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Presynaptic α2-adrenergic receptors are known to exert feedback inhibition on norepinephrine release from the sympathetic nerve terminals. To elucidate the dynamic characteristics of the inhibition, we stimulated the right cardiac sympathetic nerve according to a binary white noise signal while measuring heart rate (HR) in anesthetized rabbits ( n = 6). We estimated the transfer function from cardiac sympathetic nerve stimulation to HR and the corresponding step response of HR, with and without the blockade of presynaptic inhibition by yohimbine (1 mg/kg followed by 0.1 mg·kg−1·h−1 iv). We also examined the effect of the α2-adrenergic receptor agonist clonidine (0.3 and 1.5 mg·kg−1·h−1 iv) in different rabbits ( n = 5). Yohimbine increased the maximum step response (from 7.2 ± 0.8 to 12.2 ± 1.7 beats/min, means ± SE, P < 0.05) without significantly affecting the initial slope (0.93 ± 0.23 vs. 0.94 ± 0.22 beats·min−1·s−1). Higher dose but not lower dose clonidine significantly decreased the maximum step response (from 6.3 ± 0.8 to 6.8 ± 1.0 and 2.8 ± 0.5 beats/min, P < 0.05) and also reduced the initial slope (from 0.56 ± 0.07 to 0.51 ± 0.04 and 0.22 ± 0.06 beats·min−1·s−1, P < 0.05). Our findings indicate that presynaptic α2-adrenergic autoinhibition limits the maximum response without significantly compromising the rapidity of effector response. In contrast, pharmacologic augmentation of the presynaptic inhibition not only attenuates the maximum response but also results in a sluggish effector response.

Although muscarinic K(+) (K(ACh)) channels contribute to a rapid heart rate (HR) response to vagal stimulation, whether background sympathetic tone affects the HR control via the K(ACh)channels remains to be elucidated. In seven anesthetized rabbits with sinoaortic denervation and vagotomy, we estimated the dynamic transfer function of the HR response by using random binary vagal stimulation (0-10 Hz). Tertiapin, a selective K(ACh) channel blocker, decreased the dynamic gain (to 2.3+/- 0.9 beats.min(-1).Hz(-1), from 4.6+/- 1.1, P < 0.01, mean+/- SD) and the corner frequency (to 0.05+/- 0.01 Hz, from 0.26+/- 0.04, P < 0.01). Under 5 Hz tonic cardiac sympathetic stimulation (CSS), tertiapin decreased the dynamic gain (to 3.6+/- 1.0 beats.min(-1).Hz(-1), from 7.3+/- 1.1, P < 0.01) and the corner frequency (to 0.06+/- 0.02 Hz, from 0.23+/- 0.06, P < 0.01). Two-way analysis of variance indicated significant interaction between the tertiapin and CSS effects on the dynamic gain. In contrast, no significant interactions were observed between the tertiapin and CSS effects on the corner frequency and the lag time. In conclusion, although a cyclic AMP-dependent mechanism has been well established, an accentuated antagonism also occurred in the direct effect of ACh via the K(ACh) channels. The rapidity of the HR response obtained by the K(ACh) channel pathway was robust during the accentuated antagonism.

Aims To evaluate vagal stimulation-mediated myocardial protection against ischemia and reperfusion in in vivo ischemic myocardium. Main methods We measured myocardial interstitial myoglobin levels in the ischemic region using a cardiac microdialysis technique in anesthetized and vagotomized cats. We occluded the left anterior descending coronary artery (LAD) for 60 min and reperfused it for 60 min (VX group, n = 6). The effects of bilateral vagal stimulation (10 V, 5 Hz, 1-ms pulse duration), initiated immediately after LAD occlusion, were examined (VS group, n = 6). To examine the involvement of phosphatidylinositol 3-kinase (PI3K), vagal stimulation was performed after pretreatment with a PI3K inhibitor wortmannin (0.6 mg/kg, i.v.) (VS-W group, n = 6). To examine the contribution of bradycardia, vagal stimulation was performed with fixed-rate ventricular pacing (VS-P group, n = 6). Key findings The average myoglobin level during the ischemic period was 1170 ± 141 in VX (in ng/ml, mean ± SE), which was significantly attenuated in VS (466 ± 87, P

In an attempt to study bone remodeling by noninvasive methods, spinal bone radiodensity was assessed in five patients treated with anterior cervical decompression and fusion (ACDF) using cylindrical titanium cages. Plain radiographs were used to study specific areas of vertebral bone interposed in two-level cages with the two cephalad vertebrae for controls. Measurements were made immediately after surgery and 1, 3, 6, 12 and 18 months postoperatively. The data were analyzed quantitatively with a contrast-comparing method (CCM) using "Scion image". There were two cyclical changes in vertebral remodeling. First, in all patients there were gradual increases in bone density at the ventral part compared to the dorsal part of the vertebral body for up to 12 months; then the density decreased at 18 months. Second, a linear gradient in radiodensity from the ventral part to the dorsal part of the vertebral body observed immediately following spinal fusion gradually disappeared by 12 months; nonhomogeneous distributions of trabecular bone were appeared. Then, the linear gradient in density appeared again at 18 months. This investigation helps elucidate the radiographic evidence for the remodeling of vertebral bone in patients treated with ACDF.

Vagal control of heart rate (HR) is mediated by direct and indirect actions of ACh. Direct action of ACh activates the muscarinic K+(KACh) channels, whereas indirect action inhibits adenylyl cyclase. The role of the KAChchannels in the overall picture of vagal HR control remains to be elucidated. We examined the role of the KAChchannels in the transfer characteristics of the HR response to vagal stimulation. In nine anesthetized sinoaortic-denerved and vagotomized rabbits, the vagal nerve was stimulated with a binary white-noise signal (0–10 Hz) for examination of the dynamic characteristic and in a step-wise manner (5, 10, 15, and 20 Hz/min) for examination of the static characteristic. The dynamic transfer function from vagal stimulation to HR approximated a first-order, low-pass filter with a lag time. Tertiapin, a selective KAChchannel blocker (30 nmol/kg iv), significantly decreased the dynamic gain from 5.0 ± 1.2 to 2.0 ± 0.6 (mean ± SD) beats·min−1·Hz−1( P < 0.01) and the corner frequency from 0.25 ± 0.03 to 0.06 ± 0.01 Hz ( P < 0.01) without changing the lag time (0.37 ± 0.04 vs. 0.39 ± 0.05 s). Moreover, tertiapin significantly attenuated the vagal stimulation-induced HR decrease by 46 ± 21, 58 ± 18, 65 ± 15, and 68 ± 11% at stimulus frequencies of 5, 10, 15, and 20 Hz, respectively. We conclude that KAChchannels contribute to a rapid HR change and to a larger decrease in the steady-state HR in response to more potent tonic vagal stimulation.

There is no report that describes in detail the radiological and intraoperative findings of rickets with symptomatic cervical ossification of the posterior longitudinal ligament. Here, we describe a case of X-linked hypophosphatemic rickets with cervical ossification of the posterior longitudinal ligament presenting unique radiological and intraoperative findings. The patient presented progressive tetraparesis. Magnetic resonance imaging studies revealed severe cervical spinal cord compression caused by ossification of the posterior longitudinal ligament. Computed tomography scans revealed homogeneously increased vertebral bone density. An expansive laminoplasty was performed. At surgery, homogeneously hard lamina bone was burdened in drilling and opening of the laminae. The patient's neurological symptoms were improved postoperatively. Bony fusion of the hinges occurred postoperatively. Therefore, expansive laminoplasty could be performed for symptomatic cervical ossification of the posterior longitudinal ligament with X-linked hypophosphatemic rickets. However, unusual bone characters should be taken into consideration for careful operation during surgery.

Our previous studies showed that venous occlusion or passive stretch of the lower limb, assuming a mechanical stimulus, attenuates the vasoconstriction in the non-exercised forearm during postexercise muscle ischaemia (PEMI) of the upper limb. In this study, we investigated whether a metabolic stimulus to the lower limb induces a similar response. Eight subjects performed a 2 min static handgrip exercise at 30% maximal voluntary contraction (MVC) followed by 3 min PEMI of the upper limb, concomitant with or without 2 min static ankle dorsiflexion at 30% MVC followed by 2 min PEMI of the lower limb. During PEMI of the upper limb alone, forearm blood flow (FBF) and forearm vascular conductance (FVC) in the non-exercised arm decreased significantly, whereas during combined PEMI of the upper and lower limbs, the decreases in FBF and FVC produced by PEMI of the upper limb was attenuated. Forearm blood flow and FVC were significantly greater during combined PEMI of the upper and lower limbs than during PEMI of the upper limb alone. When PEMI of the lower limb was released after combined PEMI of the upper and lower limbs (only PEMI of the upper limb was maintained continuously), the attenuated decreases in FBF and FVC observed during combined PEMI of the upper and lower limbs was not observed. Thus, forearm vascular responses differ when muscle metaboreceptors are activated in the upper limb and when there is combined activation of muscle metaboreceptors in both the upper and lower limbs.

This study compared cardiovascular responses to static extension and flexion exercises at four upper and lower limb joints. Eight males performed a 2 min static contraction at 30% of maximal voluntary torque followed immediately by 2 min post-exercise muscle ischaemia (PEMI) using each of four joints: the wrist, elbow, ankle, and knee. In the PEMI, an occlusion cuff placed around the proximal portion of the exercising muscle was inflated to 250 mmHg immediately before the cessation of exercise. Mean arterial pressure (MAP), heart rate (HR), calf blood flow, and calf vascular conductance (CVC) in the non-exercised calf were measured. There was a significant interaction for direction of movement (extension vs. flexion) and limb (upper vs. lower) in HR and CVC during both exercise and PEMI; extension in the wrist and elbow evoked a greater increase in HR and a greater decrease in CVC than flexion, whereas flexion in the ankle and knee elicited a greater increase in HR and a greater decrease in CVC than extension. These results suggest that the cardiovascular responses to extension and flexion differ between arms and legs, partly arising from the activation of the muscle metaboreflex.

To test whether changes in oxygenation of a resting skeletal muscle, evoked by a static contraction in a contralateral muscle, is uniform within a given skeletal muscle, we used near-infrared spectroscopy (NIRS). Seven subjects performed 2 min static knee extension exercise at 30% of maximal voluntary contraction. Changes in oxygenated hemoglobin (HbO2) were monitored using multiple-channel NIRS (40 channels, 13 sources and 12 detectors) attached on the contralateral nonexercising triceps surae muscle. Changes in HbO2 were expressed as a percentage of total labile signals. To characterize the distribution of changes in HbO2, channels were compared between their positions on the triceps surae muscle, and represented as ‘proximal versus distal’ and ‘lateral versus medial’ portions. During static muscle contraction, the averaged changes in HbO2 of all channels were correlated with those in calf blood flow (plethysmography; R 2=0.188, P

Intimal formation of animal carotid arteries induced by balloon endothelial denudation has been considered to be an "accelerated atherosclerosis" model and used in primary screening methods to evaluate natural drugs and chemical candidates. The aim of the present study was to examine whether intimal formation is prevented by Bezoar Bovis (dried cattle gallbladder stones: Niuhuang in Chinese and Go-o in Japanese), which has been used to prevent heart palpitation in patients with hypertension. The intimal-to-medial area ratio in rat carotid arteries 7 days after balloon endothelial denudation was significantly reduced by oral administration of Bezoar Bovis. Bezoar Bovis also suppressed vascular smooth muscle cells (VSMCs) proliferation, which is thought to play important roles in the intimal formation after endothelial damage and also atherosclerosis resulting from long-term inappropriate lifestyle. The present findings suggest that Bezoar Bovis may be useful for preventing atherosclerosis and for protection against restenosis after percutaneous coronary intervention, for which effective reduction method is not currently available.

To test whether there is a regional difference in the exercise pressor reflex within a given muscle, we investigated the relationship between the inflection points of cardiovascular responses and muscle oxygenation during exercise. Seven subjects performed incremental exercise, which consisted of incremental 30-s static knee extensions, each separated by 30 s of recovery. The workload started at 5% maximal voluntary contraction (MVC) and increased by 5% MVC for each increment until exhaustion. Changes (Δ) in the concentrations (denoted by brackets) of oxygenated Hb (O2Hb) and deoxygenated Hb (HHb) were monitored in proximal and distal portions of the vastus lateralis by near-infrared spectroscopy. The inflection points of mean arterial pressure (MAP), calf vascular resistance (CVR), and muscle deoxygenation index (Δ[O2Hb − HHb]) were calculated as the intersection point of two regression equations obtained at lower and higher workloads. The inflection point of Δ[O2Hb − HHb] differed significantly between proximal and distal portions (28.5 ± 3.0 vs. 39.5 ± 3.0%MVC, P < 0.05). Linear regression analysis showed significant correlations between the inflection point of Δ[O2Hb − HHb] in the distal portion and MAP ( r = 0.89; P < 0.01) and CVR ( r = 0.89; P < 0.05), but no significant relationship between the inflection point in the proximal portion and MAP or CVR. These data show that the inflection point of muscle deoxygenation differs between proximal and distal portions within the vastus lateralis during incremental exercise and suggest that the distal portion of the vastus lateralis contributes more to the pressor response than does the proximal portion.

We examined the potential of [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX) for the assessment of adenosine A2A receptors in muscle. In rodents, specific binding of [11C]TMSX was observed in muscle and heart by blockade with A2A-selective CSC and non-selective theophylline, but not with A1-selective DPCPX. Swimming exercise fluctuated radioligand-receptor binding in these tissues. In a PET study of two subjects, theophylline-infusion slightly deceased the distribution volume of [11C]TMSX in the heart (20% reduction) and muscle (10% reduction), which suggested the specific binding.

✓ The authors report a rare case of intraspinal thoracic mobile neurinoma in a 51-year-old man. The clinical symptoms, especially thoracoabdominal discomfort, changed remarkably according to the patient's posture. Magnetic resonance images demonstrated that the level of the caudal end of the tumor varied between T4–5 and T9–10 with changes in the patient's position. Intraoperative myelography was useful in identifying the tumor location and choosing the level of the laminectomy.

In human subjects sustained static contractions of the quadriceps femoris in one leg were performed with the same absolute and the same relative intensity before and after partial neuromuscular blockade with either decamethonium or tubocurarine which reduced strength to about 50% of the control value. During the contractions performed with the same absolute force, the magnitude of the cardiovascular responses (heart rate and blood pressure) was greater during neuromuscular blockade than during control contractions. During the contractions involving the same relative force the magnitude of the cardiovascular responses was almost the same with and without neuromuscular blockade. These findings were independent of the drug used. The metabolic part of the exercise pressor reflex was assessed by the application of an arterial cuff 1/2 min before cessation of exercise and for the following 3 min of rest. Although heart rate and blood pressure decreased after cessation of exercise, application of the tourniquet resulted in higher post-exercise values and this effect was seen both with and without neuromuscular blockade. Muscle biopsies from the subjects' m. vastus lateralis were analysed for fast- and slow-twitch fibre composition showing 27-66% slow-twitch fibres. No correlation was found between cardiovascular responses to static exercise, with or without neuromuscular blockade, and fibre type predominance. The results suggest that the involvement of fast- or slow-twitch muscle fibres does not play a dominant role in the cardiovascular responses to static exercise in man. Both central command and reflex neural mechanisms are of importance, and it appears that these two control mechanisms are redundant and that neural occlusion may be operative. However, when partial neuromuscular blockade induces a disproportion between an increase in central command and a constant or decreasing muscle tension and metabolism, the larger signal arising from central command determines the magnitude of the cardiovascular responses.

1. In decerebrated cats the cardiovascular, heart rate and blood pressure responses to static muscle contractions were followed from the onset of stimulation of the cut L7-S1 ventral roots. Heart rate and blood pressure were also followed during maximal voluntary and electrically induced static muscle contractions in man using one leg. In both cat and man contractions were performed under control conditions and tubocurarine-induced neuromuscular blockade. 2. In the cat, heart rate and blood pressure increased 1.7 s after the onset of the contraction. No cardiovascular responses were seen when the muscle contraction was blocked by tubocurarine. 3. In man, both heart rate and blood pressure increased at the onset of voluntary contractions. Partial curarization reduced strength to 39% of control. The heart rate response was unaffected by tubocurarine while the blood pressure response was reduced from 61 to 32 mmHg. 4. Electrical stimulation of the muscles resulted in 75% of voluntary strength in man. The heart rate response was delayed one R-R interval in the electrocardiogram but was as large as during voluntary contractions. During partial curarization the heart rate response was significantly smaller and the blood pressure response was reduced from 11 to 8 mmHg. 5. In conclusion, processes in active muscles elicit an increase in heart rate and blood pressure which depends on the intensity of the muscle contraction developed. However, the immediate cardiovascular responses at the onset of voluntary muscle contractions cannot be accounted for by reflexes generated in the working muscles alone.