Heat stress-induced hyperthermia and exercise-induced hypohydration are associated with marked alterations in limb and systemic haemodynamics in humans. However, the mechanisms underlying these alterations their effects on muscle blood flow are not well understood. The present thesis examined whether whole body and local heat stresses increased limb skin and muscle blood flow (Study 1) and whether hypohydration and hyperthermia compromised leg muscle, skin and systemic haemodynamics (Study 2). The effects of heat stress and combined hypohydration and hyperthermia were examined at rest and during mild small muscle mass exercise in humans. The results from Study 1 suggested that heat stress was accompanied by vasodilation in both skeletal muscle and skin vasculatures. Therefore in line with concomitant elevations in blood flow, skeletal muscle and skin vasodilation contribute to increases in leg blood flow and vascular conductance with whole body heat stress. Furthermore, increases in leg muscle and skin blood flow with isolated elevations in leg tissue temperature accounted for at least one half of the total increase in leg blood flow with whole body heat stress. Enhanced leg blood flow owed to a net vasodilation as explained by an elevation in vasodilator activity that exceeded increases in vasoconstrictor activity. This phenomenon was closely related to increases in muscle temperature and intravascular adenosine triphosphate (ATP). The results from Study 2 demonstrated that mild and moderate hypohydration and hyperthermia do not compromise leg muscle and skin blood flow or cardiac output at rest or during mild exercise in humans. Furthermore, acute rehydration did not alter leg muscle and skin blood flow or cardiac output compared to hypohydration and hyperthermia despite large alterations in blood volume and haematological variables and the restoration of core temperature. Taken together, the findings of this thesis indicate that: 1) heat stress induces vasodilation in both skeletal muscle and cutaneous vasculature, 2) elevations in muscle temperature and intravascular ATP play a role in heat stress- and exercise-induced hyperaemia, and 3) moderate hypohydrationinduced hypovolemia and haemoconcentration and rehydration-induced hypervolaemia and haemodilution do not alter leg blood flow or cardiac output at rest and during low intensity exercise in humans when a large cardiovascular reserve is available.

To optimize muscle blood flow to the skeletal muscle during exercise, the vascular bed of the muscle is partially protected from sympathetic nervous activity (SNA) vasoconstriction via a phenomenon termed functional sympatholysis. Functional sympatholysis has been documented during exercise periods in human skeletal muscle. However, it remains unknown whether functional sympatholysis is specific to the exercising period, or if it may persist for a period of time following skeletal muscle exercise. Through this study, we aimed to confirm the presence and duration of post-exercise functional sympatholysis in the human skeletal muscle. The cold pressor test (CPT) was administered to 9 male (mean age = 21.1 ± 0.8 years) participants at various time points during four different experimental trials (Rest, Exercise, Recovery 1 and Recovery 2). Exercise consisted of 7 minutes of moderate isometric handgrip exercise (15% below critical power). Heart rate (HR) and mean arterial pressure (MAP) were recorded continuously throughout each trial. Brachial artery mean blood velocity measurements as well as brachial artery diameter measurements were recorded on each participant’s exercising arm throughout each trial. Deep venous blood samples were drawn pre- and post-CPT administration from a catheter inserted into an antecubital vein of each participant’s non-experimental arm. The cardiovascular response to the CPT was repeatable across experimental days as it consistently resulted in MAP elevations regardless of the experimental time point of administration. The CPT also resulted in a significant elevation in plasma norepinephrine concentration from 0.49 ± 0.04 ng/mL at “pre-CPT” measurement to 0.66 ± 0.05 ng/mL at the end of the CPT in the Rest trial (P < 0.05). The percentage reduction in forearm vascular conductance (FVC) due to CPT administration during Exercise (4.5 ± 6.6%) and Recovery 1 (4 minutes post-exercise; -11.6 ± 8.8%) was significantly blunted in comparison to that measured during Rest (-34.8 ± 7.4%) (P < 0.05). The percentage change in FVC during the Recovery 2 trial (10 minutes post-exercise; -20.1 ± 7.1%) was not significantly different from that measured at Rest. These findings support the concept of a lingering presence of functional sympatholysis 4 minutes, but not 10 minutes, post-moderate exercise. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2011-12-21 17:17:09.037

We sought to determine if compensatory vasodilator and/or pressor responses protect exercising muscle O2 delivery (O2D) under conditions of reduced arterial perfusion pressure, if this is exercise intensity-dependent, and if distinct cardiovascular response phenotypes exist. Ten healthy male subjects (19.5±0.4 years) completed two trials of a ramp protocol forearm isometric handgrip exercise test to exhaustion (2.5 kg increments every 3.5 minutes) in each of forearm above and below heart level (forearm arterial perfusion pressure (FAPP) difference of 29.5±0.97 mmHg). Forearm blood flow ((FBF (ml/min; brachial artery Doppler and echo ultrasound), mean arterial blood pressure (MAP; finger photoplethysmography), and exercising forearm venous effluent (ante-cubital vein catheter) measurements at the end of each work rate (WR) revealed the following. Group level (n=10) Δ FBF was compromised beyond 5 kg WR in above vs. below (P<0.05). There was no evidence of compensatory vasodilator (P=0.21) or pressor (P=0.63) responses. Peak O2D, WR and VO2 were significantly compromised by reduced FAPP (115.6±16.8 vs. 152.0±13.4 mlO2/min, 25.5±1.22 vs. 28.94±1.50 kg and 75.9±5.3 vs. 100.2±8.6 ml/min; P<0.05). In contrast, examination of individual responses revealed distinct cardiovascular response groups with (n=6) vs. without (n=4) compensatory vasodilation with the former having less compromise to submaximal O2D and peak WR (-94.12±23.42 vs. -223.40±36.01 mlO2/min), P<0.05 and -2.5±0.32 vs. -5.32±0.79 kg, P<0.05). In conclusion, exercising forearm muscle hypoperfusion due to reduced FAPP is not compensated for by pressor responses. However, there appear to be distinct phenotypes in which vasodilatory compensation does vs. does not occur, which in the former partially protects O2D and exercise performance. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2012-09-13 16:42:41.751

Doctor of Philosophy / In this thesis, three experiments were conducted to monitor: (i) muscle oxygenation and electromyographic activity of the biceps brachii after exercise-induced muscle damage (ii) muscle oxygenation after downhill walking-induced muscle damage, and, (iii) muscle oxygenation following a bout of vigorous concentric exercise. Maximal eccentric exercise (EE) of biceps brachii resulted in significantly increased mean resting oxygen saturation and decreased deoxyhaemoglobin. During isometric contractions at 50% and 80% of subjects’ maximum voluntary torque (MVT), oxygen desaturation and resaturation kinetics and volume were significantly decreased after EE, and these declines were significantly prevalent over the following 6 days. Additionally, a significant shift in median frequency intercept (measured by electromyography; EMG) towards lower frequencies was observed during isometric contractions at both 50% and 80% MVT after EE in the exercised arm. After an exhaustive session of downhill walking, another form of EE, resting total haemoglobin and oxyhaemoglobin decreased. Furthermore, during isometric contractions at 30%, 50% and 80% of MVT, prolonged and significant increases were observed in oxygen desaturation and resaturation kinetics and volumes after ambulatory EE. In contrast to the two EE experiments, concentric contractions did not evoke any prolonged changes in muscle oxygenation. Collectively, the findings of this thesis revealed significant and prolonged changes in muscle oxygenation at rest and during exercise, following sessions of strenuous eccentric exercise. Although not clear, the possible mechanism responsible for the changes in muscle oxygenation after EE could be increased resting muscle oxygen utilization due to probable muscle damage and a subsequent requirement of energy demanding repair processes. Concentric exercise resulted in fatigue, but it did not affect muscle oxygenation. Although a prolonged reduction in EMG median frequency intercept was observed after EE, this was not closely time-associated with the biochemical, anthropometric or functional markers of muscle damage.

The overall aim of this thesis was to elucidate and investigate psychophysiological aspects and effects of acupuncture and needle stimulation. Within this framework emphasis was directed toward the effects of needle stimulation (acupuncture) on muscle blood flow in the tibialis anterior and trapezius muscles in healthy subjects and patients suffering from chronic muscle pain. This study also included evaluation of a new application of photoplethysmography in noninvasive monitoring of muscle blood flow. The evaluation was based on experiments known to provocate skin or muscle blood flow. The psychological aspects studied comprised the effects of manual acupuncture on pain in fibromyalgia patients and the effects of electro-acupuncture on psychological distress and vasomotor symptoms in postmenopausal women in the clinical context. The results showed that photoplethysmography have potential to noninvasively monitor muscle blood flow and to discriminate between blood flow in skin and muscle, although some considerations still have to be accounted for. It was further shown that muscle blood flow change in response to needle stimulation differed between healthy subjects and patients. Deep needle stimulation in the muscle of healthy subjects consistently increased muscle blood flow more than subcutaneous needle stimulation. In the painful trapezius muscle of FMS patients, however, subcutaneous needling was equal or even more effective in increasing muscle blood flow than deep intramuscular stimulation. Generally, needle stimuli had weak effect on blood flow in the trapezius muscle of the severely affected trapezius myalgia patients, possibly depending on older age and lesser number of patients included in the study. The different patterns of blood flow response to needle stimulation between healthy subjects and patients with chronic muscle pain might be a manifestation of altered somatosensory processing in the patients. The clinical studies showed that best pain relief of acupuncture in FMS patients was achieved in the neck-shoulder region, while the effect on the generalised symptoms was of short duration. Well-being and sleep was found to best predict treatment outcome. The results suggest that acupuncture treatment may be used for the alleviation of neck-shoulder pain, primarily, but it is not an alternative as the sole treatment. Electro-acupuncture, significantly decreased psychological distress and climacteric symptoms in postmenopausal women, but not better than a (near-) placebo control, implying pronounced non-specific effects. / Akupunktur ingår som en del i traditionell kinesisk medicin (TCM) och har använts i över 2000 år för att lindra sjukdom och symptom. I Sverige blev akupunktur godkänd som smärtlindringsmetod inom Hälso- och Sjukvården 1984. Sedan nästan 10 år är akupunktur jämställd med övrig behandling i sjukvården vilket innebär, att akupunktur kan användas även för behandling av annat än smärta. Förutsättningen är emellertid, att det finns tillräckligt med vetenskapliga belägg, s.k. evidens, för detta. I de allra flesta fall saknas det idag. För att säkerställa att evidens föreligger krävs omfattande forskning om effekter av akupunktur. Syftet med de olika studierna i avhandlingen var att belysa och studera psykologiska och fysiologiska aspekter och effekter av akupunktur och nålstimulering. Effekt på blodflöde i hud och muskel undersöktes på friska personer och på patienter med kronisk muskelsmärta. Normalt krävs ett mindre kirurgiskt ingrepp för att mäta blodflöde i muskel, men i dessa studier användes en mätmetod, som enkelt och utan ingrepp (icke-invasivt) i normala fall används för att mäta blodflöde i huden, s.k. fotopletysmografi (PPG, eng.). Med hjälp av ny teknik användes PPG i dessa studier för att mäta även muskelblodflöde. En studie för utvärdering av den nya PPG-tekniken ingick också i avhandlingen. Utvärderingen av mätmetoden visade goda möjligheter att mäta muskelblodflöde icke-invasivt med hjälp av PPG. Hos friska personer blev effekten på blodflödet störst vid djup stimulering i muskeln och där den s.k. DeQi-känslan framkallades (som vid klassisk akupunktur). Hos patienter med fibromyalgi var nålstimulering i huden lika, eller t.o.m. mer, effektiv att öka muskelblodflödet i skuldran än den djupa nålstimuleringen. De olika mönstren av blodflödesökning mellan de friska personerna och patienterna kan bero på ett förändrat reaktionssätt i nervsystemet som svar på smärtsam stimulering. I två kliniska studier studerades den smärtlindrande effekten av manuell akupunktur vid fibromyalgi och effekten av elektroakupunktur på stress och klimakteriebesvär hos kvinnor i övergångsåldern. Akupunktur vid fibromyalgi visade sig ha bäst smärtlindrande effekt i nack-skulderområdet, medan effekten på de generella symptomen var kortvarig. Patienter som mådde och sov relativt bra erhöll bäst effekt. Efter en behandlingsserie, bestående av elektroakupunktur, minskade stress och klimakteriebesvär påtagligt hos kvinnorna i övergångsåldern, men inte mer än hos en grupp kvinnor, som fick en kontrollbehandling bestående av mycket ytligt placerade nålar i huden. Detta tyder på att en betydlig del av behandlingsresultatet utgjordes av ospecifika effekter eller, s.k. eller placeboeffekter.

The adaptations of vessel diameter represented by vascular conductance (VC), muscle blood flow (MBF) and oxygen delivery (DO2est) were investigated during rest and exercise using the effects of gravity to manipulate muscle perfusion pressure (MPP) by placing the heart above (head-up tilt) and below (head-down tilt) the level of the muscle. This experimental paradigm was used to explore VC and MBF regulation and related control mechanisms during rest and exercise. Study 1 tested the repeatability of Doppler ultra- sound measurements of muscle blood flow velocity (MBV), arterial diameter, MBF and VC. The adaptations in VC and MBF (Study 2) and changes in anterograde and retro- grade MBV patterns (Study 3) were investigated during postural challenges at rest. Study 4, determined the peak VC and its fractional recruitment during transitions from rest to lower (LPO) and higher power output (HPO) calf muscle exercise in HDT and HUT. Study 5 investigated the combined effects of altered MPP and hypoxia during exercise. During rest-HDT, increases in VC compensated for the MPP reduction to maintain MBF, while in rest-HUT, MBF was reduced. Following the start of LPO and HPO exercises, MBF and VC responses were delayed in HDT and accelerated in HUT. During LPO, MBF steady- state was reduced in HUT compared to horizontal (HOR), while the greater increase in VC during HDT maintained MBF at a similar level as HUT. Post-exercise MBF recovered rapidly in all positions after LPO exercise but did not after HPOHDT. During HPOHDT, MBF was reduced despite the increase in VC, while in HPOHUT MBF was similar to that in HPOHOR. The hypoxic challenge added in exercise was met during LPOHDT by in- creased VC to compensate reduced MPP and O2 availability such that MBF maintained DO2est. However, during HPOHDT in hypoxia, VC reached maximal vasodilatory capacity, compromising MBF and DO2est. Together, these findings indicate that LPOHDT in nor- moxia or hypoxia VC increased to maintain MBF and DO2est, but during HPO functional limitation for recruitment of VC constrained MBF and DO2 in normoxia and hypoxia. Elevated muscle electromyograpic signals in HPOHDT were consistent with challenged aer- obic metabolism. MPP reduction in HDT caused slower adaptation of MBF limiting O2 availability would result in a greater O2 deficit that could contribute to an increase in the relative stress of the exercise challenge and advance the onset of muscle fatigue.

BACKGROUND: Exercise is a critical treatment modality in persons with Type II Diabetes Mellitus (T2DM), however people with this disease experience chronic fatigue and a decreased exercise capacity, which affects their ability or willingness to participate in physical activity. Studies suggest that this exercise intolerance may be partly due to a reduced exercising muscle blood flow (MBF), and in particular to a reduced ability of red blood cells (RBCs) to evoke ATP-mediated vasodilation and an increase in MBF as they traverse areas of high O2 demand. Additional evidence suggests that caffeine may attenuate this impairment by enhancing the release of ATP from RBCs. HYPOTHESIS: Persons with T2DM would have reduced Forearm Blood Flow (FBF), oxygen consumption (VO2), and exercise tolerance responses to exercise compared to control (CON) subjects, and caffeine would attenuate these impairments. METHODS: T2DM (n = 4) and CON (n = 4) participants performed rhythmic forearm handgrip exercise at an intensity equivalent to 17.5 kg until “task failure” or 20 minutes of exercise was reached, after having consumed either a caffeine (5mg/kg; Caff) or placebo (Pl) capsule. FBF (Doppler and Echo ultrasound of the brachial artery), VO2 and lactate efflux (deep venous blood sampling), forearm vascular conductance (FVK), mean arterial pressure (MAP) and heart rate (HR) were quantified for each minute of exercise. RESULTS: Steady state FBF was similar across groups and treatment conditions (mean ± SE ml/min; CONCaff 553.80 ± 82.35, CONPl 583.42 ± 112.62, T2DMCaff 523.33 ± 105.39, T2DMPl 569.08 ± 134.20, NS), and this was due to similar MAP and FVK (across groups and treatment conditions, NS). VO2 and Time to Task Failure (TTF) were not different between groups and treatment conditions (NS), although TTF tended to be improved with caffeine versus placebo (10.00 ± 2.02 vs 8.24 ± 1.79 min, P=0.295). There was a strong positive relationship between FBF and TTF (r2=0.763; P=0.005). CONCLUSIONS: In the exercise model utilized, persons with T2DM do not have impaired cardiovascular responsiveness or reduced exercise tolerance, and caffeine does not provide any benefit. Differences in exercising MBF may be an underlying mechanism regarding differences in exercise tolerance. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2009-09-16 16:19:42.537

The adaptations of vessel diameter represented by vascular conductance (VC), muscle blood flow (MBF) and oxygen delivery (DO2est) were investigated during rest and exercise using the effects of gravity to manipulate muscle perfusion pressure (MPP) by placing the heart above (head-up tilt) and below (head-down tilt) the level of the muscle. This experimental paradigm was used to explore VC and MBF regulation and related control mechanisms during rest and exercise. Study 1 tested the repeatability of Doppler ultra- sound measurements of muscle blood flow velocity (MBV), arterial diameter, MBF and VC. The adaptations in VC and MBF (Study 2) and changes in anterograde and retro- grade MBV patterns (Study 3) were investigated during postural challenges at rest. Study 4, determined the peak VC and its fractional recruitment during transitions from rest to lower (LPO) and higher power output (HPO) calf muscle exercise in HDT and HUT. Study 5 investigated the combined effects of altered MPP and hypoxia during exercise. During rest-HDT, increases in VC compensated for the MPP reduction to maintain MBF, while in rest-HUT, MBF was reduced. Following the start of LPO and HPO exercises, MBF and VC responses were delayed in HDT and accelerated in HUT. During LPO, MBF steady- state was reduced in HUT compared to horizontal (HOR), while the greater increase in VC during HDT maintained MBF at a similar level as HUT. Post-exercise MBF recovered rapidly in all positions after LPO exercise but did not after HPOHDT. During HPOHDT, MBF was reduced despite the increase in VC, while in HPOHUT MBF was similar to that in HPOHOR. The hypoxic challenge added in exercise was met during LPOHDT by in- creased VC to compensate reduced MPP and O2 availability such that MBF maintained DO2est. However, during HPOHDT in hypoxia, VC reached maximal vasodilatory capacity, compromising MBF and DO2est. Together, these findings indicate that LPOHDT in nor- moxia or hypoxia VC increased to maintain MBF and DO2est, but during HPO functional limitation for recruitment of VC constrained MBF and DO2 in normoxia and hypoxia. Elevated muscle electromyograpic signals in HPOHDT were consistent with challenged aer- obic metabolism. MPP reduction in HDT caused slower adaptation of MBF limiting O2 availability would result in a greater O2 deficit that could contribute to an increase in the relative stress of the exercise challenge and advance the onset of muscle fatigue.

Doctor of Philosophy / In this thesis, three experiments were conducted to monitor: (i) muscle oxygenation and electromyographic activity of the biceps brachii after exercise-induced muscle damage (ii) muscle oxygenation after downhill walking-induced muscle damage, and, (iii) muscle oxygenation following a bout of vigorous concentric exercise. Maximal eccentric exercise (EE) of biceps brachii resulted in significantly increased mean resting oxygen saturation and decreased deoxyhaemoglobin. During isometric contractions at 50% and 80% of subjects’ maximum voluntary torque (MVT), oxygen desaturation and resaturation kinetics and volume were significantly decreased after EE, and these declines were significantly prevalent over the following 6 days. Additionally, a significant shift in median frequency intercept (measured by electromyography; EMG) towards lower frequencies was observed during isometric contractions at both 50% and 80% MVT after EE in the exercised arm. After an exhaustive session of downhill walking, another form of EE, resting total haemoglobin and oxyhaemoglobin decreased. Furthermore, during isometric contractions at 30%, 50% and 80% of MVT, prolonged and significant increases were observed in oxygen desaturation and resaturation kinetics and volumes after ambulatory EE. In contrast to the two EE experiments, concentric contractions did not evoke any prolonged changes in muscle oxygenation. Collectively, the findings of this thesis revealed significant and prolonged changes in muscle oxygenation at rest and during exercise, following sessions of strenuous eccentric exercise. Although not clear, the possible mechanism responsible for the changes in muscle oxygenation after EE could be increased resting muscle oxygen utilization due to probable muscle damage and a subsequent requirement of energy demanding repair processes. Concentric exercise resulted in fatigue, but it did not affect muscle oxygenation. Although a prolonged reduction in EMG median frequency intercept was observed after EE, this was not closely time-associated with the biochemical, anthropometric or functional markers of muscle damage.

Master of Science / Department of Kinesiology / Thomas J. Barstow / Limb blood flow increases linearly with exercise intensity; however, invasive measurements of microvascular muscle blood flow during incremental exercise have demonstrated submaximal plateaus. Diffuse correlation spectroscopy (DCS) noninvasively quantifies relative changes in microvascular blood flow at rest via a blood flow index (BFI). The purpose of this study was to quantify relative changes in tissue blood flow during exercise using DCS, compare the BFI of the flexor digitorum superficialis (BFI[subscript]FDS) muscle to brachial artery blood flow (Q̇[subscript]BA) measured via Doppler ultrasound, and employ near infrared spectroscopy (NIRS) alongside DCS to simultaneously measure perfusive and diffusive oxygen transport within a single volume of exercising skeletal muscle tissue. We hypothesized Q̇[subscript]BA would increase with increasing exercise intensity until task failure, BFI[subscript]FDS would plateau at a submaximal work rate, and muscle oxygenation characteristics (total-[heme], deoxy-[heme], and % saturation) measured with NIRS would demonstrate a plateau at a similar work rate as BFI[subscript]FDS. Sixteen subjects (23.3 ± 3.9 yrs; 170.8 ± 1.9 cm; 72.8 ± 3.4 kg) participated in this study. Peak power (P[subscript]peak) was determined for each subject (6.2 ± 1.4W) via an incremental handgrip exercise test to task failure. Measurements of Q̇[subscript]BA, BFI[subscript]FDS, total-[heme], deoxy-[heme], and % saturation were made during each stage of the incremental exercise test. Q̇[subscript]BA increased with exercise intensity until the final work rate transition (p < 0.05). No increases in BFI[subscript]FDS or muscle oxygenation characteristics were observed at exercise intensities greater than 51.5 ± 22.9% of P[subscript]peak and were measured simultaneously in a single volume of exercising skeletal muscle tissue. Differences in muscle recruitment amongst muscles of the whole limb may explain the discrepancies observed in Q̇[subscript]BA and BFI[subscript]FDS responses during incremental exercise and should be further investigated.