Dr. Philip J. Millar

My interest in clinical cardiovascular physiology began during an upper level undergraduate course on Coronary Artery Disease and Physical Activity at McMaster University. Single-handedly, this course propelled me to pursue a career in academia. Little did I know at the time, I would go on to teach that same course four times over my training!

I completed my Master's training at McMaster University under the supervision of Dr. Neil McCartney, investigating the ability of isometric handgrip training to lower resting blood pressure. Whilst this was a clinically relevant finding with applications for treating hypertension, the integrative mechanisms responsible for these actions remained unknown. It was here that I became interested in the role of the autonomic nervous system in the reflex and tonic control of blood pressure, and how the effects of aging, disease, or exercise can alter these responses. I was fascinated by the observation that many common cardiovascular disease states are characterized by similar reductions in parasympathetic activity and increases in sympathetic outflow. This led me to complete a Ph.D. with Drs. Neil McCartney and Maureen MacDonald, examining the role of the autonomic nervous system in responding to acute and chronic exercise.

I further established the capacity of isometric exercise to lower blood pressure acutely and, following training, while also demonstrating increased variability of heart rate, related to the modulation of autonomic inputs, in patients with primary hypertension. As reduced heart rate variability is associated with increased mortality in some clinical populations, this suggested additional benefits of isometric exercise. Unfortunately, these measures provided only indirect assessments of cardiac autonomic modulation. Therefore, I completed a post-doctoral fellowship with Dr. John Floras, Canadian Research Chair in Integrative Cardiovascular Biology at the University Health Network and Mount Sinai Hospital, learning to directly measure sympathetic outflow to skeletal muscle using microneurography. Using this technique, I studied the reflex responses of individual postganglionic sympathetic fibres to loading and unloading of the cardiopulmonary baroreflex, producing the first direct human evidence for a sympathoexcitatory reflex. These findings also provided a novel mechanism for the observed increases in sympathetic outflow in patients with heart failure; an accentuated excitatory cardiopulmonary reflex. This research has stimulated a long-term interest in studying the reflex control of individual postganglionic sympathetic fibres, determining the capacity for differential regulation and functional specificity of efferent sympathetic control in humans.

My post-doc work also examined the ability of exercise and statin therapy to modulate sympathetic outflow and systemic hemodynamics. These projects highlight a second long-term objective, studying the impact of acute and chronic interventions (exercise, diet, medications) on the neural control of the circulation in humans.

Hon B.Sc. - McMaster University
M.Sc. - McMaster University
Ph.D. - McMaster University
Post-Doctoral Fellowship - University Health Network and Mount Sinai Hospital (Toronto)

Cardiovascular disease is one of the leading causes of morbidity and mortality in Canada. A common feature of many of these disease states and associated risk factors is dysfunction of the autonomic nervous system. My research is focused on the integrative regulation of the sympathetic nervous system in human health and disease, and the functional consequences of such control on systemic and regional hemodynamics. The primary tool used by my laboratory involves direct measurements of single- and multi-unit muscle sympathetic nerve activity using microneurography. This is complimented by non-invasive assessments of blood flow, blood pressure, and vascular and cardiac function. We use a variety of stimuli to test selectively the contributions of specific peripheral afferent reflexes (e.g. lower body negative and positive pressure), while using whole-body interventions (e.g. exercise or dietary modifications) to understand the integrative actions on the cardiovascular system. These methods can be applied to testing novel therapies for the management of clinical conditions, such as hypertension or heart failure, but also have important applications for advancing our knowledge of the organization and regulation of efferent sympathetic outflow.

André L. Teixeira, Massimo Nardone, Milena Samora, Igor Alexandre Fernandes, Plinio Santos Ramos, Jeann L. Sabino-Carvalho, Djalma Rabelo Ricardo, Philip J. Millar, Lauro C. Vianna. Potentiation of GABAergic synaptic transmission by diazepam acutely increases resting beat-to-beat blood pressure variability in young adults. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. March 29, 2022. https://doi.org/10.1152/ajpregu.00291.2021

Anthony V. Incognito, Hisayoshi Murai, Takuto Hamaoka, Hiroyuki Sugimoto, Philip J. Millar, Masayuki Takamura. Elevated muscle sympathetic activity in former smokers with heart failure. Clinical Autonomic Research. February 19, 2022. DOI:10.1007/s10286-022-00857-2

Jordan Lee, Karambir Notay, Jeremy Seed, Massimao Nardone, Lucas Omazic, Philip J. Millar. Sex Differences in Muscle Metaboreflex Activation after Static Handgrip Exercise. Medicine & Science in Sports & Exercise. December 2021. doi: 10.1249/MSS.0000000000002747

Massimo Nardone, Philip J. Millar. Lower sympathetic transduction of blood pressure in uncontrolled hypertensives: physiological adaptation, methodological limitation, or both? November 18, 2021. Journal of Human Hypertension volume. DOI:10.1038/s41371-021-00638-w

Brooke Shafer, Anthony Incognito, Tyler Vermeulen, Massimo Nardone, André Teixeira, Jenna Benbaruj, Philip J. Millar, Glen Foster. Muscle Metaboreflex Control of Sympathetic Activity Is Preserved after Acute Intermittent Hypercapnic Hypoxia. Medicine & Science in Sports & Exercise. November 2021. doi: 10.1249/MSS.0000000000002716

Massimo Nardone, Carlin Katerberg, Anthony V. Incognito, André L. Teixeira, Lauro C. Vianna, Philip J. Millar. Blood pressure oscillations impact signal-averaged sympathetic transduction of blood pressure: implications for the association with resting sympathetic outflow. American Journal of Physiology - Heart and Circulatory Physiology. October 7, 2021 https://doi.org/10.1152/ajpheart.00422.2021

André L. Teixeira, Igor A. Fernandes, Philip J. Millar, Lauro C. Vianna. GABA_A receptor activation modulates the muscle sympathetic nerve activity responses at the onset of static exercise in humans. Journal of Applied Physiology. September 14, 2021. https://doi.org/10.1152/japplphysiol.00423.2021

Massimo Nardone, Anthony V. Incognito, Muhammad M. Kathia, Lucas J. Omazic, Jordan B. Lee, André L. Teixeira, Shengkun Xie, Lauro C. Vianna, Philip J. Millar. Signal-averaged resting sympathetic transduction of blood pressure: is it time to account for prevailing muscle sympathetic burst frequency? American Journal of Physiology - Regulatory, Integrative and Comparative Physiology. September 10, 2021. https://doi.org/10.1152/ajpregu.00131.2021

Jordan Lee, William Lutz, Lucas Omazic, Jordan Mitchell, Joseph Cacoilo, Mathew Garland, Geoffrey A. Power, Philip J. Millar. Blood Pressure Responses to Static and Dynamic Knee Extensor Exercise between Sexes: Role of Absolute Contraction Intensity. Medicine & Science in Sports & Exercise: September 2021. doi: 10.1249/MSS.0000000000002648

Eamon Abdullah, Jordan B. Lee, Karambir Notay, Philip J. Millar. Postprandial superior mesenteric artery blood flow is related to changes in peripheral pulse wave harmonics and heart rate: implications for wearable technology? Journal of Applied Physiology. August 11, 2021. https://doi.org/10.1152/japplphysiol.00903.2020

Anthony V. Incognito, André L. Teixeira,* Brooke M. Shafer, Massimo Nardone, Tyler D. Vermeulen, Glen E. Foster, Philip J. Millar. Muscle sympathetic single-unit responses during rhythmic handgrip exercise and isocapnic hypoxia in males: the role of sympathoexcitation magnitude. Journal of Neurophysiology. July 6, 2021. https://doi.org/10.1152/jn.00678.2020

Keri S. Taylor, Daniel A. Keir, Nobuhiko Haruki, Derek S. Kimmerly, Philip J. Millar, Hisayoshi Murai, John S. Floras. Comparison of Cortical Autonomic Network-Linked Sympathetic Excitation by Mueller Maneuvers and Breath-Holds in Subjects With and Without Obstructive Sleep Apnea. Front. Physiol., 26 May 26, 2021 https://doi.org/10.3389/fphys.2021.678630

Alexandra M. Coates, Heather L. Petrick, Philip J. Millar, Jamie F. Burr. Exercise alters cardiac function independent of acute systemic inflammation in healthy men. American Journal of Physiology-Heart and Circulatory Physiology. April 21, 2021. https://doi.org/10.1152/ajpheart.00809.2020

Kozlowski B, Pageaux B, Hubbard EF, St. Peters B, Millar PJ, Power GA. Perception of Effort During an Isometric Contraction is Influenced by Prior Muscle Lengthening or Shortening. bioRxiv. March 30, 2021.

Lee, JB, Lutz W, Omazic LJ, Jordan MA, Cacoilo J, Garland M, Power GA, Millar PJ. Blood Pressure Responses to Static and Dynamic Knee Extensor Exercise between Sexes: Role of Absolute Contraction Intensity. Medicine & Science in Sports & Exercise. March 19, 2021 - Volume Publish Ahead of Print.

Daniel A. Keir, Catherine F. Notarius, Mark B. Badrov, Philip J. Millar, and John S. Floras. Heart failure-specific inverse relationship between the muscle sympathetic response to dynamic leg exercise and V̇O_2peak. Applied Physiology, Nutrition, and Metabolism. March 18, 2021. https://doi.org/10.1139/apnm-2020-1074

Christian P. Cheung, Alexandra M. Coates, Philip J. Millar, Jamie F. Burr. Habitual cannabis use is associated with altered cardiac mechanics and arterial stiffness, but not endothelial function in young healthy smokers. Journal of Applied Physiology. March 11, 2021. https://doi.org/10.1152/japplphysiol.00840.2020

Anthony V. Incognito, Philip J. Millar, W. Glen Pyle. Remote ischemic conditioning for acute respiratory distress syndrome in COVID-19. American Journal of Physiology - Lung Cellular and Molecular Physiology. March 2, 2021. https://doi.org/10.1152/ajplung.00223.2020

Benjamin Kozlowski, Benjamin Pageaux, Emma F. Hubbard, Benjamin St. Peters, Philip J. Millar, Geoffrey A. Power. Perception of effort during an isometric contraction is influenced by prior muscle lengthening or shortening. bioRxiv. March 2021. doi: https://doi.org/10.1101/2021.03.29.437599

Massimo Nardone, Anthony V. Incognito, André L. Teixeira, Joseph A. Cacoilo, Lauro C. Vianna, Philip J. Millar. Effects of muscle sympathetic burst size and burst pattern on time-to-peak sympathetic transduction. Applied Physiology, Nutrition, and Metabolism. January 11, 2021. https://doi.org/10.1139/apnm-2020-0721

Nardone M, Incognito AV, Teixeira AL, Cacoilo JA, Vianna LC, Millar PJ. Effects of Muscle Sympathetic Burst Size and Burst Pattern on Time-to-Peak Sympathetic Transduction. Applied Physiology, Nutrition, and Metabolism. January 11, 2021.

Massimo Nardone, John S. Floras, Philip J. Millar. Sympathetic neural modulation of arterial stiffness in humans. American Journal of Physiology - Heart and Circulatory Physiology. December 2, 2020. https://doi.org/10.1152/ajpheart.00734.2020

Millar PJ, Floras JS. Statins and the Autonomic Nervous System. Clin. Sci. (Lond). 2014; 126:401-15.

Carlson DJ, Dieberg G, Hess NC, Millar PJ, Smart NA. Isometric Exercise Training for Blood Pressure Management: A Systematic Review and Meta-Analysis. Mayo Clin. Proc. 2014; 89:327-34.

Millar PJ, McGowan CL, Cornelissen VA, Araujo CG, Swaine IL. Evidence for the Role of Isometric Exercise Training in Reducing Blood Pressure: Potential Mechanisms and Future Directions. Sports Med. 2014; 44:345-56.

Notarius CF, Millar PJ, Murai H, Morris BL, Floras JS. Inverse Relationship between Muscle Sympathetic Activity During Exercise and Peak Oxygen Uptake in Subjects With and Without Heart Failure. J. Am. Coll. Cardiol. 2014; 63:605-6.

Millar PJ, O'Donnell E. Alpha Males: Muscle Sympathetic Discharge on Beat-to-Beat Forearm Vascular Conductance. J. Physiol. 2013; 591:4375-6.

Millar PJ, Murai H, Morris BL, Floras JS. Microneurographic Evidence in Healthy Middle-Aged Humans for a Sympathoexcitatory Reflex Activated by Atrial Pressure. Am. J. Physiol. Heart Circ. Physiol. 2013; 305:H931-8.

Currie KD, Rosen LM, Millar PJ, McKelvie RS, Macdonald MJ. Heart Rate Recovery and Heart Rate Variability are Unchanged in Patients with Coronary Artery Disease following 12 Weeks of High-Intensity Interval and Moderate-Intensity Endurance Exercise Training. Appl. Physiol. Nutr. Metab. 2013; 38:644-50.

Badrov MB, Bartol CL, DiBartolomeo MA, Millar PJ, McNevin NH, McGowan CL. Effects of Isometric Handgrip Training Dose on Resting Blood Pressure and Resistance Vessel Endothelial Function in Normotensive Women. Eur. J. Appl. Physiol. 2013; 113:2091-100.

Millar PJ, Proudfoot NA, Dillenburg RF, Macdonald MJ. Reduced Heart Rate Variability and Baroreflex Sensitivity in Normotensive Children with Repaired Coarctation of the Aorta. Int. J. Cardiol. 2013; 168:587-8.

Badrov MB, Horton S, Millar PJ, McGowan CL. Cardiovascular Stress Reactivity Tasks Successfully Predict the Hypotensive Response of Isometric Handgrip Training in Hypertensives. Psychophysiology. 2013; 50:407-14.

Taranto Montemurro L, Floras JS, Millar PJ, Kasai T, Gabriel JM, Spaak J, Coelho FM, Bradley TD. Inverse Relationship of Subjective Daytime Sleepiness to Sympathetic Activity in Patients with Heart Failure and Obstructive Sleep Apnea. Chest. 2012; 142:1222-8.

McGowan CL, Murai H, Millar PJ, Notarius CF, Morris BL, Floras JS. Simvastatin Reduces Sympathetic Outflow and Augments Endothelium-Independent Dilation in Non-Hyperlipidaemic Primary Hypertension. Heart. 2013; 99:240-6.

Currie KD, Martin AA, Millar PJ, Stone ND, Timmons BW, Dillenburg RF, MacDonald MJ. Vascular and Autonomic Function in Preschool-Aged Children with Congenital Heart Disease. Congenit. Heart Dis. 2012; 7:289-97.

Millar PJ, Swaine IL, McGowan CL. Impact of Resistance Training on Blood Pressure: Are All Contractions Created equal? Hypertension. 2012; 59:e35.

Millar PJ, Levy AS, McGowan CL, McCartney N, MacDonald MJ. Isometric Handgrip Training Lowers Blood Pressure and Increases Heart Rate Complexity in Medicated Hypertensive Patients. Scand J. Med. Sci. Sports. 2013; 23:620-6.

Millar PJ, Murai H, Floras JS. Neurogenic Retrograde Arterial Flow during Obstructive Sleep Apnea: A Novel Mechanism for Endothelial Dysfunction? Hypertension. 2011; 58:e17-8.

Millar PJ, MacDonald MJ, McCartney N. Effects of Isometric Handgrip Protocol on Blood Pressure and Neurocardiac Modulation. Int. J. Sports Med. 2011; 32:174-80.

Millar PJ, Cotie LM, St Amand T, McCartney N, Ditor DS. Effects of Autonomic Blockade on Nonlinear Heart Rate Dynamics. Clin. Auton. Res. 2010; 20:241-7.

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