No description available.

No description available.

Microvascular oxygen transport has been studied using many experimental methods. The three wavelength photometric method of Pittman and Duling (6) was the basis for this project. An optical triplicator was introduced into the microscopy assembly. The triplicator’s function was to take the image seen in the eyepiece of the microscope, triplicate it, filter it at three known wavelengths and direct each image onto the active area of a video camera. When used in-vivo, the triplicator allowed for three simultaneous intensity measurements, one at each wavelength, to be made. This measurement removed any assumptions concerning the uniformity of the blood sample which was inherent in Pittman and Duling’s design. Measurements were performed in vivo on several hamster retractor muscles. The intensity information obtained was then used to calculate oxygen saturation at regions near an arterial bifurcation. Oxygen saturation values ranged from 42.99 ± 4.20 to 96.46 ± 4.46% depending upon the location along the vessel. It was also concluded that the oxygen saturation profile across the vessel was altered near a bifurcation. The oxygen saturation profile prior to and following a bifurcation appeared to be uniform. However, in the region of a bifurcation, the asymmetry introduced nonuniformities in the profile. This paper briefly discusses the theory behind the three wavelength photometric method, the development and fabrication of the optical triplicator and the measurement techniques used to obtain oxygen saturation profiles. It will be shown that the optical triplicator has the potential to advance the study of microvascular oxygen transport beyond previously unachievable levels. / Master of Science

Doctor of Philosophy / Department of Anatomy and Physiology / Thomas J. Barstow / The physiological mechanisms determining the tolerable duration of exercise dictate human physical accomplishments across all spectrums of life. Despite extensive study, these specific mechanisms, and their dependence on oxygen delivery and oxygen utilization, remain, a certain extent, undefined. The purpose of this dissertation was to test the overarching hypothesis that muscle contraction characteristics (i.e., intensity of contraction, muscle contraction-relaxation duty cycle, etc.) alter oxygen delivery and oxygen utilization, which directly influence the power-duration relationship and fatigue development, and therefore, exercise tolerance. To accomplish this, specific interventions of altered muscle contraction-relaxation duty cycle and blood flow occlusion were utilized. In the first investigation (Chapter 2), we utilized low and high muscle contraction-relaxation duty cycles to alter blood flow to the active skeletal muscle, demonstrating that critical power (CP) was reduced with the high muscle contraction-relaxation duty cycle due to a reduction in blood flow, while the curvature constant (W’) was not altered. The second investigation (Chapter 3) utilized blood flow occlusion to show that CP was reduced and W’ increased for blood flow occlusion exercise conditions compared to control blood flow exercise conditions. The final investigation (Chapter 4) utilized periods of blood flow occlusion during and post-exercise to reveal greater magnitudes of peripheral and central fatigue development during blood flow occlusion exercise compared to control blood flow exercise. Moreover, this investigation demonstrated that W’ was significantly related to the magnitude of fatigue development. Collectively, alterations in oxygen delivery and oxygen utilization via muscle contraction characteristics and blood flow occlusion directly influence CP and the magnitude of fatigue development. However, W’ does not appear to be influenced by manipulations in oxygen delivery and oxygen utilization, per se. Rather, W’ may be determined by the magnitude of fatigue accrued during exercise, which is dependent upon oxygen delivery and oxygen utilization. The novel findings of the investigations presented in this dissertation highlight important physiological mechanisms that determine exercise tolerance and demonstrate the need for interventions that improve oxygen delivery and oxygen utilization in specific populations, such as those with chronic heart failure or chronic obstructive pulmonary disease, to improve exercise tolerance.

Master of Science / Department of Kinesiology / Timothy I. Musch / Both cardiac and peripheral vasculature dysfunction likely contribute, in part, to elevations in TNF-[alpha] and exercise intolerance in chronic heart failure (CHF). The pharmaceutical TNF-[alpha] synthesis suppressor pentoxifylline (PTX) reduces plasma [TNF-[alpha]] and improves left ventricular (LV) function in CHF rats, but the effects of PTX on skeletal muscle blood flow (BF) and vascular conductance (VC) during exercise are unknown. We tested the hypothesis that PTX would elevate skeletal muscle BF and VC at rest and during submaximal treadmill exercise in CHF rats (coronary artery ligation). CHF rats received i.p. injections of 30 mg·kg[superscript]-[superscript]1·day[superscript]-[superscript]1 of PTX (CHF+PTX, n=13) or saline (CHF, n=8) for 21 days. Mean arterial pressure (MAP) and BF (radiolabeled microsphere infusions) were measured at rest and during treadmill exercise (20 m/min, 5% grade). Myocardial infarct (MI) size was not different between groups (CHF: 37±4, CHF+PTX: 37±3% of LV wall; p>0.05). Resting and exercising MAP was greater in CHF+PTX compared to CHF (p<0.05 for both). At rest, total hindlimb skeletal muscle BF and VC were not different between groups (p>0.05). However, during exercise PTX increased total hindlimb BF (CHF: 83±9, CHF+PTX: 114±8 ml·min[superscript]-[superscript]1·100g[superscript]-[superscript]1, p<0.05) and VC (CHF: 0.75±0.08, CHF+PTX: 0.88±0.06 ml·min[superscript]-[superscript]1·100g[superscript]-[superscript]1·mmHg[superscript]-[superscript]1, p<0.05). Furthermore, exercising BF was increased in 21, and VC in 11, of the 28 individual hindlimb muscles or muscle parts with no apparent fiber-type specificity. Thus, PTX administration augments skeletal muscle BF and VC during locomotory exercise in CHF rats, which carries important therapeutic implications for CHF patients.

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

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.

Doctor of Philosophy / Department of Anatomy and Physiology / Thomas J. Barstow / The interaction between dynamic muscle contractions and the associated muscle blood flow is very intriguing leading to questions regarding the net effect of these contractions on oxygen delivery and utilization by the working muscle. Study 1 examined the impact of contractions on muscle blood flow at the level of the femoral artery. We demonstrated that muscle contractions had either a facilitory, neutral, or net impedance effect during upright knee extension exercise as intensity increased from very light to ~70% peak work rate. This led to the question of what impact a change in contraction frequency might have on the coupling of blood flow to metabolic rate during cycling exercise. The blood flow/VO2 relationship has been shown to be linear and robust at both the central (i.e., cardiac output/pulmonary VO2) and peripheral (leg blood flow/leg VO2) levels. However, an increase in contraction frequency has been reported to either decrease, have no effect, or increase the blood flow response during exercise. Study 2 determined if the steady state coupling between muscle blood flow and metabolic rate (centrally and/or peripherally) would be altered by varying contraction frequency. Our results indicate that both central and peripheral blood flow/VO2 relationships are robust and remain tightly coupled regardless of changes in contraction frequency. Study 3 examined muscle microvascular hemoglobin concentration and oxygenation within the contraction/relaxation cycle to determine if microvascular RBC volume was preserved and if oxygen extraction occurred during contractions. We concluded that microvascular RBC volume was preserved during muscle contractions (i.e., RBCs remained in the capillaries), which could facilitate continued oxygen delivery. Further, there was a cyclic pattern of deoxygenation/oxygenation that corresponded with the contraction/relaxation phases of the contraction cycle, with deoxyhemoglobin increasing significantly during the contractile phase. These data suggest that oxygen extraction continues to occur during muscle contractions. Significant insight has been gained on the impact of muscle contractions on oxygen delivery to and exchange in active skeletal muscle. This series of studies forms a base of knowledge that furthers our understanding of the mechanisms which govern the control of skeletal muscle blood flow and its coupling to muscle metabolic rate.

The objective of this study was to evaluate the relationship between tissue oxygen saturation (StO2) and oxygen delivery index (DO2I). Oxygen delivery index is product of two factors arterial oxygen content (CaO2) and cardiac index (CI). In this study the relationship between DO2I and StO2 was evaluated by manipulating both of these factors independently. In phase one of the study, CaO2 was altered by manipulating the fractional inspired oxygen (FiO2) concentration. Anesthetized dogs were evaluated at both high (0.40 and 0.95) and low (0.15 and 0.10) FiO2 sequences. In phase two of the study, CI was altered by manipulating the volemic state. Anesthetized dogs were evaluated at hypovolemic, normovolemic and hypervolemic states. In each phase dogs were instrumented for thermodilution cardiac index (CI) and sartorius muscle StO2. Data collected included hemoglobin concentration, heart rate (HR), MAP, CI, StO2. Arterial oxygen content and DO2I were calculated at each time point. Data analysis included Pearson's correlation and mixed model ANOVA (p < 0.05). In both phases one (r = 0.97; p = 0.0013) and two (r = 0.97; p = 0.005) there was a strong correlation between StO2 and DO2I. Under the conditions of this study, there was a strong correlation between StO2 and DO2I, suggesting that StO2 may be used to estimate the adequacy of oxygen delivery in dogs. / Master of Science

With old age, blood flow to the high-oxidative red skeletal muscle is reduced and blood flow to the low-oxidative white muscle is elevated during exercise. Changes in the number of feed arteries perforating the muscle are thought to contribute to this altered hyperemic response during exercise. We tested the hypothesis that exercise training would ameliorate age-related differences in blood flow during exercise and feed artery structure in skeletal muscle. Young (6–7 mo old, n = 36) and old (24 mo old, n = 25) male Fischer 344 rats were divided into young sedentary (Sed), old Sed, young exercise-trained (ET), and old ET groups, where training consisted of 10–12 wk of treadmill exercise. In Sed and ET rats, blood flow to the red and white portions of the gastrocnemius muscle (GastRed and GastWhite) and the number and luminal cross-sectional area (CSA) of all feed arteries perforating the muscle were measured at rest and during exercise. In the old ET group, blood flow was greater to GastRed (264 ± 13 and 195 ± 9 ml·min−1·100 g−1 in old ET and old Sed, respectively) and lower to GastWhite (78 ± 5 and 120 ± 6 ml·min−1·100 g−1 in old ET and old Sed, respectively) than in the old Sed group. There was no difference in the number of feed arteries between the old ET and old Sed group, although the CSA of feed arteries from old ET rats was larger. In young ET rats, there was an increase in the number of feed arteries perforating the muscle. Exercise training mitigated old age-associated differences in blood flow during exercise within gastrocnemius muscle. However, training-induced adaptations in resistance artery morphology differed between young (increase in feed artery number) and old (increase in artery CSA) animals. The altered blood flow pattern induced by exercise training with old age would improve the local matching of O2 delivery to consumption within the skeletal muscle.