American Journal of Physiology - Heart and Circulatory Physiology, 2015
Low-dose aspirin inhibits thromboxane production and augments the sensitivity of carotid barorefl... more Low-dose aspirin inhibits thromboxane production and augments the sensitivity of carotid baroreflex (CBR) control of heart rate (HR) during concurrent muscle mechanoreflex and metaboreflex activation in healthy young humans. However, it is unknown how aging affects this response. Therefore, the effect of low-dose aspirin on carotid-cardiac baroreflex sensitivity during muscle mechanoreflex with and without metaboreflex activation in healthy older humans was examined. Twelve older subjects (6 men; mean age 62 ± 1y) performed 2 trials during 2 visits, preceded by 7 days' low-dose aspirin (81mg) or placebo. One trial involved 3min passive calf stretch (mechanoreflex) during 7.5min limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5min 70% maximal voluntary contraction isometric calf exercise (mechanoreflex and metaboreflex). HR (ECG) and mean arterial blood pressure (MAP; Finometer) were recorded. CBR function was assessed using rapid neck pressure application (+40 to -80mmHg). Aspirin significantly decreased baseline thromboxane B2 production by 83 ± 4% (P < 0.05) but did not affect 6-keto prostaglandin F1α. Following aspirin, CBR-HR maximal gain (GMAX) and operating point gain (GOP) were significantly higher during stretch with metabolite accumulation compared to placebo (GMAX; -0.23 ± 0.03 vs. -0.14 ± 0.02, and GOP; -0.11 ± 0.03 vs. -0.04 ± 0.01 b.min(-1).mmHg(-1) for aspirin and placebo, respectively; P < 0.05). In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in healthy older humans. This increased sensitivity appears linked to reduced thromboxane sensitization of muscle mechanoreceptors, which consequently improves CBR-HR control.
American journal of physiology. Regulatory, integrative and comparative physiology, 2015
Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympa... more Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP). We hypothesized that the application of suction to the human limbs would activate this venous distension reflex and raise sympathetic outflow. We placed airtight pressure tanks and applied 100 mmHg negative pressure to an arterially occluded limb (occlusion and suction, O&S) to induce tissue deformation without fluid translocation. BP, heart rate (HR), and MSNA were assessed in 19 healthy subjects during 2 minutes of arm or leg O&S. Occlusion without suction served as a control. During a separate visit, saline (5% forearm volume) was infused into veins of the arterially occluded arm (N = 13). The O&S increased limb circumference, MSNA burst rate (arm: Δ6.7 ± 0.7; leg: Δ6.8 ± 0.7 bursts/min) and total activity (arm: Δ199 ± 14; leg: Δ172 ± 22 units/min) and BP (arm: Δ4.3 ± 0.3; leg: Δ9.4 ± 1.4 mmHg) from the baseline. The MSNA and BP re...
American journal of physiology. Heart and circulatory physiology, Jan 8, 2015
Prostanoids are produced during skeletal muscle contraction and subsequently stimulate muscle aff... more Prostanoids are produced during skeletal muscle contraction and subsequently stimulate muscle afferent nerves, thereby contributing to the exercise pressor reflex. Humans with peripheral arterial disease (PAD) have an augmented exercise pressor reflex but the metabolite(s) responsible for this augmented response are not known. We tested the hypothesis that intravenous injection of ketorolac, which blocks the activity of cyclooxygenase, would attenuate the rise in mean arterial blood pressure (MAP) and heart rate (HR) evoked by plantar flexion exercise. Seven PAD patients underwent four minutes of single-leg dynamic plantar flexion (30 contractions/min) in the supine posture (workload 0.5 kg to 2.0 kg). MAP and HR were measured on a beat-by-beat basis; changes from baseline in response to exercise were determined. Ketorolac did not affect MAP or HR at rest. During the first 20 seconds of exercise with the most symptomatic leg, ΔMAP was significantly attenuated with ketorolac (2 ± 2 m...
In this presentation we describe an application of value-focused thinking and decision analysis t... more In this presentation we describe an application of value-focused thinking and decision analysis to the design and evaluation of strategies for housing development especially in urban communities affected by the ongoing foreclosure crisis. This is part of a multi-campus, multi-disciplinary effort to study decision processes of community development corporations (CDCs) acquiring and redeveloping foreclosed properties for neighborhood stabilization.
Reactive oxygen species (ROS), produced acutely during skeletal muscle contraction, are known to ... more Reactive oxygen species (ROS), produced acutely during skeletal muscle contraction, are known to stimulate group IV muscle afferents and accentuate the exercise pressor reflex (EPR) in rodents. The effect of ROS on the EPR in humans is unknown. We conducted a series of studies using ischemic fatiguing rhythmic handgrip to acutely increase ROS within skeletal muscle, ascorbic acid infusion to scavenge free radicals, and hyperoxia inhalation to further increase ROS production. We hypothesized that ascorbic acid would attenuate the EPR and that hyperoxia would accentuate the EPR. Ten young healthy subjects participated in two or three experimental trials on separate days. Beat-by-beat measurements of heart rate (HR), mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and renal vascular resistance index (RVRI) were measured and compared between treatments (saline and ascorbic acid; room air and hyperoxia). At fatigue, the reflex increases in MAP (31 ± 3 versus 29 ± ...
ABSTRACT A multi-site case study applies value-focused thinking methods in a community-engaged re... more ABSTRACT A multi-site case study applies value-focused thinking methods in a community-engaged research framework within three organizations. All three organizations are community development corporations (CDCs), a type of community-based organization which directs assets and efforts toward housing stock and neighborhood improvement. Objectives hierarchies were developed for the three sites. A set of common aspects of these structures suggest ways to operationalize the generic mission of CDCs. Other aspects which vary across sites can be related to specific characteristics of the organizations and the communities in which they operate. The process of applying value-focused thinking is also compared across the organizations. The organizations made judgments about which modeling efforts would be useful at different stages of the study. These judgments are interpreted with respect to the technology acceptance model. They suggest that community-based operations research practitioners will find organizations similar to those in the study to be especially receptive to qualitative construction of objectives hierarchies.
We examined whether spontaneous baroreflex modulation of heart rate and other indexes of cardiac ... more We examined whether spontaneous baroreflex modulation of heart rate and other indexes of cardiac vagal tone could be altered by passive stretch of the human calf muscle during graded concurrent activation of the muscle metaboreflex. Ten healthy subjects performed four trials: a control trial, resting for 1.5 min (0% trial); or 1.5 min of one-legged isometric plantar flexor exercise at 30, 50, and 70% maximal voluntary contraction. The incremental increases in blood pressure (BP) caused were then partially sustained by subsequent local circulatory occlusion (CO). After 3.5 min of CO alone, sustained calf stretch and CO were applied for 3 min. Spontaneous baroreflex sensitivity (SBRS) was progressively decreased with increasing exercise intensity (P < 0.05). During CO, stretch decreased SBRS and increased BP similarly in all trials (P < 0.05). Within 15 s of stretch onset, heart rate (HR) increased by 6 +/- 1, 6 +/- 1, 8 +/- 1, and 6 +/- 2 beats/min in the 0, 30, 50, and 70% trials, respectively (P < 0.05), and root mean square of successive differences was decreased from CO-alone levels (P < 0.05). During the second and third minutes of stretch, HR fell back but remained significantly above CO levels, and common coefficient of variance of R-R interval decreased progressively with increasing prior exercise intensity (P < 0.05; 70% trial). This suggests that passive stretch of the human calf muscles decreases cardiac vagal outflow irrespective of the levels of BP increase caused by muscle metaboreflex activation and implies that central modulation of baroreceptor input, mediated by the actions of stretch-activated mechanoreceptive muscle afferent fibers, continues.
Muscle mechanoreflex activation decreases the sensitivity of carotid baroreflex (CBR)-heart rate ... more Muscle mechanoreflex activation decreases the sensitivity of carotid baroreflex (CBR)-heart rate (HR) control during local metabolite accumulation in humans. However, the contribution of thromboxane A2 (TXA2) toward this response is unknown. Therefore, the effect of inhibiting TXA2 production via low-dose aspirin on CBR-HR sensitivity during muscle mechanoreflex and metaboreflex activation in humans was examined. Twelve young subjects performed two trials during two visits, preceded by 7 days' low-dose aspirin (81 mg) or placebo. One trial involved 3-min passive calf stretch (mechanoreflex) during 7.5-min limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise to accumulate metabolites during CO and stretch (mechanoreflex and metaboreflex). HR (ECG) and mean arterial pressure (Finometer) were recorded. CBR function was assessed using rapid neck pressures ranging from +40 to -80 mmHg. Aspirin significantly decreased baseline thromboxane B2 production by 84 ± 4% (P < 0.05) but did not affect 6-keto prostaglandin F1α. Following aspirin, stretch with metabolite accumulation significantly augmented maximal gain (GMAX) and operating point gain (GOP) of CBR-HR (GMAX; -0.71 ± 0.14 vs. -0.37 ± 0.08 and GOP; -0.69 ± 0.13 vs. -0.35 ± 0.12 beats·min(-1)·mmHg(-1) for aspirin and placebo, respectively; P < 0.05). CBR-HR function curves were reset similarly with aspirin and placebo during stretch with metabolite accumulation. In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in humans. This increased sensitivity appears linked to reduced TXA2 production, which likely plays a role in metabolite sensitization of muscle mechanoreceptors.
The effects of cold air inhalation and isometric exercise on coronary blood flow are currently un... more The effects of cold air inhalation and isometric exercise on coronary blood flow are currently unknown, despite the fact that both cold air and acute exertion trigger angina in clinical populations. In this study, we used transthoracic Doppler echocardiography to measure coronary blood flow velocity (CBV; left anterior descending coronary artery) and myocardial function during cold air inhalation and handgrip exercise. Ten young healthy subjects underwent the following protocols: 5 min of inhaling cold air (cold air protocol), 5 min of inhaling thermoneutral air (sham protocol), 2 min of isometric handgrip at 30% of maximal voluntary contraction (grip protocol), and 5 min of isometric handgrip at 30% maximal voluntary contraction while breathing cold air (cold + grip protocol). Heart rate, blood pressure, inspired air temperature, CBV, myocardial function (tissue Doppler imaging), O(2) saturation, and pulmonary function were measured. The rate-pressure product (RPP) was used as an index of myocardial O(2) demand, whereas CBV was used as an index of myocardial O(2) supply. Compared with the sham protocol, the cold air protocol caused a significantly higher RPP, but there was a significant reduction in CBV. The cold + grip protocol caused a significantly greater increase in RPP compared with the grip protocol (P = 0.045), but the increase in CBV was significantly less (P = 0.039). However, myocardial function was not impaired during the cold + grip protocol relative to the grip protocol alone. Collectively, these data indicate that there is a supply-demand mismatch in the coronary vascular bed when cold ambient air is breathed during acute exertion but myocardial function is preserved, suggesting an adequate redistribution of blood flow.
American Journal of Physiology - Heart and Circulatory Physiology, 2015
Low-dose aspirin inhibits thromboxane production and augments the sensitivity of carotid barorefl... more Low-dose aspirin inhibits thromboxane production and augments the sensitivity of carotid baroreflex (CBR) control of heart rate (HR) during concurrent muscle mechanoreflex and metaboreflex activation in healthy young humans. However, it is unknown how aging affects this response. Therefore, the effect of low-dose aspirin on carotid-cardiac baroreflex sensitivity during muscle mechanoreflex with and without metaboreflex activation in healthy older humans was examined. Twelve older subjects (6 men; mean age 62 ± 1y) performed 2 trials during 2 visits, preceded by 7 days' low-dose aspirin (81mg) or placebo. One trial involved 3min passive calf stretch (mechanoreflex) during 7.5min limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5min 70% maximal voluntary contraction isometric calf exercise (mechanoreflex and metaboreflex). HR (ECG) and mean arterial blood pressure (MAP; Finometer) were recorded. CBR function was assessed using rapid neck pressure application (+40 to -80mmHg). Aspirin significantly decreased baseline thromboxane B2 production by 83 ± 4% (P < 0.05) but did not affect 6-keto prostaglandin F1α. Following aspirin, CBR-HR maximal gain (GMAX) and operating point gain (GOP) were significantly higher during stretch with metabolite accumulation compared to placebo (GMAX; -0.23 ± 0.03 vs. -0.14 ± 0.02, and GOP; -0.11 ± 0.03 vs. -0.04 ± 0.01 b.min(-1).mmHg(-1) for aspirin and placebo, respectively; P < 0.05). In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in healthy older humans. This increased sensitivity appears linked to reduced thromboxane sensitization of muscle mechanoreceptors, which consequently improves CBR-HR control.
American journal of physiology. Regulatory, integrative and comparative physiology, 2015
Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympa... more Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP). We hypothesized that the application of suction to the human limbs would activate this venous distension reflex and raise sympathetic outflow. We placed airtight pressure tanks and applied 100 mmHg negative pressure to an arterially occluded limb (occlusion and suction, O&S) to induce tissue deformation without fluid translocation. BP, heart rate (HR), and MSNA were assessed in 19 healthy subjects during 2 minutes of arm or leg O&S. Occlusion without suction served as a control. During a separate visit, saline (5% forearm volume) was infused into veins of the arterially occluded arm (N = 13). The O&S increased limb circumference, MSNA burst rate (arm: Δ6.7 ± 0.7; leg: Δ6.8 ± 0.7 bursts/min) and total activity (arm: Δ199 ± 14; leg: Δ172 ± 22 units/min) and BP (arm: Δ4.3 ± 0.3; leg: Δ9.4 ± 1.4 mmHg) from the baseline. The MSNA and BP re...
American journal of physiology. Heart and circulatory physiology, Jan 8, 2015
Prostanoids are produced during skeletal muscle contraction and subsequently stimulate muscle aff... more Prostanoids are produced during skeletal muscle contraction and subsequently stimulate muscle afferent nerves, thereby contributing to the exercise pressor reflex. Humans with peripheral arterial disease (PAD) have an augmented exercise pressor reflex but the metabolite(s) responsible for this augmented response are not known. We tested the hypothesis that intravenous injection of ketorolac, which blocks the activity of cyclooxygenase, would attenuate the rise in mean arterial blood pressure (MAP) and heart rate (HR) evoked by plantar flexion exercise. Seven PAD patients underwent four minutes of single-leg dynamic plantar flexion (30 contractions/min) in the supine posture (workload 0.5 kg to 2.0 kg). MAP and HR were measured on a beat-by-beat basis; changes from baseline in response to exercise were determined. Ketorolac did not affect MAP or HR at rest. During the first 20 seconds of exercise with the most symptomatic leg, ΔMAP was significantly attenuated with ketorolac (2 ± 2 m...
In this presentation we describe an application of value-focused thinking and decision analysis t... more In this presentation we describe an application of value-focused thinking and decision analysis to the design and evaluation of strategies for housing development especially in urban communities affected by the ongoing foreclosure crisis. This is part of a multi-campus, multi-disciplinary effort to study decision processes of community development corporations (CDCs) acquiring and redeveloping foreclosed properties for neighborhood stabilization.
Reactive oxygen species (ROS), produced acutely during skeletal muscle contraction, are known to ... more Reactive oxygen species (ROS), produced acutely during skeletal muscle contraction, are known to stimulate group IV muscle afferents and accentuate the exercise pressor reflex (EPR) in rodents. The effect of ROS on the EPR in humans is unknown. We conducted a series of studies using ischemic fatiguing rhythmic handgrip to acutely increase ROS within skeletal muscle, ascorbic acid infusion to scavenge free radicals, and hyperoxia inhalation to further increase ROS production. We hypothesized that ascorbic acid would attenuate the EPR and that hyperoxia would accentuate the EPR. Ten young healthy subjects participated in two or three experimental trials on separate days. Beat-by-beat measurements of heart rate (HR), mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and renal vascular resistance index (RVRI) were measured and compared between treatments (saline and ascorbic acid; room air and hyperoxia). At fatigue, the reflex increases in MAP (31 ± 3 versus 29 ± ...
ABSTRACT A multi-site case study applies value-focused thinking methods in a community-engaged re... more ABSTRACT A multi-site case study applies value-focused thinking methods in a community-engaged research framework within three organizations. All three organizations are community development corporations (CDCs), a type of community-based organization which directs assets and efforts toward housing stock and neighborhood improvement. Objectives hierarchies were developed for the three sites. A set of common aspects of these structures suggest ways to operationalize the generic mission of CDCs. Other aspects which vary across sites can be related to specific characteristics of the organizations and the communities in which they operate. The process of applying value-focused thinking is also compared across the organizations. The organizations made judgments about which modeling efforts would be useful at different stages of the study. These judgments are interpreted with respect to the technology acceptance model. They suggest that community-based operations research practitioners will find organizations similar to those in the study to be especially receptive to qualitative construction of objectives hierarchies.
We examined whether spontaneous baroreflex modulation of heart rate and other indexes of cardiac ... more We examined whether spontaneous baroreflex modulation of heart rate and other indexes of cardiac vagal tone could be altered by passive stretch of the human calf muscle during graded concurrent activation of the muscle metaboreflex. Ten healthy subjects performed four trials: a control trial, resting for 1.5 min (0% trial); or 1.5 min of one-legged isometric plantar flexor exercise at 30, 50, and 70% maximal voluntary contraction. The incremental increases in blood pressure (BP) caused were then partially sustained by subsequent local circulatory occlusion (CO). After 3.5 min of CO alone, sustained calf stretch and CO were applied for 3 min. Spontaneous baroreflex sensitivity (SBRS) was progressively decreased with increasing exercise intensity (P < 0.05). During CO, stretch decreased SBRS and increased BP similarly in all trials (P < 0.05). Within 15 s of stretch onset, heart rate (HR) increased by 6 +/- 1, 6 +/- 1, 8 +/- 1, and 6 +/- 2 beats/min in the 0, 30, 50, and 70% trials, respectively (P < 0.05), and root mean square of successive differences was decreased from CO-alone levels (P < 0.05). During the second and third minutes of stretch, HR fell back but remained significantly above CO levels, and common coefficient of variance of R-R interval decreased progressively with increasing prior exercise intensity (P < 0.05; 70% trial). This suggests that passive stretch of the human calf muscles decreases cardiac vagal outflow irrespective of the levels of BP increase caused by muscle metaboreflex activation and implies that central modulation of baroreceptor input, mediated by the actions of stretch-activated mechanoreceptive muscle afferent fibers, continues.
Muscle mechanoreflex activation decreases the sensitivity of carotid baroreflex (CBR)-heart rate ... more Muscle mechanoreflex activation decreases the sensitivity of carotid baroreflex (CBR)-heart rate (HR) control during local metabolite accumulation in humans. However, the contribution of thromboxane A2 (TXA2) toward this response is unknown. Therefore, the effect of inhibiting TXA2 production via low-dose aspirin on CBR-HR sensitivity during muscle mechanoreflex and metaboreflex activation in humans was examined. Twelve young subjects performed two trials during two visits, preceded by 7 days' low-dose aspirin (81 mg) or placebo. One trial involved 3-min passive calf stretch (mechanoreflex) during 7.5-min limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise to accumulate metabolites during CO and stretch (mechanoreflex and metaboreflex). HR (ECG) and mean arterial pressure (Finometer) were recorded. CBR function was assessed using rapid neck pressures ranging from +40 to -80 mmHg. Aspirin significantly decreased baseline thromboxane B2 production by 84 ± 4% (P < 0.05) but did not affect 6-keto prostaglandin F1α. Following aspirin, stretch with metabolite accumulation significantly augmented maximal gain (GMAX) and operating point gain (GOP) of CBR-HR (GMAX; -0.71 ± 0.14 vs. -0.37 ± 0.08 and GOP; -0.69 ± 0.13 vs. -0.35 ± 0.12 beats·min(-1)·mmHg(-1) for aspirin and placebo, respectively; P < 0.05). CBR-HR function curves were reset similarly with aspirin and placebo during stretch with metabolite accumulation. In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in humans. This increased sensitivity appears linked to reduced TXA2 production, which likely plays a role in metabolite sensitization of muscle mechanoreceptors.
The effects of cold air inhalation and isometric exercise on coronary blood flow are currently un... more The effects of cold air inhalation and isometric exercise on coronary blood flow are currently unknown, despite the fact that both cold air and acute exertion trigger angina in clinical populations. In this study, we used transthoracic Doppler echocardiography to measure coronary blood flow velocity (CBV; left anterior descending coronary artery) and myocardial function during cold air inhalation and handgrip exercise. Ten young healthy subjects underwent the following protocols: 5 min of inhaling cold air (cold air protocol), 5 min of inhaling thermoneutral air (sham protocol), 2 min of isometric handgrip at 30% of maximal voluntary contraction (grip protocol), and 5 min of isometric handgrip at 30% maximal voluntary contraction while breathing cold air (cold + grip protocol). Heart rate, blood pressure, inspired air temperature, CBV, myocardial function (tissue Doppler imaging), O(2) saturation, and pulmonary function were measured. The rate-pressure product (RPP) was used as an index of myocardial O(2) demand, whereas CBV was used as an index of myocardial O(2) supply. Compared with the sham protocol, the cold air protocol caused a significantly higher RPP, but there was a significant reduction in CBV. The cold + grip protocol caused a significantly greater increase in RPP compared with the grip protocol (P = 0.045), but the increase in CBV was significantly less (P = 0.039). However, myocardial function was not impaired during the cold + grip protocol relative to the grip protocol alone. Collectively, these data indicate that there is a supply-demand mismatch in the coronary vascular bed when cold ambient air is breathed during acute exertion but myocardial function is preserved, suggesting an adequate redistribution of blood flow.
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