Positron emission tomography detects greater blood flow and less blood flow heterogeneity in the exercising skeletal muscles of old compared with young men during fatiguing contractions

摘要

The purpose of this study was to investigate blood flow and its heterogeneity within and among the knee muscles in five young (26 ± 6 years) and five old (77 ± 6 years) healthy men with similar levels of physical activity while they performed two types of submaximal fatiguing isometric contraction that required either force or position control. Positron emission tomography (PET) and [¹⁵O]-H2O were used to determine blood flow at 2 min (beginning) and 12 min (end) after the start of the tasks. Young and old men had similar maximal forces and endurance times for the fatiguing tasks. Although muscle volumes were lower in the older subjects, total muscle blood flow was similar in both groups (young men: 25.8 ± 12.6 ml min⁻¹; old men: 25.1 ± 15.4 ml min⁻¹; age main effect, P = 0.77) as blood flow per unit mass of muscle in the exercising knee extensors was greater in the older (12.5 ± 6.2 ml min⁻¹ (100 g)⁻¹) than the younger (8.6 ± 3.6 ml min⁻¹ (100 g)⁻¹) men (age main effect, P = 0.001). Further, blood flow heterogeneity in the exercising knee extensors was significantly lower in the older (56 ± 27%) than the younger (67 ± 34%) men. Together, these data show that although skeletal muscles are smaller in older subjects, based on the intact neural drive to the muscle and the greater, less heterogeneous blood flow per gram of muscle, old fit muscle achieves adequate exercise hyperaemia.Key points class="unordered" style="list-style-type:disc">The results of previous studies that attempted to demonstrate the effects of ageing on skeletal muscle blood flow are controversial because these studies used indirect assessments of skeletal muscle blood flow obtained via whole limb blood flow measurements that provide no information on the distribution of blood flow within particular muscles.We used positron emission tomography to measure blood flow per gram of muscle in old and young men with similar levels of physical activity.Resting muscle blood flow was similar in both groups and exercising muscle blood flow was greater and less heterogeneous in the older men.Old and young men achieved similar maximal voluntary contraction forces and endurance times during two types of fatiguing isometric task.These findings indicate that physically active old men have intact neural drive to the muscle and achieve adequate exercise hyperaemia despite the age-induced decrease in their muscle volume. class="head no_bottom_margin" id="__sec2title">IntroductionThe magnitude or rate of decline in a performance element relative to a reference value over a given time of task performance, also known as fatigability (Kluger et al. ), is often reduced in old adults compared with their younger counterparts (Ditor & Hicks ; Hunter et al. ; Bilodeau et al. ), but this is not a universal finding (Allman & Rice ; Stackhouse et al. ). Because the mechanisms underlying fatigability depend on the specific demands of the task being performed, it cannot be generalized that muscles of old adults are more or less fatigable than those of young adults (Enoka et al. ).As suggested previously (Allman & Rice, ; Kent-Braun, ), one important mechanism related to skeletal muscle fatigue in elderly subjects is muscle energetics. Accordingly, muscle blood flow is likely to play a significant role in the development of muscle fatigue because an adequate blood supply is important to the delivery of oxygen and nutrients, and the removal of fatigue-inducing metabolic byproducts from the exercising muscles. It has been suggested that an inadequate blood supply to working muscles will ultimately affect their contractile properties, resulting in a decrease in force production (Bigland-Ritchie et al. ). Moreover, whereas some studies have suggested that blood flow to exercising muscles decreases with age (Degens, ; Proctor et al. ), others have demonstrated no differences between age groups in blood flow to exercising muscles during unilateral or bilateral knee extension exercises (Jasperse et al. ; Magnusson et al. ; Proctor et al. ). Discrepancies in the literature may reflect differences in study design, including in the types of task performed and blood flow measurement techniques. For example, indirect assessment of skeletal muscle perfusion via limb blood flow measurements is likely to over- or underestimate muscle blood flow because of differences in the proportions of muscle mass, which is often decreased in older subjects, and the inability to distinguish blood flow in different tissues of the limbs (Cooper et al. ; Raitakari et al. href="#b57" rid="b57" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_425073320">1996). Furthermore, limb blood flow measurements provide no information on the distribution of blood flow within particular muscles.Blood flow distribution between and within working muscles may help to explain muscle fatigability and differences in fatigability between young and old adults. Although previous studies have shown that muscle blood flow is not uniformly distributed among and within working muscles in trained and untrained younger adults both at rest and during intermittent static exercise (Kalliokoski et al. href="#b31" rid="b31" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_425073333">2000, href="#b33" rid="b33" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_425073306">2003a, bhref="#b34" rid="b34" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_425073302">2003b), no study has examined muscle blood flow distribution during isometric contractions in older adults. Because ageing is associated with smaller muscle size and changes in muscle contractile properties and associated vascular properties (Doherty, href="#b16" rid="b16" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_425073307">2003; Kragstrup et al. href="#b41" rid="b41" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_425073295">2011), blood flow distribution may change with ageing.Positron emission tomography (PET) and [¹⁵O]-H2O provide a unique tool for the direct measurement of muscle blood flow (perfusion) in specific muscle regions, which has been used in studies concerning vascular responsiveness to sustained and intermittent knee extension (Kalliokoski et al. href="#b35" rid="b35" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_425073263">2006). PET is based on the use of short-lived positron-emitting radioisotopes such as oxygen-15 (half-life: 123 s). Tracers such as [¹⁵O]-H2O are labelled with radioisotopes and applied to conduct muscle blood flow measurements. Specifically, the tracer is injected into the blood circulation and its concentration in the tissue is detected with the PET scanner. Based on the kinetics of [¹⁵O]-H2O in the arterial blood and tissues of interest, it is possible to obtain quantitative blood flow measurements in specific regions of interest (RoIs) (Iida et al. href="#b28" rid="b28" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_425073321">1986; Ruotsalainen et al. href="#b62" rid="b62" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_425073311">1997).The purpose of this study was to investigate the effects of two types of fatiguing isometric contraction on blood flow and blood flow heterogeneity within and among knee extensors and flexors in healthy and equally physically active young and old men using PET and [¹⁵O]- H2O.