Effects of Acute BP Elevation on the Vessel Wall

1
Effects of AcuteBP Elevation onthe Vessel Wall
2
Pathophysiology overview

• Sustained neurohormonal activation and
  vasoconstriction leads to
• Endothelial decompensation
• Altered vascular structure

• Vicious cycle of homeostatic failure begins,
  leading to
• Loss of cerebral and local autoregulation
• Organ system ischemia and dysfunction
• Myocardial infarction

3
Pathophysiology of hypertension
INAPPROPRIATELY HIGH SYMPATHETIC OUTFLOW
Increased large arterial stiffness
Abnormal venoconstriction and high venous return
Increased systemic resistance
Inappropriately high cardiac output
INAPPROPRIATELY HIGH RENIN RELEASE
ABNORMAL RENAL SALT/WATER HANDLING
Courtesy of JL Izzo Jr, MD.
4
The endothelium modulates vascular tone
Catecholamines
NO
AT-II
TxA2
Endogenous vasoconstrictors
Endogenous vasodilators
ET1
PGI2
Aldosterone
ADH (vasopressin)
Courtesy of JJ Ferguson III, MD.
5
Proposed vascular pathophysiology of
hypertensive urgency
Acute ? BP triggers ? cellular adhesion molecular
expression
Vaughan CJ, Delanty N. Lancet. 2000356411-7.Cou
rtesy of JJ Ferguson III, MD.
6
Proposed vascular pathophysiology of
hypertensive emergency

• 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. 2000356411-7.
Courtesy of JJ Ferguson III, MD.
7
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.
2007492379-93.
8
Endothelial mechanoreceptors sense changes in
shear stress
ESS endothelial shear stress
Chatzizisis YS et al. J Am Coll Cardiol.
2007492379-93.
9
Shear stress rapidly activates endothelial signal
transduction and gene expression
Signal Transduction
Gene Expression
Maximum activation
Maximum activation
Activation
Activation
Basal activity
Basal activity
Ras
ERK
MCP-1 mRNA
JNK
C-fos mRNA
min
min
0
30
60
0
60
120
180
240
Chien S et al. Hypertension. 199831part
2162-9.
10
Definition and example of pulsatile, low, and
oscillatory ESS
ESS endothelial shear stress
Chatzizisis YS et al. J Am Coll Cardiol.
2007492379-93.
11
Implications of low and high shear stress
Effects of low shear stress
Effects of high shear stress
Endothelial dysfunction Vascular
injury Thrombosis Neurohumoral activation
Atherosclerosis Plaque rupture
Chatzizisis YS et al. J Am Coll Cardiol.
2007492379-93.
12
Perioperative triggers of adverse physiologic
states

• Surgical trauma
• Anesthesia/analgesia
• Intubation/extubation
• Pain
• Hypothermia
• Bleeding/anemia
• Fasting
• Transfusion

Physiologic state
Inflammatory Hypercoagulable Stress Hypoxia
Devereaux PJ et al. CMAJ. 2005173627-34.
13
Proposed mechanisms of perioperative MI
Inflammation
Hypercoagulablestate
Stress
Hypoxia
?TNF-a ?IL-1 ?IL-6 ?CRP
?PAI-1 ?Factor VIII ?Platelet reactivity ?Antithro
mbin III
?Catecholamine and cortisol levels
?Oxygen delivery
Coronary artery shear stress
?BP ?HR ?FFAs ?Relative insulin deficiency
Plaque fissuring
Plaque fissuring
?Oxygen demand
Myocardial ischemia
Acute coronary thrombosis
Perioperative myocardial infarction
Devereaux PJ et al. CMAJ. 2005173627-34.
14
Summary The pathophysiology of acute
hypertensive syndromes
Mechanical stress on the vessel wall
Release of humoral vasoconstrictors
?BP
?BP
Further release of humoral vasoconstrictors
Pressure natriuresis
Volume depletion
Fibrinoid necrosis of small blood vessels
Endothelial damage
Vasopressin endothelin catecholamines
RAAS activation
Activation of the clotting cascade
Courtesy of JJ Ferguson III, MD.
15
Pathophysiology of acute hypertensive syndromes
A vicious cycle
Courtesy of JJ Ferguson III, MD.
16
Summary Acute hypertension

• Nonsurgical patients
• Little studied in past decade
• Multiple knowledge gaps
• Patient characteristics
• Treatment patterns
• Outcomes
• Perioperative patients
• Frequent finding
• Emerging data demonstrate importance of tighter
  BP control than currently recommended

17
Acute hypertension Conclusions

• New options are needed
• Need for long-term patient follow-up in
  hypertensive urgencies/emergencies