Transcript Vascular Dysfunction: Sequelae of Acute Severe Hypertension
Effects of Acute BP Elevation on the Vessel Wall
Pathophysiology overview
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Sustained neurohormonal activation and vasoconstriction leads to Endothelial decompensation Altered vascular structure
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Vicious cycle of homeostatic failure begins, leading to Loss of cerebral and local autoregulation Organ system ischemia and dysfunction Myocardial infarction
Pathophysiology of hypertension INAPPROPRIATELY HIGH SYMPATHETIC OUTFLOW Increased large arterial stiffness Abnormal venoconstriction and high venous return INAPPROPRIATELY HIGH RENIN RELEASE Inappropriately high cardiac output Increased systemic resistance ABNORMAL RENAL SALT/WATER HANDLING
Courtesy of JL Izzo Jr, MD.
The endothelium modulates vascular tone
NO Endogenous vasodilators PGI 2 Catecholamines AT-II Endogenous vasoconstrictors TxA 2 ET 1 Aldosterone ADH (vasopressin) Courtesy of JJ Ferguson III, MD.
Proposed vascular pathophysiology of hypertensive urgency
NO Endogenous vasodilators ( - ) PGI 2 CAMs ( + ) Catecholamines AT-II Endogenous vasoconstrictors TxA 2 ET 1 Aldosterone ADH (vasopressin)
Acute ↑ BP triggers ↑ cellular adhesion molecular expression
Vaughan CJ, Delanty N.
Lancet.
2000;356:411-7.
Courtesy of JJ Ferguson III, MD.
Proposed vascular pathophysiology of hypertensive emergency
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Overwhelmed control of vascular tone leads to coagulation cascade activation Loss of endothelial activity coupled with coagulation and platelets promotes DIC
Vaughan CJ, Delanty N.
Lancet.
2000;356:411-7.
Courtesy of JJ Ferguson III, MD.
Endothelial shear stress Proportional to the product of blood viscosity ( μ) and spatial gradient of blood velocity at the wall (dv/dy).
ESS = endothelial shear stress
Chatzizisis YS et al.
J Am Coll Cardiol.
2007;49:2379-93.
Endothelial mechanoreceptors sense changes in shear stress ESS = endothelial shear stress
Chatzizisis YS et al.
J Am Coll Cardiol.
2007;49:2379-93.
Shear stress rapidly activates endothelial signal transduction and gene expression Signal Transduction Maximum activation Ras ERK JNK 0 30 60 min Basal activity Gene Expression Maximum activation 0 60 C-fos mRNA 120 180 Basal activity MCP-1 mRNA 240 min
Chien S et al.
Hypertension.
1998;31[part 2]:162-9.
Definition and example of pulsatile, low, and oscillatory ESS Low and oscillatory ESS (<10-12 dyne/cm 2 ) - Direction: Bidirectional (oscillatory) - Magnitude: Low time-average Cross-section ESS = endothelial shear stress Pulsatile ESS (15-70 dyne/cm 2 ) - Direction: Unidirectional - Magnitude: Physiologic time-average Blood flow
Chatzizisis YS et al.
J Am Coll Cardiol.
2007;49:2379-93.
Implications of low and high shear stress Effects of low shear stress Atherosclerosis Plaque rupture Effects of high shear stress Endothelial dysfunction Vascular injury Thrombosis Neurohumoral activation
Chatzizisis YS et al.
J Am Coll Cardiol.
2007;49:2379-93.
Perioperative triggers of adverse physiologic states
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Surgical trauma
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Anesthesia/analgesia
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Intubation/extubation
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Pain
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Hypothermia
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Bleeding/anemia
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Fasting
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Transfusion Physiologic state Inflammatory Hypercoagulable Stress Hypoxia
Devereaux PJ et al.
CMAJ.
2005;173:627-34.
Proposed mechanisms of perioperative MI Inflammation Hypercoagulable state Stress Hypoxia ↑TNF-α ↑IL-1 ↑IL-6 ↑CRP Plaque fissuring ↑PAI-1 ↑Factor VIII ↑Platelet reactivity ↑Antithrombin III ↑Catecholamine and cortisol levels Coronary artery shear stress Plaque fissuring ↑BP ↑HR ↑FFAs ↑Relative insulin deficiency ↓Oxygen delivery ↑Oxygen demand Acute coronary thrombosis Myocardial ischemia Perioperative myocardial infarction
Devereaux PJ et al.
CMAJ.
2005;173:627-34.
Summary: The pathophysiology of acute hypertensive syndromes ↑BP Mechanical stress on the vessel wall Release of humoral vasoconstrictors Further release of humoral vasoconstrictors Fibrinoid necrosis of small blood vessels Activation of the clotting cascade ↑BP Pressure natriuresis Endothelial damage Volume depletion Major physiologic derangements RAAS activation Vasopressin endothelin catecholamines
Courtesy of JJ Ferguson III, MD.
Pathophysiology of acute hypertensive syndromes: A vicious cycle Vasoconstrictor release Tissue ischemia Vascular injury
Courtesy of JJ Ferguson III, MD.
Summary: Acute hypertension Nonsurgical patients
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Little studied in past decade
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Multiple knowledge gaps
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Patient characteristics
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Treatment patterns
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Outcomes Perioperative patients
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Frequent finding
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Emerging data demonstrate importance of tighter BP control than currently recommended
Acute hypertension: Conclusions
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New options are needed
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Need for long-term patient follow-up in hypertensive urgencies/emergencies