Biomedical subjects

Paul J Fadel

Publications and source records attributed to Paul J Fadel.

24 records · Page 2Linked to original sources

PubMed2003

Does pulsatile and sustained neck pressure or neck suction produce differential cardiovascular and sympathetic responses in humans?

Although square-wave sustained and R wave-triggered pulsatile stimuli have been used to assess carotid baroreflex (CBR) function in humans, it remains unclear whether these different stimulus protocols elicit comparable responses and whether CBR responses adapt during prolonged stimulation. Thus, we measured muscle sympathetic nerve activity (MSNA), heart rate (HR) and mean arterial pressure (MAP) in response to +30 Torr neck pressure (NP) and -30 Torr neck suction (NS) delivered for 20 s either as a sustained or pulsatile stimulus. CBR-mediated changes in MSNA, HR and MAP were similar with sustained and pulsatile stimuli. The time course of MSNA and HR responses identified that significant changes occurred during the initial 5 s and were better maintained over 20 s with NP than with NS. Changes in MAP exhibited a slower onset with the peak increase during NP occurring at 10 s (sustained, 7 +/- 1 mmHg; pulsatile, 7 +/- 1 mmHg; P > 0.05) and the nadir during NS occurring at 20 s (sustained, -7 +/- 1 mmHg; pulsatile, -9 +/- 2 mmHg; P > 0.05). These data demonstrate that sustained and pulsatile NP and NS produce comparable CBR-mediated responses. Furthermore, despite MSNA and HR returning towards baseline during NS, CBR-mediated changes in MAP are well maintained over 20 s of NS and NP.

Adaptation, Physiological↗

PubMed2003

Recent insights into carotid baroreflex function in humans using the variable pressure neck chamber.

The variable pressure neck chamber has provided an invaluable research tool for the non-invasive assessment of carotid baroreflex (CBR) function in human investigations. The ability to construct complete stimulus-response curves and define specific parameters of the reflex function curve permits statistical comparisons of baroreflex function between different experimental conditions, such as rest and exercise. Results have convincingly indicated that the CBR stimulus-response curve is reset during exercise in an intensity-dependent manner to functionally operate around the prevailing pressure elicited by the exercise workload. Furthermore, both at rest and during exercise, alterations in stroke volume do not contribute importantly to the maintenance of arterial blood pressure by the carotid baroreceptors, and therefore, any reflex-induced changes in cardiac output (Q) are the result of CBR-mediated changes in heart rate. However, more importantly, the CBR-induced changes in mean arterial pressure (MAP) are primarily mediated by alterations in vascular conductance with only minimal contributions from Q to the initial reflex MAP response. Thus, the capacity of the CBR to regulate blood pressure depends critically on its ability to alter vascular tone both at rest and during exercise. This review will emphasize the utility of the variable pressure neck chamber to assess CBR function in human experimental investigations and the mechanisms by which the CBR responds to alterations in arterial blood pressure both at rest and during exercise.

Baroreflex↗

PubMed2002

Basis for the cardiac-related rhythm in muscle sympathetic nerve activity of humans.

We tested the hypothesis that the cardiac-related rhythm in muscle sympathetic nerve activity (MSNA) of humans reflects entrainment of a central oscillator by pulse-synchronous baroreceptor nerve activity. Partial autospectral analysis was used to mathematically remove the portion of cardiac-related power in MSNA autospectra that was attributable to its linear relationship to the ECG. In 54 of 98 cases, > or =15% of cardiac-related power remained after partialization with the ECG; peak residual cardiac-related power was often at a frequency different than heart rate. When assessed on a cardiac-related burst-by-burst basis, there was a progressive and cyclic change in the ECG-MSNA interval (delay from R wave to peak of cardiac-related burst) on the time scale of respiration in four subjects. In these subjects, as well as in some in which the interval appeared to change randomly, there was an inverse relationship between the ECG-MSNA interval and cardiac-related burst amplitude. However, in 45% of the cases, these parameters were not related. These results support the view that the cardiac-related rhythm in MSNA reflects forcing of a nonlinear oscillator rather than periodic inhibition of unstructured, random activity.

Adult↗

PubMed2002

Carotid baroreflex control of leg vascular conductance at rest and during exercise.

We sought to test the hypothesis that the carotid baroreflex (CBR) alters mean leg blood flow (LBF) and leg vascular conductance (LVC) at rest and during exercise. In seven men and one woman, 25 +/- 2 (SE) yr of age, CBR control of LBF and LVC was determined at rest and during steady-state one-legged knee extension exercise at approximately 65% peak O(2) uptake. The application of 5-s pulses of +40 Torr neck pressure and -60 Torr neck suction significantly altered mean arterial pressure (MAP) and LVC both at rest and during exercise. CBR-mediated changes in MAP were similar between rest and exercise (P > 0.05). However, CBR-mediated decreases in LVC (%change) to neck pressure were attenuated in the exercising leg (16.4 +/- 1.6%) compared with rest (33 +/- 2.1%) and the nonexercising leg (23.7 +/- 1.9%) (P < 0.01). These data suggest CBR control of blood pressure is partially mediated by changes in leg vascular tone both at rest and during exercise. Furthermore, despite alterations in CBR-induced changes in LVC during exercise, CBR control of blood pressure was well maintained.

Adult↗

PubMed2002

Mechanism of the blood pressure--raising effect of cocaine in humans.

BACKGROUND: Although the sympathomimetic actions and cardiovascular complications of cocaine are ascribed to inhibition of norepinephrine (NE) reuptake, this hypothesis has not been tested in humans. We asked (a) whether cocaine can inhibit NE reuptake in the human peripheral circulation and (b) whether the NE-mediated peripheral vasoconstriction is the main mechanism mediating blood pressure-raising effect of cocaine. METHODS AND RESULTS: In 15 healthy cocaine-naive subjects, we measured blood pressure, forearm blood flow, and forearm venous NE concentration during administration of (a) intrabrachial cocaine (0.15 and 15 mg), which produced no systemic neurohormonal effects, and (b) intranasal cocaine (2 mg/kg). Intrabrachial cocaine (0.15 mg) increased venous forearm NE concentration by 82% and vascular resistance by 71% (P<0.01). Increasing the intrabrachial cocaine dose by 100-fold to match the venous cocaine level of massive cocaine overdose caused a small additional increase in venous forearm NE concentration without causing significant additional vasoconstriction. Although intranasal cocaine (2 mg/kg) matched the venous cocaine concentrations caused by 0.15 mg of intrabrachial cocaine, venous NE concentration was unchanged as sympathetic nerve activity (SNA) decreased reflexively as the result of an increase in blood pressure. When SNA was restored to baseline by blunting the cocaine-induced rise in blood pressure (baroreflex activation) with nitroprusside, venous NE concentration increased to the same level caused by intrabrachial cocaine. CONCLUSIONS: In healthy cocaine-naive individuals, cocaine can inhibit NE reuptake in the human peripheral circulation. However, this mechanism does not contribute importantly to the blood pressure-raising effect of cocaine because activation of baroreceptor reflexes decreases SNA, the neural stimulus for NE release.

Administration, Intranasal↗

PubMed2002

The influence of central command on baroreflex resetting during exercise.

The arterial baroreflex functions as a negative feedback system regulating blood pressure around an established operating point. Paradoxically, a parallel increase in heart rate and blood pressure manifests during exercise. Experimental evidence suggests these events are caused, in part, by a rapid resetting of the baroreflex by central command.

Animals↗