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1.
J Hypertens ; 34(2): 266-73, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26599223

ABSTRACT

BACKGROUND: Both altered shear rate and endothelin-1 (ET-1) are associated with the age-related development of atherosclerosis. However, the role of ET-1, a potent endogenous vasoconstrictor, in altering shear rate in humans, especially in the atherosclerotic-prone vasculature of the leg, is unknown. Therefore, this study examined the contribution of ET-1 to the age-related alterations in common femoral artery (CFA) shear rate. METHOD: BQ-123, a specific endothelin type A (ET(A)) receptor antagonist, was infused into the CFA, and diameter and blood velocity were measured by Doppler ultrasound in young (n = 8, 24 ±â€Š2 years) and old (n = 9, 70 ±â€Š2 years) study participants. RESULTS AND CONCLUSION: The old had greater intima-media thickening in the CFA, indicative of a preatherogenic phenotype. Prior to infusion, the old study participants exhibited reduced mean shear rate (27 ±â€Š3/s) compared with the young study participants (62 ±â€Š9/s). This difference was likely driven by attenuated antegrade shear rate in the old as retrograde shear rate was similar in the young and old. Inhibition of ETA receptors, by BQ-123, increased leg blood flow in the old, but not in the young, abolishing age-related differences. Older study participants had a larger CFA (young: 0.82 ±â€Š0.03 cm, old: 0.99 ±â€Š0.03 cm) in which BQ-123 induced significant vasodilation (5.1 ±â€Š1.0%), but had no such effect in the young (-0.8 ±â€Š0.8%). Interestingly, despite the age-specific, BQ-123-induced increase in leg blood flow and CFA diameter, shear rate patterns remained largely unchanged. Therefore, ET-1, acting through the ETA receptors, exerts a powerful age-specific vasoconstriction. However, removal of this vasoconstrictor stimulus does not augment mean shear rate in the old.


Subject(s)
Atherosclerosis/physiopathology , Endothelin-1/physiology , Femoral Artery/physiopathology , Adult , Age Factors , Aged , Blood Flow Velocity/drug effects , Endothelin Receptor Antagonists/pharmacology , Endothelium, Vascular/diagnostic imaging , Endothelium, Vascular/drug effects , Hemodynamics/drug effects , Humans , Peptides, Cyclic/pharmacology , Ultrasonography, Doppler , Vasodilation/drug effects , Young Adult
2.
Am J Physiol Heart Circ Physiol ; 309(9): H1479-89, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26386110

ABSTRACT

We investigated the influence of aging on the group III/IV muscle afferents in the exercise pressor reflex-mediated cardiovascular response to rhythmic exercise. Nine old (OLD; 68 ± 2 yr) and nine young (YNG; 24 ± 2 yr) males performed single-leg knee extensor exercise (15 W, 30 W, 80% max) under control conditions and with lumbar intrathecal fentanyl impairing feedback from group III/IV leg muscle afferents. Mean arterial pressure (MAP), cardiac output, leg blood flow (QL), systemic (SVC) and leg vascular conductance (LVC) were continuously determined. With no hemodynamic effect at rest, fentanyl blockade during exercise attenuated both cardiac output and QL ∼17% in YNG, while the decrease in cardiac output in OLD (∼5%) was significantly smaller with no impact on QL (P = 0.8). Therefore, in the face of similar significant ∼7% reduction in MAP during exercise with fentanyl blockade in both groups, LVC significantly increased ∼11% in OLD, but decreased ∼8% in YNG. The opposing direction of change was reflected in SVC with a significant ∼5% increase in OLD and a ∼12% decrease in YNG. Thus while cardiac output seems to account for the majority of group III/IV-mediated MAP responses in YNG, the impact of neural feedback on the heart may decrease with age and alterations in SVC become more prominent in mediating the similar exercise pressor reflex in OLD. Interestingly, in terms of peripheral hemodynamics, while group III/IV-mediated feedback plays a clear role in increasing LVC during exercise in the YNG, these afferents seem to actually reduce LVC in OLD. These peripheral findings may help explain the limited exercise-induced peripheral vasodilation often associated with aging.


Subject(s)
Aging/physiology , Autonomic Nervous System/physiology , Cardiovascular Physiological Phenomena , Cardiovascular System/innervation , Muscle Contraction/physiology , Quadriceps Muscle/physiology , Reflex/physiology , Adult , Aged , Analgesics, Opioid/pharmacology , Arterial Pressure/drug effects , Arterial Pressure/physiology , Autonomic Nervous System/drug effects , Cardiac Output/drug effects , Cardiac Output/physiology , Cardiovascular Physiological Phenomena/drug effects , Cardiovascular System/drug effects , Femoral Artery/drug effects , Femoral Artery/physiology , Fentanyl/pharmacology , Humans , Leg/blood supply , Male , Muscle, Skeletal/physiology , Quadriceps Muscle/drug effects , Reflex/drug effects , Regional Blood Flow/drug effects , Regional Blood Flow/physiology , Vasodilation/drug effects , Vasodilation/physiology , Young Adult
3.
J Cardiothorac Vasc Anesth ; 29(1): 82-8, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25440641

ABSTRACT

OBJECTIVE: Review the findings and use of rescue echocardiography performed by the Division of Perioperative Echocardiography and its impact on patient management. DESIGN: Retrospective observational study. SETTING: Single institution, tertiary care hospital. PARTICIPANTS: Three hundred sixty-four consecutive rescue echocardiograms in the perioperative setting. INTERVENTIONS: Rescue transesophageal or rescue transthoracic echocardiography. MEASUREMENTS AND MAIN RESULTS: Of a total of 1,675 perioperative echocardiograms performed in a 28-month period, 364 (21.8%) were rescue studies. Of these, 95.9% were transesophageal and 4.1% were transthoracic. Location at time of rescue echocardiography was intraoperative (55.5%), postoperative (44.2%), and preoperative (0.3%). No single diagnosis predominated the intraoperative or postoperative environment, and the frequency of common etiologies did not allow for assumption. There was a change in management for 214 patients (59%) as the result of findings. The methods used in performing rescue echocardiography at the authors' institution are reported. CONCLUSIONS: The heterogeneity of diagnoses and the frequency with which rescue echocardiography changed management further supports the growing body of evidence that the hemodynamically unstable perioperative patient benefits from its use.


Subject(s)
Anesthesiology/methods , Echocardiography, Transesophageal/methods , Perioperative Care/methods , Physicians , Adult , Aged , Anesthesiology/standards , Echocardiography, Transesophageal/standards , Electronic Health Records/standards , Female , Humans , Male , Middle Aged , Perioperative Care/standards , Physicians/standards , Retrospective Studies
4.
J Gerontol A Biol Sci Med Sci ; 70(5): 554-65, 2015 May.
Article in English | MEDLINE | ID: mdl-24821105

ABSTRACT

The endothelin-1 vasoconstrictor pathway contributes to age-related elevations in resting peripheral vascular tone primarily through activation of the endothelin subtype A (ET(A)) receptor. However, the regulatory influence of ET(A)-mediated vasoconstriction during exercise in the elderly is unknown. Thus, in 17 healthy volunteers (n = 8 young, 24±2 years; n = 9 old, 70±2 years), we examined leg blood flow, mean arterial pressure, leg arterial-venous oxygen (O2) difference, and leg O2 consumption (VO2) at rest and during knee-extensor exercise before and after intra-arterial administration of the ET(A) antagonist BQ-123. During exercise, BQ-123 administration increased leg blood flow to a greater degree in the old (+29±5 mL/min/W) compared with the young (+16±3 mL/min/W). The increase in leg blood flow with BQ-123 was accompanied by an increase in leg VO2 in both groups, suggesting a reduced efficiency following ET(A) receptor blockade. Together, these findings have identified an age-related increase in ET(A)-mediated vasoconstrictor activity that persists during exercise, suggesting an important role of this pathway in the regulation of exercising skeletal muscle blood flow and maintenance of arterial blood pressure in the elderly.


Subject(s)
Aging/physiology , Endothelin Receptor Antagonists/administration & dosage , Exercise/physiology , Peptides, Cyclic/administration & dosage , Vasoconstriction/drug effects , Vasoconstriction/physiology , Aged , Arterial Pressure/physiology , Female , Healthy Volunteers , Humans , Leg/blood supply , Lipids/blood , Male , Oxygen Consumption/physiology , Young Adult
5.
J Physiol ; 592(22): 5011-24, 2014 Nov 15.
Article in English | MEDLINE | ID: mdl-25172953

ABSTRACT

We investigated the influence of group III/IV lower limb muscle afferents on the development of supraspinal fatigue and the responsiveness of corticospinal projections to an arm muscle. Eight males performed constant-load leg cycling exercise (80% peak power output) for 30 s (non-fatiguing) and to exhaustion (∼9 min; fatiguing) both under control conditions and with lumbar intrathecal fentanyl impairing feedback from µ-opioid receptor-sensitive lower limb muscle afferents. Voluntary activation (VA) of elbow flexors was assessed via transcranial magnetic stimulation (TMS) during maximum voluntary contraction (MVC) and corticospinal responsiveness was monitored via TMS-evoked potentials (MEPs) during a 25% MVC. Accompanied by a significant 5 ± 1% reduction in VA from pre- to post-exercise, elbow flexor MVC progressively decreased during the fatiguing trial (P < 0.05). By contrast, with attenuated feedback from locomotor muscle afferents, MVC and VA remained unchanged during fatiguing exercise (P > 0.3). MEPs decreased by 36 ± 6% (P < 0.05) from the start of exercise to exhaustion under control conditions, but this reduction was prevented with fentanyl blockade. Furthermore, fentanyl blockade prevented the significant increase in elbow flexor MEP observed from rest to non-fatiguing exercise under control conditions and resulted in a 14% lower corticospinal responsiveness during this short bout (P < 0.05). Taken together, in the absence of locomotor muscle fatigue, group III/IV-mediated leg muscle afferents facilitate responsiveness of the motor pathway to upper limb flexor muscles. By contrast, in the presence of cycling-induced leg fatigue, group III/IV locomotor muscle afferents facilitate supraspinal fatigue in remote muscle not involved in the exercise and disfacilitate, or inhibit, the responsiveness of corticospinal projections to upper limb muscles.


Subject(s)
Extremities/innervation , Muscle Fatigue , Muscle, Skeletal/physiology , Pyramidal Tracts/physiology , Receptors, Opioid, mu/agonists , Adult , Afferent Pathways/drug effects , Afferent Pathways/physiology , Evoked Potentials, Motor , Extremities/physiology , Feedback, Physiological , Fentanyl/pharmacology , Humans , Male , Muscle Contraction , Muscle, Skeletal/innervation
6.
Am J Physiol Heart Circ Physiol ; 304(1): H162-9, 2013 Jan 01.
Article in English | MEDLINE | ID: mdl-23103494

ABSTRACT

The cardiovascular response to exercise is governed by a combination of vasodilating and vasoconstricting influences that optimize exercising muscle perfusion while protecting mean arterial pressure (MAP). The degree to which endogenous endothelin (ET)-1, the body's most potent vasoconstrictor, participates in this response is unknown. Thus, in eight young (24 ± 2 yr), healthy volunteers, we examined leg blood flow, MAP, tissue oxygenation, heart rate, leg arterial-venous O(2) difference, leg O(2) consumption, pH, and net ET-1 and lactate release at rest and during knee extensor exercise (0, 5, 10, 15, 20, and 30 W) before and after an intra-arterial infusion of BQ-123 [ET subtype A (ET(A)) receptor antagonist]. At rest, BQ-123 did not evoke a change in leg blood flow or MAP. During exercise, net ET-1 release across the exercising leg increased approximately threefold. BQ-123 increased leg blood flow by ~20% across all work rates (changes of 113 ± 76, 176 ± 83, 304 ± 108, 364 ± 130, 502 ± 117, and 570 ± 178 ml/min at 0, 5, 10, 15, 20, and 30 W, respectively) and attenuated the exercise-induced increase in MAP by ~6%. The increase in leg blood flow was accompanied by a ~9% increase in leg O(2) consumption with an unchanged arterial-venous O(2) difference and deoxyhemoglobin, suggesting a decline in intramuscular efficiency after ET(A) receptor blockade. Together, these findings identify a significant role of the ET-1 pathway in the cardiovascular response to exercise, implicating vasoconstriction via the ET(A) receptor as an important mechanism for both the restraint of blood flow in the exercising limb and maintenance of MAP in healthy, young adults.


Subject(s)
Arterial Pressure , Endothelin-1/metabolism , Exercise , Muscle Contraction , Muscle, Skeletal/blood supply , Muscle, Skeletal/metabolism , Vasoconstriction , Adult , Arterial Pressure/drug effects , Endothelin A Receptor Antagonists , Heart Rate , Humans , Hydrogen-Ion Concentration , Infusions, Intra-Arterial , Lactic Acid/metabolism , Muscle, Skeletal/drug effects , Oxygen Consumption , Peptides, Cyclic/administration & dosage , Receptor, Endothelin A/metabolism , Regional Blood Flow , Time Factors , Vasoconstriction/drug effects , Young Adult
7.
Reg Anesth Pain Med ; 34(1): 29-32, 2009.
Article in English | MEDLINE | ID: mdl-19258985

ABSTRACT

BACKGROUND AND OBJECTIVES: Paresthesias are relatively common during spinal needle insertion, however, the clinical significance of the paresthesia is unknown. A paresthesia may result from needle-to-nerve contact with a spinal nerve in the epidural space, or, with far lateral needle placement, may result from contact with a spinal nerve within the intervertebral foramen. However, it is also possible and perhaps more likely, that paresthesias occur when the spinal needle contacts a spinal nerve root within the subarachnoid space. This study was designed to test this latter hypothesis. METHODS: Patients (n = 104) scheduled for surgery under spinal anesthesia were observed during spinal needle insertion. If a paresthesia occurred, the needle was fixed in place and the stylet removed to observe whether cerebrospinal fluid (CSF) flowed from the hub. The presence of CSF was considered proof that the needle had entered the subarachnoid space. RESULTS: Paresthesias occurred in 14/103 (13.6%) of patients; 1 patient experienced a paresthesia twice. All paresthesias were transient. Following a paresthesia, CSF was observed in the needle hub 86.7% (13/15) of the time. CONCLUSIONS: Our data suggest that the majority of transient paresthesias occur when the spinal needle enters the subarachnoid space and contacts a spinal nerve root. Therefore, when transient paresthesias occur during spinal needle placement it is appropriate to stop and assess for the presence of CSF in the needle hub, rather than withdraw and redirect the spinal needle away from the side of the paresthesia as some authors have suggested.


Subject(s)
Anesthesia, Spinal , Anesthetics, Local/administration & dosage , Injections, Spinal/adverse effects , Paresthesia/etiology , Aged , Female , Humans , Male , Middle Aged , Paresthesia/cerebrospinal fluid , Prospective Studies , Spinal Nerve Roots/physiology , Subarachnoid Space
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