CARDIOPATIA ISQUÉMICA

Figure 1. Participation of inflammation in all stages of atherosclerosis. A, Leukocyte recruitment to the nascent atherosclerotic lesion. Blood leukocytes adhere poorly to the
normal endothelium. When the endothelial monolayer becomes inflamed, it expresses adhesion molecules that bind cognate ligands on leukocytes. Selectins mediate a rolling, or
saltatory, interaction with the inflamed luminal endothelium. Integrins mediate firmer attachment. Proinflammatory cytokines expressed within atheroma provide a chemotactic
stimulus to the adherent leukocytes, directing their migration into the intima. Inflammatory mediators such as M-CSF can augment expression of macrophage scavenger receptors
leading to uptake of modified lipoprotein particles and formation of lipid-laden macrophages. M-CSF and other mediators produced in plaques can promote the replication of
macrophages within the intima as well. B, T lymphocytes join macrophages in the intima during lesion evolution. These leukocytes, as well as resident vascular wall cells, secrete
cytokines and growth factors that can promote the migration and proliferation of SMCs. Medial SMCs express specialized enzymes that can degrade the elastin and collagen in
response to inflammatory stimulation. This degradation of the arterial extracellular matrix permits the penetration of the SMCs through the elastic laminae and collagenous matrix
of the growing plaque. C, Ultimately, inflammatory mediators can inhibit collagen synthesis and evoke the expression of collagenases by foam cells within the intimal lesion. These
alterations in extracellular matrix metabolism thin the fibrous cap, rendering it weak and susceptible to rupture. Cross-talk between T lymphocytes and macrophages heightens the
expression of the potent procoagulant tissue factor. Thus, when the plaque ruptures, as shown here, the tissue factor induced by the inflammatory signaling triggers the thrombus

that causes most acute complications of atherosclerosis.

Libby P. y cols. (2002) Circulation 105: 1135

Endres M. (2006) Atheroscler Suppl. Apr. 7(1): 31-5
EICOSANOIDES Y TROMBOSIS

Gryglewski RJ (1980) TIPS 1: 164-6

The Effect of Aspirin Alone and of Ibuprofen plus Aspirin on Platelet Cyclooxygenase-1.
The platelet prostaglandin G/H synthase-1 (cyclooxygenase-1) is depicted as a dimer. The arachidonic acid substrate gains
access to the catalytic site (red area) through a hydrophobic channel that leads into the core of the enzyme (Panel A).
Aspirin blocks the access of arachidonic acid to the catalytic site by irreversibly acetylating a serine residue at position 529
in platelet cyclooxygenase-1, near but not within the catalytic site (Panel B). Interpolation of the bulky acetyl residue
prevents metabolism of arachidonic acid into the cyclic endoperoxides PGG2 and PGH2 for the lifetime of the platelet.
Because PGH2 is metabolized by thromboxane synthase into thromboxane A2, aspirin prevents the formation of
thromboxane A2 by the platelets until new platelets are generated. Nonsteroidal antiinflammatory drugs, such as ibuprofen,
are reversible, competitive inhibitors of the catalytic site (Panel C) whose use results in the reversible inhibition of
thromboxane A2 formation during the dosing interval. Prior occupancy of the catalytic site by ibuprofen prevents aspirin
from gaining access to its target serine.

Catella-Lawson y cols. (2001) N Engl J Med 345: 1809-17

Mean Inhibition of Platelet Cyclooxygenase-1 Activity, as Assessed by Measurement of Serum
Thromboxane B2 (Panel A) and Inhibition of Platelet Aggregation (Panel B) in Subjects Taking
Ibuprofen before Aspirin or Aspirin before Ibuprofen on Day 6 of Prolonged Dosing

Catella-Lawson F et al. N Engl J Med 2001;345:1809-1817

Parker JE , Parker JO (1998) N Engl J Med 338:520-531
 Canales de Ca+2 ATP

Bloqueantes
Canales Ca+2
- + Agonistas β2-adrenérgicos
Ca+2 (intracelular)
AMPc
Calmodulina (Cm)
+
Complejo Ca+2-Cm
+ Miosina-CL Kinasa
MCLK* MCLK- P04
(MCLK)
+
MCL MCL-P04 MCL RELAJACIÓN

CONTRACCIÓN
GMP GMPc GTP
FDE5 +
- GUANIL CICLASA*

-SH
GUANIL CICLASA

SILDENAFIL
NITRATOS NO Celulas Endoteliares
REDISTRIBUCION FAVORABLE DEL FLUJO CORONARIO
α,β Dolor
β−BLOQUEANTES
α,β

VC
↑Actividad Simpatica

↓ATP ↑ADO α,β

↑PGs

VC
NITRATOS
α,β
 REACCIONES ADVERSAS A LOS
NITRATOS

• Hipotensión Ortostática
• Cefaleas
• Taquicardia
• Tolerancia:
↓ -SH
Hipótesis Neurohormonal
↑ Radicales Libres
 MECANISMOS DE ACCIÓN ANTIANGINOSA DE LOS F.
BLOQUEANTES DE RECEPTORES β-ADRENÉRGICOS

• DISMINUCIÓN DEMANDA O2 Y NUTRIENTES:

- REDUCCIÓN TONO SIMPÁTICO: INO Y CRONOTROPISMO

- REDUCCIÓN DE POSTCARGA

• INCREMENTO DE OFERTA O2 Y NUTRIENTES:

- PROLONGACIÓN DE LA DIASTOLE

- REDISTRIBUCIÓN FLUJO CORONARIO

 USO DE BLOQUEANTES β-ADRENERGICOS TRAS INFARTO DE MIOCARDIO

AV indicates atrioventricular; BP, blood pressure; DM, diabetes mellitus; HR, heart rate; LV, left ventricular; PVD,
peripheral vascular disease

Gheorghiade, M. et al. Circulation 2002;106:394-398

 A 39-year-old man with a history of smoking,
alcohol abuse, and cocaine use but no other
medical problems presented to the
emergency department with frequent
episodes of chest pain, shortness of breath,
and diaphoresis while at rest. The episodes
of chest pain usually awakened him early in
the morning and lasted a few minutes.
Toxicologic screening on admission to the
hospital was negative for alcohol and for
controlled substances. During an episode of
angina, transient ST-segment elevation (in
lead II) was noted on continuous telemetry
(Panel A). Video A is a continuous telemetric
recording demonstrating dynamic ST-
segment elevation over a period of 6 minutes
and 30 seconds (but accelerated to play in 37
seconds). The base-line artifact was
generated by the patient's rubbing of his
chest because of chest pain. Subsequent
cardiac catheterization revealed
hyperventilation-induced total occlusion of the
proximal left circumflex artery (visible on
angiography from the right anterior oblique
caudal view, Panel B) that resolved with the
administration of intracoronary nitroglycerine
and diltiazem (Panel C). Video B shows this
process during real-time coronary
angiography. The diagnosis of Prinzmetal's
angina was made. The patient's symptoms
have been controlled with oral nitrates and
calcium-channel blockade during a follow-up
of two years.

Cheng HSV y Pinto DS (2003) N Engl J Med 349: e1

Parker JE , Parker JO (1998) N Engl J Med 338:520-531
Change in Treadmill Exercise Duration From Baseline at Trough Ranolazine Levels
Over Time

Chaitman, B. R. et al. JAMA 2004;291:309-316.

Angina Frequency and Nitroglycerin Consumption in the Intent-to-Treat Population

Chaitman, B. R. et al. JAMA 2004;291:309-316.

Measurement of the Ankle–Brachial Index (ABI).
Systolic blood pressure is measured by Doppler ultrasonography in each arm and in the dorsalis pedis (DP) and posterior tibial
(PT) arteries in each ankle. The higher of the two arm pressures is selected, as is the higher of the two pressures in each ankle. The
right and left ankle–brachial index values are determined by dividing the higher ankle pressure in each leg by the higher arm
pressure.16 The ranges of the ankle–brachial index values are shown, with a ratio greater than 1.30 suggesting a noncompressible,
calcified vessel. In this condition, the true pressure at that location cannot be obtained, and additional tests are required to diagnose
peripheral arterial disease. Patients with claudication typically have ankle–brachial index values ranging from 0.41 to 0.90, and
those with critical leg ischemia have values of 0.40 or less.

Hiatt WT (2001) N Engl J Med 344: 1608-21

EVALUACION DE PACIENTES CON SOSPECHA DE CI

Hiatt WT (2001) N Engl J Med 344: 1608-21

EVALUACIÓN Y TRATAMIENTO DE PACIENTES CON CI

Hiatt WT (2001) N Engl J Med 344: 1608-21

AHA-ACC Guidelines for Pharmacologic Management of Claudication

White C. N Engl J Med 2007;356:1241-1250

Figure 1. Aortic Aneurysm and the Extracellular Matrix.
Aortic aneurysm results from chronic inflammation, oxidative stress, mechanical forces, and risk factors in the
patient (such as cigarette smoking). These events disrupt the extracellular matrix (ECM), resulting in the loss of
elastin and collagen; smooth-muscle cells within the aortic wall are also depleted. A recent study by Yoshimura et
al.1 implicates the transcription factor Jun N-terminal kinase (JNK), along with matrix metalloproteinases (MMPs),
as critical mediators of the degradation of the elastin and collagen fibers in two mouse models of aortic aneurysm.
Treatment with a JNK inhibitor (SP600125) prevented the formation of aortic aneurysms and caused such aneurysms
to regress in these models.
Verma y Lindsay (2006) N Engl J Med 354: 2067