Perfusion heterogeneity does not explain excess muscle oxygen uptake during variable intensity exercise Marko S. Laaksonen 1 , Glenn Bjo ¨rklund 1 , Ilkka Heinonen 2,3 , Jukka Kemppainen 2,3 , Juhani Knuuti 2 , Heikki Kyro ¨la¨inen 4 and Kari K. Kalliokoski 2 1 Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, O ¨ stersund, Sweden, 2 Turku PET Centre and 3 Department of Clinical Physiology and Nuclear Medicine, University of Turku, Turku, and 4 Neuromuscular Research Centre, Department of Biology of Physical Activity, University of Jyva ¨skyla ¨, Jyva ¨skyla ¨, Finland Correspondence Dr Marko S. Laaksonen, Mid Sweden University, Swedish Winter Sports Research Centre, Department of Health Sciences, SE-831 25 O ¨ stersund, Sweden E-mail: marko.laaksonen@miun.se Accepted for publication Received 8 October 2009; accepted 1 March 2010 Key words blood flow; knee extension; oxygen delivery; positron emission tomography; skeletal muscle Summary The association between muscle oxygen uptake (VO 2 ) and perfusion or perfusion heterogeneity (relative dispersion, RD) was studied in eight healthy male subjects during intermittent isometric (1 s on, 2 s off) one-legged knee-extension exercise at variable intensities using positron emission tomography and a-v blood sampling. Resistance during the first 6 min of exercise was 50% of maximal isometric voluntary contraction force (MVC) (HI-1), followed by 6 min at 10% MVC (LOW) and finishing with 6 min at 50% MVC (HI-2). Muscle perfusion and O 2 delivery during HI-1 (26 ± 5 and 5Æ4±1Æ0 ml 100 g )1 min )1 ) and HI-2 (28 ± 4 and 5Æ8±0Æ7 ml 100 g )1 min )1 ) were similar, but both were higher (P<0Æ01) than during LOW (15 ± 3 and 3Æ0±0Æ6 ml 100 g )1 min )1 ). Muscle VO 2 was also higher during both HI workloads (HI-1 3Æ3±0Æ4 and HI-2 4Æ1±0Æ6 ml 100 g )1 min )1 ) than LOW (1Æ4±0Æ4 ml 100 g )1 min )1 ; P<0Æ01) and 25% higher during HI-2 than HI-1 (P<0Æ05). O 2 extraction was higher during HI workloads (HI-1 62 ± 7 and HI-2 70 ± 7%) than LOW (45 ± 8%; P<0Æ01). O 2 extraction tended to be higher (P =0Æ08) during HI-2 when compared to HI-1. Perfusion was less heterogeneous (P<0Æ05) during HI workloads when compared to LOW with no difference between HI workloads. Thus, during one-legged knee- extension exercise at variable intensities, skeletal muscle perfusion and O 2 delivery are unchanged between high-intensity workloads, whereas muscle VO 2 is increased during the second high-intensity workload. Perfusion heterogeneity cannot explain this discrepancy between O 2 delivery and uptake. We propose that the excess muscle VO 2 during the second high-intensity workload is derived from working muscle cells. Introduction Muscle and limb blood flow is correlated with muscle oxygen (O 2 ) uptake during increasing exercise intensity (Radegran & Saltin, 1998), and these parameters remain stable during prolonged (2 h) knee-extension exercise at a constant workload (Kiens et al., 1993). However, repeated exercise bouts have shown conflicting results. While one study (MacDonald et al., 2001) did not observe any changes in limb blood flow and O 2 uptake during consecutive exercise bouts, another showed increases in both variables (Krustrup et al., 2001). There is also evidence that potentially limited O 2 utilization at the onset of exercise is not attributed to insufficient O 2 availability (Bangsbo et al., 2000; Nyberg et al., 2010). However, both limb blood flow and O 2 uptake kinetics have been shown to be faster when exercise bouts are repeated, indicating that muscle blood flow limits O 2 availability at the onset of exercise (Krustrup et al., 2001; MacDonald et al., 2001; DeLorey et al., 2007). Thus, prior exercise might result in increased muscle O 2 delivery mediated by vasodilation (Gerbino et al., 1996; Jones et al., 2003). Oxidative metabolism in muscle is regulated, at least in part, by the balance between muscle O 2 delivery and uptake (Saitoh et al., 2009). During maximal exercise with a large activated muscle mass, the cardiac function and peripheral vasoconstric- tion may limit muscle O 2 availability (Saltin, 1985; Mortensen et al., 2008). When a smaller muscle mass is engaged, the central Clin Physiol Funct Imaging (2010) 30, pp241–249 doi: 10.1111/j.1475-097X.2010.00934.x Ó 2010 The Authors Journal compilation Ó 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine 30, 4, 241–249 241