Changes in pharyngeal corticobulbar excitability and swallowing behavior after oral stimulation

Faucial pillar (FP) stimulation is commonly used in swallowing rehabilitation, yet its physiological basis remains uncertain. We investigated the effects of intraoral FP stimulation on human corticobulbar excitability and swallowing behavior, to explore the possibility of a central mechanism for functional change. In 10 healthy subjects, corticobulbar projections to pharynx were investigated with transcranial magnetic stimulation, via intraluminal electrodes, before and up to 1 h after 10 min of electrical FP stimulation with three frequencies (0.2, 1, and 5 Hz) or sham and peripheral (median nerve) stimulation. In a second study, swallowing behavior was assessed with videofluoroscopy before and after FP stimulation. FP stimulation at 5 Hz inhibited the corticobulbar projection (-14 +/- 6%, P < 0.02) and lengthened swallow response time (+114 +/- 24%, P = 0.02). By comparison, FP stimulation at 0.2 Hz facilitated this projection (+60 +/- 28%, P < 0.04), without enhancing swallowing behavior. Neither 1-Hz, sham, nor median nerve stimulation altered excitability. Thus changes in corticobulbar excitability to FP stimulation are frequency dependent with implications for the treatment for neurogenic swallowing dysfunction.     

Aspects of turnover and biogenesis of synaptic vesicles at locust neuromuscular junctions as revealed by zinc iodide-osmium tetroxide (ZIO) reacting with intravesicular SH-groups

Retractor unguis nerve muscle preparations from the locust were subjected to the zinc iodide-osmium tetroxide reaction (ZIO) after pre-fixation in glutaraldehyde. Applied for 18 h at 4 degrees C in the dark, ZIO reacts at pH 4.2--4.0 fairly selectively with the matrix of synaptic vesicles. Approximately 53% of the vesicles are completely and 4% partially stained. The percentage of ZIO-positive vesicles is increased to nearly 90% and reduced to 4% or less by pretreatment with SH-protecting (dithiothreitol) or SH-blocking (N-ethylmaleimide, p-chloromercuriphenyl sulfonic acid) and SH-oxidizing (azodicarboxylic acid-bis-dimethylamide) reagents, respectively. Stimulation of the motor nerve at 20 Hz for 7 min, partially fatiguing synaptic transmission, reduces the number of vesicles per square micrometer of terminal area by approximately 52%; 2 min of rest restores this number of its pre-stimulation level. These changes are chiefly accounted for by changes in the number of completely ZIO-positive vesicles. 2 min after the end of stimulation, partially ZIO-positive vesicles are three times more frequent than before. With all experimental conditions, the average volume of vesicles was as follows: ZIO-negative less than partially ZIO-positive less than completely ZIO-positive. The average volume of ZIO-positive vesicles is almost unaffected by stimulation; that of ZIO-negative vesicles is decreased by 25% immediately after stimulation, increasing with subsequent rest to the initial level after 1 h. It is suggested (a) that ZIO demonstrates intravesicular protein(s) containing SH-groups and (b) that the completely ZIO-positive vesicles represent the mature ones ready to be used for transmitter release. How the ZIO reaction differentiates between different developmental stages of vesicles which could arise from the smooth endoplasmic reticulum is discussed.     

Effect of glucose on plasma glucagon and free fatty acids during prolonged exercise

The effects of glucose ingestion on the changes in blood glucose, FFA, insulin and glucagon levels induced by a prolonged exercise at about 50% of maximal oxygen uptake were investigated. Healthy volunteers were submitted to the following procedures: 1. a control test at rest consisting of the ingestion of 100 g glucose, 2. an exercise test without, or 3. with ingestion of 100 g of glucose. Exercise without glucose induced a progressive decrease in blood glucose and plasma insulin; plasma glucagon rose significantly from the 60th min onward (+45 pg/ml), the maximal increase being recorded during the 4th h of exercise (+135 pg/ml); plasma FFA rose significantly from the 60th min onward and reached their maximal values during the 4th h of exercise (2177 +/- 144 muEq/l, m +/- SE). Exercise with glucose ingestion blunted almost completely the normal insulin response to glucose. Under these conditions, exercise did not increase plasma glucagon before the 210th min; similarly, the exercise-induced increase in plasma FFA was markedly delayed and reduced by about 60%. It is suggested that glucose availability reduces exercise-induced glucagon secretion and, possibly consequently, FFA mobilization.     

Reactive hyperemia in the human liver

We tested whether hepatic blood flow is altered following central hypovolemia caused by simulated orthostatic stress. After 30 min of supine rest, hemodynamic, plasma density, and indocyanine green (ICG) clearance responses were determined during and after release of a 15-min 40 mmHg lower body negative pressure (LBNP) stimulus. Plasma density shifts and the time course of plasma ICG concentration were used to assess intravascular volume and hepatic perfusion changes. Plasma volume decreased during LBNP (-10%) as did cardiac output (-15%), whereas heart rate (+14%) and peripheral resistance (+17%) increased, as expected. On the basis of ICG elimination, hepatic perfusion decreased from 1.67 +/- 0.32 (pre-LBNP control) to 1.29 +/- 0.26 l/min (-22%) during LBNP. Immediately after LBNP release, we found hepatic perfusion 25% above control levels (to 2.08 +/- 0.48 l/min, P = 0.0001). Hepatic vascular conductance after LBNP was also significantly higher than during pre-LBNP control (21.4 +/- 5.4 vs. 17.1 +/- 3.1 ml.min(-1).mmHg(-1), P < 0.0001). This indicates autoregulatory vasodilatation in response to relative ischemia during a stimulus that has cardiovascular effects similar to normal orthostasis. We present evidence for physiological post-LBNP reactive hyperemia in the human liver. Further studies are needed to quantify the intensity of this response in relation to stimulus duration and magnitude, and clarify its mechanism.     

Exercise-induced abdominal muscle fatigue in healthy humans.

The abdominal muscles have been shown to fatigue in response to voluntary isocapnic hyperpnea using direct nerve stimulation techniques. We investigated whether the abdominal muscles fatigue in response to dynamic lower limb exercise using such techniques. Eleven male subjects [peak oxygen uptake (VO2 peak) = 50.0 +/- 1.9 (SE) ml.kg(-1).min(-1)] cycled at >90% VO2 peak to exhaustion (14.2 +/- 4.2 min). Abdominal muscle function was assessed before and up to 30 min after exercise by measuring the changes in gastric pressure (Pga) after the nerve roots supplying the abdominal muscles were magnetically stimulated at 1-25 Hz. Immediately after exercise there was a decrease in Pga at all stimulation frequencies (mean -25 +/- 4%; P < 0.001) that persisted up to 30 min postexercise (-12 +/- 4%; P = 0.001). These reductions were unlikely due to changes in membrane excitability because amplitude, duration, and area of the rectus abdominis M wave were unaffected. Declines in the Pga response to maximal voluntary expiratory efforts occurred after exercise (158 +/- 13 before vs. 145 +/- 10 cmH2O after exercise; P = 0.005). Voluntary activation, assessed using twitch interpolation, did not change (67 +/- 6 before vs. 64 +/- 2% after exercise; P = 0.20), and electromyographic activity of the rectus abdominis and external oblique increased during these volitional maneuvers. These data provide new evidence that the abdominal muscles fatigue after sustained, high-intensity exercise and that the fatigue is primarily due to peripheral mechanisms.     

Epinephrine, norepinephrine, and dopamine during a 4-day head-down bed rest

Head-down bed rest at an angle of 6 degrees was used as an experimental model to simulate the hemodynamic effects of microgravity, i.e., the shift of fluids from the lower to the upper part of the body. The sympathoadrenal activity during acute (from 0.5 to 10 h) and prolonged (4 days) head-down bed rest was assessed in eight healthy men (24 +/- 1 yr) by measuring epinephrine (E), norepinephrine (NE), dopamine (DA), and methoxylated metabolite levels in their plasma and urine. Catecholamine (CA) and methoxyamine levels were essentially unaltered at any time of bed rest. Maximal changes in plasma were on the second day (D2): NE, 547 +/- 84 vs. 384 +/- 55 pg/ml; DA, 192 +/- 32 vs. 141 +/- 16 pg/ml; NS. After 24 h of bed rest, heart rate decreased from 71 +/- 1 to 63 +/- 3/min (P less than 0.01). Daily dynamic leg exercise [50% maximum O2 uptake (VO2 max)] used as a countermeasure did not alter the pattern of plasma CA during bed rest but resulted in a higher urinary NE excretion during postexercise recovery (+45% on D2; P less than 0.05). The data indicate no evident relationship between sympathoadrenal function and stimulation of cardiopulmonary receptors or neuroendocrine changes induced by central hypervolemia during head-down bed rest.     

Synaptic vesicle pools at the frog neuromuscular junction

We have characterized the morphological and functional properties of the readily releasable pool (RRP) and the reserve pool of synaptic vesicles in frog motor nerve terminals using fluorescence microscopy, electron microscopy, and electrophysiology. At rest, about 20% of vesicles reside in the RRP, which is depleted in about 10 s by high-frequency nerve stimulation (30 Hz); the RRP refills in about 1 min, and surprisingly, refilling occurs almost entirely by recycling, not mobilization from the reserve pool. The reserve pool is depleted during 30 Hz stimulation with a time constant of about 40 s, and it refills slowly (half-time about 8 min) as nascent vesicles bud from randomly distributed cisternae and surface membrane infoldings and enter vesicle clusters spaced at regular intervals along the terminal. Transmitter output during low-frequency stimulation (2-5 Hz) is maintained entirely by RRP recycling; few if any vesicles are mobilized from the reserve pool.     

Leukocyte, lymphocyte and platelet response to dynamic exercise. Duration or intensity effect?

The influence of work intensity and duration on the white blood cell (WBC), lymphocyte (L) and platelet (P) count response to exercise was studied in 16 trained subjects (22 +/- 5.4 years, means +/- SD). They performed three cyclo-ergospirometric protocols: A) 10 min at 150 W followed by a progressive test (30 W/3 min) till exhaustion; B) constant maximal work (VO2max); C) a 45 min Square-Wave Endurance Exercise Test (SWEET), (n = 5). Arterial blood samples were taken: at rest, submaximal and maximal exercise in A; maximal exercise in B; 15th, 30th and 45th min in the SWEET. Lactate, [H+], PaCO2, PaO2, [Hct], Hb, cortisol, ACTH, total platelet volume (TPV), total blood red cell (RBC), WBC, L and P were measured. At 150 W, WBC, L, P, and TPV increased. VO2max did not differ between A and B, but a difference was found in total exercise time (A = 25 +/- 3 min; B = 7 +/- 2 min, p less than 0.001). In A, at VO2max, the increase was very small for Hct, [Hb], and RBC (10%), in contrast with large changes for WBC (+93%), L (+137%), P (+32%), TPV (+35%), [H+] (+39%), lactate (+715%), and ACTH (+95%). At VO2max there were no differences in these variables between A and B. During the SWEET: WBC, L, P, TPV and ACTH increased at the 15th min as much as in VO2max, but no difference was observed between the 15th, 30th and 45th min, except for ACTH which continued to rise; the lactate increase during the SWEET was about half (+341%) the value observed at VO2max, and [H+] did not vary with respect to values at rest.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional electrical stimulation using microstimulators to correct foot drop: a case study

This paper presents a case study that tested the feasibility and efficacy of using injectable microstimulators (BIONs) in a functional electrical stimulation (FES) device to correct foot drop. Compared with surface stimulation of the common peroneal nerve, stimulation with BIONs provides more selective activation of specific muscles. For example, stimulation of the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles with BIONs produces ankle flexion without excessive inversion or eversion of the foot (i.e., balanced flexion). Efficacy was assessed using a 3-dimensional motion analysis of the ankle and foot trajectories during walking with and without stimulation. Without stimulation, the toe on the affected leg drags across the ground. BION stimulation of the TA muscle and deep peroneal nerve (which innervates TA and EDL) elevates the foot such that the toe clears the ground by 3 cm, which is equivalent to the toe clearance in the less affected leg. The physiological cost index (PCI) measured effort during walking. The PCI equals the change in heart rate (from rest to activity) divided by the walking speed; units are beats per metre. The PCI is high without stimulation (2.29 +/- 0.37, mean +/- SD) and greatly reduced with surface (1.29 +/- 0.10) and BIONic stimulation (1.46 +/- 0.24). Also, walking speed increased from 9.4 +/- 0.4 m/min without stimulation to 19.6 +/- 2.0 m/min with surface and 17.8 +/- 0.7 m/min with BIONic stimulation. These results suggest that FES delivered by a BION is an alternative to surface stimulation and provides selective control of muscle activation.     

Influence of acute inspiratory loading upon diaphragm motor-evoked potentials in healthy humans.

Acute prior activity of the inspiratory muscles can enhance inspiratory muscle strength and reduce effort perception during subsequent inspiratory efforts. However, the mechanisms subserving these changes are poorly understood. Responses to magnetic stimulation in 10 subjects were studied after an acute bout of nonfatiguing inspiratory muscle loading (IML), corresponding to 40% of subjects' initial maximal inspiratory pressure (MIP), and after an acute bout of nonloaded, forced inspiration (NLF). Motor-evoked potentials elicited by cortical stimulation (MEP(c)) and by phrenic nerve stimulation (MEP(p)) were recorded transcutaneously from the diaphragm before, immediately after, and 15 min after two sets of 30 inspiratory efforts, at rest and during an MIP effort. After IML, MIP increased to 113 +/- 3% (SE) of baseline and diaphragm MEP(p) (during MIP) significantly increased (129 +/- 10% of baseline). Diaphragmatic MEP(c) (during MIP), expressed as a percentage of maximal MEP(p), decreased after IML (from 29 +/- 9% to 20 +/- 6%; P = 0.017) and after NLF (from 43 +/- 5% to 31 +/- 5%; P = 0.032). Observations from the biceps brachi demonstrated that changes after IML and NLF were specific to the inspiratory muscle, since no significant changes were observed in biceps force generation or in MEP(p) or MEP(c) amplitudes. These data indicate that after IML increased global inspiratory strength is accompanied by increased peripheral excitability and by a dampening of corticospinal excitability of the diaphragm.     

Electrotonic load triggers remodeling of repolarizing current Ito in ventricle

A change in activation sequence electrically remodels ventricular myocardium, causing persistent changes in repolarizing currents (T-wave memory). However, the underlying mechanism for triggering activation sequence-dependent remodeling is unknown. Optical action potentials were mapped with high resolution from the epicardial surface of the arterially perfused canine wedge preparation (n = 23) during 30 min of baseline endocardial stimulation, followed by 40 min of epicardial stimulation, and, finally, restoration of endocardial stimulation. Immediately after the change from endocardial to epicardial stimulation, phase 1 notch amplitude of epicardial cells was attenuated by 74 +/- 8% (P < 0.001) compared with baseline and continued to diminish during the period of epicardial pacing, suggesting progressive remodeling of the transient outward current (Ito). When endocardial pacing was restored, notch amplitude did not immediately recover but remained attenuated by 23 +/- 10% (P < 0.001), also consistent with a remodeling effect. Peak Ito current measured from isolated epicardial myocytes changed by 12 +/- 4% (P < 0.025), providing direct evidence for Ito remodeling occurring on a surprisingly short time scale. The mechanism for triggering remodeling of Ito was a significant reduction (by 14 +/- 4%, P < 0.001) of upstroke amplitude in epicardial cells during epicardial stimulation. Reduction in upstroke amplitude during epicardial pacing was explained by electrotonic load on epicardial cells by fully repolarized downstream endocardial cells. These data suggest a novel mechanism for triggering electrical remodeling in the ventricle. Electrotonic load imposed by a change in activation sequence reduces upstroke amplitude, which, in turn, attenuates Ito according to its known voltage-dependent properties, triggering downregulation of current.     

The effects of previous severe exercise upon the respiratory Vco2/Vo2 exchange ratio as a predictor of maximum oxygen uptake

The present study examined the effect of previous severe exercise upon (i) respiratory exchange during maximal exercise, and (ii) the respiratory Vco2/Vo2 exchange ratio (R) as a predictor of maximum oxygen uptake (Vo2max). Thirteen healthy males performed a progressive treadmill test to Vo2max: at rest (T1); after a 1 h run on the level treadmill at a speed corresponding 82.4 +/- 7.3% of their Vo2max (T2); after 1 h recovery (T3); and after 24 h recovery (T4). Respiratory gases were continuously monitored. No changes in average work Vo2, Vo2max or maximum heart rate were found between trials. Average work Vco2 was lower in T2 (2.055 +/- 0.093 1.min-1, p less than 0.001), T3 (2.080 +/- 0.087 1.min-1, p less than 0.001) and T4 (2.337 +/- 0.154 1.min-1, NS) compared with T1 (2.360 +/- 0.147 1.min-1). This resulted in lower average R values in T2 (0.81 +/- 0.02, p less than 0.001), T3 (0.83 +/- 0.02, p less than 0.001) and T4 (0.94 +/- 0.02, NS) in relation to T1 (0.95 +/- 0.02). Analysis of the %Vo2max/R relationship over the final 5 min of each test showed a shift to the left during T2 (p less than 0.001), T3 (p less than 0.001) and T4 (NS) compared with T1. As a result predictions of Vo2max based on R (Vo2max/R) were similar to recorded Vo2max in T1 (+ 0.6%) and T4 (+ 2.2%). But higher in T2 (+ 8.7%, p less than 0.001) and T3 (+ 6.9%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Sympathetic adaptations to one-legged training.

The purpose of the present study was to determine the effect of leg exercise training on sympathetic nerve responses at rest and during dynamic exercise. Six men were trained by using high-intensity interval and prolonged continuous one-legged cycling 4 day/wk, 40 min/day, for 6 wk. Heart rate, mean arterial pressure (MAP), and muscle sympathetic nerve activity (MSNA; peroneal nerve) were measured during 3 min of upright dynamic one-legged knee extensions at 40 W before and after training. After training, peak oxygen uptake in the trained leg increased 19 +/- 2% (P < 0.01). At rest, heart rate decreased from 77 +/- 3 to 71 +/- 6 beats/min (P < 0.01) with no significant changes in MAP (91 +/- 7 to 91 +/- 11 mmHg) and MSNA (29 +/- 3 to 28 +/- 1 bursts/min). During exercise, both heart rate and MAP were lower after training (108 +/- 5 to 96 +/- 5 beats/min and 132 +/- 8 to 119 +/- 4 mmHg, respectively, during the third minute of exercise; P < 0.01). MSNA decreased similarly from rest during the first 2 min of exercise both before and after training. However, MSNA was significantly less during the third minute of exercise after training (32 +/- 2 to 22 +/- 3 bursts/min; P < 0.01). This training effect on MSNA remained when MSNA was expressed as bursts per 100 heartbeats. Responses to exercise in five untrained control subjects were not different at 0 and 6 wk. These results demonstrate that exercise training prolongs the decrease in MSNA during upright leg exercise and indicates that attenuation of MSNA to exercise reported with forearm training also occurs with leg training.     

Antigravity suit inflation: kidney function and cardiovascular and hormonal responses in men

To investigate the effects of lower body positive pressure (LBPP) on kidney function while controlling certain cardiovascular and endocrine responses, seven men [35 +/- 2 (SE) yr] underwent 30 min of sitting and then 4.5 h of 70 degrees head-up tilt. An antigravity suit was applied (60 Torr legs, 30 Torr abdomen) during the last 3 h of tilt. A similar noninflation experiment was conducted where the suited subjects were tilted for 3.5 h. To provide adequate urine flow, the subjects were hydrated during the course of both experiments. Immediately after inflation, mean arterial pressure increased by 8 +/- 3 Torr and pulse rate decreased by 16 +/- 3 beats/min. Plasma renin activity and aldosterone were maximally suppressed (P less than 0.05) after 2.5 h of inflation. Plasma vasopressin decreased by 40-50% (P less than 0.05) and plasma sodium and potassium remained unchanged during both experiments. Glomerular filtration rate was not increased significantly by inflation, whereas inflation induced marked increases (P less than 0.05) in effective renal plasma flow (ERPF), urine flow, osmolar and free water clearances, and total and fractional sodium excretion. No such changes occurred during control. Thus, LBPP induces 1) a significant increase in ERPF and 2) significant changes in kidney excretory patterns similar to those observed during water immersion or the early phase of bed rest, situations that also result in central vascular volume expansion.     

Role of skin blood flow and sweating rate in exercise thermoregulation after bed rest.

Two potential mechanisms, reduced skin blood flow (SBF) and sweating rate (SR), may be responsible for elevated intestinal temperature (T(in)) during exercise after bed rest and spaceflight. Seven men underwent 13 days of 6 degrees head-down bed rest. Pre- and post-bed rest, subjects completed supine submaximal cycle ergometry (20 min at 40% and 20 min at 65% of pre-bed rest supine peak exercise capacity) in a thermoneutral room. After bed rest, T(in) was elevated at rest (+0.31 +/- 0.12 degrees C) and at the end of exercise (+0.33 +/- 0.07 degrees C). Percent increase in SBF during exercise was less after bed rest (211 +/- 53 vs. 96 +/- 31%; P < or = 0.05), SBF/T(in) threshold was greater (37.09 +/- 0.16 vs. 37.33 +/- 0.13 degrees C; P < or = 0.05), and slope of SBF/T(in) tended to be reduced (536 +/- 184 vs. 201 +/- 46%/ degrees C; P = 0.08). SR/T(in) threshold was delayed (37.06 +/- 0.11 vs. 37.34 +/- 0.06 degrees C; P < or = 0.05), but the slope of SR/T(in) (3.45 +/- 1.22 vs. 2.58 +/- 0.71 mg x min-1 x cm-2 x degrees C-1) and total sweat loss (0.42 +/- 0.06 vs. 0.44 +/- 0.08 kg) were not changed. The higher resting and exercise T(in) and delayed onset of SBF and SR suggest a centrally mediated elevation in the thermoregulatory set point during bed rest exposure.     

Correlation of left phrenic arterial flow with regional diaphragmatic blood flow

Previous work has assumed that left phrenic arterial blood flow (Qpa) reflects diaphragmatic blood flow. We have tested this assumption in four anesthetized mechanically ventilated dogs by measuring Qpa with a Doppler flow probe and regional diaphragmatic blood flow with radiolabeled microspheres. Flows were examined during control 1 (diaphragm at rest), pacing (phrenic pacing: rate 20/min, duty cycle 0.33), control 2, hypotension (rest with mean arterial pressure reduced by 45% of the control 1 value), and hypotension and pacing. As a percent of the control 1 value, Qpa was 511 +/- 107% during pacing, 139 +/- 12% during control 2, 40 +/- 13% during hypotension, and finally 347 +/- 31% during hypotension and pacing. Similarly, percent left hemidiaphragmatic blood flow (Qlh) was 362 +/- 91% during pacing, 91 +/- 10% during control 2, 14 +/- 2% during hypotension, and finally 213 +/- 50% during hypotension and pacing. The changes in flow to the left costal and crural diaphragm were similar to those recorded for Qlh. We conclude that Qpa correlates with total and regional diaphragmatic blood flow (r = 0.77-0.81, P less than 0.001) under conditions of supramaximal phrenic nerve stimulation in which the metabolic demands of the region perfused by the phrenic artery are presumed to be similar to the metabolic demands of the rest of the diaphragm.     

Cardiac responsiveness to beta-adrenergic stimulation in experimental anemia.

Cardiac reactivity of beta-adrenergic stimulation was assessed by isoproterenol dose-reponse curves (dose range 0.025-0.4 mug/kg) before and 1 h after the rapid induction of anemia in dogs anesthetized with halothane:N2O:O2. Anemai (hematocrit = 16 +/- 4%) was induced by an isovolumic exchange transfusion with Dextran 70, and was followed by significant increments in cardiac output (+57 +/- 9%), max dP/dt of the left ventricle (+37 +/- 7%), and in peak acceleration of blood flow in the ascending aorta (+46 +/- 13%). Anemia was associated with a significant reduction of the chronotropic responses to all but the lowest dose of isoproterenol. The simultaneously determined inotropic responses (max dP/dt) where the same before and after the induction of anemia. The responses in terms of peak acceleration of aortic blood flow tended to be greater in the anemic than in the control phase, at all dose levels used. These findings indicate that in rapidly induced experimental anemia the heart is capable of responding to marked degrees of beta-adrenergic stimulation, representing a more than two-fold increase in the dP/dt.     

Sympathetic, sensory, and nonneuronal contributions to the cutaneous vasoconstrictor response to local cooling

Previous work indicates that sympathetic nerves participate in the vascular responses to direct cooling of the skin in humans. We evaluated this hypothesis further in a four-part series by measuring changes in cutaneous vascular conductance (CVC) from forearm skin locally cooled from 34 to 29 degrees C for 30 min. In part 1, bretylium tosylate reversed the initial vasoconstriction (-14 +/- 6.6% control CVC, first 5 min) to one of vasodilation (+19.7 +/- 7.7%) but did not affect the response at 30 min (-30.6 +/- 9% control, -38.9 +/- 6.9% bretylium; both P < 0.05, P > 0.05 between treatments). In part 2, yohimbine and propranolol (YP) also reversed the initial vasoconstriction (-14.3 +/- 4.2% control) to vasodilation (+26.3 +/- 12.1% YP), without a significant effect on the 30-min response (-26.7 +/- 6.1% YP, -43.2 +/- 6.5% control; both P < 0.05, P > 0.05 between sites). In part 3, the NPY Y1 receptor antagonist BIBP 3226 had no significant effect on either phase of vasoconstriction (P > 0.05 between sites both times). In part 4, sensory nerve blockade by anesthetic cream (Emla) also reversed the initial vasoconstriction (-20.1 +/- 6.4% control) to one of vasodilation (+213.4 +/- 87.0% Emla), whereas the final levels did not differ significantly (-37.7 +/- 10.1% control, -37.2 +/- 8.7% Emla; both P < 0.05, P > 0.05 between treatments). These results indicate that local cooling causes cold-sensitive afferents to activate sympathetic nerves to release norepinephrine, leading to a local cutaneous vasoconstriction that masks a nonneurogenic vasodilation. Later, a vasoconstriction develops with or without functional sensory or sympathetic nerves.     

Morning-to-evening differences in oxygen uptake kinetics in short-duration cycling exercise

This study analyzed diurnal variations in oxygen (O(2)) uptake kinetics and efficiency during a moderate cycle ergometer exercise. Fourteen physically active diurnally active male subjects (age 23+/-5 yrs) not specifically trained at cycling first completed a test to determine their ventilatory threshold (T(vent)) and maximal oxygen consumption (VO(2max)); one week later, they completed four bouts of testing in the morning and evening in a random order, each separated by at least 24 h. For each period of the day (07:00-08:30 h and 19:00-20:30 h), subjects performed two bouts. Each bout was composed of a 5 min cycling exercise at 45 W, followed after 5 min rest by a 10 min cycling exercise at 80% of the power output associated with T(vent). Gas exchanges were analyzed breath-by-breath and fitted using a mono-exponential function. During moderate exercise, the time constant and amplitude of VO(2) kinetics were significantly higher in the morning compared to the evening. The net efficiency increased from the morning to evening (17.3+/-4 vs. 20.5+/-2%; p<0.05), and the variability of cycling cadence was greater during the morning than evening (+34%; p<0.05). These findings suggest that VO(2) responses are affected by the time of day and could be related to variability in muscle activity pattern.     

Enhanced cAMP-induced nitric oxide-dependent coronary dilation during myocardial stunning in conscious pigs

The goal of the current study was to determine the effects of cAMP-mediated coronary reactivity in conscious pigs with stunned myocardium induced by 1.5 h coronary stenosis (CS) and 12 h coronary artery reperfusion (CAR). Domestic swine (n = 5) were chronically instrumented with a coronary artery blood flow (CBF) probe, hydraulic occluder, left ventricular pressure gauge, wall-thickening crystals in the ischemic and nonischemic zones, and a coronary sinus catheter. The hydraulic occluder was inflated to induce a CS with a stable 38 +/- 1% reduction in CBF for 1.5 h. Before flow reduction and during CAR, cAMP-induced coronary vasodilation was investigated by forskolin (20 nmol. kg(-1). min(-1)). Enhanced CBF responses [+62 +/- 9%, P < 0.05, compared with pre-CS (+37 +/- 3%)] were observed for forskolin at 12 h after CAR as well as for bradykinin and reactive hyperemia. With the use of a similar protocol during systemic nitric oxide (NO) synthase inhibition with N(omega)-nitro-L-arginine (30 mg. kg(-1). day(-1) for 3 days), the enhanced CBF responses to forskolin, bradykinin, and reactive hyperemia were not observed after CS. Isolated microvessel preparations from pigs (n = 8) also demonstrated enhanced NO production to direct stimulation of adenylyl cyclase with forskolin (+71 +/- 12%) or NKH-477 (+60 +/- 10%) and administration of 8-bromo-cAMP (+74 +/- 13%), which were abolished by protein kinase A or NO synthase inhibition. These data indicate that cAMP stimulation elicits direct coronary vasodilation and that this action is amplified in the presence of sustained myocardial stunning after recovery from CS. This enhanced cAMP coronary vasodilation is mediated by an NO mechanism that may be involved in myocardial protection from ischemic injury.