Shigeru Sugano

Power Spectral Analysis of Heart Rate Variability as a New Method for Assessing Autonomic Activity in the Rat

The authors studied power spectral analysis of heart rate variability in the rat, hypothesizing that the quantitative information provided by this analysis reflects the interaction between sympathetic and parasympathetic regulatory activities. For this purpose, an electrocardiogram was recorded from conscious and unrestrained Wistar rats (Nippon, Shizuoka) (12-16 weeks old) by a telemetry system and analyzed by a power spectrum. Because it was thought that the electrocardiogram recorded by the telemetry system could provide more reliable data to assess autonomic nervous activity than the tethering system, the telemetry recording system was used. There were two major spectral components in the power spectrum at low frequency (LF) (0.6 Hz) and high frequency (HF) (approximately 1.4 Hz). On the basis of these data, the authors defined two frequency bands of interest: LF (0.04-1.0 Hz) and HF (1.0-3.0 Hz). The power of LF was higher than that of HF in the normal rat. Atropine (2 mg/kg intraperitoneally) significantly reduced both HF and LF power. Propranolol (4 mg/kg intraperitoneally) also significantly reduced LF power; however, it had no significant effect on HF power. Thus, this study in the rat confirmed earlier observations in the conscious dog and human. Furthermore, the decrease in the parasympathetic mechanism produced by atropine was reflected by a slight increase in the LF/HF ratio. The LF/HF ratio appeared to follow the reductions of sympathetic activity produced by propranolol. From these results, the LF/HF ratio seemed to be a convenient index of parasympathetic and sympathetic interactions in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of autonomic nervous function by power spectral analysis of heart rate variability in the horse

We studied power spectral analysis of heart rate (HR) variability in the horse, with the hypothesis that the quantitative information provided by the spectral analysis of HR variability reflects the interaction between sympathetic and parasympathetic regulatory activities. For this purpose, electrocardiogram, blood pressure (BP) and respiratory (Resp) waveform were simultaneously recorded from Thoroughbred horses (3-5 years old) and analyzed by power spectrum. There were two major spectral components at low-frequency (LF) and high-frequency (HF) bands for HR variability. The peak of Resp variability clearly occurred at the HF range. In contrast to Resp variability, the power spectra of BP variability occurred at lower frequencies. The maximum coherence between HR and Resp variabilities and HR and BP variabilities occurred at approximately 0.15 and approximately 0.03 Hz, respectively. These relationships were similar to the ensemble spectra. On the basis of these data, we have defined two frequency bands of interest: LF (0.01-0.07 Hz) and HF (0.07-0.6 Hz). Therefore, we believe that power spectral analysis of HR variability provides a very powerful technique for assessing autonomic nervous activity in the horse.

Autonomic nervous function in mice and voles (Microtus arvalis): investigation by power spectral analysis of heart rate variability

We have studied the autonomic nervous function in voles (Microtus arvalis) and mice. For this purpose, ECGs were recorded from conscious and unrestrained voles and mice using radiotelemetry and the autonomic nervous function was investigated by the power spectral analysis of heart rate variability. Heart rate in voles was lower than mice and the coefficient of variance was larger in voles. In the power spectra of voles and mice, there were two major spectral components with the high frequency (HF) peak generally appearing between 2.0 and 4.0 Hz, and the low frequency (LF) peak appearing below 0.6 Hz. On the basis of this data, we set the two frequency bands as LF (0.1-1.0 Hz) and HF (1.0-5.0 Hz) to evaluate autonomic nervous function. The LF and HF powers were larger in voles than mice. The LF/HF ratio was thought to provide a convenient index of autonomic nervous balance and was smaller in voles than mice. The LF powers in both species were reduced by atropine, but propranolol reduced the LF power only in mice. The HF power was reduced by atropine only in voles. The intrinsic heart rate produced by a double blockade with atropine and propranolol in voles was almost the same as control levels, but in mice was lower than controls. The ratio of the LF and HF powers by a double blockade were almost the same as those of the administration of atropine in voles, but nearer to propranolol in mice. These results suggested that the parasympathetic nervous function was predominant in voles, but the sympathetic one was predominant in mice.

Diurnal Variation of Autonomic Nervous Activity in the Rat Investigation by Power Spectral Analysis of Heart Rate Variability

We studied the diurnal variations of autonomic nervous function in rats. For this purpose, a long-term electrocardiogram (ECG) was recorded from conscious and unrestrained rats using a telemetry system, and the autonomic nervous function was investigated by the power spectral analysis of heart rate variability. No arrhythmias were observed in the ECG of any of the rats. Nocturnal patterns, in which the values of heart rate in the dark phase (2000-0600) were higher than those in the light phase (0600-2000), were observed. All normal rats shared a characteristic pattern in their power spectrum analysis. Both low-frequency and high-frequency power in the light phase were higher than those in the dark phase. However, these differences were not statistically significant (P > .05). The low frequency to high frequency ratio also showed a nocturnal pattern. The value in the dark phase was significantly higher (P < .05) than that in the light phase. These results suggest that the sympathetic nervous activity is predominant in the dark phase in rats. Therefore, we believe that this information may be useful for future biobehavioral studies.

Antihypertensive effect of angiotensin I-converting enzyme inhibitory peptides derived from hemoglobin

From proteolytic digest of swine hemoglobin, we isolated four peptide, E-1 (Phe-Gln-Lys-Val-Val-Ala), E-2 (Phe-Gln-Lys-Val-Val-Ala-Gly), peptide 30-3 (Phe-Gln-Lys-Val-Val-Ala-Lys) and H-1 (Gly-Lys-Lys-Val-Leu-Gln). These peptides inhibited angiotensin I-converting enzyme activity with an IC50 of 5.8, 7.4, 2.1 and 1.9 microM, respectively. Oral administration of 50 mg/kg E-1 and 50 mg/kg H-1 decreased blood pressure in spontaneously hypertensive rats. In normotensive rats, oral administration of 500 mg/kg E-1 and 500 mg/kg H-1 inhibited the pressor effect of i.v. administrated 300 ng/kg angiotensin I, possibly by inhibiting its conversion to angiotensin II. These results suggest that these peptides are orally effective inhibitors of angiotensin I-converting enzyme that have a hypotensive effect.

ECG changes during furosemide-induced hypokalemia in the rat

Electrolyte abnormalities have become an increasingly important cause of arrhythmias owing to the widespread use of high-potency diuretics. Hypokalemia is one of the common complications of diuretic use. Although some studies of hypokalemia induced by furosemide as well as of potassium-deficient diets in the rat have been reported, the electrocardiographic (ECG) changes during hypokalemia in the rat are poorly understood. This study was designed to examine such changes. For this purpose, hypokalemia was induced by furosemide administration, and the diagnostic criteria for ECG manifestations of hypokalemia were determined. During hypokalemia, conduction in most parts of the heart was suppressed to an extent depending on plasma potassium concentration. Prolongation of the QT interval was also observed, which agrees with findings in humans and dogs. Furthermore, prolonged durations of the P wave and QRS complex were observed during hypokalemia in the rat. The extent of alteration of the PR interval induced by hypokalemia was less significant than that of P wave and QRS complex durations. These results suggest that the excitabilities of the myocardium in the atria and ventricles may be affected by extracellular potassium level rather than by the atrioventricular conduction system in the rat. Wave amplitude, except that of the P wave, was decreased by severe hypokalemia. These changes were not dependent on the plasma potassium concentration. Typical T wave changes observed with hypokalemia in humans and dogs did not occur in the rat. The ECG manifestations of acute hypokalemia in the rat did not include the typical T wave changes seen in species with ST-segment type ECGs; however, other ECG parameter changes occurring with hypokalemia were qualitatively similar to those in other species. These results may be useful for testing the toxicity of potassium-depleting drugs in the rat.

Does histamine stimulate trigeminal nasal afferents

The response to histamine of nasal afferents has been studied in guinea pigs by recording the electrical activity of the whole ethmoidal nerve (EN) or that of single units. Guinea pigs were anaesthetized with urethane and breathed through a tracheostomy. Prior to intranasal instillation of histamine (1 x 10(-4)-10(-1) M), the nasal mucosa was treated with 20 microl of saline (0.9% NaCl) or HCl (pH = 2), and in some cases, H2SO4 (pH = 2). In other experiments, following HCl instillation animals were pretreated by tripelennamine (1 x 10(-2) M) and/or cimetidine (1 x 10(-2) M) in order to determine the histamine receptor type of sensory nerve endings. Whole EN activity was not stimulated even by the highest dose (1 x 10(-1) M) of histamine when the nose was pretreated with saline, but was substantially stimulated by histamine in a dose-response fashion (1 x 10(-2) M) after pretreatment with HCI or H2SO4. Pretreatment with tripelennamine and HCl prevented the effect of histamine on the afferent EN activity; but after cimetidine and HCl pretreatment histamine still had a marked stimulant effect. In the case of single unit activities, histamine with HCl pretreatment had a long-lasting stimulatory effect (110.2 +/- 26.6 sec). It is concluded that the EN in guinea pigs include histamine-sensitive fibers whose sensitivity is mediated by H1 receptors and can respond to histamine only under abnormal conditions of the nasal mucosa.

ECG changes under hyperkalemia with nephrectomy in the rat

Electrolyte abnormalities have become an increasingly important cause of arrhythmias. Although the electrocardiographic (ECG) changes under hyperkalemia in the rat are poorly understood, it is conceivable that excess plasma potassium may also alter the cardiac excitations in the rat. Further, effects of hyperkalemia on ECG in the rat may differ from other species that have ST-segment and longer QT intervals in ECG. The present study was designed to determine the diagnostic criteria for ECG manifestations to various levels of plasma potassium concentration. For this purpose, hyperkalemia was induced by nephrectomy with and without infusions. Because it was difficult to produce various levels of plasma potassium concentration by only nephrectomy, we used two kinds of infusions to obtain especially moderate levels of nephrectomy-induced hyperkalemia. ECGs were recorded 24, 36, and 48 hours after nephrectomy. Plasma potassium concentration and number of abnormal ECGs were increased time-dependently. Increased T wave amplitude was present with mild hyperkalemia. The typical T wave change observed with so-called sinoventricular conduction levels of potassium concentration in species with long QT intervals did not occur in the rat. PR interval and QRS duration became slightly shorter within moderate hyperkalemia. P wave disappeared in most rats at potassium levels above 8.0 mEq/l. In advanced hyperkalemia (plasma potassium concentration above 7.5 mEq/l), conduction in all parts of the heart was suppressed. Moreover, sinoventricular conduction appeared. Thus, the diagnostic criteria for ECG manifestations to various levels of plasma potassium concentration in the rat were demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Establishment of a 24-hour electrocardiogram recording system using a Holter recorder for miniature swine

A Holter recording system was established for the Göttingen miniature swine. For this purpose, we first developed a jacket to hold a Holter recording set, and subsequently determined a bipolar lead suitable for obtaining stable electrocardiogram (ECG) recording without artifacts. To make the jacket, we measured the lengths of eight sites of the body of 14 miniature swine. Several types of jackets were made and tested. We observed the behaviour of animals with these jackets by videotape recorder (VTR) recording. These observations permitted development of a jacket suitable for Holter recording. The jacket permits easy placement of the recorder, and long-term ECG recording can be performed without difficulty. In order to determine a suitable lead for long-term recording, we recorded ECGs from six adult miniature swine using three types of leads, the M-X, R-L and A-B leads. The R-L lead frequently exhibited baseline drift, and QRS complexes often disappeared in this lead due to low amplitude. ECG recording with the M-X and A-Bleads was of sufficient quality to permit analysis. This system is expected to be useful for further cardiovascular research in miniature swine.

Cardiovascular responses mediated by two types of endothelin ETB receptor in spontaneously hypertensive and Wistar-Kyoto rats

This study shows the effects of a selective endothelin ET(B) receptor agonist, IRL 1720 {Ac-[Ala11,15]endothelin-1-(8-21)}, on cardiovascular responses in anesthetized spontaneously hypertensive rats and Wistar-Kyoto rats. Single intravenous bolus injection of IRL 1720 caused a dose-related short-lasting fall in blood pressure, left ventricular pressure and myocardial contractility. However, repeated intravenous bolus injection of 10(-5) mol/kg IRL 1720 produced a biphasic response consisting of an initial short-lasting decrease followed by a sustained increase in these parameters. The initial decrease was reduced, whereas the following increase was enhanced with the repeated injections of IRL 1720. The cardiovascular pressor response was not inhibited by the endothelin ET(A) receptor antagonist, FR139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl] amino-4-+methylpentanoyl] amino-3-[3-(1-methyl-1H-indolyl)]propionyl]amino -3- (2-pyridyl)propionic acid). The effects of IRL 1720 were qualitatively similar but more potent in spontaneously hypertensive rats than in Wistar-Kyoto rats. These results suggest the existence of two types of endothelin ET(B) receptor for IRL 1720: a tachyphylactic endothelin ET(B) receptor that mediates cardiovascular depressor responses and a less tachyphylactic endothelin ET(B) receptor that mediates pressor responses in the rat.