Biomedical subjects

Toru Kawada

Publications and source records attributed to Toru Kawada.

48 records · Page 3Linked to original sources

PubMed2003

Biphasic response of action potential duration to sudden sympathetic stimulation in anesthetized cats.

Although certain roles of the sympathetic nervous system have been suggested as possible mechanisms of life-threatening arrhythmias and sudden cardiac death, the dynamic electrophysiological response to sympathetic activation remains unclear. The aim of this study was to investigate the dynamic response of action potential duration (APD) to sudden sympathetic stimulation (SYM) using monophasic action potential (MAP) recording. In 10 anesthetized cats, MAPs were continuously recorded from the right ventricular endocardium under constant pacing. The dynamic response of the APD to SYM (3 Hz) were examined before and after the administration of propranolol (0.5 mg/kg i.v.) (n=5) or phentolamine (1.0 mg/kg i.v.) (n=5). In response to SYM, the APD was transiently prolonged by 5.5+/-3.2 ms at 7.0+/-1.3 s, and monotonically shortened toward a steady-state level (-14.5+/-6.9 ms). Propranolol almost abolished both the transient prolongation (6.6+/-4.5 to 0.2+/-0.4 ms, p<0.05) and the steady-state shortening (-13.7+/-3.6 to -1.1+/-2.4 ms, p<0.005), whereas phentolamine did not have a significant effect on the response of APD to SYM. These findings might partly account for the propensity of ventricular arrhythmias to occur immediately after sudden sympathetic activation.

Action Potentials↗

PubMed2003

Intravenous angiotensin II does not affect dynamic baroreflex characteristics of the neural or peripheral arc.

Although the elevation of angiotensin II (Ang II) associated with cardiovascular diseases has been considered to suppress the arterial baroreflex function, how Ang II affects dynamic arterial pressure (AP) regulation remains unknown. The aim of the present study was to elucidate the acute effects of Ang II on dynamic AP regulation by the arterial baroreflex. In seven anesthetized Japanese white rabbits, we randomly perturbed intra-carotid sinus pressure (CSP) according to a binary white noise sequence while recording renal sympathetic nerve activity (RSNA) and AP. We estimated the neural arc transfer function from CSP to RSNA and the peripheral arc transfer function from RSNA to AP before and after 30-min intravenous administration of Ang II (100 ng/kg/min). Ang II increased mean AP from 75.7 +/- 3.1 to 95.5 +/- 5.1 mmHg (p < 0.01), while it did not affect mean RSNA (from 5.9 +/- 1.3 to 5.7 +/- 1.2 a.u.). The neural arc transfer functions did not differ before or after Ang II administration (dynamic gain: -0.94 +/- 0.04 vs. -0.94 +/- 0.13, corner frequency: 0.06 +/- 0.01 vs.0.06 +/- 0.01 Hz, pure delay: 0.16 +/- 0.01 vs. 0.17 +/- 0.02 s). The peripheral arc transfer function did not differ before or after Ang II administration (dynamic gain: 1.18 +/- 0.05 vs. 1.06 +/- 0.11, natural frequency: 0.07 +/- 0.01 vs. 0.08 +/- 0.01 Hz, damping ratio: 1.19 +/- 0.06 vs. 1.24 +/- 0.19, pure delay: 0.83 +/- 0.06 vs. 0.78 +/- 0.05 s). Intravenous Ang II hardly affects the dynamic characteristics of neural and peripheral arc around the physiological operating pressure.

Algorithms↗

PubMed2002

Input-size dependence of the baroreflex neural arc transfer characteristics.

Static characteristics of the baroreflex neural arc from pressure input to sympathetic nerve activity (SNA) show sigmoidal nonlinearity, whereas its dynamic characteristics approximate a derivative filter where the magnitude of SNA response becomes greater as the input frequency increases. To reconcile the static nonlinear and dynamic linear components, we examined the effects of input amplitude on the apparent linear transfer function of the neural arc. In nine anesthetized rabbits, we perturbed isolated carotid sinus pressure by using binary white noise while varying the input amplitude among 5, 10, 20, and 40 mmHg. With increasing input amplitude, the transfer gain at 0.01 Hz decreased from 1.21 +/- 0.27 to 0.49 +/- 0.28 arbitrary units/mmHg (P < 0.01). Moreover, the slope of the transfer gain between 0.03 and 0.3 Hz decreased from 14.3 +/- 3.7 to 6.5 +/- 2.5 dB/decade (P < 0.01). We conclude that the model consisting of a sigmoidal component following rather than preceding a derivative component explains the observed results and thus can be used as a first approximation of the overall neural arc transfer characteristics.

Acoustic Stimulation↗

PubMed2002

Disruption of vagal efferent axon and nerve terminal function in the postischemic myocardium.

Despite the importance of vagal control over the ventricle, little is known regarding vagal efferent conduction and nerve terminal function in the postischemic myocardium. To elucidate postischemic changes in the cardiac vagal efferent neuronal function, we measured myocardial interstitial acetylcholine (ACh) levels by using in vivo cardiac microdialysis and examined the ACh responses to electrical stimulation of the vagi or local administration of ouabain in anesthetized cats. Sixty-minute occlusions of the left anterior descending coronary artery (LAD) followed by 60-min reperfusion abolished electrical stimulation-induced ACh release (20.4 +/- 3.9 vs. 0.9 +/- 0.4 nmol/l; means +/- SE, P < 0.01). In different groups of animals, 60-min LAD occlusion followed by 60-min reperfusion decreased but did not completely abolish ouabain-induced release of ACh (9.2 +/- 1.8 vs. 3.9 +/- 0.7 nmol/l; P < 0.05). These results indicate that function of the vagal efferent axon was completely interrupted, whereas the local ACh release was partially suppressed in the postischemic myocardium. The postischemic disruption of vagal efferent neuronal function might exert deleterious effects on cardiac regulation.

Acetylcholine↗

PubMed2002

Bionic technology revitalizes native baroreflex function in rats with baroreflex failure.

BACKGROUND: We developed a bionic technology for the treatment of baroreflex failure and tested its efficacy in restoration of arterial pressure against head-up tilt (HUT) in rats with baroreflex failure. METHODS AND RESULTS: The bionic baroreflex system (BBS) was a negative feedback system controlled by a computer, the artificial vasomotor center. It sensed systemic arterial pressure (SAP) through a micromanometer placed in the aortic arch and automatically computed the frequency of a pulse train to stimulate sympathetic efferent nerves. We selected the celiac ganglion as the sympathetic vasomotor interface. To make this system bionic, the operational rule of the artificial vasomotor center (H(BRP-->STM); BRP indicates baroreceptor pressure; STM, electrical stimulation) was actively matched to that of the native center. First, we identified the open-loop transfer functions of the native baroreflex control of SAP (H(Native)) and the response of SAP to electrical stimulation of the celiac ganglion (H(STM-->SAP)). We computed H(BRP-->STM) from H(Native)/H(STM-->SAP) and transplanted the operational rule into the computer. In 10 rats with baroreflex failure, we evaluated the performance of the BBS during rapid hypotension induced by HUT. Abrupt HUT dropped SAP by 34+/-6 mm Hg in 2 seconds and by 52+/-5 mm Hg in 10 seconds. During real-time execution of the BBS, on the other hand, the fall in SAP was 21+/-5 mm Hg at 2 seconds and 15+/-6 mm Hg at 10 seconds after HUT. These arterial responses controlled by the BBS were indistinguishable from those by the native baroreflex. CONCLUSIONS: We concluded that the BBS revitalized the native baroreflex function in rats with baroreflex failure.

Animals↗

PubMed2002

Modulatory effects of ketamine on catecholamine efflux from in vivo cardiac sympathetic nerve endings in cats.

With the use of the microdialysis technique, we examined the modulatory effect of ketamine on catecholamine efflux from in vivo cardiac sympathetic nerve endings. A dialysis probe was implanted in the left ventricular myocardium, and dialysate norepinephrine (NE) levels in anesthetized cats were measured with liquid chromatogram-electrical detection. A 60-min occlusion of the left anterior descending coronary artery caused increases in dialysate NE levels. Through the dialysis probe, locally applied ketamine (10 mM) augmented the dialysate NE responses to coronary occlusion in the presence and absence of desipramine (membrane NE transport blocker). Thus, the ketamine-induced NE increment is not mediated through the neuronal NE transporter. The sympathomimetic action of ketamine may augment the NE efflux evoked by myocardial ischemia.

Adrenergic Uptake Inhibitors↗

PubMed2002

Effects of brief ischaemia on myocardial acetylcholine and noradrenaline levels in anaesthetized cats.

Although brief ischaemic events make the myocardium tolerant to subsequent prolonged ischaemia, known as ischaemic preconditioning, whether brief ischaemia also affects neural regulation at the in vivo heart remains unknown. We examined the effects of brief ischaemia on myocardial interstitial acetylcholine (ACh) and noradrenaline (NA) levels in anaesthetized cats (n = 6). Baseline ACh and NA levels were 0.65 +/- 0.13 and 0.66 +/- 0.17 nmol l(-1) (mean +/- SE), respectively. Two sets of 5-min brief occlusion followed by 20-min reperfusion of the left anterior descending coronary artery (LAD) significantly increased the myocardial interstitial ACh level to 4.6 +/- 0.7 nmol l(-1) (P < 0.01), while not affecting the myocardial interstitial NA level. Subsequent 60-min LAD occlusion significantly increased the ACh and NA levels to 34.9 +/- 6.0 and 96.5 +/- 17.0 nmol l(-1) (P < 0.01), respectively. Vagotomy abolished the myocardial interstitial ACh release during brief ischaemia and attenuated the ACh release during subsequent 60-min ischaemia (n = 6). In contrast, vagotomy did not affect the subsequent ischaemia-induced myocardial interstitial NA release. We conclude that the brief ischaemia affects myocardial interstitial ACh release but not NA release in the ischaemic myocardium in vivo.

Acetylcholine↗

PubMed2002

A novel photocurable insulator material for autonomic nerve activity recording.

The two-component, addition-curing silicone glue is widely used as an insulator for autonomic nerve activity recording. Due to its high fluidity before curing, a sizable mass of the glue is needed to completely cover the electrode tips, which may cause mechanical stress on the nerve. To overcome this problem, we designed a novel photocurable insulator material composed of Vaseline and 1,12-dodecanediol diacrylate (50:50wt%) together with a photoinitiator, camphorquinone, at 0.25wt%. This material had an appropriate viscosity of 0.18 Pa s at 25 degrees C and was converted to a soft solid upon an arbitrary timing of photoirradiation. The compressive force per mm deformation of the resulting solid was 155.5 kPa at 1 min of photoirradiation. The impedance of the solid for 1 mm length and 10 mm2 cross-sectional area was above 1 Mohm. In anesthetized rabbits, a very small mass of the photocurable material was able to cover the electrode tips and the nerve in situ. Changes in both the aortic depressor nerve activity and renal sympathetic nerve activity were stably recorded. These results indicate that the photocurable material developed is useful as an in vivo insulator material for autonomic nerve activity recording.

Animals↗

PubMed2002

Right ventricular dP/dt/P(max), not dP/dt(max), noninvasively derived from tricuspid regurgitation velocity is a useful index of right ventricular contractility.

BACKGROUND: Although right ventricular (RV) contractility is important in determining functional capacity, few quantification methods are clinically available. RV dP/dt(max) can be assessed by Doppler echocardiography by using tricuspid regurgitation (TR) but is not routinely used because of its dependency on a Doppler incident angle and preload. Doppler-derived dP/dt/P(max) is relatively insensitive to preload and theoretically independent of the incident angle. We investigated the clinical feasibility of this index as an RV contractility index. METHODS: We computed RV dP/dt(max) and dP/dt/P(max) from the TR-derived RV pressure in 68 patients with dominant RV failure (13 in New York Heart Association [NYHA] class I, 33 in class II, 17 in class III, and 5 in class IV). Peak oxygen consumption (peak VO(2)) was measured in 20 patients during a maximal bicycle ergometer test. RESULTS: dP/dt(max) did not significantly correlate with NYHA class. In contrast, dP/dt/P(max) decreased monotonically with the functional class (r = -0.49, P <.0001), and correlated with peak VO(2) (r = 0.66, P <.002). CONCLUSION: TR-derived dP/dt/P(max), not dP/dt(max), is a clinically useful index of RV contractility, allowing researchers to account for the functional capacity.

Adolescent↗

PubMed2002

High-cut characteristics of the baroreflex neural arc preserve baroreflex gain against pulsatile pressure.

A transfer function from baroreceptor pressure input to sympathetic nerve activity (SNA) shows derivative characteristics in the frequency range below 0.8 Hz in rabbits. These derivative characteristics contribute to a quick and stable arterial pressure (AP) regulation. However, if the derivative characteristics hold up to heart rate frequency, the pulsatile pressure input will yield a markedly augmented SNA signal. Such a signal would saturate the baroreflex signal transduction, thereby disabling the baroreflex regulation of AP. We hypothesized that the transfer gain at heart rate frequency would be much smaller than that predicted from extrapolating the derivative characteristics. In anesthetized rabbits (n = 6), we estimated the neural arc transfer function in the frequency range up to 10 Hz. The transfer gain was lost at a rate of -20 dB/decade when the input frequency exceeded 0.8 Hz. A numerical simulation indicated that the high-cut characteristics above 0.8 Hz were effective to attenuate the pulsatile signal and preserve the open-loop gain when the baroreflex dynamic range was finite.

Animals↗

PubMed2002

Estimation of baroreflex gain using a baroreflex equilibrium diagram.

Two types of closed-loop perturbations can be applied to the arterial baroreflex system. The first (P(D1)) is introduced into the baroreceptors without a direct effect on arterial pressure (AP), whereas the second (P(D2)) initially affects AP. Neck suction and hemorrhage are examples of P(D1) and P(D2), respectively. To estimate the baroreflex open-loop gain (G(Baro)) without knowing the absolute magnitudes of P(D1) and P(D2), we explored a new strategy to estimate G(Baro) by combining P(D1) and P(D2) in a baroreflex equilibrium diagram. In this diagram, the neural arc presents the input-output relationship between baroreceptor pressure input and sympathetic nerve activity (SNA). The peripheral arc presents the input-output relationship between SNA and AP. In 8 anesthetized rabbits, we estimated G(Baro) by multiplying the slopes of the peripheral arc determined from P(D1) and the neural arc determined from P(D2). We also estimated G(Baro) by a conventional open-loop analysis. The G(Baro) values estimated by the equilibrium diagram and the open-loop analysis showed a positive correlation (y = 0.80x + 0.22, r(2) = 0.95) and a standard error of estimate of 0.21 across the animals. We conclude that G(Baro) was estimated well by combining P(D1) and P(D2) in the equilibrium diagram.

Animals↗

PubMed2002

Convenient automated conductance volumetric system.

Conventional conductance volumetric systems require ex-vivo calibrations for blood conductivity and parallel conductance. It is often impractical to repeat blood sampling and hypertonic saline infusion for these calibrations. To overcome these limitations, we developed a useful, self-calibrating conductance volumetric system that does not require ex-vivo calibrations. On a conventional 6-electrode catheter, we added an extra electrode close to one of the recording electrodes to estimate blood conductivity. These two electrodes were placed close (0.5 mm) enough so that conductance between them reflected only blood conductivity regardless of cardiac volume. We estimated parallel conductance by the dual-frequency excitation (2 and 20 kHz) method. In 18 anesthetized rabbits, blood conductivity (sigma(est)) thus estimated agreed well with that (sigma(conv)) measured by the conventional ex-vivo blood sampling method (sigma(est) = 1.04sigma(conv)-0.25, R(2) = 0.98, SEE = 0.01 mS/cm, 1.2% error). Parallel conductance (G(p est)) estimated by dual-frequency excitation also agreed well with that (G(p conv)) estimated by the saline injection method (G(p est) = 0.95G(p conv)+4.25, R(2) = 0.87, SEE = 4.0 mS, 6.0% error). Estimated ventricular volume (V(est)) by our system agreed reasonably well with that (V(conv)) by the conventional method (V(est) = 0.93V(conv)+0.01, R(2) = 0.86, SEE = 0.22 ml, 14.7% error). The fact that this self-calibrating conductance volumetric system drastically simplifies volume measurement makes it an attractive tool for the assessment of cardiac function where significant changes in blood conductivity and parallel conductance are inevitable, such as in cardiac surgery.

Animals↗