BP is literally the property of liquid in a conduit

B. VESSELS

BLOODPulsatile [ejected by a pump]Non Nowtonian

MECHANICALFLOW DYNAMICS

MECHANICALFLOW DYNAMICS

NEUROTROPHICENDOCRINE PARACRINE AUTOCRINE

NEUROTROPHICENDOCRINE PARACRINE AUTOCRINE

Structure is tuned by

By: Prof. Dr. OMNIA NAYELPharmacol Dept, Faculty of Medicine, Alex. University

How it influence: Etiopathogenesis Diagnosis & Prognosis Therapy

Normally FLOW DYNAMICS comprises

It propagates along the longitudinal axes of the vessel.SS: is a friction force acting on the interface between flowing blood & vessel wall, due to the drag between the thin stationary layer of fluid adjacent to the luminal endothelial surface and the outer layers of moving blood.

Shear StressShear Stress

CS: is a tensile strain [stretch] imposed circumferentially at right angles to blood flowing in vessel.

Tensile Stress=Cyclic Stretch Tensile Stress=Cyclic Stretch

It is cyclic due to the rhythmic distension and expansion of arteries / cardiac cycle

It is governed by the varied arterial properties:

Dispensability

Compliance

Dispensability: Fraction change in arterial caliber as

pressure change; it is a determinant of pulsatile stress on

the vessel wall & reflects the yielding property of the artery.

Compliance: The magnitude increase in artery dimension in response to an increment in pressure & reflects the buffering capacity of the artery.

The rate at which the created AORTIC PRESSURE WAVES travel PULSE WAVE VELOCITY (PWV)

CAPACITANT VESSELS: are normally compliant structures capable of buffering BP changes that occur during the cardiac cycle [SBP/DBP (PP) ] to maintain distribution of tissue BF via the CONDUIT VESSELS.

This pulse wave is then REFLECTED from periphery as a REFLECTION WAVE (RW) and normally returns in diastole, thus serving to maintain CBF.

Capillaries Arterioles RESISTANCE VESSELS < 400 m > 400 m

SS generated by each PW excites the release of a spurt of NO allowing balanced tone that ensures: * Forward progression of PW more distally to pertain the peripheral tissue distribution. * Limit / delay the amplitude of RW to reach during diastole to pertain CBF.

Endothelial DysfunctionDisturbed Flow Dynamics

ACUTE VASOMOTOR TONE CHANGES CHRONIC VESSEL RESTRUCTURING

VASOCONSTRICTION BLUNTED NO - MEDIATED VASODILATATION

Fracture & fragmentation of elastic lamillae

Hypertrophic & Euotrophic Remodeling

Vessels are capable of:Vessels are capable of:SENSING SENSING by mechanosensors by mechanosensors IntegrinIntegrinTRANSDUCING it TRANSDUCING it Mechanically/Chemically Mechanically/ChemicallyTRANSLATING itTRANSLATING it to a Response whether to a Response whether

- acute - acute Functional Functional - chronic - chronic Structural Structural

Vessels are capable of:Vessels are capable of:SENSING SENSING by mechanosensors by mechanosensors IntegrinIntegrinTRANSDUCING it TRANSDUCING it Mechanically/Chemically Mechanically/ChemicallyTRANSLATING itTRANSLATING it to a Response whether to a Response whether

- acute - acute Functional Functional - chronic - chronic Structural Structural

Am J Physiol Endocrinol Metab 2002; 282: E1-E10

CS

Integrin

Rapid mechanotransduction

SS

Integrinv3

Delayed Adaptive Responses [ 20 min. - 1hrs]

IA: How different mechanosensor integrins perpetuate the etiopathogenisis of hypertension ?

Mechanical constrain [SS & CS ] are important determinants in Vasomotor Alteration & Vessel Remodeling

J Vasc Res 2000 Aug: 37: 147-57.Hypertension 2000 Sept; 36: 312-18.Circulation 2001 Jan ; 103: 597-603.

Hypertrophic & Euotrophic Remodeling

StiffenWidening PP

Amplitude of RW This accelerates it to arrive at systole This leads to its summation with the Aortic Pulse Wave

PWV

Central Peak Systolic Pressure > Brachial BP

Ventricular Hypertrophy

IB: How does such structure alteration perpetuate How does such structure alteration perpetuate more more etiopathogenic flow disturbance in hypertension. flow disturbance in hypertension.

Fracture & fragmentation of elastic lamillae

Recording of radial, carotid, femoral … waveform is achieved by an applanation tonometry; composed of a hand-held pencil type probe incorporating a high fidelity strain-gauge transducer at the tip of which is a small pressure sensitive ceramic sensor area.

It is applied by gentle pressure at max pulsating area against underlying bone / 10 consecutive beats to cover a resp. cyc.

From the P wavefrom recordings the Augmentation Index [AIx] is calculated = Difference between 1st & 2nd systolic pressure

[SP] expressed as % of PP. It is attributable to RW.

Best indexed by PULSE WAVE ANALYSIS [PWA] of ARTERIAL PRESSURE WAVEFORM using a recently-developed

computerized, portable simple-to-use device [SphygmoCor ]. ARTERIAL STIFFNESS

vs COMPLIANCE

IIA: How does measurement of flow dynamics [CS] aid in diagnosis & prognosis of hypertension

Augmentation Index [AIx]

-ve in young / zero at 35y / +ve thereafter

Reveals extent of ED

Measures addition load imposed on LV due to RW / correlated with LVM

Partly depend on PWV which is # to dispensability / compliance

Partly dependent on EF & duration

Partly dependent on amount & site of RW (m. art. / arterioles)

> Higher in women ??? Because they are of shorter stature

Short stature [>RW] is a risk to CVD !!!!!!

IIA: How does measurement of flow dynamics [CS] aid in diagnosis & prognosis of hypertension

Also indexed by PWV determination

Complior Device (Colson)

ARTERIAL STIFFNESS vs COMPLIANCE

Using a foot-to-foot flow wave velocity method through application of TWO TRANSDUCERS with known distant apart

HR – related variation of PWV may be limiting for its use in clinical trials assessing arterial stiffness !!!

It is +ve correlated with BP & Age

That is why in JNC 7 report [Age (>55 y/ men, >65 y / women) is one of the major CV risk factors because PP & PWV

(JAMA. 2003;289) Molecular biology recently cleared that men with shorter telomere length are prone to PP & PWV artery stiffness

SS = Blood viscosity x Blood velocity / Internal diameter

By:Cone / Plate Viscometer

Internal diameter is measured just before and during the systolic wave passage of cardiac cycle i.e at the narrowest vs

largest luminal diameter and the mean is taken.

IIB: How does measurement of flow dynamics [SS] aid in diagnosis & prognosis of hypertension

By: High Resolution Echo DopplerApplied at common carotid arteries

1 to 2 cm proximal to the bulb.

Equals the distance between the leading edge of the echo produced by the intima-lumen interface of the near wall and that

produced by the lumen-intima interface of the far wall.

BF profile drawn according to velocity values

Positions of the sample volume

BFV recorded in different sites across the arterial lumen

SS is directly proportional to Blood viscosity [Rheology] Velocity gradient of the arterial wall Inversely proportional to Vessel diameter

N.B. SS can arbitrary be indexed using Forearm BF by Plethmography

Improve COMPLIANCE by affecting AIx RW through its role on conduit

arteries & arterioles.

Normalization of vessel function & structure is a deemed goal so interplaying on the flow dynamics should be considered.It was for long thought that COMPLIANCE is better achieved by the use of CCBs, vasodilators, ACIs/ARBs >selective -blockers and just some diuretics !!!!! But now it is proved that

NITRATES NITRATES

III: How does knowledge on flow dynamics aid in choice & innovations of antihypertensve therapy

MODIFYING MECHANOTRANSDUCTION

MODIFYING MECHANOTRANSDUCTION

INTEGRINS

Recombinant Bioengineering.

ANTI - INTEGRINS

Monoclonal Ab or Peptide Inhibitors against them.

EXERCISE is an ANTIDOTE for HYPERTENSION

NO IS & GLUT Sk. m. capillarityTG LDL HDL oxid. enzCytokines & InflammationROS

C S C S

SSSS

III: How does knowledge on flow dynamics aid in adopting a preventive therapy to hypertension