The assessment of forearm oxygen consumption (VO₂) and forearm blood flow (FBF) by means of near infrared spectroscopy has become widespread in adults, whereas in children and adolescents no data are available. The aim of the present study was to analyze VO₂ and FBF in healthy children and adolescents. Methods: In a prospective cohort study, 20 male and 20 female healthy children and adolescents were investigated. The measurements of VO₂ and FBF were performed by means of near infrared spectroscopy in combination with the venous occlusion method. Results: Mean VO₂ was 0.08 ± 0.04 ml 100 g⁻¹ min⁻¹ in male and 0.09 ± 0.05 ml 100 g⁻¹ min⁻¹ in female subjects. Mean FBF was 1.95 ± 1.25 ml 100 g⁻¹ min⁻¹ in male and 1.82 ± 0.98 ml 100 g⁻¹ min⁻¹ in female subjects. No significant difference was found between male and female subjects. A significant negative correlation of VO₂ and FBF to age was observed in both groups. Conclusion: In the present study we were able to show that VO₂ and FBF decreased with increasing age in children and adolescents without significant differences between male and female subjects.

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The present study examined the influences of the muscle contraction (MCP) and relaxation (MRP) phases, as well as systole and diastole, on the blood velocity profile and flow in the conduit artery at different dynamic muscle contraction forces. Eight healthy volunteers performed one-legged dynamic knee-extensor exercise at work rates of 5, 10, 20, 30, and 40 W at 60 contractions per minute. The time- and space-averaged, amplitude-weighted, mean (V_mean) and maximum (V_max) blood flow velocities were continuously measured in the common femoral artery during the cardiosystolic (CSP) and cardiodiastolic (CDP) phases during MCP and MRP, respectively. The V_max/V_mean ratio was used as a flow profile index where a ratio of approximately (∼) 1 indicates a “flat” velocity profile, and a ratio significantly greater than (>>) 1 indicates a “parabolic” velocity profile. At rest, a “steeper” parabolic velocity profile was found during the CDP (ratio: 1.75 ± 0.06) than during the CSP (ratio: 1.31 ± 0.02). During the MRP of exercise, the V_max/V_mean ratio shifted to be less steep (p < 0.05) than at rest during the CDP (ratio: 1.41–1.54) at 5, 10, 20, 30, and 40 W; whereas it was slightly higher (p < 0.05) at 30 and 40 W than at rest during the CSP (ratio: 1.43–1.46). During the MCP, the parabolic blood velocity profile was enhanced (p < 0.05) at higher contraction forces, 20 W during the CDP (ratio: 2.15–2.52) and 30 W during the CSP (ratio: 1.49–1.77), potentially because of a greater retrograde flow component. A higher blood flow furthermore appeared during the MRP compared to during the MCP, coinciding with a greater uniformity of the red blood cells moving at higher blood velocities during the MRP. Thus part of the difference in the magnitude of blood flow during the MRP vs. MCP may be due to the alterations of the blood velocity flow profile.

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To gain more insight into the molecular mechanism of muscle growth and fiber-type transformations, we analyzed the effects of β₂-adrenergic agonist clenbuterol (CB) and/or cyclosporin A (CsA), a potent inhibitor of calcineurin (CaN), on the muscle mass as well as on the mRNA levels of myosin heavy chains (MHC I, IIa, IId/x, IIb), using a real-time RT-PCR with specific primers in rat masseter. In comparison with control, the CB treatment significantly decreased the MHC I mRNA level (p < 0.01), but increased the MHC IId/x mRNA level (p < 0.01), and the CsA treatment significantly decreased the MHC I mRNA level (p < 0.05) in association with the significant decrease in MHC IIb mRNA level (p < 0.05). The CB+CsA treatment significantly decreased the levels of MHC I (p < 0.01) and IIa mRNAs (p < 0.05), but increased the MHC IId/x mRNA level (p < 0.001) in association with a significant decrease in MHC IIb mRNA level (p < 0.01), in comparison with control. The masseter muscle mass was significantly (p < 0.001) increased by either the CB or the CB + CsA treatment, but decreased with the CsA treatment (p < 0.01). These results suggest that in rat masseter muscle, CB has an anabolic action accompanying MHC mRNA I IIa IId/x sequence transition independently of CaN-signaling pathways, and CaN is involved in the type I fiber gene expression and the muscle mass maintenance of type IIb fiber.

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The Na⁺/Ca²⁺ exchanger (NCX) is the major Ca²⁺ efflux system in cardiac myocytes, and thereby its global knockout is embryonically lethal. However, Henderson et al. (2004) found that mice with the cardiospecific knockout of NCX1 lived to adulthood. No adaptation was detected in expression levels of other proteins except for a 50% reduction in the L-type Ca²⁺ current (I_CaL) as revealed in electrophysiological studies. To predict mechanisms of survival, we simulated cardiac myocyte activity in the absence of NCX using a mathematical model of guinea pig ventricular myocytes. The NCX knockout resulted in contracture of the model cell because of a rise in the cytoplasmic Ca²⁺ ([Ca²⁺]_i). However, up-regulation of the sarcolemmal Ca²⁺ pump (PMCA) and/or down-regulation of I_CaL enables steady rhythmic contractions even if NCX is totally excluded. The simulation predicted that the steady activities are maintained by a functional up-regulation of PMCA by about 2.3 times in addition to the down-regulation of I_CaL to a half, as observed in the experiment. However, the model analysis predicted that the myocyte depending on PMCA for Ca²⁺ extrusion is unstable against any changes in ionic fluxes and energetically unfavorable in comparison with the control. The reason for the instability is that the activity of PMCA driven by the ATP hydrolysis is hardly affected by changes in [Ca²⁺]_i, but NCX has a reversal potential in the middle level of the action potential and is immediately affected by the Ca²⁺ flux via NCX itself. The source code of the model is available at http://www.sim-bio.org/.

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We previously estimated the myofilament responsiveness to Ca²⁺ in isolated intact ventricular myocytes, using the steady-state relationship between cytosolic Ca²⁺ concentration ([Ca²⁺]_i) and cell-shortening during tetanus (Ca-L trajectory). This method was useful and easy; however, it could not be used for a high dose of Ca sensitizer because the instantaneous plots after the application of Ca sensitizer did not make a fixed point of shortening (we used 5% shortening). Therefore we must produce another method to investigate Ca²⁺ responsiveness. For an estimation of a wider range of the Ca-L trajectory, we fitted the Ca-L trajectory data with the Hill equation to construct the Ca-shortening curve. To fit this curve, we measured the maximal shortening, which was on average 31.6%. The value of [Ca²⁺]_i to produce the half-maximal shortening (Ca₅₀) was dose-dependently decreased by EMD57033 (sensitization). Either isoproterenol or 3-isobutyl-1-methylxanthine increased Ca₅₀ (desensitization) with a concomitant increase in intracellular c-AMP. EMD57439, a selective PDE-III inhibitor, did not significantly increase the c-AMP concentration and produced little change in Ca₅₀. These results are in agreement with previous reports with skinned or intact multicellular preparations. The Ca-shortening curve constructed in intact cardiac myocytes can be used to estimate the myofibrillar responsiveness to Ca²⁺ in a wide range of [Ca²⁺]_i.

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The influence of the carotid-cardiac baroreflex on blood pressure regulation was evaluated during supine rest and 40° head-up tilt (HUT) in 9 healthy young subjects with and without full cardiac vagal blockade. The carotid baroreflex responsiveness, or maximal gain (G_MAX), was assessed from the beat-to-beat changes in heart rate (HR) and mean arterial pressure (MAP) by the variable neck pressure and suction technique ranging in pressure from +40 to −80 Torr, with and without glycopyrrolate (12.0 ± 1.0 μg/kg body weight; mean ± SE). In the supine position, glycopyrrolate increased the HR to 91 ± 3 bpm, from 54 ± 3; MAP to 89 ± 2 mmHg, from 76 ± 2; and cardiac output to 6.8 ± 0.3 l·min⁻¹, from 4.9 ± 0.3 (P < 0.05). The G_MAX of the carotid baroreflex control of HR was reduced to −0.06 ± 0.01 bpm·mmHg⁻¹, from −0.30 ± 0.02 (P < 0.05) with no significant effect on the G_MAX of the carotid baroreflex control of MAP. During HUT the carotid baroreflex control of MAP was unchanged, though the G_MAX of the carotid baroreflex control of HR was increased (P < 0.05). During HUT, central blood volume, assessed by electrical thoracic admittance, and total vascular conductance were decreased with and without glycopyrrolate. Furthermore, glycopyrrolate reduced G_MAX of the carotid baroreflex control of HR during HUT (P < 0.05) with no significant effect on G_MAX of the carotid baroreflex control of MAP. These data suggest that during supine rest and HUT-induced decreases in central blood volume, the carotid baroreflex control of HR is mediated primarily via parasympathetic activity. Furthermore, the maintenance of arterial blood pressure during postural stress is primarily mediated by arterial and cardiopulmonary reflex regulation of sympathetic activity and its effects on the systemic vasculature.

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The sympathetic regulation of heart rate (HR) may be attained by neural and humoral factors. With respect to the humoral factor, plasma noradrenaline (NA) and adrenaline (Adr) can reportedly increase to levels approximately 10 times higher than resting level during severe exercise. Whether such high plasma NA or Adr interfered with the sympathetic neural regulation of HR remained unknown. We estimated the transfer function from cardiac sympathetic nerve stimulation (SNS) to HR in anesthetized and vagotomized rabbits. An intravenous administration of NA (n = 6) at 1 and 10 μg·kg⁻¹·h⁻¹ increased plasma NA concentration (pg/ml) from a baseline level of 438 ± 117 (mean ± SE) to 974 ± 106 and 6,830 ± 917 (P < 0.01), respectively. The dynamic gain (bpm/Hz) of the transfer function did not change significantly (from 7.6 ± 1.2 to 7.5 ± 1.1 and 8.1 ± 1.1), whereas mean HR (in bpm) during SNS slightly increased from 280 ± 24 to 289 ± 22 (P < 0.01) and 288 ± 22 (P < 0.01). The intravenous administration of Adr (n = 6) at 1 and 10 μg·kg⁻¹·h⁻¹ increased plasma Adr concentration (pg/ml) from a baseline level of 257 ± 86 to 659 ± 172 and 2,760 ± 590 (P < 0.01), respectively. Neither the dynamic gain (from 8.0 ± 0.6 to 8.4 ± 0.8 and 8.2 ± 1.0) nor the mean HR during SNS (from 274 ± 13 to 275 ± 13 and 274 ± 13) changed significantly. In contrast, the intravenous administration of isoproterenol (n = 6) at 10 μg·kg⁻¹·h⁻¹ significantly increased mean HR during SNS (from 278 ± 11 to 293 ± 9, P < 0.01) and blunted the transfer gain value at 0.0078 Hz (from 5.9 ± 1.0 to 1.0 ± 0.4, P < 0.01). In conclusion, high plasma NA or Adr hardly affected the dynamic sympathetic neural regulation of HR.

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There is enough evidence that erythropoietin (EPO) may be involved in cardiovascular function. Therefore we have investigated the possible effects of EPO on left ventricular developed pressure, +dP/dt_max, heart rate, tissue cAMP, and nitrite levels. Isolated rat hearts were perfused under constant flow (10 ml/min) conditions with modified Krebs-Henseleit solution and recombinant human erythropoietin at doses of 100, 200, 500, and 1,000 IU/kg was administered as bolus injections. EPO at 100 IU/kg decreased, but higher doses (500 and 1,000 IU/kg) raised the developed pressure and +dP/dt_max. However, it did not affect heart rate or coronary perfusion pressure when all the respective doses were applied. EPO at 100 IU/kg increased nitrite, and at 1,000 IU/kg it raised cAMP. Our results suggest that EPO may produce dose-dependently negative and positive inotropic effects on myocardial contractility in isolated rat hearts. NO and cAMP may be involved in negative and positive inotropic effects of EPO, respectively.

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Walking produced increases in both the extracellular acetylcholine level and regional blood flow in the hippocampus in aged rats 26–29 months old. The present results in aged rats were compared with our previous data in young adult rats (Nakajima et al., 2003), and it was found that both the acetylcholine and blood flow responses in the hippocampus were well maintained in aged rats.

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The technique of rotating acupuncture needles has long been used to enhance the effects of acupuncture in Oriental medicine. However, it is difficult to standardize and quantify this stimulation condition. Thus we developed an automatically controlled rotating acupuncture (ACRA) system. The present study was conducted to evaluate the analgesic effects of ACRA using 4 different stimulation conditions (i.e., angle and frequency of rotation: 90° + 1 Hz, 90° + 1/4 Hz, 360° + 1 Hz, and 360° + 1/4 Hz) in Sprague-Dawley rats. Tail-flick latency to a noxious radiant heat stimulus in lightly anesthetized rats was measured before and after 15 min of ACRA stimulation at the Zusanli (ST36) acupoint. ACRA stimulations under all of the conditions above produced more potent analgesic effects than plain acupuncture (PA, acupuncture needle insertion only), but only the 90° + 1/4 Hz ACRA condition showed a statistically significant effect versus PA (P < 0.01). Further, the analgesic effect of 90° + 1/4 Hz ACRA was reversed by pretreatment with naloxone (2 mg/kg, i.p.). These results indicate that the 90° + 1/4 Hz ACRA stimulation has the most potent analgesic effect in rats and that this is mediated by the endogenous opioid system.

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Using real-time hard disk recording, we have developed an optical system for the long-duration detection of changes in membrane potential from 1,020 sites with a high temporal resolution. The signal-to-noise ratio was sufficient for analyzing the spreading pattern of excitatory waves in frog atria in a single sweep.

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