Biomedical subjects

Kenji Sunagawa

Publications and source records attributed to Kenji Sunagawa.

At least 91 records · Page 5Linked to original sources

PubMed2004

Faster oscillometric manometry does not sacrifice the accuracy of blood pressure determination.

Faster oscillometry enables one to track rapid pressure changes. We therefore examined whether it was possible to shorten the measurement time without sacrificing accuracy. We accelerated and linearized cuff deflation and determined systolic and diastolic pressure values by the appearance and disappearance of oscillometric waves based on the interpolated cuff pressure-oscillometric wave amplitude relationship. The accuracy of faster oscillometry was examined by comparing correlations between invasive radial and oscillometric brachial pressure with either the conventional or the faster oscillometry in 23 patients (32+/-16 measurement pairs). Faster oscillometry shortened the measurement time from 27.7+/-3.5 s to 17.1+/-2.6 s. Neither pressure levels nor heart rate altered the time required for measurement. Bland-Altman analysis indicated that mean and standard deviation of difference between oscillometric and invasive systolic pressure was comparable (conventional, 2.1+/-7.5 mmHg; faster, 1.4+/-7.3 mmHg) without correlations between difference and average of systolic pressure. Similar differences (conventional, 5.0+/-6.8 mmHg; faster, 4.9+/-5.8 mmHg) and lack of correlations were also found for diastolic pressure. In conclusion, we succeeded in shortening the oscillometric measurement time to approximately 60% of the original time without sacrificing accuracy. This was achieved by acceleration and linearization of cuff deflation and by interpolation of the relationship between cuff pressure and oscillometric wave amplitude.

Adolescent↗

PubMed2004

Excessive increase in QT interval and dispersion of repolarization predict recurrent ventricular tachyarrhythmia after amiodarone.

Although chronic amiodarone has been proven to be effective to suppress ventricular tachycardia (VT) and ventricular fibrillation (VF), how we predict the recurrence of VT/VF after chronic amiodarone remains unknown. This study evaluated the predictive value of the QT interval, spatial, and transmural dispersions of repolarization (SDR and TDR) for further arrhythmic events after chronic amiodarone. Eighty-seven leads body surface ECGs were recorded before (pre) and one month after (post) chronic oral amiodarone in 50 patients with sustained monomorphic VT associated with organic heart disease. The Q-Tend (QTe), the Q-Tpeak (QTp), and the interval between Tpeak and Tend (Tp-e) as an index of TDR were measured automatically from 87-lead ECG, corrected Bazett's method (QTce, QTcp, Tcp-e), and averaged among all 87 leads. As an index of SDR, the maximum (max) minus minimum (min) QTce (max-min QTce) and standard deviation of QTce (SD-QTce) was obtained among 87 leads. All patients were prospectively followed (15 +/- 10 months) after starting amiodarone, and 20 patients had arrhythmic events. The univariate analysis revealed that post max QTce, post SD-QTce, post max-min QTce, and post mean Tcp-e from 87-lead but not from 12-lead ECG were the significant predictors for further arrhythmic events. ROC analysis indicated the post max-min QTce > or = 106 ms as the best predictor of events (hazard ratio = 10.4, 95%, CI 2.7 to 40.5, P = 0.0008). Excessive QT prolongation associated with increased spatial and transmural dispersions of repolarization predict the recurrence of VT/VF after amiodarone treatment.

Amiodarone↗

PubMed2004

Adaptive predictive control of arterial blood pressure based on a neural network during acute hypotension.

In acute hypotension, an automated drug infusion system to control mean arterial blood pressure (MAP) has not been previously studied, though many investigations have examined the use of vasodilating drugs to control MAP in postoperative hypertension. Therefore, we examined an automated control of MAP during acute hypotension using a neural network (NN) approach. A proportional-integral-derivative (PID) control, an adaptive predictive control using a NN (APC(NN)), a combined control of APC(NN) and PID (APC(NN-PID)), a fuzzy control, and a model predictive control were tested in computer simulation based on the MAP response to norepinephrine (NE) of 25 microg ml(-1). In six anesthetized rabbits, using the NE of 25 microg ml(-1), the PID control, APC(NN), and APC(NN-PID) prevented severe hypotension compared to an uncontrolled condition. Under PID control, four of the six animals showed MAP oscillation. Using NE of 50 microg ml(-1), the rabbits recovered from acute hypotension for all systems tested but showed sustained MAP oscillation during PID control. In conclusion, utilization of a NN for adaptive predictive control systems could facilitate the development of an automated drug infusion apparatus because it provides robust control even when acute or large perturbations and inter-individual differences in the sensitivity to therapeutic agents occur.

Acute Disease↗

PubMed2004

A self-calibrating telemetry system for measurement of ventricular pressure-volume relations in conscious, freely moving rats.

Using Bluetooth wireless technology, we developed an implantable telemetry system for measurement of the left ventricular pressure-volume relation in conscious, freely moving rats. The telemetry system consisted of a pressure-conductance catheter (1.8-Fr) connected to a small (14-g) fully implantable signal transmitter. To make the system fully telemetric, calibrations such as blood resistivity and parallel conductance were also conducted telemetrically. To estimate blood resistivity, we used four electrodes arranged 0.2 mm apart on the pressure-conductance catheter. To estimate parallel conductance, we used a dual-frequency method. We examined the accuracy of calibrations, stroke volume (SV) measurements, and the reproducibility of the telemetry. The blood resistivity estimated telemetrically agreed with that measured using an ex vivo cuvette method (y=1.09x - 11.9, r2= 0.88, n=10). Parallel conductance estimated by the dual-frequency (2 and 20 kHz) method correlated well with that measured by a conventional saline injection method (y=1.59x - 1.77, r2= 0.87, n=13). The telemetric SV closely correlated with the flowmetric SV during inferior vena cava occlusions (y=0.96x + 7.5, r2=0.96, n=4). In six conscious rats, differences between the repeated telemetries on different days (3 days apart on average) were reasonably small: 13% for end-diastolic volume, 20% for end-systolic volume, 28% for end-diastolic pressure, and 6% for end-systolic pressure. We conclude that the developed telemetry system enables us to estimate the pressure-volume relation with reasonable accuracy and reproducibility in conscious, untethered rats.

Animals↗

PubMed2004

Diagnostic value of the recovery time-course of st slope on exercise ECG in discriminating false-from true-positive ST-segment depressions.

BACKGROUND: Using the exercise ECG for diagnosing coronary artery disease (CAD) is hampered by the occurrence of false-positive (FP) ST-segment depression. Because it is known that the recovery ST-T time-course in CAD differs from that in FP subjects, the ST slope may help discriminate FP from true-positive (TP) results. METHODS AND RESULTS: Treadmill digitized ECG from patients with significant ST-segment depressions and normal resting ECG were analyzed in 134 patients with CAD on angiography (>50% narrowing) and reversible perfusion defects (TP group), and 64 subjects with normal perfusion (FP group) on exercise single photon emission computed tomography. The ST slope between the J-point and J(80) was measured every minute up to 6-min postexercise. The ST slope was significantly higher in FP than in TP at peak exercise, and at postexercise 1-, 2- and 3-min (p<0.01, all). Thereafter, it gradually increased in TP, while monotonically decreasing in FP. Its decrease from 3- to 6-min could correctly diagnose 88% of FP subjects, whereas it was found in only 19% of TP patients (total accuracy 83%). CONCLUSIONS: The ST slope change from early to late recovery is a simple yet reliable marker for discriminating FP from TP ST-segment responses in subjects with a normal resting ECG.

Aged↗

PubMed2003

Bed rest attenuates sympathetic and pressor responses to isometric exercise in antigravity leg muscles in humans.

Although spaceflight and bed rest are known to cause muscular atrophy in the antigravity muscles of the legs, the changes in sympathetic and cardiovascular responses to exercises using the atrophied muscles remain unknown. We hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. Ten healthy male volunteers were subjected to 14-day 6 degrees head-down bed rest. Before and after bed rest, they performed isometric exercises using leg (plantar flexion) and forearm (handgrip) muscles, followed by 2-min postexercise muscle ischemia (PEMI) that continues to stimulate the muscle metaboreflex. These exercises were sustained to fatigue. We measured muscle sympathetic nerve activity (MSNA) in the contralateral resting leg by microneurography. In both pre- and post-bed-rest exercise tests, exercise intensities were set at 30 and 70% of the maximum voluntary force measured before bed rest. Bed rest attenuated the increase in MSNA in response to fatiguing plantar flexion by approximately 70% at both exercise intensities (both P < 0.05 vs. before bed rest) and reduced the maximal voluntary force of plantar flexion by 15%. In contrast, bed rest did not alter the increase in MSNA response to fatiguing handgrip and had no effects on the maximal voluntary force of handgrip. Although PEMI sustained MSNA activation before bed rest in all trials, bed rest entirely eliminated the PEMI-induced increase in MSNA in leg exercises but partially attenuated it in forearm exercises. These results do not support our hypothesis but indicate that bed rest causes a reduction in isometric exercise-induced sympathetic activation in (probably atrophied) antigravity leg muscles.

Adult↗

PubMed2003

NG-nitro-L-arginine methyl ester-induced norepinephrine release from cardiac sympathetic nerve endings in anesthetized cats.

Using the cardiac dialysis technique in the anesthetized cat, we examined the effects of NG-nitro-L-arginine methyl ester (L-NAME, a nitric oxide (NO) synthase inhibitor, 100 mM) on sympathetic modulation. Local administration of L-NAME induced increases in dialysate norepinephrine (NE) levels, which were not affected by the addition of omega-conotoxinGVIA. High-potassium (high K+)-evoked increases in dialysate NE levels were suppressed by addition of L-NAME. To confirm the involvement of NO in the NE releasing action, we compared dialysate NE levels during the administration of L-NAME or D-NAME and no significant differences between them. L-NAME induces spontaneous non-exocytotic NE release but suppresses exocytotic NE release by high K+. L-NAME may interact with both NE transport and NE release mechanisms. However, NO may contribute little to the amounts of NE released by L-NAME.

Anesthesia↗

PubMed2003

Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats.

BACKGROUND: Diminished cardiac vagal activity and higher heart rate predict a high mortality rate of chronic heart failure (CHF) after myocardial infarction. We investigated the effects of chronic electrical stimulation of the vagus nerve on cardiac remodeling and long-term survival in an animal model of CHF after large myocardial infarction. METHODS AND RESULTS: Two weeks after the ligation of the left coronary artery, surviving rats were randomized to vagal- and sham-stimulated groups. Using an implantable miniature radio-controlled electrical stimulator, we stimulated the right vagal nerve of CHF rats for 6 weeks. The intensity of electrical stimulation was adjusted for each rat, so that the heart rate was lowered by 20 to 30 beats per minute. The treated rats had significantly lower left ventricular end-diastolic pressure (17.1+/-5.9 versus 23.5+/-4.2 mm Hg, P<0.05) and higher maximum dp/dt of left ventricular pressure (4152+/-237 versus 2987+/-192 mm Hg/s, P<0.05) than the untreated rats. Improvement of cardiac pumping function was accompanied by a decrease in normalized biventricular weight (2.75+/-0.25 versus 3.14+/-0.22 g/kg, P<0.01). Although the 140-day survival of the untreated group was only half, vagal stimulation markedly improved the survival rate (86% versus 50%, P=0.008). Vagal stimulation therapy achieved a 73% reduction in a relative risk ratio of death. CONCLUSIONS: Vagal nerve stimulation markedly improved the long-term survival of CHF rats through the prevention of pumping failure and cardiac remodeling.

Animals↗

PubMed2003

Myosin light chain isoforms modify force-generating ability of cardiac myosin by changing the kinetics of actin-myosin interaction.

OBJECTIVE: To investigate the functional role of myosin light chain (MLC) isoforms in cardiac muscles, we examined the motor function of two different myosins the structure of which differed only in the MLC. METHODS: We purified myosin from atria (A-myosin) and ventricles (V-myosin) of young rats, which contained atrial-type and ventricular-type MLCs, respectively, but having identical alpha-heavy chain isoform. Actin filament velocity (Vel) was determined in the in vitro motility assay. Average force of myosin molecules (F) was estimated and single events of actin-myosin interaction were recorded with the laser trap technique. RESULTS: Vel was slightly higher in A-myosin than in V-myosin, while actin-activated ATPase activity was not different. F, determined from force versus actin filament length relation, was approximately 60% higher in V-myosin (3.3 vs. 2.1 pN/microm). The mean duration of isometric force events was longer in V-myosin than in A-myosin (323+/-13 vs. 294+/-30 ms, p<0.05), while the amplitudes of unitary displacement and force of a single myosin molecule did not differ between them. CONCLUSION: The MLC isoform can be a determinant of force-generating ability of cardiac myosin by modulating crossbridge kinetics without affecting the catalytic activity.

Actin Cytoskeleton↗

PubMed2003

Muscle mechanoreflex induces the pressor response by resetting the arterial baroreflex neural arc.

The effects of the muscle mechanoreflex on the arterial baroreflex neural control have not previously been analyzed over the entire operating range of the arterial baroreflex. In anesthetized, vagotomized, and aortic-denervated rabbits (n = 8), we isolated carotid sinuses and changed intracarotid sinus pressure (CSP) from 40 to 160 mmHg in increments of 20 mmHg every minute while recording renal sympathetic nerve activity (SNA) and arterial pressure (AP). Muscle mechanoreflex was induced by passive muscle stretch (5 kg of tension) of the hindlimb. Muscle stretch shifted the CSP-SNA relationship (neural arc) to a higher SNA, whereas it did not affect the SNA-AP relationship (peripheral arc). SNA was almost doubled [from 63 +/- 15 to 118 +/- 14 arbitrary units (au), P < 0.05] at the CSP level of 93 +/- 8 mmHg, and AP was increased approximately 50% by muscle stretch. When the baroreflex negative feedback loop was closed, muscle stretch increased SNA from 63 +/- 15 to 81 +/- 21 au (P < 0.05) and AP from 93 +/- 8 to 109 +/- 12 mmHg (P < 0.05). In conclusion, the muscle mechanoreflex resets the neural arc to a higher SNA, which moves the operating point towards a higher SNA and AP under baroreflex closed-loop conditions. Analysis of the baroreflex equilibrium diagram indicated that changes in the neural arc induced by the muscle mechanoreflex might compensate for pressure falls resulting from exercise-induced vasodilatation.

Action Potentials↗

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↗