Evaluation of the arterial baroreflex Peter B. Raven, Ph.D. University of North Texas Health Science Center Fort Worth, TX, U.S.A.
Methods of Investigating Arterial Baroreflex 1. Valsalva - arterial (aortic + carotid) 2. Carotid massage - carotid 3. Oxford technique - arterial (aortic + carotid) 4. Dynamic baroreflex( sequence technique)- arterial (aortic + carotid) 5. Dynamic baroreflex (transfer function gain ) - arterial (aortic + carotid) 6. Static baroreflex - Carotid baroreflex i) Rapid Train of NP/NS - carotid baroreflex ii) Building carotid baroreflexes with NP/NS iii) Aortic baroreflex - isolation Pharmacological Mechanical
Oxford technique Nitroprusside Phenylephrine BP ABR Cardiac - ∆HR/∆SBP, Vasomotor - ∆MSNA/∆DBP HR MSNA
Phenylephrine Phenylephrine Nitroprusside Nitroprusside MSNA 150 BP (mmHg) 100 HR (beats/min) 50 100 50 Resp. SBF (unit) 200 100 0 1 min A: Normothermia B: Hyperthermia Cui, Wilson, Crandall, Am. J. Physiol. Reg Comp. Physiol. 2002
Heat Stress (R 2 =0.92) Normothermia (R2=0.94) Operating Point 90 Heart Rate (bpm) 75 60 100 110 120 130 Systolic Blood Pressure (mmHg) Cui, Wilson, Crandall, Am. J. Physiol. Reg Comp. Physiol. 2002
Heat Stress (R2=0.93) 3000 Normothermia (R2=0.92) Normalized MSNA (units/beat) Operating Point 2500 2000 1500 1000 500 0 50 55 60 65 70 75 Diastolic Blood Pressure (mmHg) Cui, Wilson, Crandall, Am. J. Physiol. Reg Comp. Physiol. 2002
Arterial Baroreflex Testing • Bolus injections of graded concentrations of sodium nitroprusside (I.V.) induced hypotensive stimuli that activated both aortic and carotid baroreceptors. • Bolus injections of graded concentrations of phenylephrine (I.V.) induced hypertensive stimuli that activated both aortic and carotid baroreceptors NOTE: Technique characterizes global arterial baroreflex function.
Aortic Baroreflex Testing • An appropriate level of neck pressure was applied to negate phenylephrine induced increases in mean arterial pressure at the carotid sinus preventing activation of carotid baroreceptors. • An appropriate level of neck suction was applied to negate sodium nitroprusside induced decreases in mean arterial pressure at the carotid sinus preventing activation of carotid baroreceptors. NOTE: Technique isolates aortic baroreflex function
Carotid Baroreflex Testing • Method 1 (Built Curves): – Neck pressure and neck suction applied as 5 sec stimuli – Neck pressure applied to mimic the hypotension induced by systemic administration of sodium nitroprusside – Neck suction applied to mimic the hypertension induced by systemic administration of phenyleprhine • Method 2 (Pulsed Train Curves): – Neck suction and neck pressure applied as pulsed train stimuli gated to the cardiac cycle R-wave NOTE: Techniques characterize carotid baroreflex function. No differences existed in curve parameters between either method of carotid baroreflex testing.
EXAMPLE Smith et al., Autonomic Neuroscience (2001), 74-85
Smith et al., Autonomic Neuroscience (2001), 74-85
Smith et al., Autonomic Neuroscience (2001), 74-85
NP NS Carotid sinus baroreceptor Arterial Pressure Carotid-sinus nerve Aortic Aortic nerve baroreceptor Sympath. cardiac nerves Heart Rate Exercise Sympath. vasoconstrictor nerves Blood Pressor pressure Reflex Vasoconstriction Vasodilation
Querry et al. AJP 2001
Built Neck Pressure and Suction Reflex Function Curves Protocol 60 40 20 Chamber Pressure Operating 0 Responding Range Point -20 (Torr) -40 -60 MAP or HR -80 Max gain (A1) -100 Slope (A2) Centering 80 Point 75 (A3) 70 Minimum HR (bpm) Response 65 Operating Range (A4) 60 Threshold Saturation 55 50 20 40 60 80 100 120 140 160 Estimated Carotid Sinus Pressure Estimated Carotid Sinus Pressure (mmHg)
NP/NS stimulation (5s NP/NS protocol) The 5s NP/NS can be used to analyze CBR function during relatively long duration, steady-state conditions. Example- rest, dynamic exercise, heat stress, etc. Advantage- can measure MSNA & blood flow responses, can distinguish latency of cardiac and vasomotor component Limitation- time (rapid NP/NS protocol) The rapid NP/NS can be used to analyze CBR function during relatively short duration, steady-state conditions. Example- static exercise, tilt, LBNP, etc. Advantage- time Limitation- cannot be used during high HR conditions (RRI<stimulation time=500ms)
Breath-hold during NP/NS stimulation (Rest) The NP/NS pulse train was conducted during 10 to 15s breath-hold at end-expiration to minimize the respiratory-related modulation of HR and MAP (Eckberg 1976) (Exercise) During exercise, NP/NS pulse train are applied without the presence of a breath-hold. Eckberg et al.(1980) reported no differences between the responses to neck collar stimuli during inspiration and expiration at a breathing frequency of >24 breaths/min.
The HR responses to NS (-60mmHg) 8 0 Carotid-HR baroreflex Curve 7 0 7 0 6 5 6 0 HR (bpm) 6 0 5 0 HR (bpm) 5 5 4 0 5 0 Average of 3 0 4 5 peak values * 4 0 2 0 CP (mmHg) 0 3 5 - 2 0 2 0 4 0 6 0 8 0 1 0 0 1 2 0 1 4 0 1 6 0 - 4 0 E s t i m a t e d c r a o t i d s i n u e p r e s s u r e - 6 0 ( m m H g ) 024681 0 1 2 T i m e ( s ) ECSP=MAP-CP
MAP responses to NS (-60mmHg) 1 0 0 Carotid-MAP baroreflex Curve 8 0 8 0 7 5 MAP (mmHg) 7 0 MAP (mmHg) 6 0 6 5 6 0 Average of 4 0 5 5 peak values * 5 0 CP (mmHg) 0 - 2 0 4 5 2 0 4 0 6 0 8 0 1 0 0 1 2 0 1 4 0 1 6 0 - 4 0 - 6 0 E s t i m a t e d c a r o t i d s i n u s p r e s s u r e ( m m H g ) 024681 0 1 2 T i m e ( s ) ECSP=MAP-CP
The HR and MAP responses to rapid changes in NP and NS Carotid-HR baroreflex Curve 8 0 9 beats 7 0 HR (bpm) 7 0 6 0 Curve 5 0 6 5 calculated 4 0 from 5 s 6 0 protocol 3 0 HR (bpm) 9 0 5 5 MAP (mmHg) 9 beats 8 0 5 0 7 0 4 5 6 0 4 0 5 0 6 0 CP (mmHg) 4 0 3 5 2 0 2 0 4 0 6 0 8 0 1 0 0 1 2 0 1 4 0 1 6 0 0 - 2 0 E C S P ( m m H g ) - 4 0 - 6 0 - 8 0 - 1 0 0 0 2 4 6 8 1 0 1 2 1 4 1 6 T i m e ( s )
The HR and MAP responses to rapid changes in NP and NS Carotid-MAP baroreflex Curve 8 0 9 beats 7 0 HR (bpm) 8 0 6 0 Curve 5 0 7 5 calculated 4 0 from 5 s 7 0 MAP (mmHg) protocol 3 0 9 0 9 beats 6 5 MAP (mmHg) 8 0 6 0 7 0 5 5 6 0 5 0 5 0 6 0 CP (mmHg) 4 0 4 5 2 0 2 0 4 0 6 0 8 0 1 0 0 1 2 0 1 4 0 1 6 0 0 - 2 0 E C S P ( m m H g ) - 4 0 - 6 0 - 8 0 - 1 0 0 0 2 4 6 8 1 0 1 2 1 4 1 6 T i m e ( s )
? Heart rate Blood pressure Workload
OP CP Heart Rate Ex (heavy) Ex (moderate) Ex (light) Rest ECSP Operating Range Ogoh et al. J Physiol. 2003
OP Mean Arterial Pressure CP Ex (heavy) Ex (moderate) Ex (light) Rest ECSP Operating Range Potts et al. AJP 1993 Norton et al. JAP 1999
Relocated OP underestimates max Gain during exercise by using data points around OP!! (Exercise) max gain gain at OP <gain at CP OP Mean Arterial Pressure CP Heart Rate or Exercise Rest (Rest) max gain gain at OP gain at CP ECSP
SV responses to 100 NP/NS during Stroke Volume (mmL) exercise 80 Chamber Pressure (Torr) 60 80 40 40 0 -40 -80 20 -120 Estimated Carotid Sinus Pressure (mmHg) Rest EX90 EX120 EX150 1 6 0 1 4 0 1 2 0 1 0 0 8 0 6 0 4 0 2 0 0 - 8 0- 4 004 0 - 8 0- 4 004 0 - 8 0 - 4 004 0 - 8 0 - 4 004 0 Neck Chamber Pressure (mmHg) Ogoh et al. J Physiol. 2003
The change of HR or MAP (bpm or mmHg) Cntribution of TPR HR 15 Contribution of Q MAP 10 MAP= HR× SV× SVC 5 0 5 sec NP (40mmHg) -5 0 2 4 6 8 10 12 Time (sec.) 100 MAP= HR×k× SVC Stroke Volume (mmL) 80 Flow Chamber Pressure (Torr) 60 Vasomotor 80 40 Reaction 40 0 -40 -80 20 -120 Estimated Carotid Sinus Pressure (mmHg) Ogoh et al. J Physiol. 2002
The contribution to changes in arterial blood pressure (%) Q TVC 100 50 0 Rest 120EX
Rowell & O’Leary JAP 1990 SNA (BP) CNS Central SNA Baroreflex Command (BP) OP Neurons A SNA (CSP) BP (BP) OP A+B Sympathetic Muscle Nervous (CSP) BP Chemoreflex OP System B (CSP) BP
Static Exercise Dynamic Exercise Carotid Sinus Pressure (mmHg) Gallagher et al. J Physiol. 2001
Gallagher et al. J Physiol. 2001
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