Biomedical subjects

Kenji Sunagawa

Publications and source records attributed to Kenji Sunagawa.

At least 19 recordsLinked to original sources

PubMed2003

Inhibition of cholinesterase elicits muscarinic receptor-mediated synaptic transmission in the rat adrenal medulla.

To determine the role of acetylcholinesterase in cholinergic synaptic transmission in the adrenal medulla in vivo, we applied a dialysis technique to the adrenal medulla of anesthetized rats and examined the effect of acetylcholinesterase inhibitor on the contribution of nicotinic and muscarinic receptors to catecholamine release. Exogenous acetylcholine-induced epinephrine release was inhibited by atropine (a muscarinic receptor antagonist) as well as hexamethonium (a nicotinic receptor antagonist). Endogenous acetylcholine (nerve stimulation)-induced epinephrine release was inhibited by hexamethonium but not atropine. In the presence of neostigmine (an acetylcholinesterase inhibitor), both exogenous and endogenous acetylcholine-induced catecholamine release was enhanced. In either case, epinephrine release was inhibited by atropine as well as hexamethonium. In the presence of eserine (another acetylcholinesterase inhibitor), endogenous acetylcholine-induced epinephrine release was also inhibited by atropine. Exogenous or endogenous acetylcholine-induced norepinephrine release was primarily inhibited by hexamethonium regardless of whether neostigmine was absent or present. In the rat adrenal medulla, the inhibition of acetylcholinesterase not only enhanced cholinergic synaptic transmission but also elicited muscarinic receptor-mediated synaptic transmission for epinephrine release.

Acetylcholinesterase↗

PubMed2003

Alpha-adrenergic vascular responsiveness to sympathetic nerve activity is intact after head-down bed rest in humans.

Space-flight and its ground-based simulation model, 6 degrees head-down bed rest (HDBR), cause cardiovascular deconditioning in humans. Because sympathetic vasoconstriction plays a very important role in circulation, we examined whether HDBR impairs alpha-adrenergic vascular responsiveness to sympathetic nerve activity. We subjected eight healthy volunteers to 14 days of HDBR and before and after HDBR measured calf muscle sympathetic nerve activity (MSNA; microneurography) and calf blood flow (venous occlusion plethysmography) during sympathoexcitatory stimulation (rhythmic handgrip exercise). HDBR did not change the increase in total MSNA (P = 0.97) or the decrease in calf vascular conductance (P = 0.32) during exercise, but it did augment the increase in calf vascular resistance (P = 0.0011). HDBR augmented the transduction gain from total MSNA into calf vascular resistance, assessed as the least squares linear regression slope of vascular resistance on total MSNA (0.05 +/- 0.02 before HDBR, 0.20 +/- 0.06 U.min-1.burst-1 after HDBR, P = 0.0075), but did not change the transduction gain into calf vascular conductance (P = 0.41). Our data indicate that alpha-adrenergic vascular responsiveness to sympathetic nerve activity is preserved in the supine position after HDBR in humans.

Adult↗

PubMed2003

Attenuated thermoregulatory sweating and cutaneous vasodilation after 14-day bed rest in humans.

We investigated the effect of head-down bed rest (HDBR) for 14 days on thermoregulatory sweating and cutaneous vasodilation in humans. Fluid intake was ad libitum during HDBR. We induced whole body heating by increasing skin temperature for 1 h with a water-perfused blanket through which hot water (42 degrees C) was circulated. The experimental room was air-conditioned (27 degrees C, 30-40% relative humidity). We measured skin blood flow (chest and forearm), skin temperatures (chest, upper arm, forearm, thigh, and calf), and tympanic temperature. We also measured sweat rate by the ventilated capsule method in which the skin area for measurement was drained by dry air conditioned at 27 degrees C under similar skin temperatures in both trials. We calculated cutaneous vascular conductance (CVC) from the ratio of skin blood flow to mean blood pressure. From tympanic temperature-sweat rate and -CVC relationships, we assessed the threshold temperature and sensitivity as the slope response of variables to a given change in tympanic temperature. HDBR increased the threshold temperature for sweating by 0.31 degrees C at the chest and 0.32 degrees C at the forearm, whereas it reduced sensitivity by 40% at the chest and 31% at the forearm. HDBR increased the threshold temperature for cutaneous vasodilation, whereas it decreased sensitivity. HDBR reduced plasma volume by 11%, whereas it did not change plasma osmolarity. The increase in the threshold temperature for sweating correlated with that for cutaneous vasodilation. In conclusion, HDBR attenuated thermoregulatory sweating and cutaneous vasodilation by increasing the threshold temperature and decreasing sensitivity. HDBR increased the threshold temperature for sweating and cutaneous vasodilation by similar magnitudes, whereas it decreased their sensitivity by different magnitudes.

Adolescent↗

PubMed2003

Reduced oxygen uptake increase to work rate increment (DeltaVO2/DeltaWR) is predictable by VO2 response to constant work rate exercise in patients with chronic heart failure.

Patients with reduced peak oxygen uptake (VO2) due to chronic heart failure (CHF) exhibit abnormal VO2 kinetics even during mild to moderate exercise. This is characterized by a reduced ratio of the VO2 increase to the work rate increment (DeltaVO2/DeltaWR) during ramp exercise, and by a slow increase in VO2 during constant work rate exercise. Because the slow kinetics alone is unlikely to explain the reduced DeltaVO2/DeltaWR on theoretical grounds, we can postulate that the linearity between work rate and VO2 may be impaired when exercise is imposed in a ramp fashion. The present study was designed to address this issue. In 21 CHF patients and 17 normal controls, we performed both symptom-limited exercise testing (15 W. min(-1) ramp) and a constant work rate exercise test (0 W followed by 50-W step). The VO2 step response was used to mathematically derive the hypothetical VO2 ramp response by time integration. Although peak VO2 and work rate were both significantly lower in patients, the attenuation in peak VO2 was more prominent ( p<0.05), which could be explained by a lower DeltaVO2/DeltaWR in patients compared with controls [8.1 (SD 1.0) and 9.8 (0.5) ml. min(-1). W(-1), p<0.01]. The hypothetical DeltaVO2/DeltaWR derived from the VO2 step response was also significantly lower in patients [8.7 (1.0) and 10.0 (0.7) ml. min(-1). W(-1), p<0.01]. The hypothetical and measured DeltaVO2/DeltaWR were highly correlated ( r=0.78, p<0.001). Thus, we can reasonably predict the VO2 ramp response from the VO2 response to a step increase in work rate, indicating that linearity between VO2 and work rate is held constant irrespective of loading patterns. Additional studies, such as those including evaluation of anaerobic bioenergetics, are needed to further elucidate the precise mechanism(s) of this phenomenon.

Chronic Disease↗

PubMed2003

Pathophysiology of orthostatic hypotension after bed rest: paradoxical sympathetic withdrawal.

Although orthostatic hypotension is a common clinical syndrome after spaceflight and its ground-based simulation model, 6 degrees head-down bed rest (HDBR), the pathophysiology remains unclear. The authors' hypothesis that a decrease in sympathetic nerve activity is the major pathophysiology underlying orthostatic hypotension after HDBR was tested in a study involving 14-day HDBR in 22 healthy subjects who showed no orthostatic hypotension during 15-min 60 degrees head-up tilt test (HUT) at baseline. After HDBR, 10 of 22 subjects demonstrated orthostatic hypotension during 60 degrees HUT. In subjects with orthostatic hypotension, total activity of muscle sympathetic nerve activity (MSNA) increased less during the first minute of 60 degrees HUT after HDBR (314% of resting supine activity) than before HDBR (523% of resting supine activity, P < 0.05) despite HDBR-induced reduction in plasma volume (13% of plasma volume before HDBR). The postural increase in total MSNA continued during several more minutes of 60 degrees HUT while arterial pressure was maintained. Thereafter, however, total MSNA was paradoxically suppressed by 104% of the resting supine level at the last minute of HUT (P < 0.05 vs. earlier 60 degrees HUT periods). The suppression of total MSNA was accompanied by a 22 +/- 4-mmHg decrease in mean blood pressure (systolic blood pressure <80 mmHg). In contrast, orthostatic activation of total MSNA was preserved throughout 60 degrees HUT in subjects who did not develop orthostatic hypotension. These data support the hypothesis that a decrease in sympathetic nerve activity is the major pathophysiological factor underlying orthostatic hypotension after HDBR. It appears that the diminished sympathetic activity, in combination with other factors associated with HDBR (e.g., hypovolemia), may predispose some individuals to postural hypotension.

Adult↗

PubMed2003

Bezold-Jarisch reflex attenuates dynamic gain of baroreflex neural arc.

Although acute myocardial ischemia or infarction may induce the Bezold-Jarisch (BJ) reflex through the activation of serotonin receptors on vagal afferent nerves, the mechanism by which the BJ reflex modulates the dynamic characteristics of arterial pressure (AP) regulation is unknown. The purpose of this study was to examine the effects of the BJ reflex induced by intravenous phenylbiguanide (PBG) on the dynamic characteristics of the arterial baroreflex. In seven anesthetized rabbits, we perturbed intracarotid sinus pressure (CSP) according to a white noise sequence while renal sympathetic nerve activity (RSNA), AP, and heart rate (HR) were recorded. We estimated the transfer function from CSP to RSNA (neural arc) and from RSNA to AP (peripheral arc) before and after 10 min of intravenous administration of PBG (100 microg. kg-1. min-1). The intravenous PBG decreased mean AP from 84.5 +/- 4.0 to 68.2 +/- 4.7 mmHg (P < 0.01), mean RSNA to 76.2 +/- 7.0% (P < 0.05), and mean HR from 301.6 +/- 7.7 to 288.4 +/- 9.0 beats/min (P < 0.01). The intravenous PBG significantly decreased neural arc dynamic gain at 0.01 Hz (1.06 +/- 0.08 vs. 0.59 +/- 0.17, P < 0.05), whereas it did not affect that of the peripheral arc (1.20 +/- 0.12 vs. 1.18 +/- 0.41). In six different rabbits without intravenous PBG, the neural arc transfer function did not change between two experimental runs with intervening interval of 10 min, excluding the possibility that the cumulative effects of anesthetics had altered the neural arc transfer function. In conclusion, excessive activation of the BJ reflex during acute myocardial ischemia may exert an adverse effect on AP regulation, not only by sympathetic suppression, but also by attenuating baroreflex dynamic gain.

Animals↗

PubMed2003

High plasma norepinephrine attenuates the dynamic heart rate response to vagal stimulation.

To better understand the pathophysiological significance of high plasma norepinephrine (NE) concentration in regulating heart rate (HR), we examined the interactions between high plasma NE and dynamic vagal control of HR. In anesthetized rabbits with sinoaortic denervation and vagotomy, using a binary white noise sequence (0-10 Hz) for 10 min, we stimulated the right vagus and estimated the transfer function from vagal stimulation to HR response. The transfer function approximated a first-order low-pass filter with pure delay. Infusion of NE (100 microg. kg(-1) x h(-1) iv) attenuated the dynamic gain from 6.2 +/- 0.8 to 3.9 +/- 1.2 beats x min(-1) x Hz(-1) (n = 7, P < 0.05) without affecting the corner frequency or pure delay. Simultaneous intravenous administration of phentolamine (1 mg x kg(-1) x h(-1)) and NE (100 microg x kg(-1) x h(-1)) abolished the inhibitory effect of NE on the dynamic gain (6.3 +/- 0.8 vs. 6.4 +/- 1.3 beats x min(-1) x Hz(-1), not significant, n = 7). The inhibitory effect of NE at infusion rates of 10, 50, and 100 microg x kg(-1) x h(-1) on dynamic vagal control of HR was dose-dependent (n = 5). In conclusion, high plasma NE attenuated the dynamic HR response to vagal stimulation, probably via activation of alpha-adrenergic receptors on the preganglionic and/or postganglionic cardiac vagal nerve terminals.

Adrenergic alpha-Agonists↗

PubMed2003

Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome.

OBJECTIVES: This study was designed to test the hypothesis that epinephrine infusion may be a provocative test able to unmask nonpenetrant KCNQ1 mutation carriers. BACKGROUND: The LQT1 form of congenital long QT syndrome is associated with high vulnerability to sympathetic stimulation and appears with incomplete penetrance. METHODS: The 12-lead electrocardiographic parameters before and after epinephrine infusion were compared among 19 mutation carriers with a baseline corrected QT interval (QTc) of > or =460 ms (Group I), 15 mutation carriers with a QTc of <460 ms (Group II), 12 nonmutation carriers (Group III), and 15 controls (Group IV). RESULTS: The mean corrected Q-Tend (QTce), Q-Tpeak (QTcp), and Tpeak-end (Tcp-e) intervals among 12-leads before epinephrine were significantly larger in Group I than in the other three groups. Epinephrine (0.1 microg/kg/min) increased significantly the mean QTce, QTcp, Tcp-e, and the dispersion of QTcp in Groups I and II, but not in Groups III and IV. The sensitivity and specificity of QTce measurements to identify mutation carriers were 59% (20/34) and 100% (27/27), respectively, before epinephrine, and the sensitivity was substantially improved to 91% (31/34) without the expense of specificity (100%, 27/27) after epinephrine. The mean QTce, QTcp, and Tcp-e before and after epinephrine were significantly larger in 15 symptomatic than in 19 asymptomatic mutation carriers in Groups I and II, and the prolongation of the mean QTce with epinephrine was significantly larger in symptomatic patients. CONCLUSIONS: Epinephrine challenge is a powerful test to establish electrocardiographic diagnosis in silent LQT1 mutation carriers, thus allowing implementation of prophylactic measures aimed at reducing sudden cardiac death.

Adolescent↗

PubMed2003

Uniformity in dynamic baroreflex regulation of left and right cardiac sympathetic nerve activities.

Functional laterality of cardiac sympathetic nerve stimulation in chronotropic and inotropic effects is well known. Whether left (LSNA) and right (RSNA) cardiac sympathetic nerve activities show laterality during dynamic baroreflex activation remains to be determined. In nine anesthetized, vagotomized, and aortic-denervated rabbits, we randomly perturbed intracarotid sinus pressure (CSP) in both carotid sinus regions while simultaneously recording LSNA and RSNA. The baroreflex neural arc transfer function from CSP to LSNA and from CSP to RSNA revealed derivative characteristics, i.e., the magnitude of LSNA and RSNA responses became greater as the input frequency of CSP perturbation increased. The average slope of increasing gain in the frequencies between 0.03 and 0.3 Hz showed no difference between LSNA and RSNA responses (9.7 +/- 2.9 vs. 9.7 +/- 3.1 dB/decade, means +/- SD). The amplitude ratio and phase difference between LSNA and RSNA approximated unity and zero radians, respectively, in the frequencies from 0.01 to 1 Hz. In addition, the LSNA-RSNA relationship during stepwise CSP perturbation from 40 to 160 mmHg showed a straight line (r(2) ranged from 0.969 to 0.999). These findings indicate no laterality in the dynamic as well as static baroreflex regulation of LSNA and RSNA as far as grouped axonal activity is concerned.

Adrenergic Fibers↗

PubMed2003

Effects of ketamine on exocytotic and non-exocytotic noradrenaline release.

To characterise ketamine-induced sympathomimetic action, we examined the effects of ketamine on in vivo cardiac sympathetic nerve endings function. Using adult cats given anaesthesia with pentobarbital, dialysis probes were implanted in the left ventricular myocardium and dialysate noradrenaline (NA) concentrations were measured as an indicator of NA output at the cardiac sympathetic nerve endings. Ketamine was locally administered through the dialysis probe, and dialysate NA responses were obtained in the following conditions. (1) In the resting state, ketamine (10 mM) increased dialysate NA concentration. This increase in dialysate NA was not altered by addition of omega-conotoxin GVIA (N-type Ca(2+) channel blocker) or desipramine (membrane NA uptake blocker). (2) Sympathetic activation by electrical stimulation of the stellate ganglia (ES-SG; exocytotic NA release): ES-SG caused an increase in dialysate NA, which was further augmented by addition of desipramine. During co-administration of desipramine and ketamine, dialysate NA response to ES-SG was smaller than with desipramine alone. Further, there was no significant difference in the dialysate NA response to ES-SG between ketamine and ketamine + desipramine. These data suggested that both exocytosis and NA uptake function were impaired by ketamine. (3) Non-exocytotic NA release by ouabain: ouabain caused increases in dialysate NA. These increases in dialysate NA were suppressed by ketamine, which impaired the membrane outward NA transport evoked by ouabain. We conclude that ketamine impaired exocytotic and non-exocytotic NA release. However, ketamine spontaneously evoked NA efflux that was independent of exocytosis and insensitive to NA transporter.

Animals↗

PubMed2003

Dynamics of sympathetic baroreflex control of arterial pressure in rats.

By a white noise approach, we characterized the dynamics of the sympathetic baroreflex system in 11 halothane-anesthetized rats. We measured sympathetic nerve activity (SNA) and systemic arterial pressure (SAP), while carotid sinus baroreceptor pressure (BRP) was altered randomly. We estimated the transfer functions from BRP to SNA (mechanoneural arc), from SNA to SAP (neuromechanical arc), and from BRP to SAP (total arc). The gain of the mechanoneural arc gradually increased about threefold as the frequency of BRP change increased from 0.01 to 0.8 Hz. In contrast, the gain of the neuromechanical arc rapidly decreased to 0.4% of the steady-state gain as the frequency increased from 0.01 to 1 Hz. Although the total arc also had low-pass characteristics, the rate of attenuation in its gain was significantly slower than that of the neuromechanical arc, reflecting the compensatory effect of the mechanoneural arc for the sluggish response of the neuromechanical arc. We conclude that the quantitative estimation of the baroreflex dynamics is vital for an integrative understanding of baroreflex function in rats.

Animals↗

PubMed2003

Transmural heterogeneity of the action potential configuration in the feline left ventricle.

There are M cells in the canine, rabbit, guinea pig, and human left ventricle (LV), but it is not known if they are present in the feline LV. Arterially perfused feline LV preparations were used for the recording of transmembrane action potentials from the epicardium (Epi), midmyocardium (M) and endomyocardium (Endo) under control conditions (n=12) and in the presence of I(Ks) blocker (chromanol 293B: 10 micromol/L, n=6) or I(Kr) blocker (E-4031: 2 micromol/L, n=6). The steady-state action potential duration at 90% repolarization and cycle length (APD90/CL) relation was obtained and fitted by the hyperbolic function APD(90) = CL/[(a x CL) + b]. In control, the shortest and longest action potential duration (APD) were observed in Epi and M, respectively, and the APD(90)/CL-relation curve was steeper in the M or Endo than in the Epi. Chromanol 293B prolonged APD in Epi, but not in M or Endo, resulting in no significant difference of the APD(90)/CL-relation curve among the 3 regions. E-4031 markedly, but homogeneously, prolonged APD in all regions, giving rise to decreased transmural dispersion of repolarization. In conclusion, there exists an M cell layer with a longer APD than the Epi and Endo layers and there is transmural electrical heterogeneity in the feline LV; however, the response to I(Kr) blocker is different from that of the canine LV probably because of species differences in the I(Kr) and I(Ks).

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↗

PubMed2003

Effects of moderate hypothermia on norepinephrine release evoked by ouabain, tyramine and cyanide.

Using the dialysis technique, we examined the effect of moderate hypothermia on the norepinephrine efflux evoked by ouabain, tyramine and cyanide in anesthetized cats. Dialysis probes were implanted in the left ventricular myocardium, and we measured the dialysate norepinephrine levels as an indicator of norepinephrine output at the cardiac sympathetic nerve endings. Through the dialysis probe, locally applied ouabain, tyramine and cyanide induced the norepinephrine efflux. The addition of desipramine (neuronal norepinephrine transport blocker, 100 microM) suppressed the norepinephrine efflux evoked by ouabain, tyramine and cyanide. This finding suggests that pharmacological agent-induced norepinephrine efflux was due to carrier-mediated outward norepinephrine transport. Moderate hypothermia (27.4 +/- 0.2 degrees C) caused suppression of the norepinephrine efflux evoked by ouabain, tyramine and cyanide. We conclude that moderate hypothermia suppresses the non-exocytotic norepinephrine release evoked by ouabain, tyramine and cyanide.

Animals↗

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

Differential effects of beta-blockade on dispersion of repolarization in the absence and presence of sympathetic stimulation between the LQT1 and LQT2 forms of congenital long QT syndrome.

OBJECTIVES: This study compared the effects of beta-blockade on transmural and spatial dispersion of repolarization (TDR and SDR, respectively) between the LQT1 and LQT2 forms of congenital long QT syndrome (LQTS). BACKGROUND: The LQT1 form is more sensitive to sympathetic stimulation and more responsive to beta-blockers than either the LQT2 or LQT3 forms. METHODS: Eighty-seven-lead, body-surface electrocardiograms (ECGs) were recorded before and after epinephrine infusion (0.1 microg/kg body weight per min) in the absence and presence of oral propranolol (0.5-2.0 mg/kg per day) in 11 LQT1 patients and 11 LQT2 patients. The Q-T(end) interval, the Q-T(peak) interval and the interval between T(peak) and T(end) (T(p-e)), representing TDR, were measured and averaged from 87-lead ECGs and corrected by Bazett's method (corrected Q-T(end) interval [cQT(e)], corrected Q-T(peak) interval [cQT(p)] and corrected interval between T(peak) and T(end) [cT(p-e)]). The dispersion of cQT(e) (cQT(e)-D) was obtained among 87 leads and was defined as the interval between the maximum and minimum values of cQT(e). RESULTS: Propranolol in the absence of epinephrine significantly prolonged the mean cQT(p) value but not the mean cQT(e) value, thus decreasing the mean cT(p-e) value in both LQT1 and LQT2 patients; the differences with propranolol were significantly larger in LQT1 than in LQT2 (p < 0.05). The maximum cQT(e), minimum cQT(e) and cQT(e)-D were not changed with propranolol. Propranolol completely suppressed the influence of epinephrine in prolonging the mean cQT(e), maximum cQT(e) and minimum cQT(e) values, as well as increasing the mean cT(p-e) and cQT(e)-D values in both groups. CONCLUSIONS: Beta-blockade under normal sympathetic tone produces a greater decrease in TDR in the LQT1 form than in the LQT2 form, explaining the superior effectiveness of beta-blockers in LQT1 versus LQT2. Beta-blockers also suppress the influence of sympathetic stimulation in increasing TDR and SDR equally in LQT1 and LQT2 syndrome.

Adolescent↗