Ishio Ninomiya

Changes in functional and histological distributions of nitric oxide synthase caused by chronic hypoxia in rat small pulmonary arteries

Chronic hypoxia (CH) increases lung tissue expression of all types of nitric oxide synthase (NOS) in the rat. However, it remains unknown whether CH‐induced changes in functional and histological NOS distributions are correlated in rat small pulmonary arteries. We measured the effects of NOS inhibitors on the internal diameters (ID) of muscular (MPA) and elastic (EPA) pulmonary arteries (100–700 μm ID) using an X‐ray television system on anaesthetized rats. We also conducted NOS immunohistochemical localization on the same vessels. Nonselective NOS inhibitors induced ID reductions in almost all MPA of CH rats (mean reduction, 36±3%), as compared to ∼60% of control rat MPA (mean, 10±2%). The inhibitors reduced the ID of almost all EPA with similar mean values (∼26%) in both CH and control rats. On the other hand, inducible NOS (iNOS)‐selective inhibitors caused ID reductions in ∼60% of CH rat MPA (mean, 15±3%), but did so in only ∼20% of control rat MPA (mean, 2±2%). This inhibition caused only a small reduction (mean, ∼4%) in both CH and control rat EPA. A neuronal NOS‐selective inhibitor had no effect. The percentage of endothelial NOS (eNOS)‐positive vessels was ∼96% in both MPA and EPA from CH rats, whereas it was 51 and 91% in control MPA and EPA, respectively. The percentage for iNOS was ∼60% in both MPA and EPA from CH rats, but was only ∼8% in both arteries from control rats. The data indicate that in CH rats, both functional and histological upregulation of eNOS extensively occurs within MPA. iNOS protein increases sporadically among parallel‐arranged branches in both MPA and EPA, but its vasodilatory effect is predominantly observed in MPA. Such NOS upregulation may serve to attenuate hypoxic vasoconstriction, which occurs primarily in MPA and inhibit the progress of pulmonary hypertension.

Effects of mental stress on cardiac and motor rhythms

To identify whether spontaneous cardiac rhythm and voluntary motor rhythm are modified in parallel or influenced separately when imposing mental stress, we recorded simultaneously the two rhythms during finger tapping as a simple model of rhythmical motion in 10 healthy human subjects (6 males, 4 females each). Each subject performed finger tapping with an arbitrary tapping rhythm. Mental stress was given intermittently three times for 10-15 s at intervals of 40 s during tapping for 150 s. Heart rate (HR) and tapping rate (TR) and their variations (standard deviation; SD) during finger tapping with and without mental stress were compared. HR and TR increased significantly in response to mental stress during tapping. After mental stress was ended, HR returned rapidly to the initial level, but TR remained at a higher level. Moreover, SD of TR, but not SD of HR, during tapping was increased by mental stress. The present results indicate that the cardiac and motor rhythms are influenced simultaneously by mental stress. However, a difference was seen about the sustained effect of mental stress on the two rhythms.

Segmental differences in vasodilatation due to basal NO release in in vivo cat pulmonary vessels

This study was conducted to examine segmental differences in vasodilatation caused by the basal release of nitric oxide (NO) in the serially connected pulmonary vessels and to estimate the relative contributions of endothelial and neuronal NO synthase (NOS), and inducible NOS to the vasodilatation. Using an X-ray TV system on in vivo cat lungs, we measured internal diameter (ID) changes in resistance (100-400 microm ID), small conduit (600-1000 microm) and large conduit (1200-1700 microm) arteries, and veins of the same size. Non-selective NOS inhibitors, L-NAME (30-50 mg/kg i.v.) and L-NMMA (40-60 mg/kg i.v.), decreased the ID of all vessels studied, although their D-isomers had no effect. The decrease was larger in conduit arteries than in resistance arteries, with maximum response of small conduit arteries (25 +/- 2%), while venous segments displayed relatively uniform response (10-12%). L-Arginine completely abolished the ID decrease but hexamethonium bromide and phentolamine had no effect. Selective inhibitors of inducible NOS, L-canavanine (100 mg/kg i.v.) and S-methylisothiourea (10 mg/kg i.v.) did not affect any of the vessels. The data suggest that basal release of NO chiefly derived from endothelial NOS serves to dilate cat pulmonary arteries and veins, particularly small conduit arteries.

A wireless breathing-training support system for kinesitherapy

We have developed a new wireless breathing-training support system for kinesitherapy. The system consists of an optical sensor, an accelerometer, a microcontroller, a Bluetooth module and a laptop computer. The optical sensor, which is attached to the patient’s chest, measures chest circumference. The low frequency components of circumference are mainly generated by breathing. The optical sensor outputs the circumference as serial digital data. The accelerometer measures the dynamic acceleration force produced by exercise, such as walking. The microcontroller sequentially samples this force. The acceleration force and chest circumference are sent sequentially via Bluetooth to a physical therapist’s laptop computer, which receives and stores the data. The computer simultaneously displays these data so that the physical therapist can monitor the patient’s breathing and acceleration waveforms and give instructions to the patient in real time during exercise. Moreover, the system enables a quantitative training evaluation and calculation the volume of air inspired and expired by the lungs.

An implantable telemetry system powered by a capacitor having high capacitance

An implantable telemetry system, using a capacitor having high capacitance instead of the rechargeable batteries, has been designed for chronic unanaesthetized animal studies. This system can simultaneously record the cardiac sympathetic nerve activity and ECG. The power of the system is inductively coupled and transmitted to a 2.5 farad capacitor. The system, which is constructed by ultralow power analog and digital standard integrated circuits, has a transmission range up to 5 m, depending on intervening tissue depth and FM receiver characteristics. With the capacitor charging time of 5 minutes, the system can be driven for 120 minutes.

Augmentation of somato-sympathetic reflex in the ischemic hindlimb of anesthetized rats

Activities of the visceral sympathetic nerve increase with noxious mechanical stimulation. This study investigated the effects of noxious mechanical stimulation of hindlimb on arterial blood pressure, heart rate (HR) and renal sympathetic nerve activities (RNA) in anesthetized rats intact or under ischemic conditions. This study utilized two methods of noxious mechanical stimulation. One was pinching of the hindpaw; the other, strangulation of the ankle joint. Twenty-three male Wistar rats were used in the experiment. Pinching and strangulation of the intact hindlimb caused an increase in RNA. The increased RNA was greater during strangulation than during pinch stimulation (p < 0.0001). In the ischemic hindlimb produced by occlusion of the left common iliac artery, pinching and strangulation caused a further increase in RNA (p < 0.0001). Arterial blood pressure and HR significantly increased during strangulation with ischemic condition (p < 0.05). These results suggest that the reflex effects of somatosensory input on RNA were augmented in the ischemic hindlimb.

Sympathetic Control of the Coronary Circulation

For better understanding of the neural coronary regulatory mechanism, the efferent pericoronary nerve activity (PCNA), cardiac sympathetic nerve activity (CSNA), and coronary vascular resistance were measured in the anesthetized animal. The presence of tonic sympathetic PCNA, which shows a temporal and spatial nonuniformity and induces a vasoconstrictor tone, was clarified. Baroreflex control of sympathetic PCNA, but not of parasympathetic PCNA, was observed. During systemic hypotension, a reflex increase in CSNA and sympathetic PCNA resulted in a biphasic change (increase and decrease) in coronary vascular resistance due to a combined activation of alpha- and beta-adrenergic receptors in the coronary vessel and myocardium.

A new venous infusion pathway monitoring system

A new infusion catheter pathway monitoring system employing linear integrated circuits and a low-power 8-bit single chip microcomputer has been developed for hospital and home use. The sensor consists of coaxial three-layer conductive tapes wrapped around the polyvinyl chloride infusion tube. The inner tape is the main electrode, which records an AC (alternating current) voltage induced on the patients body by electrostatic coupling from the normal 100 volt, 60 Hz AC power line wiring field in the patients room. The outside tape layer is a reference electrode to monitor the AC voltage around the main electrode. The center tape layer is connected to system ground and functions as a shield. The microcomputer calculates the ratio of the induced AC voltages recorded by the main and reference electrodes and if the ratio indicates a detached infusion, alerts the nursing station, via the nurse call system or low transmitting power mobile phone.