Contribution of anaerobic metabolism to reactive hyperemia in skeletal muscle

Abstract

Tó th A, Pal M, Intaglietta M, Johnson PC. Contribution of anaerobic metabolism to reactive hyperemia in skeletal muscle. Am J Physiol Heart Circ Physiol 292: H2643-H2653, 2007. First published February 16, 2007 doi:10.1152/ajpheart.00207.2006.-Elevated blood flow (reactive hyperemia) is seen in many organs after a period of blood flow stoppage. This hyperemia is often considered to be due in part to a shift to anaerobic metabolism during tissue hypoxia. The aim of our study was to test this hypothesis in skeletal muscle. For this purpose we measured NADH fluorescence at localized tissue areas in cat sartorius muscle during and after arterial occlusions of 5-300 s. In parallel studies, red blood cell (RBC) velocity was measured in venules. Tissue NADH fluorescence rose significantly with occlusions of 45 s or greater, reaching a maximum of 44% above control at 180 s. Peak RBC velocity rose to four times control as occlusion duration was increased from 5 to 45 s, but hyperemia duration was stable at ϳ70 s. With occlusions of 45-240 s, hyperemia duration increased progressively to 210 s while peak flow was unchanged. However, after 300-s occlusions, peak flow rose to six times above control and hyperemia duration fell to 140 s. With occlusions of 45-300 s the time integral both of increased NADH fluorescence and of reduced fluorescence following occlusion release showed a high degree of correlation with the additional hyperemia. We conclude that in this muscle anaerobic vasodilator metabolites are responsible for the increase in reactive hyperemia with arterial occlusions longer than 45 s. Since the durations of reactive hyperemia and reduced fluorescence are substantially different, vasodilator metabolite removal may be due to washout by the bloodstream rather than metabolic uptake. anoxia; vasodilator metabolites; metabolic feedback; NADH fluorescence; red blood cell velocity; microcirculation; blood flow regulation REACTIVE HYPEREMIA is the increase in blood flow above resting levels that occurs after a period of blood flow stoppage, usually induced by arterial occlusion. This phenomenon has been demonstrated in a wide variety of vascular beds including skeletal muscle (4), myocardium (9), liver (14), kidney (16), intestine (36), and skin (27). The hyperemia is often attributed to accumulation of vasodilator metabolites produced by anaerobic metabolism during tissue hypoxia (1,13,28,47). However, occlusions of a few seconds' duration also elicit a hyperemic response, although this is too brief to deplete oxygen stores as noted initially by Bayliss in 1902 (3). This finding suggests that other mechanisms such as the myogenic response may contribute, since a fall in intravascular pressure during arterial occlusion would lead to arteriolar relaxation and a subsequent hyperemia when the pressure is restored. Studies on skeletal muscle (21, 25) supported the suggestion that the response following short-term (5-30 s) occlusions in resting skeletal muscle is primarily myogenic. However, with reports of additional flo...

Vascular responsiveness measured by tissue oxygen saturation reperfusion slope is sensitive to different occlusion durations and training status

“…For example, Maiorana et al (2001b) were unable to detect differences between a trained and an untrained group of middle-aged subjects. Metabolite build-up (including nitric oxide, ATP and prostaglandins) is known to influence the vascular responsiveness (Joannides et al 1995;Toth et al 2007;Kooijman et al 2008;Crecelius et al 2011), and it is possible that the 5 min occlusion duration may elicit a maximal dilatory response in all individuals. Therefore, a single long-duration occlusion period may not best reflect vascular differences between different subject populations.…”

Hyperaemic changes in forearm skin perfusion and RBC concentration after increasing occlusion times

“…The techniques that have been used include those commonly used with isolated arteries, such as myography (Rogers and Sheriff, 2005) and intravital microscopy (Toth et al, 2007). In human studies, PORH has been measured by plethysmography techniques (Acree et al, 2007;Faizi et al, 2009), ultrasound (van Langen et al, 2001) and laser Doppler flowmetry (Beinder and Schlembach, 2001;Hashimoto, 1994;Thorfinn et al, 2007;Yamamoto-Suganuma and Aso, 2009).…”

Post-Occlusive Reactive Hyperemia in Basal Cell Carcinoma and Its Potential Application to Improve the Efficacy of Solid Tumor Therapies

“…PORH consists in a distal bed vasodilatation (Wood et al 1955) principally induced by ischemia-induced vasodilators synthesis (Tóth et al 2007) and myogenic response (Schubert and Mulvany 1999). Thereby, pre-occlusion vasodilatation induced by lidocaine decreased the vasodilatatory reserve of BCC supplying vessels and/or BCC vessels themselves, thus resulting in decreased PORH.…”