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In this thesis, we included results from two studies. The first one considered the effects of the blood volume changes, during blood donation, on the heart rate variability (HRV) measured, non-invasively, form electrocardiographic (ECG) and photoplethysmographic (PPG) signals. Our results showed that, during blood donation, there were no significant changes in the pulsatile area of PPG signal, while heart rate increased. No significant changes were noticed in HRV extracted from both signals. Error analysis between the HRV extracted from ECG and peak interval variability (PIV) suggested that the error during blood donation was increased which means that the use of PIV extracted from PPG signal, used as a replacement diagnostic tool in clinical applications, needs further investigations and should be carefully studied in non-stationary cardiovascular situations such as blood donation. The imbalance between the two branches of the autonomic nervous system, sympathetic and parasympathetic, vagal, may result in a harmful activation of myocardial tissues which cause arrhythmias and sudden cardiac death. Although the study of the sympathovagal balance have been attracting many researchers, further studies are needed to elucidate the effects of many kinds of drugs on the autonomic modulation of the cardiac muscle, specifically, the cells of sinoatrial (SA) node. The aim of the second part of this thesis was to assess the effects of calcium channel blocker (Verapamil), calcium channel sensitizer (Levosimendan), calcium chloride (CaCl2), the combinations of verapamil/ CaCl2, levosimendan/ CaCl2, and noradrenaline infusion on beat-to-beat cardiovascular variability represented, in this research, by systolic blood pressure variability (SBPV), and stroke volume variability (SVV) signals. We used Fat Fourier Transform (FFT) to evaluate the power spectral density of the fluctuations in both signals to evaluate the effects of short-term treatments with those drugs on the sympathovagal balance in normal rats. Then, we compared the spectra obtained from SBPV and SVV to decide which of these fluctuations along with corresponding spectrum was more able to provide a clear feedback about the autonomic nervous system. Our data suggests that there were a significant correlations between low- (LF), mid- (MF), and high-frequency (HF) spectra obtained from SBPV and SVV except between the HF spectra estimated from after the infusion of levosimendan where a poor correlation (r = 0.530, p = 0.281) was noticed. This that both HF components obtained provide different information regarding the autonomic nervous system modulation of the SA node cells, while the results obtained from the rest of experiments showed that both signals provide same information about the modulation of sympathetic and parasympathetic tone due to all stages of different drugs infusion studied in this thesis. Besides that, we found that both spectra may be used to track the fluctuations in the cardiac output as a result of the drugs infusion.

In this thesis, we included results from two studies. The first one considered the effects of the blood volume changes, during blood donation, on the heart rate variability (HRV) measured, non-invasively, form electrocardiographic (ECG) and photoplethysmographic (PPG) signals. Our results showed that, during blood donation, there were no significant changes in the pulsatile area of PPG signal, while heart rate increased. No significant changes were noticed in HRV extracted from both signals. Error analysis between the HRV extracted from ECG and peak interval variability (PIV) suggested that the error during blood donation was increased which means that the use of PIV extracted from PPG signal, used as a replacement diagnostic tool in clinical applications, needs further investigations and should be carefully studied in non-stationary cardiovascular situations such as blood donation. The imbalance between the two branches of the autonomic nervous system, sympathetic and parasympathetic, vagal, may result in a harmful activation of myocardial tissues which cause arrhythmias and sudden cardiac death. Although the study of the sympathovagal balance have been attracting many researchers, further studies are needed to elucidate the effects of many kinds of drugs on the autonomic modulation of the cardiac muscle, specifically, the cells of sinoatrial (SA) node. The aim of the second part of this thesis was to assess the effects of calcium channel blocker (Verapamil), calcium channel sensitizer (Levosimendan), calcium chloride (CaCl2), the combinations of verapamil/ CaCl2, levosimendan/ CaCl2, and noradrenaline infusion on beat-to-beat cardiovascular variability represented, in this research, by systolic blood pressure variability (SBPV), and stroke volume variability (SVV) signals. We used Fat Fourier Transform (FFT) to evaluate the power spectral density of the fluctuations in both signals to evaluate the effects of short-term treatments with those drugs on the sympathovagal balance in normal rats. Then, we compared the spectra obtained from SBPV and SVV to decide which of these fluctuations along with corresponding spectrum was more able to provide a clear feedback about the autonomic nervous system. Our data suggests that there were a significant correlations between low- (LF), mid- (MF), and high-frequency (HF) spectra obtained from SBPV and SVV except between the HF spectra estimated from after the infusion of levosimendan where a poor correlation (r = 0.530, p = 0.281) was noticed. This that both HF components obtained provide different information regarding the autonomic nervous system modulation of the SA node cells, while the results obtained from the rest of experiments showed that both signals provide same information about the modulation of sympathetic and parasympathetic tone due to all stages of different drugs infusion studied in this thesis. Besides that, we found that both spectra may be used to track the fluctuations in the cardiac output as a result of the drugs infusion.

Ce travail a eu pour but (1) de comparer les différentes méthodes d'évaluation de la balance sympatho-vagale (BSV) actuellement utilisées chez le rat, et (2) d'évaluer les effets d'une altération de la BSV en faveur d'une prédominance vagale sur l'instabilité électrique atriale spontanée chez le rat spontanément hypertendu (SHR) vieillissant. L'électrocardiogramme a été mesuré chez les rats éveillés grâce à une sonde télémétrique chroniquement implantée. La méthode de référence pour l'estimation de la BSV repose sur le calcul du rapport de la fréquence cardiaque (FC) de repos à la FC intrinsèque. Selon que l'index est supérieur ou inférieur à 1, on peut conclure respectivement à une prédominance sympathique ou à une prédominance vagale. La FC intrinsèque est obtenue par l'administration combinée d'antagonistes sélectifs des deux branches du système nerveux autonome, c'est-à-dire un bloqueur β-adrénergique (aténolol) et un antagoniste des récepteurs muscariniques (méthylatropine). Les autres méthodes (mesure séparée des tonus autonomes, index extraits de l'analyse de la variabilité sinusale) fournissent des résultats incohérents ou contradictoires. L'administration chronique d'un inhibiteur de l'acétylcholinestérase (pyridostigmine) chez des rats SHR vieillissants induit une hypertonie vagale relative (BSV=0,81±0,02) par rapport aux rats non traités (BSV=1,06±0,01) qui s'accompagne d'une bradycardie sinusale et d'une augmentation de la fréquence et de la durée des épisodes de tachyarythmie atriale. Ces études démontrent l'intérêt de la méthode de référence pour l'estimation de la BSV chez le rat éveillé. La potentialisation de l'activité vagale endogène aggrave l'instabilité électrique atriale chez le rat SHR vieillissant, ce qui confirme le rôle pathogénique du système nerveux parasympathique dans ce modèle / The aim of the present work was (1) to compare the different methods currently used to assess sympathovagal balance (SVB) in rats, and (2) to assess SVB alterations towards vagal predominance on atrial electrical instability in aging spontaneously hypertensive rats (SHR). The electrocardiogram was measured in conscious rats using chronically implanted telemetric probes. The reference method to estimate SVB is based on the calculation of the ratio of intrinsic heart rate (HR) to resting HR. Depending on whether the index is greater or lower than 1, one can conclude to sympathetic or vagal predominance, respectively. Intrinsic HR is obtained after the combined administration of selective antagonists of both branches of the autonomic nervous system, i.e. β- adrenergic blocker (atenolol) and muscarinic receptor antagonist (methylatropine). Other methods (autonomic tones measured separately, calculation of indices derived from heart rate variability analysis) provide inconsistent or conflicting results. The chronic infusion of an acetylcholinesterase inhibitor (pyridostigmine) in aging SHRs induced relative vagal hypertonia (SVB=0.81±0.02) in comparison with untreated rats (SVB=1.06±0.01) along with sinus bradycardia and increased frequency and duration of atrial tachyarrhythmia episodes. These studies highlight the value of the reference method for evaluating SVB in conscious rats. Potentiation of endogenous vagal activity aggravates atrial electrical instability in aging SHRs, consistent with a pathogenic role of the parasympathetic nervous system in this model

Indications are that autonomic under-arousal exists in children with ADHD. Published results are, however, controversial and few studies examine the relationship between the autonomic nervous system and focussed attention. In line with the indications of sympathetic under-arousal, patients with the disorder are treated with sympathomimetic stimulants such as Ritalin (methylphenidate). Since these medications stimulate the sympathetic nervous system, they possess the potential to influence cardiac function. The aims of this study were a) to assess autonomic nervous system functioning in 20 children with ADHD, as compared to controls, and to examine the effects of focussed attention and sympathomimetic medication on this system, b) to investigate cardiac functioning in 20 children with ADHD, as compared to controls, and to examine the effects of sympathomimetic medication on this system and c) to assess EEG functioning in children with ADHD, as compared to controls, and to examine the effects of sympathomimetic medication on this functioning. Children with ADHD were tested while they were stimulant-free and during a period in which they were on stimulant medication, while controls were tested once. Autonomic nervous system activity of the children was assessed at baseline and during focussed attention by means of heart rate variability (HRV) and skin conductivity. Attention was evoked by means of a program on the BioGraph Infiniti biofeedback apparatus, which is used specifically to train ADHD individuals to increase their attentive abilities. HRV was determined by time-domain, frequency-domain and Poincaré analysis of RR interval data. Skin conductivity was determined by BioGraph Infiniti biofeedback apparatus. Cardiac functioning of the children was assessed at baseline by means of blood pressure recordings and electrocardiograms (ECGs). Blood pressure was measured by means of a stethoscope and mercurial sphygmomanometer. ECGs were obtained by means of a Schiller CardioLaptop AT-110 ECG recorder using the standard 12-lead cable positioning for a resting ECG and parameters measured included HR, RR, QT, JT, QTc, JTc, QTd, JTd, QTcd and JTcd. EEG values were determined at baseline and during focussed attention by means of BioGraph Infiniti biofeedback apparatus. EEG values measured in this study included theta/beta ratios, theta/SMR ratios and thalpha, low alpha and high alpha power. The main findings of this study are that: <ul> <li>Stimulant-free ADHD children show a parasympathetic dominance of the sympathovagal balance relative to controls.</li> <li>Methylphenidate usage shifts the autonomic balance of children with ADHD towards normal levels; however a normal autonomic balance is not reached.</li> <li>Stimulant-free ADHD children exhibit a shift in the sympathovagal balance towards the sympathetic nervous system from baseline to focussed attention; however, methylphenidate abolishes this shift.</li> <li>Methylphenidate usage does not, in general, cause QTc or JTc prolongation but it may cause QTc or JTc prolongation in susceptible individuals.</li> <li>Children with ADHD can not be differentiated from normal children on the basis of theta/beta ratios, theta/SMR ratios or alpha power.</li> <li>Methylphenidate increases the level of centering in children with ADHD.</li> <li>Stimulant-free ADHD children display an alpha block from baseline to focussed attention; however, methylphenidate abolishes this alpha block.</li></ul> Copyright / Dissertation (MSc)--University of Pretoria, 2009. / Physiology / unrestricted