The time course and magnitude of increases in brachial artery mean blood velocity (MBV; pulsed Doppler), diameter (D; echo Doppler), mean perfusion pressure (MPP; Finapres), shear rate (gamma = 8.MBV/D), and forearm blood flow (FBF = MBV.pi r2) were assessed to investigate the effect that prostaglandins (PGs) have on the hyperemic response on going from rest to rhythmic exercise in humans. While supine, eight healthy men performed 5 min of dynamic handgrip exercise by alternately raising and lowering a 4.4-kg weight (approximately 10% maximal voluntary contraction) with a work-to-rest cycle of 1:1 (s/s). When the exercise was performed with the arm positioned below the heart, the rate of increase in MBV and gamma was faster compared with the same exercise performed above the heart. Ibuprofen (Ibu; 1,200 mg/day, to reduce PG-induced vasodilation) and placebo were administered orally for 2 days before two separate testing sessions in a double-blind manner. Resting heart rate was reduced in Ibu (52 +/- 3 beats/min) compared with placebo (57 +/- 3 beats/min) (P < 0.05) without change to MPP. With placebo, D increased in both arm positions from approximately 4.3 mm at rest to approximately 4.5 mm at 5 min of exercise (P < 0.05). This response was not altered with Ibu (P > 0.05). Ibu did not alter the time course of MBV or forearm blood flow (P > 0.05) in either arm position. The gamma was significantly greater in Ibu vs. placebo at 30 and 40 s of above the heart exercise and for all time points after 25 s of below the heart exercise (P < 0.05). Because PG inhibition altered the time course of gamma at the brachial artery, but not FBF, it was concluded that PGs are not essential in regulating the blood flow responses to dynamic exercise in humans.

Background-Exercise intolerance in heart failure (HF) may be due to inadequate vasodilation, augmented vasoconstriction, and/or altered muscle metabolic responses that lead to fatigue. Methods and Results-Vascular and metabolic responses to rhythmic forearm exercise were tested in 9 HF patients and 9 control subjects (CTL) during 2 protocols designed to examine the effect of HF on the time course of oxygen delivery versus uptake (protocol 1) and on vasoconstriction during exercise with 50 mm Hg pressure about the forearm to evoke a metaboreflex (protocol 2). In protocol 1, venous lactate and H ϩ were greater at 4 minutes of exercise in HF versus CTL (PϽ0.05) despite similar blood flow and oxygen uptake responses. In protocol 2, mean arterial pressure increased similarly in each group during ischemic exercise. In CTL, forearm blood flow and vascular conductance were similar at the end of ischemic and ambient exercise. In HF, forearm blood flow and vascular conductance were reduced during ischemic exercise compared with the ambient trial. Conclusions-Intrinsic differences in skeletal muscle metabolism, not vasodilatory dynamics, must account for the augmented glycolytic metabolic responses to moderate-intensity exercise in class II and III HF. The inability to increase forearm vascular conductance during ischemic handgrip exercise, despite a normal pressor response, suggests that enhanced vasoconstriction of strenuously exercising skeletal muscle contributes to exertional fatigue in HF.(Circulation. 1999;99:3002-3008.)

We used an exercise paradigm with repeated bouts of heavy forearm exercise to test the hypothesis that alterations in local acid-base environment that remain after the first exercise result in greater blood flow and O(2) delivery at the onset of the second bout of exercise. Two bouts of handgrip exercise at 75% peak workload were performed for 5 min, separated by 5 min of recovery. We continuously measured blood flow using Doppler ultrasound and sampled venous blood for O(2) content, PCO(2), pH, and lactate and potassium concentrations, and we calculated muscle O(2) uptake (VO(2)). Forearm blood flow was elevated before the second exercise compared with the first and remained higher during the first 30 s of exercise (234 +/- 18 vs. 187 +/- 4 ml/min, P < 0.05). Flow was not different at 5 min. Arteriovenous O(2) content difference was lower before the second bout (4.6 +/- 0.9 vs. 7.2 +/- 0.7 ml O(2)/dl) and higher by 30 s of exercise (11.2 +/- 0.7 vs. 10.8 +/- 0.7 ml O(2)/dl, P < 0. 05). Muscle VO(2) was unchanged before the start of exercise but was elevated during the first 30 s of the transition to the second exercise bout (26.0 +/- 2.1 vs. 20.0 +/- 0.9 ml/min, P < 0.05). Changes in venous blood PCO(2), pH, and lactate concentration were consistent with reduced reliance on anaerobic glycolysis at the onset of the second exercise bout. These data show that limitations of muscle blood flow can restrict the adaptation of oxidative metabolism at the onset of heavy muscular exertion.