Andrew M. Alexander

Sex differences in the cardiovascular consequences of the inspiratory muscle metaboreflex

It is currently unknown whether sex differences exist in the cardiovascular consequences of the inspiratory muscle metaboreflex. We hypothesized that the activation of the inspiratory muscle metaboreflex will lead to less of an increase in mean arterial pressure (MAP) and limb vascular resistance (LVR) and less of a decrease in limb blood flow (Q̇L) in women compared with men. Twenty healthy men (n = 10, 23 ± 2 yr) and women (n = 10, 22 ± 3 yr) were recruited for this study. Subjects performed inspiratory resistive breathing tasks (IRBTs) at 2% or 65% of their maximal inspiratory mouth pressure (PIMAX). During the IRBTs, the breathing frequency was 20 breaths/min with a 50% duty cycle. At rest and during the IRBTs, MAP was measured via automated oscillometry, Q̇L was measured via Doppler ultrasound, and LVR was calculated. EMG was recorded on the leg to ensure no muscle contraction occurred. The 65% IRBT led to attenuated increases (P < 0.01) from baseline in women compared with men for MAP (W: 7.3 ± 2.0 mmHg; M: 11.1 ± 5.0 mmHg) and LVR (W: 17.7% ± 14.0%; M: 47.9 ± 21.0%), as well as less of a decrease (P < 0.01) in Q̇L (W: -7.5 ± 9.9%; M: -23.3 ± 10.2%). These sex differences in MAP, Q̇L, and LVR were still present in a subset of subjects matched for PIMAX The 2% IRBT resulted in no significant changes in MAP, Q̇L, or LVR across time or between men and women. These data indicate premenopausal women exhibit an attenuated inspiratory muscle metaboreflex compared with age-matched men.

Cardiovascular Consequences of the Inspiratory Muscle Metaboreflex: Effects of Age and Sex

With inspiratory muscle metaboreflex activation, we hypothesized that, compared with their younger counterparts, older men and women would exhibit greater 1) increases in mean arterial pressure (MAP) and limb vascular resistance (LVR) and 2) decreases in limb blood flow (Q̇L) but 3) no sex differences would be present in older adults. Sixteen young adults [8 young men (YM) and 8 young women (YW), 18-24 yr] and 16 older adults [8 older men (OM) and 8 older women (OW), 60-73 yr] performed inspiratory resistive breathing tasks (IRBTs) at 2% and 65% of their maximal inspiratory pressure. During the IRBTs, breathing frequency was 20 breaths/min with a 50% duty cycle. At baseline and during the IRBTs, MAP was measured via automated oscillometry, Q̇L was determined via Doppler ultrasound, and LVR was calculated. The 65% IRBT led to significantly greater increases in MAP in OW (15.9 ± 8.1 mmHg) compared with YW (6.9 ± 1.4 mmHg) but not (P > 0.05) between OM (12.3 ± 5.7 mmHg) and YM (10.8 ± 5.7 mmHg). OW (-20.2 ± 7.2%) had greater (P < 0.05) decreases in Q̇L compared with YW (-9.4 ± 10.2%), but no significant differences were present between OM (-22.8 ± 9.7%) and YM (-22.7 ± 11.3%) during the 65% IRBT. The 65% IRBT led to greater (P < 0.05) increases in LVR in OW (48.2 ± 25.5%) compared with YW (19.7 ± 15.0%), but no differences (P > 0.05) existed among OM (54.4 ± 17.8%) and YM (47.1 ± 23.3%). No significant differences were present in MAP, Q̇L, or LVR between OM and OW. These data suggest that OW exhibit a greater inspiratory muscle metaboreflex compared with YW, whereas no differences between OM and YM existed. Finally, sex differences in the inspiratory muscle metaboreflex are not present in older adults.NEW & NOTEWORTHY Premenopausal women exhibit an attenuated inspiratory muscle metaboreflex compared with young men; however, it is unknown whether these sex differences are present in older adults. Older women exhibited a greater inspiratory muscle metaboreflex compared with premenopausal women, whereas no differences were present between older and younger men.

Effect of cyclooxygenase inhibition on the inspiratory muscle metaboreflex-induced cardiovascular consequences in men

Inspiratory muscle metaboreflex activation increases mean arterial pressure (MAP) and limb vascular resistance (LVR) and decreases limb blood flow (Q̇L). Cyclooxygenase (COX) inhibition has been found to attenuate limb skeletal muscle metaboreflex-induced increases in muscle sympathetic nerve activity. We hypothesized that compared with placebo (PLA), COX inhibition would attenuate inspiratory muscle metaboreflex-induced 1) increases in MAP and LVR and 2) decreases in Q̇L Seven men (22 ± 1 yr) were recruited and orally consumed ibuprofen (IB; 10 mg/kg) or PLA 90 min before performing the cold pressor test (CPT) for 2 min and inspiratory resistive breathing task (IRBT) for 14.9 ± 2.0 min at 65% of maximal inspiratory pressure. Breathing frequency was 20 breaths/min with a 50% duty cycle during the IRBTs. MAP was measured via automated oscillometry, Q̇L was determined via Doppler ultrasound, and LVR was calculated as MAP divided by Q̇L Electromyography was recorded on the leg to ensure no muscle contraction occurred. The 65% IRBT led to greater increases (P = 0.02) in 6-keto-prostaglandin-F1α with PLA compared with IB. IB, compared with PLA, led to greater (P < 0.01) increases in MAP (IB: 17 ± 7 mmHg vs. PLA: 8 ± 5 mmHg) and LVR (IB: 69 ± 28% vs. PLA: 52 ± 22%) at the final minute of the 65% IRBT. The decrease in Q̇L was not different (P = 0.72) between IB (-28 ± 11%) and PLA (-27 ± 9%) at the final minute. The increase in MAP during the CPT was not different (P = 0.87) between IB (25 ± 11 mmHg) and PLA (24 ± 6 mmHg). Contrary to our hypotheses, COX inhibition led to greater inspiratory muscle metaboreflex-induced increases in MAP and LVR.NEW & NOTEWORTHY Cyclooxygenase (COX) products play a role in activating the muscle metaboreflex. It is not known whether COX products contribute to the inspiratory muscle metaboreflex. Herein, we demonstrate that COX inhibition led to greater increases in blood pressure and limb vascular resistance compared with placebo during inspiratory muscle metaboreflex activation.

The noninvasive simultaneous measurement of tissue oxygenation and microvascular hemodynamics during incremental handgrip exercise

Limb blood flow increases linearly with exercise intensity; however, invasive measurements of muscle microvascular blood flow during incremental exercise have demonstrated submaximal plateaus. We tested the hypotheses that 1) brachial artery blood flow (Q̇BA) would increase with increasing exercise intensity until task failure, 2) blood flow index of the flexor digitorum superficialis (BFIFDS) measured noninvasively via diffuse correlation spectroscopy would plateau at a submaximal work rate, and 3) muscle oxygenation characteristics (total-[heme], deoxy-[heme], and percentage saturation) measured noninvasively with near-infrared spectroscopy would demonstrate a plateau at a similar work rate as BFIFDS. Sixteen subjects (23.3 ± 3.9 yr, 170.8 ± 1.9 cm, 72.8 ± 3.4 kg) participated in this study. Peak power (Ppeak) was determined for each subject (1.8 ± 0.4 W) via an incremental handgrip exercise test. Q̇BA, BFIFDS, total-[heme], deoxy-[heme], and percentage saturation were measured during each stage of the exercise test. On a subsequent testing day, muscle activation measurements of the FDS (RMSFDS) were collected during each stage of an identical incremental handgrip exercise test via electromyography from a subset of subjects ( n = 7). Q̇BA increased with exercise intensity until the final work rate transition ( P < 0.05). No increases in BFIFDS or muscle oxygenation characteristics were observed at exercise intensities greater than 51.5 ± 22.9% of Ppeak. No submaximal plateau in RMSFDS was observed. Whereas muscle activation of the FDS increased until task failure, noninvasively measured indices of perfusive and diffusive muscle microvascular oxygen delivery demonstrated submaximal plateaus. NEW & NOTEWORTHY Invasive measurements of muscle microvascular blood flow during incremental exercise have demonstrated submaximal plateaus. We demonstrate that indices of perfusive and diffusive microvascular oxygen transport to skeletal muscle, measured completely noninvasively, plateau at submaximal work rates during incremental exercise, even though limb blood flow and muscle recruitment continued to increase.