Nonlinearity and fractality in the variability of cardiac period in the lizard, Gallotia galloti: effects of autonomic blockade

Both nonlinear and fractal properties of beat-to-beat R-R interval variability signal (RRV) of freely moving lizards (Gallotia galloti) were studied in baseline and under autonomic nervous system blockade. Nonlinear techniques allowed us to study the complexity, chaotic behavior, nonlinearity, stationarity, and regularity over time of RRV. Scaling behavior of RRV was studied by means of fractal techniques. The autonomic nervous system blockers used were atropine, propranolol, prazosin, and yohimbine. The nature of RRV was linear in baseline and under beta-, alpha(1)- and alpha(2)-adrenoceptor blockades. Atropine changed the linear nature of RRV to nonlinear and increased its stationarity, regularity and fractality. Propranolol increased the complexity and chaotic behavior, and decreased the stationarity, regularity, and fractality of RRV. Both prazosin and yohimbine did not change any of the nonlinear and fractal properties of RRV. It is suggested that 1) the use of both nonlinear and fractal analysis is an appropriate approach for studying cardiac period variability in reptiles; 2) the cholinergic activity, which seems to make the alpha(1)-, alpha(2)- and beta-adrenergic activity interaction unnecessary, determines the linear behavior in basal RRV; 3) fractality, as well as both RRV regularity and stationarity over time, may result from the balance between cholinergic and beta-adrenergic activities opposing actions; 4) beta-adrenergic activity may buffer both the complexity and chaotic behavior of RRV, and 5) neither the alpha(1)- nor the alpha(2)-adrenergic activity seem to be involved in the mediation of either nonlinear or fractal components of RRV.     

Relationship between cortical electrical and cardiac autonomic activities in the awake lizard, Gallotia galloti

ECG and EEG signals were simultaneously recorded in lizards, Gallotia galloti, both in control conditions and under autonomic nervous system (ANS) blockade, in order to evaluate possible relationships between the ANS control of heart rate and the integrated central nervous system activity in reptiles. The ANS blockers used were prazosin, propranolol, and atropine. Time-domain summary statistics were derived from the series of consecutive R-R intervals (RRI) of the ECG to measure beat-to-beat heart rate variability (HRV), and spectral analysis techniques were applied to the EEG activity to assess its frequency content. Both prazosin and atropine did not alter the power spectral density (PSD) of the EEG low frequency (LF: 0.5-7.5 Hz) and high frequency (HF: 7.6-30 Hz) bands, whereas propranolol decreased the PSD in these bands. These findings suggest that central beta-adrenergic receptor mechanisms could mediate the reptilian waking EEG activity without taking part any alpha(1)-adrenergic and/or cholinergic receptor systems. In 55% of the lizards in control conditions, and in approximately 43% of the lizards under prazosin and atropine, a negative correlation between the coefficient of variation of the series of RRI value (CV(RRI)) and the mean power frequency (MPF) of the EEG spectra was found, but not under propranolol. Consequently, the lizards' HRV-EEG-activity relationship appears to be independent of alpha(1)-adrenergic and cholinergic receptor systems and mediated by beta-adrenergic receptor mechanisms.     

Effect of adrenergic and cholinergic antagonists on post-hemorrhagic erythropoiesis in rats

Experiments were carried out in albino rats to find out the effect of propranolol, priscol and atropine on post-hemorrhagic erythropoiesis. Administration of either propranolol or priscol decreased reticulocyte response following hemorrhage, whereas administration of atropine produced no change. The results indicate that alpha as well as beta adrenergic systems participate in the control of erythropoiesis following hemorrhage, whereas parasympathetic system does not take part.     

Peripheral nervous control of cold-induced reduction in the respiratory quotient of the rat

Cold-exposed rats show a reduction in the respiratory quotient which is indicative of a relative shift from carbohydrates to lipids as substrates for oxidative metabolism. In the present study, the effects of food deprivation and cold exposure on the respiratory quotient were observed. In addition, the involvement of the three main branches of the peripheral nervous system (sympathetic, parasympathetic, and somatic) was investigated by means of synaptic blockade with propranolol, atropine, and quinine, respectively. Both propranolol and quinine blocked the cold-induced decrease in respiratory quotient and increase in heat production, whereas atropine had only minor and very brief effects. It is concluded that both the sympathetic and somatic branches are involved in the metabolic changes associated with cold-induced thermogenesis and that the increase in metabolic heat production involves a shift from carbohydrate to lipid utilization irrespective of which of the two branches is activated.     

Effects of atropine and propranolol on the respiratory, circulatory, and ECG responses to high altitude in man

In order to analyze the respiratory, cardiovascular, and ECG responses to acute hypoxic hypoxia, three experimental series were carried out in a randomized manner on 11 healthy, unacclimatized volunteers at rest during standardized stepwise exposure to 6000 m (PAO2 35.2 +/- 2.9 mmHg/4.7 +/- 0.4 kPa) in a low-pressure chamber a) without (control), b) with propranolol, and c) with atropine combined with propranolol. The results show that hypoxic hyperventilation and alveolar gases are not affected by activation of the sympatho-adrenal axis or by parasympathetic withdrawal. Sympathetic activity, however, increases heart rate, stroke volume (pulse pressure), estimated cardiac output and systolic blood pressure, whereas decreased parasympathetic activity increases heart rate and estimated cardiac output, but lowers stroke volume. The fall in peripheral resistance, observed during progressive hypoxia in all three groups, is thought to be due to hypoxia-induced depression of the vasomotor center. At altitude catecholamine secretion and vagal withdrawal synergistically account in the ECG for the R-R shortening, the relative Q-T lengthening, the elevation of the P wave and the ST-T flattening. Probable direct hypoxic effects on the heart are the increase in P-Q duration and the minor but still significant depression of the T wave. It is concluded that at altitude increased sympatho-adrenal and decreased parasympathetic activity is without effect on hypoxic hyperventilation, but accounts for most of the cardiovascular and ECG changes. Diminution of sympathetic activity and imminent vagotonia arising after acute ascent to 6000 m probably reflect hypoxia of the central nervous system.     

Regional regulation of choroidal blood flow by autonomic innervation in the rat

Regional influences of parasympathetic and sympathetic innervation on choroidal blood flow were investigated in anesthetized rats. Parasympathetic pterygopalatine neurons were activated by electrically stimulating the superior salivatory nucleus, whereas sympathetic neurons were activated by cervical sympathetic trunk stimulation and uveal blood flow was measured by laser Doppler flowmetry. Parasympathetic stimulation increased flux in the anterior choroid and nasal vortex veins but not in the posterior choroid. Vasodilation was blocked completely by the neuronal nitric oxide synthase inhibitor 1-(2-trifluoromethylphenyl)imidazole but was unaffected by atropine. Sympathetic stimulation decreased flux in all regions, and this was blocked by prazosin. Parasympathetic stimulation did not affect vasoconstrictor responses to sympathetic stimulation in the posterior choroid but attenuated the decrease in blood flow through the anterior choroid and vortex veins via a nitrergic mechanism. We conclude that sympathetic alpha-noradrenergic vasoconstriction occurs throughout the choroid, whereas parasympathetic nitrergic vasodilation plays a selective role in modulating blood flow in anterior tissues of the eye.     

Ontogeny of cholinergic and adrenergic cardiovascular regulation in the domestic chicken (Gallus gallus)

Adrenergic and cholinergic tone on the cardiovascular system of embryonic chickens was determined during days 12, 15, 19, 20, and 21 of development. Administration of the muscarinic antagonist atropine (1 mg/kg) resulted in no significant change in heart rate or arterial pressure at any developmental age. In addition, the general cardiovascular depressive effects of hypoxia were unaltered by pretreatment with atropine. In addition, the ganglionic blocking agent hexamethonium (25 mg/kg) did not induce changes in heart rate. The beta-adrenergic antagonist propranolol (3 mg/kg) induced a bradycardia of similar magnitude on all days studied, with a transient hypertensive action on days 19-20, indicating the existence of an important cardiac and vascular beta-adrenergic tone. Injections of the alpha-adrenergic antagonists prazosin or phentolamine (1 mg/kg) reduced arterial pressure significantly on all days of incubation studied. Collectively, the data indicate that embryonic chickens rely primarily on adrenergic control of cardiovascular function, with no contribution from the parasympathetic nervous system.     

Sympathetic nervous system representation in time and frequency domain indices of heart rate variability

This study evaluated the contributions of sympathetic and parasympathetic modulation to heart rate variability during situations in which vagal and sympathetic tone predominated. In a placebo-controlled, randomized, double blind blockade study, six young healthy male individuals received propranolol (0.2 mg x kg(-1)), atropine (0.04 mg x kg(-1)), propranolol plus atropine, or placebo infusions over 4 days. Time-domain indices were calculated during 40 min of rest and 20 min of exercise at 70% of maximal exercise intensity. Spectrum analysis, using fast Fourier transformation, was also performed at rest and during the exercise. The time-domain indices standard deviation of R-R intervals, mean of the standard deviations of all R-R intervals for all 5-min segments, percentage of number of pairs of adjacent R-R intervals differing by more than 50 ms, and square root of the mean of the sum of squares of differences between adjacent R-R intervals were reduced after atropine and propranolol plus atropine. Propranolol alone caused no appreciable change in any of the time-domain indices. At rest, all spectrum components were similar after placebo and propranolol infusions, but following parasympathetic and double autonomic blockade there was a reduction in all components of the spectrum analysis, except for the low:high ratio. During exercise, partial and double blockade did not change significantly any of the spectrum components. Thus, time and frequency-domain indices of heart rate variability were able to detect vagal activity, but could not detect sympathetic activity. During exercise, spectrum analysis is not capable of evaluating autonomic modulation of heart rate.     

Moderate hypothermia induces a preferential increase in pancreatic islet blood flow in anesthetized rats

The aim of the study was to characterize the effects of induced moderate hypothermia on splanchnic blood flow, with particular reference to that of the pancreas and the islets of Langerhans. We also investigated how interference with the autonomic nervous system at different levels influenced the blood perfusion during hypothermia. For this purpose, hypothermia (body temperature of 28 degrees C) was induced by external cooling, whereas normothermic (37.5 degrees C) anesthetized Sprague-Dawley rats were used as controls. Some rats were pretreated with either propranolol, yohimbine, atropine, hexamethonium, or a bilateral abdominal vagotomy. Our findings suggest that moderate hypothermia elicits complex, organ-specific circulatory changes, with increased perfusion noted in the pylorus, as well as the whole pancreas and the pancreatic islets. The pancreatic islets maintain their high blood perfusion through mechanisms involving both sympathetic and parasympathetic mediators, whereas the increased pyloric blood flow is mediated through parasympathetic mechanisms. Renal blood flow was decreased, and this can be prevented by ganglionic blockade and is also influenced by beta-adrenoceptors.     

Atrial natriuretic factor alters autonomic interactions in the control of heart rate in conscious rats

Regulation of heart rate was studied in rats receiving either i.v. saline at 64 microL/min or synthetic 28-residue rat atrial natriuretic peptide (ANF) at a dose sufficient to decrease mean arterial blood pressure by 10%. Autonomic influences were deduced from steady-state heart rate responses of each group to propranolol, atropine, or propranolol and atropine combined. A multiplicative model of heart rate control was used to derive quantitatively from the data the modulation of intrinsic heart rate by sympathetic and parasympathetic mechanisms. Animals receiving ANF showed a lower heart rate than control animals. This relative bradycardia was abolished by atropine. Blocking of sympathetic effects with propranolol had no effect on basal heart rate in either group, and atropinization led to significant increases in heart rate in both groups of rats. Mathematical analysis of the results showed that the bradycardia produced by ANF was due predominantly to a reduced intrinsic heart rate and to enhanced vagal inhibition of postganglionic sympathetic activity. Parasympathetic contribution to heart rate in the absence of sympathetic activity was negligible in control rats and small during ANF. We conclude that the major influences of ANF on heart rate control are a decrease of intrinsic heart rate and enhanced parasympathetic inhibition of postganglionic presynaptic sympathetic activity.     

Depletion of neuropeptides in rat parotid glands and declining atropine-resistant salivary secretion upon continuous parasympathetic nerve stimulation

In rats the parasympathetic auriculo-temporal nerve on one side was continuously stimulated at 40 Hz for 20-80 min in the presence of adrenergic blockers (dihydroergotamine and propranolol) +/- atropine. During the first 10 min this gave rise to a flow of saliva from the parotid gland that in the atropinized rats amounted to 35% of that found in rats not treated with atropine, while the protein and amylase outputs were 75% of those in non-atropinized rats. The atropine-resistant secretion of fluid and proteins declined to 5-10% of the initial value within 40 min but did not cease completely even after 80 min. The marked reduction in secretory responses was not due to desensitization or exhaustion of the gland cells. The nerve stimulation reduced the parotid gland content of vasoactive intestinal peptide (VIP) and substance P (SP) to approximately 60 and 25% of that of contralateral glands after 20 and 60 min, respectively. The probable explanation for the decline in secretory response seems to be depletion of non-adrenergic, non-cholinergic transmitter(s). The present results suggest that neuropeptides are involved in the regulation of salivary secretion but provide no direct evidence that either VIP or SP is responsible for the atropine-resistant salivary secretion.     

Genetic selection on a behavioural fear trait is associated with changes in heart rate variability in quail

This study investigated whether genetic selection on a divergent behavioural trait of fearfulness (tonic immobility duration) was related to changes in the nervous control of the heart. Quail selected for either long or short tonic immobility (LTI or STI, respectively) duration was compared with an unselected control line (CTI). The autonomic control of the heart was assessed by heart rate variability analysis and pharmacological blockades. Quail were surgically fitted with a telemetric device. Heart rate before injection did not differ between the three lines. The vagal-sympathetic effect (VSE) at rest differed significantly from 1 in CTI and STI quail, suggesting that parasympathetic activity was dominant. In LTI quail, VSE did not differ from 1, suggesting a balance between parasympathetic and sympathetic activities. The intrinsic heart rate reached after the successive injections of propranolol and atropine did not differ between lines and was higher than the heart rate at rest in STI, which was in line with results of VSE at rest. After atropine injection, the sympathetic activity indicated by the low-frequency power was lower in CTI than in the two selected quail. After propranolol injection, the parasympathetic activity indicated by the root of the mean squares of successive differences and the high-frequency power was higher in STI than in CTI and LTI quail. Selection on tonic immobility duration thus appears to be associated with changes in the sympathovagal control of the heart, which may influence behavioural responses to stressful situations.     

The relationship between respiratory sinus arrhythmia and heart rate during anesthesia in rat.

During inspiration the heart rate (HR) increases and during expiration it decreases. Contribution of respiratory sinus arrhythmia (RSA) to spontaneous heart rate variability (HRV) can be measured as the high frequency (HF) component of variation in consecutive R-R intervals on ECG. In conscious rats, slowing of HR is associated with an increase in HF. The aim of this study was to investigate whether this relationship between HF and HR is preserved during anesthesia in rat. A 15 minutes long ECG signal was recorded from rats (N=15) under moderate chloral hydrate (CHL) anesthesia. Recordings were extended with 45 minutes to investigate the effect of atropine (N=3), against controls (N=3). Short term HRV was investigated in 30 seconds long epochs. HF was considered the frequency band between 0.8 and 1.6 Hz. RSA was quantified as the relative spectral power of the HF. Respiratory frequency (RF) was quantified as the mean spectral frequency within the HF band. One minute estimates of HR, RSA and HF were calculated by averaging 3 epochs of 30 seconds overlapped 50%. The average HR was 427 +/- 3 bpm. The magnitude of RSA was 45 +/- 1% at a RF of 71 +/- 1 rpm. We found that: (1) the decrease in HR that occurs during CHL anesthesia in rat correlates with an increase in RSA; (2) atropine reduces RSA and the time-dependent decrease in HR; (3) the time-dependent increase in RSA is preserved after atropine. We conclude that the correlation between RSA and HR reflects the cardio-pulmonary coupling under parasympathetic control.     

Pharmacological analysis of the mechanisms involved in the tachycardic and vasopressor responses to the antimigraine agent, isometheptene, in pithed rats

The present study set out to investigate the pharmacological profile of the cardiovascular responses induced by the antimigraine agent, isometheptene, in pithed rats. For this purpose, intravenous (i.v.) administration of blocking doses of the antagonists prazosin (alpha1; 100 microg/kg), rauwolscine (alpha2; 300 microg/kg), the combination of prazosin (100 microg/kg) plus rauwolscine (300 microg/kg), propranolol (beta; 1000 microg/kg), ritanserin (5-HT2; 100 microg/kg) or equivalent volumes of saline (1 ml/kg) were used. Isometheptene (0.03, 0.1, 0.3, 1 and 3 mg/kg, i.v.) produced dose-dependent increases in heart rate and diastolic blood pressure which were highly reproducible as they remained unaltered after saline. These tachycardic responses to isometheptene remained unaffected after prazosin, rauwolscine, ritanserin or the combination prazosin plus rauwolscine, but were abolished after propranolol. In contrast, the isometheptene-induced vasopressor responses were not significantly modified after the above doses of rauwolscine, ritanserin or propranolol, but were markedly blocked after prazosin or the combination of prazosin plus rauwolscine; the latter blockade did not significantly differ from that produced by prazosin alone. Interestingly, in rats pretreated intraperitoneally (i.p.) with reserpine (5 mg/kg; -24 h), isometheptene-induced tachycardic responses were abolished whereas the corresponding vasopressor responses were markedly attenuated and subsequently blocked by prazosin. It is concluded that isometheptene-induced tachycardic responses seem to involve only an indirect (tyramine-like action) mechanism mediated by beta-adrenoceptors, whilst the corresponding vasopressor responses are mediated by a predominantly indirect (tyramine-like action), as well as a minor direct (alpha1-adrenoceptors), sympathomimetic mechanism.     

Autonomic control of heart rate in the neonatal rhesus monkey

Autonomic control of resting heart rate was assessed using atropine and propranolol in 20 neonatal (2 to 3 weeks old) male Rhesus monkeys. After release from restraint for placement of a venous catheter, the average heart rate significantly decreased from 220 +/- 7 beats/min to 181 +/- 6 beats/min within 15 minutes and remained stable for the 2 hours. Autonomic control of resting heart rate is mediated through both divisions of the autonomic nervous system with the sympathetic system having a dominant influence. This is in contrast to the adult Rhesus, where the parasympathetic nervous system controls resting heart rate.     

Frequency-dependent baroreflex modulation of blood pressure and heart rate variability in conscious mice

The goal of this study was to determine the baroreflex influence on systolic arterial pressure (SAP) and pulse interval (PI) variability in conscious mice. SAP and PI were measured in C57Bl/6J mice subjected to sinoaortic deafferentation (SAD, n = 21) or sham surgery (n = 20). Average SAP and PI did not differ in SAD or control mice. In contrast, SAP variance was enhanced (21 +/- 4 vs. 9.5 +/- 1 mmHg2) and PI variance reduced (8.8 +/- 2 vs. 26 +/- 6 ms2) in SAD vs. control mice. High-frequency (HF: 1-5 Hz) SAP variability quantified by spectral analysis was greater in SAD (8.5 +/- 2.0 mmHg2) compared with control (2.5 +/- 0.2 mmHg2) mice, whereas low-frequency (LF: 0.1-1 Hz) SAP variability did not differ between the groups. Conversely, LF PI variability was markedly reduced in SAD mice (0.5 +/- 0.1 vs. 10.8 +/- 3.4 ms2). LF oscillations in SAP and PI were coherent in control mice (coherence = 0.68 +/- 0.05), with changes in SAP leading changes in PI (phase = -1.41 +/- 0.06 radians), but were not coherent in SAD mice (coherence = 0.08 +/- 0.03). Blockade of parasympathetic drive with atropine decreased average PI, PI variance, and LF and HF PI variability in control (n = 10) but had no effect in SAD (n = 6) mice. In control mice, blockade of sympathetic cardiac receptors with propranolol increased average PI and decreased PI variance and LF PI variability (n = 6). In SAD mice, propranolol increased average PI (n = 6). In conclusion, baroreflex modulation of PI contributes to LF, but not HF PI variability, and is mediated by both sympathetic and parasympathetic drives in conscious mice.     

Revealing deterministic structures in click-evoked otoacoustic emissions.

Click-evoked otoacoustic emissions (CEOAEs) were studied by means of recurrence quantification analysis (RQA) and were found to be endowed with a relevant amount of deterministic structuring. Such a structure showed highly significant correlation with the clinical evaluation of the signal over a data set including 56 signals. Moreover, 1) one of the RQA variables, Trend, was very sensitive to phase transitions in the dynamical regime of CEOAEs, and 2) appropriate use of principal component analysis proved able to isolate the individual character of the studied signals. These results are of general interest for the study of auditory signal transduction and generation mechanisms.     

α1-And β-adrenergic and muscarinic-cholinergic regulation in the spontaneous beating and Ca2+ oscillations in cultured neonatal rat cardiac myocytes

α₁-and β-adrenergic and muscarinic-cholinergic regulation in spontaneous beating and Ca²⁺ oscillations in neonatal rat cardiac myocytes at day 6 of culture was investigated. The spontaneous beating in myocytes decreased in the presence of 10 μM norepinephrine (NE). This negative chronotropic action was antagonized by prazosin. Carbachol (CCh) also showed negative chronotropic action which was inhibited by atropine. On the other hand, isoproterenol (ISP) increased the beating rate which was antagonized by propranolol. NE increased inositol phosphate formation whereas CCh and ISP did not. NE and CCh suppressed the frequency of the spontaneous Ca²⁺ oscillations but ISP increased. The present results suggest that α₁-adrenergic and muscarinic receptors regulate chronotropism to be negative whereas β-adrenoceptor regulates chronotropism to be positive in cultured neonatal rat cardiac myocytes.     

Pyridostigmine Restores Cardiac Autonomic Balance after Small Myocardial Infarction in Mice

The effect of pyridostigmine (PYR) - an acetylcholinesterase inhibitor - on hemodynamics and cardiac autonomic control, was never studied in conscious myocardial infarcted mice. Telemetry transmitters were implanted into the carotid artery under isoflurane anesthesia. Seven to ten days after recovery from the surgery, basal arterial pressure and heart rate were recorded, while parasympathetic and sympathetic tone (ΔHR) was evaluated by means of methyl atropine and propranolol. After the basal hemodynamic recording the mice were subjected to left coronary artery ligation for producing myocardial infarction (MI), or sham operation, and implantation of minipumps filled with PYR or saline. Separate groups of anesthetized (isoflurane) mice previously (4 weeks) subjected to MI, or sham coronary artery ligation, were submitted to cardiac function examination. The mice exhibited an infarct length of approximately 12%, no change in arterial pressure and increased heart rate only in the 1st week after MI. Vagal tone decreased in the 1^st week, while the sympathetic tone was increased in the 1^st and 4^th week after MI. PYR prevented the increase in heart rate but did not affect the arterial pressure. Moreover, PYR prevented the increase in sympathetic tone throughout the 4 weeks. Concerning the parasympathetic tone, PYR not only impaired its attenuation in the 1^st week, but enhanced it in the 4^th week. MI decreased ejection fraction and increased diastolic and systolic volume. Therefore, the pharmacological increase of peripheral acetylcholine availability by means of PYR prevented tachycardia, increased parasympathetic and decreased sympathetic tone after MI in mice.     

Peculiarities of regulation of high-frequency oscillations of cardiac rhythm in rat ontogenesis

Dynamics of high-frequency components of heart periodogram whose main part is respiratory arrhythmia (RA) as well as consequences of vagotomy, block of M-cholinoreceptors by atropine and of β-adrenoreceptors by propranolol was studied in Wistar white rats in a large age diapason from 2–4 days to adults. It was established that results of the actions in immature rats did not essentially differ from those observed in adult rats and described in animals of other species and in human. In rats of young age, predominant in genesis of RA is peripheral mechanism. Vagotomy produces an elevation of the RA amplitude due to a sharp increase of the inspiration time as well as to deafferentation. Sympathetic nervous system produces restricting action on RA. This role is preserved in animals of all age groups. Participation of parasympathetic innervation in the RA genesis is revealed from the third week and continues increasing to the mature age. However, in adult rats, the peripheral mechanism of the RA formation is preserved, as disturbance of parasympathetic innervation leads not to the disappearance of RA, but only to a decrease of its amplitude.