The Exercise Pressor Reflex Dr. James P. Fisher School of Sport, Exercise & Rehabilitation Sciences College of Life & Environmental Sciences University of Birmingham, UK Copenhagen, 2018
Based on work of Secher, 1977. from Saltin, B. J Physiol 2007;583:819-823
Original blood pressure tracing of one subject with exercise-induced hypotension (idiopathic orthostatic hypotension). Vertical lines are at 10-second intervals. Patients with autonomic disorders, in which the normal exercise-induced increase in sympathetic nerve activity is markedly attenuated, can experience hypotension potentially leading to reduced physical capacity, fatigue, dizziness and even syncope Marshall et al., (1961)
Presentation Overview i. Classic studies ii. Group III and IV skeletal muscle afferents Fisher et al. Compr Physiol. 2015; 5:1-38 iii. iv. EPR and autonomic nervous system EPR in disease states
Exercise Pressor Reflex: Classic studies in humans Rhythmic handgrip exercise (A) Performed under free-flow conditions (B, top) Or with ischemia (C, bottom), which augmented the blood pressure (BP) response Augmented BP response absent in patient with sensory loss Alam & Smirk (1937) J Physiol. 89: 372-383 Figure from; Mitchell (2013) Exp Physiol. 98, 867-878.
Exercise Pressor Reflex: Classic studies in animals (I) Mitchell J H (2012) Exp Physiol. 97:14-19 Pressor response No pressor response after section of dorsal root A laminectomy performed (in cat) Ventral roots of L7 & S1 sectioned Peripheral ends stimulated to contract the hindlimb muscles HR, BP and tension recorded Coote et al., (1971) J Physiol. 215: 789-804.
Exercise Pressor Reflex: Classic studies in animals (II) Mitchell J H (2012) Exp Physiol. 97:14-19 A) Stim B) Stim Experimental preparation for studying the effect of anaesthetic (lidocaine) block on muscle afferent nerves in the dorsal root C) A & C) control BP response to contraction B) administration of lidocaine at dorsal root to block group III and IV afferents (but not group I and II afferents) abolishes BP response to contraction Stim McCloskey & Mitchell (1972) J Physiol. 224: 173-186.
Neurophysiological basis for the Exercise Pressor Reflex Kaufman M (2002) Clin Auton Res. 12 : 429 439 Group III (Ad fibres): Located near myotendinous junction Group IV (C fibres): Located near blood vessels Anatomical-functional coupling? Stacey et al. (1969) J Anton. 105: 231-254
Neurophysiological basis of the exercise pressor reflex Rapid initial burst Secondary burst? Response latency Greaney et al. Auton Neurosci. 2015; 188:51-57 Kaufman M P Exp Physiol 2012;97:51-58
Muscle metaboreceptors evoke muscle SNA HR (bpm) 76 88 83 67 63 67 MAP (mmhg) 100 114 127 122 122 107 Mark et al., (1985) Circ Res. 57:461-469. A B Measurement of muscle sympathetic nerve activity from human peroneal nerve at level of fibular head
Muscle acidosis is linked to increased muscle SNA McArdles disease: Genetic myophosphorylase deficiency. Therefore, no glycogen degradation in exercising muscle. No acidosis, No sympatho-excitation But, heart rate still increases (central command?). Fadel et al., (2003) J Physiol 548: 983-993. Pryor et al., (1990) J Clin Invest. 85:1444-9. Victor et al., (1988) J Clin Invest. 82(4):1301-5.
Muscle metaboreceptors evoke muscle SNA HR (bpm) 76 88 83 67 63 67 MAP (mmhg) 100 114 127 122 122 107 Mark et al., (1985) Circ Res. 57:461-469. A B Measurement of muscle sympathetic nerve activity from human peroneal nerve at level of fibular head
Why isn t heart rate elevated with muscle metaboreceptor activation during post-exercise ischaemia? Central command Peripheral vasculature Muscle metaboreflex Muscle mechanoreflex BP Heart Green line Sympathetic Blue line Parasympathetic Arterial baroreceptors Fisher et al. (2010) Physiology News
Does parasympathetic blockade unmask a muscle metaboreflex mediated sympathetic tachycardia during PEI? A) Heart Rate (b min -1 ) B) rt Rate in -1 ) 160 120 80 40 70 60 50 40 0 60 25% MVC 120 180 240 300 360 Time (s) 420 480 540 600 660 720 B) D Heart Rate (b min -1 ) 0 60 120 70 60 50 40 30 20 10 0 180 240 40% MVC 300 360 IHG Time (s) Rest IHG PEI-M Recovery Rest IHG PEI-H Recovery Control Beta-adrenergic blockade Parasympathetic blockade # # # Control Beta-adrenergic blockade Control Parasympathetic blockade Beta-adrenergic blockade Parasympathetic blockade Time (s) 420 480 540 600 * * PEI-M 660 720 Drug P<0.001 Phase P<0.001 Trial P<0.001 Interaction P<0.001 *
Clinical perspective: Skeletal muscle afferents and cardiac autonomic control during exercise Sudden cardiac death due to ventricular tachy-arrhythmias is the leading cause of death in industrially developed countries Subnormal cardiac parasympathetic tone and baroreflex sensitivity, and elevated cardiac sympathetic drive may allow for the formation of malignant ventricular arrhythmias Implications for patient populations with exaggerated muscle afferent drive during exercise (e.g. CHF, COPD, hypertension). Improved cardiac parasympathetic tone and baroreflex sensitivity via exercise training (treadmill running) reduces risk of VF in dog model of sudden cardiac death Billman, (2006)
USA Triathlon (USAT) Fatality Incidents Study reviewed data from 2003 to 2011. Of the 38 deaths, 30 occurred during the swim. Autonomic Conflict (AC) occurs when both divisions of the autonomic nervous system are co-activated resulting in cardiac arrhythmias and, possibly, death. Br J Sports Med. 2014 Aug;48(15):1134-5.
Original record showing the neural and cardiovascular responses to trigeminal nerve stimulation in one participant. Fisher et al. Am J Physiol Heart Circ Physiol 2015;308:H367-H375
Percentage change from rest in mean arterial pressure (A), heart rate (B), femoral vascular conductance (C), heart rate variability (RMSSD; D), and MSNA (E and F) during TGS, post-exercise ischemia (PEI), and combined PEI + TGS. Fisher et al. Am J Physiol Heart Circ Physiol 2015;308:H367-H375
Presentation Overview i. Classic studies ii. Group III and IV skeletal muscle afferents Fisher et al. Compr Physiol. 2015; 5:1-38 iii. iv. EPR and autonomic nervous system EPR in disease states
Exaggerated sympathetic and pressor responses to handgrip in type 2 diabetic patients: role of the muscle metaboreflex (I) Holwerda et al. Am J Physiol Heart Circ Physiol 2016;310:H300-H309
Exaggerated pressor responses to exercise in hypertension eliminated by intrathecal fentanyl Fentanyl, a μ-opioid receptor agonist, attenuates the central projection of opioid-sensitive group III and IV muscle afferents NT: Normotensive controls. HT CTRL: Hypertensive control. HT FENT: Hypertensive with fentanyl. Leg cycling at 40W Barbosa et al. 2016. J Physiol. 594.3 pp 715 725
Intrathecal fentanyl in human heart failure (HF) increases leg blood flow and oxygen delivery during exercise Amann et al. International Journal of Cardiology 174 (2014) 368 375
Exercise Pressor reflex Sympathetic Response Modulation of a-adrenergic vasoconstriction (impaired functional sympatholysis) Active Muscle Vasoconstrictor Tone Muscle Blood Flow Blood Pressure Response VO 2max / exercise tolerance Adapted from Dinenno & Joyner (2006) Microcirculation. 13(4):329-41. (Ventilation and cardiac implications too)
Exercise with blood flow restriction could precipitate adverse cardiovascular or cerebrovascular events (e.g., cardiac arrhythmia, myocardial infarction, stroke and sudden cardiac death)
Key points Muscle metaboreflex powerfully increases SNA. Muscle metaboreflex activation is heightened in several disease states (e.g., T2DM, HTN, HF). This has potential implications for cardiac electrical stability, skeletal muscle and brain blood flow, blood pressure and exercise tolerance/performance.
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