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David A. MacLean, PhD

NOSM University
NOSM U – East Campus
935 Ramsey Lake Road
Sudbury ON Canada P3E 2C6
Phone:  (705) 662-7240
Fax:  (705) 675-4858
E-mail: david.maclean@nosm.ca
Professor of Physiology, Division of Medical Sciences, NOSM University
Cross Appointment, Department of Biology Laurentian University

Education/Training

2021-present

 Affiliate Scientist, Health Sciences North Research Institute

2014-present

 Professor of Physiology, Division of Medical Sciences
Northern Ontario School of Medicine, Laurentian University Campus

2013-2018

 Assistant Dean, Research
Northern Ontario School of Medicine, Laurentian University Campus

2007-2007

 Interim Director of Faculty Development
Northern Ontario School of Medicine, Laurentian University Campus

2006-present

 Core Faculty, Biomolecular Sciences Doctoral Program
Laurentian University

2005-present

 Cross-Appointment, Department of Human Kinetics
Laurentian University

2005-present

 Cross-Appointment, Department of Biology
Laurentian University

2004-2014

 Associate Professor of Physiology, Division of Medical Sciences
Northern Ontario School of Medicine, Laurentian University Campus

 2001-2004

 Associate Professor, Exercise Science
School of Exercise, Leisure and Sport, Kent State University, Kent, OH.

1999-2001

 Director, Microdialysis Core Laboratory, General Clinical Research Center (GCRC)
The Pennsylvania State University College of Medicine
The Milton S. Hershey Medical Center, Hershey, PA

 1998-2001

 Assistant Professor of Medicine and Cellular and Molecular Physiology
The Pennsylvania State University College of Medicine
The Milton S. Hershey Medical Center, Hershey, PA

1996-1997

 Post-doctoral fellow, Division of Cardiology
The Pennsylvania State University College of Medicine
The Milton S. Hershey Medical Center, Hershey, PA

1994-1996

 Post-doctoral fellow, Copenhagen Muscle Research Centre.
Rigshospitalet, section 7652, Copenhagen N, Denmark

1993

 Ph.D. Biophysics
University of Guelph

1989

 M.Sc. Human Biology
University of Guelph

1987

 B.Sc. Human Kinetics
University of Guelph

Research Investigations

My research is focused on the better understanding of cardiovascular physiology as it pertains to the regulation of blood flow under conditions of hypoxia, vascular insufficiency and end stage disease states such as heart disease. I employ both human and animal models to examine these questions including muscle tissue sampling arterio-venous blood collections. Although these have methods have provide valuable information regarding the vascular mechanisms associated with blood flow, they do not sample all the physiological compartments. More specifically, the interstitial space. Therefore, I utilize a very unique procedure, the microdialysis technique to directly sample and quantitate compounds in the interstitial space, hence investigating physiological parameters directly at the tissue level. This is a very powerful technique that is only performed in a handful of laboratories and represents a considerable advance in our ability to understand the mechanisms associated with cardiovascular regulation.

An associated area of research is protein and amino acid metabolism under both normal and abnormal physiological conditions. For example, I examine the incorporation of amino acids into muscle protein during anabolic conditions such as exercise as well as during end stage disease states such as heart failure. These studies will hopefully provide new insights into the regulation and potential countermeasures associated with heath and disease.

Selected Publications

  1. MacLean DA, Spriet LL, Hultman E, Graham TE. Plasma and muscle amino acid and ammonia responses during prolonged exercise in humans.  J Appl Physiol 70(5): 2095-2103, 1991.
  2. MacLean DA, Spriet LL, Graham TE. Plasma amino acid and ammonia responses to altered dietary intakes prior to prolonged exercise in humans.  Can J Physiol Pharmacol 70(4): 420-427, 1992.
  3. Spriet LL, MacLean DA, Dyck DJ, Hultman E, Cederblad G, Graham TE. Caffeine ingestion and muscle metabolism during prolonged exercise in humans.  Am J Physiol 262: E891-E898, 1992.
  4. Graham TE, MacLean DA. Ammonia and amino acid metabolism in human skeletal muscle during exercise.  Can J Physiol Pharmacol 70(1): 132-141, 1992.
  5. MacLean DA, Graham TE. Branched-chain amino acid supplementation augments plasma ammonia responses during exercise in humans.  J Appl Physiol 74(6): 2711-2717, 1993.
  6. MacLean DA, Graham TE, Saltin B. Branched-chain amino acids augment ammonia metabolism while attenuating protein breakdown during exercise.  Am J Physiol 267: E1010-E1022, 1994.
  7. Rush JW, MacLean DA, Hultman E, Graham TE. Exercise causes branched-chain oxoacid dehydrogenase dephosphorylation but not AMP deaminase binding.  J Appl Physiol 78(6): 2193-2200, 1995.
  8. MacLean DA, Barclay JK, Graham TE. Electrical stimulation and amino acid and ammonia metabolism in the canine gastrocnemius muscle.  Am J Physiol Regulatory Integrative Comp Physiol 268(3): R759-R770, 1995.
  9. MacLean DA, Graham TE, Saltin B. Stimulation of muscle ammonia production during exercise following branched-chain amino acid supplementation in humans.  J Physiol (Lond) 493: 909-922, 1996.
  10. Madsen K, MacLean DA, Kiens B, Christensen D. Effects of glucose, glucose plus branched-chain amino acids, or placebo on bike performance over 100 km.  J Appl Physiol 81(6): 2644-2650, 1996.
  11. van Hall G, MacLean DA, Saltin B, Wagenmakers AJ. Mechanisms of activation of muscle branched-chain alpha-keto acid dehydrogenase during exercise in man.  J Physiol (Lond) 494: 899-905, 1996.
  12. Rohde T, MacLean DA, Pedersen BK.  Glutamine, lymphocyte proliferation and cytokine production.  Scand J Immunol 44(6): 648-650, 1996.
  13. Rohde T, MacLean DA, Hartkopp A, Pedersen BK. The immune system and serum glutamine during a triathlon.  Eur J Appl Physiol 74(5): 428-434, 1996.
  14. Rohde T, MacLean DA, Richter EA, Kiens B, Pedersen BK. Prolonged submaximal eccentric exercise is associated with increased levels of plasma IL-6.  Am J Physiol 273: E85-E91, 1997.
  15. MacLean DA, Saltin B, Radegran G, Sinoway L. Femoral arterial injection of adenosine in humans elevates MSNA via central but not peripheral mechanisms.  J Appl Physiol 83(4): 1045-1053, 1997.
  16. Gibala MJ, MacLean DA, Graham TE, Saltin B. Anaplerotic processes in human skeletal muscle during brief dynamic exercise.  J Physiol (Lond) 502: 703-713, 1997.
  17. Calbet JA, MacLean DA. Role of caloric content on gastric emptying in humans.  J Physiol (Lond) 498(2): 553-559, 1997.
  18. Pedersen BK, Bruunsgaard H, Klokker M, Kappel M, MacLean DA, Nielsen HB, Rohde T, Ullum H, Zacho M. Exercise-induced immunomodulation–possible roles of neuroendocrine and metabolic factors.  Int J Sports Med 18: S2-S7, 1997.
  19. Bruunsgaard H, Galbo H, Halkjaer-Kristensen J, Johansen TL, MacLean DA, Pedersen BK. Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage.  J Physiol 499: 833-841, 1997.
  20. Vissing J, Vissing SF, MacLean DA, Saltin B, Quistorff B, Haller RG. Sympathetic activation in exercise is not dependent on muscle acidosis: direct evidence from studies in metabolic myopathies.  J Clin Invest 101(8): 1654-1660, 1998.
  21. Graham TE, MacLean DA. Ammonia and amino acid metabolism in skeletal muscle: human, rodent and canine models.  Med Sci Sports Exerc 30(1): 34-46, 1998.
  22. Rohde T, MacLean DA, Pedersen BK. Effect of glutamine supplementation on changes in the immune system induced by repeated exercise.  Med Sci Sports Exerc 30(6): 856-862, 1998.
  23. MacLean DA, LaNoue KF, Gray KS, Sinoway LI. Effects of hindlimb contraction on pressor and muscle interstitial metabolite responses in the cat.  J Appl Physiol 85(4): 1583-1592, 1998.
  24. MacLean DA, Sinoway LI, Leuenberger UA: Systemic hypoxia elevates skeletal muscle interstitial adenosine levels in humans.  Circulation 98(19): 1990-1992, 1998.
  25. Hellsten Y, MacLean DA, Rådegran G, Saltin B, Bangsbo J. Adenosine concentrations in the interstitium of resting and contracting human skeletal muscle.  Circulation 98: 6-8, 1998.
  26. MacLean DA, Vissing J, Vissing S, Haller RG. Oral branched chain amino acids do not improve exercise capacity in McArdle disease.  Neurology 51: 1456-1459, 1998.
  27. Gibala MJ, MacLean DA, Graham TE, Saltin B. Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exercise.  Am J Physiol 275: E235-E242, 1998.
  28. Rohde T, Asp S, MacLean DA, Pedersen BK. Competitive sustained exercise in humans, lymphokine activated killer cell activity, and glutamine-an intervention study. Eur J Appl Physiol 78: 448-453, 1998.
  29. MacLean DA, Bangsbo J, Saltin B. Muscle interstitial glucose and lactate levels during dynamic exercise in humans determined by microdialysis.  J Appl Physiol 87(4): 1483-1490, 1999.
  30. MacLean DA, Imadojemu VA, Sinoway LI. Interstitial pH, K+, lactate and phosphate determined with MSNA during exercise in humans.  Am J Physiol  278: R563-R571, 2000.
  31. Graham TE, Helge JW, MacLean DA, Kiens B, Richter EA. Caffeine ingestion does not alter carbohydrate or fat metabolism in skeletal muscle during exercise.  J Physiol Lond 529.3: 837-847, 2000.
  32. MacLean DA, Vickery LM, Sinoway LI. Elevated interstitial adenosine concentrations do not activate the muscle reflex.  Am J Physiol  280: H546-H553, 2001.
  33. MacLean DA, Ettinger SM, Sinoway LI, LaNoue KF. Determination of muscle specific glucose flux using radioactive stereoisomers and microdialysis.  Am J Physiol 280(1): E187-E192, 2001.
  34. Crandall CG, MacLean DA. Cutaneous interstitial nitric oxide concentration does not increase during heat stress in humans.  J Appl Physiol 90: 1020-1024, 2001.
  35. Lott MEJ, Hogeman CS, Vickery L, Kunselman AR, Sinoway LI, MacLean DA. Effects of dynamic exercise on mean blood velocity and muscle interstitial metabolite responses in humans.  Am J Physiol 281: H1734-1741, 2001.
  36. Vissing J, MacLean DA, Vissing SF, Sander M, Saltin B, Haller RG. The exercise metaborereflex is maintained in the absence of muscle acidosis:  insights from muscle microdialysis in humans with McArdle’s disease.  J Physiol 2: 641-649, 2001.
  37. Lang CH, Frost RA, NaimAC, MacLean DA, Vary TC. TNF-alpha impairs heart and skeletal muscle protein synthesis by altering translation initiation. Am J Physiol 282: E336-347, 2002
  38. Anthony CJ, Reiter AK, Anthony TG, Crozier SJ, Lang CH, MacLean DA, Kimball SR, Jefferson LS. Orally administered leucine enhances protein synthesis in skeletal muscle of diabetic rats in the absence of increases in 4E-BP1 or S6K1 phosphorylation.  Diabetes 51: 928-936, 2002.
  39. Anthony CJ, Lang CH, Crozier SJ, Anthony TG, MacLean DA, Kimball SR, Jefferson LS. Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine.  Am J Physiol 282: E1092-E1101, 2002.
  40. Calbet JAL, MacLean DA. Plasma glucagon and insulin responses depend on the rate of appearance of amino acids after ingestion of different protein solutions in humans.  J Nutr 132: 2174-2182, 2002.  .
  41. Khan MH, Sinoway LI, MacLean DA. The effects of graded LBNP on MSNA and interstitial norepinephrine.  Am J Physiol 283: H2038-H2044, 2002.
  42. Proctor DN, Newcomer SC, Koch DW, Le KU, MacLean DA, Leuenberger UA. Leg blood flow during submaximal cycle ergometry is not reduced in healthy older normally active men.  J Appl Physiol 94: 1859-1869, 2003.
  43. Samii S, Khan M, MacLean DA, King N, Herr MD, Sinoway LI. Muscle interstitial calcium during head-up tilt in humans. Circulation 109: 215-219, 2004.
  44. Miller S, Chinkes D, MacLean DA, Gore D, Wolfe RR. In Vivo Muscle Amino Acid Transport Involves Two Distinct Processes.  Am J Physiol 287: E136-141, 2004.
  45. Bolster DR, Pikosky MA, Bennett BT, Maresh CM, Tipton KD, MacLean DA, Rodriguez NR. Dietary Protein Intake Impacts Human Skeletal Muscle Protein Fractional Synthetic Rates Following Endurance Exercise. Am J Physiol. 289: E678-E683, 2005.
  46. Rush JWE, Green, HG, MacLean DA, Code LM. Oxidative Stress Determinants and Nitric Oxide Synthase in Skeletal Muscle of Rats with Chronic Heart Failure.  Acta Physiol Scand 185:211-218, 2005.
  47. Andrews RD, MacLean DA, Riechman SE. Protein intake and for skeletal muscle hypertrophy with resistance training in seniors.  Int J Sport Nutr Metab 16:362-372, 2006.
  48. Riechman SE, Andrews R, MacLean DA. Statins and dietary and serum cholesterol are associated with increased lean mass following resistance training.  Gerontol A Biol Sci Med Sci, 62(10): 1164-1171, 2007.
  49. Leuenberger UA, Johnson D, Loomis J, Gray KS, MacLean DA. Venous but not skeletal muscle interstitial nitric oxide is increased during hypobaric hypoxia. Eur J. Appl Physiol Nov 6 (Epub ahead of print), 2008.
  50. Veitch ZW, Baoqing G, Hembruff S, Bewick AJ, Heibein AD, Eng J, Cull, S, MacLean DA, Parisennti AM. Induction of IC aldoketoreductases and other drug does-dependent genes upon acquisition of anthracycline resistance. Pharmacogenet Genomics, 19(6): 477-488, 2009.
  51. Pellinger TK, Simmons GH, MacLean DA, Halliwill JR. Local histamine H1 and H2-receptor blockade reduces postexercise skeletal muscle interstitial glucose concentrations in humans. Appl Physiol Nutr Metab, 35(5): 617-26, 2010.
  52. Heibein AD, Guo B, Sprowl JA, MacLean DA and Parissenti AM. Role of the AKRs and other doxorubicin pharmacokinetic genes in doxorubicin resistance, DNA binding and subcellular localization. BMC Cancer, Aug 31;12(1): 381, 2012. (Epub ahead of print).
  53. Fabris S, MacLean DA. Skeletal Muscle an Active Compartment in the Sequestering and Metabolism of Doxorubicin Chemotherapy.  PLoS ONE 10(9): e0139070. doi:10.1371/journal.pone.0139070, 2015.
  54. Fabris S and MacLean DA. Doxorubicin chemotherapy affects intracellular and interstitial nitric oxide concentrations in skeletal muscle. Cell Biol Toxicol. 2016 Apr; 32(2):121-131. doi: 10.1007/s10565-016-9325-1. Epub 2016 Apr 8.
  55. Romero SA, McCord JL, Ely MR, Sieck DC, Buck TM, Luttrell MJ, MacLean DA, Halliwill JR. Mast cell degranulation, de novo histamine formation, and sustained post-exercise vasodilation in humans. Appl Physiol  (1985). 122(3):603-610, 2017.  First published August 25, 2016; doi:10.1152/japplphysiol.00633.2016.
  56. Zhao L, Fabris S and MacLean DA. The effects of adenine nucleotide perfusion on interstitial adenosine production in rat skeletal muscle.  Can J Physiol Phram. Aug; 96(8):823-829. doi: 10.1139/cjpp-2017-0347. Epub 2018 Apr 10.
  57. Fabris S and MacLean DA. Doxorubicin chemotherapy affects the intracellular and interstitial free amino acid pools in skeletal muscle. PLoS ONE 13(4): e0195330. doi:10.1371/journal.pone.0185330, 2018.