoregulation is maintained in the subepicardium. This is illustrated in Figure 6-11, where at a perfusion pressure of 50 mm Hg, flow has declined in the subendocardium, whereas the subepicardium retains autoregulatory reserve. Dilation of the subepicardial arterioles, R2, will then increase flow across the stenosis (R1) causing P2 to fall and resulting in decreased flow to the subendocardium as subepicardial flow increases. The term steal is most appropriate when the vasodilation is caused by a pharmacologic agent (adenosine, dipyridamole) producing “luxury” flow (beyond metabolic requirements) in the vascular bed with coronary reserve (R2). The same redistribution of blood flow also occurs during exercise in response to metabolically mediated vasodilation. The study of coronary steal demonstrates well the complex interrelations among the determinants of myocardial blood flow. Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011

49 Gracias ! Raul Fernando Vasquez

50 Hemodinamia Flujo Coronario - Estenosis Coronaria 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). Edward R.M. O'Brien. Coronary Physiology and Atherosclerosis. Kaplan Anesthesia 2011