Proefschrift Universiteit Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Research Doctorate - Doctor of Philosophy (PhD) / There is no consistency between studies of mammalian autonomic systems controlling the coronary circulation, particularly with respect to vagal cholinoceptor activity. Therefore, integrated autonomic control of regional coronary blood flow and conductance was investigated in chronically prepared awake sheep, and compared with data from this laboratory found in the awake dog. Coronary blood flow was measured simultaneously in the circumflex (Cx), right (R) and anterior descending (AD) beds by pulsed Doppler probes. Heart rate (HR) was controlled over the range of 100 to 180 beats/min by atrioventricular pacing. Baroreflex responses were evoked by elevating upper-body aortic pressure (Pa) using an external aortic occluder at HR of 150 and 180 beats/min. Specific agonists determined that effective populations of α-, β-adrenoceptors and cholinoceptors exist in all three coronary beds. Cholinoceptors (ch) and β-adrenoceptors (β) evoke vasodilatation, whereas α-adrenoceptors (α) evoke vasoconstriction. By contrast, electrical vagal stimulation constricts all 3 coronary beds, an effect blocked by methscopolamine. Pacing the heart upward raised baroreflex and metabolic activity and a differential rise in coronary conductance where Cx was greatest followed by R then AD. Block of ch, β and α alone, and together, at different HR revealed that, 1. in all 3 beds an underlying ch constrictor effect is balanced by the summed dilator effects of β, plus a probable α-enhanced vagal, vasointestinal peptide (VIP) interaction mechanism, 2. the net effects summate to enhance flow and conductance in Cx, but not in R and AD. At high HR, there is some waning of the neural mechanisms but raising and sustaining Pa at constant HR can recruit these mechanisms in each bed indicating ch, β and α/VIP, are baroreflex dependent even at the highest physiological HR. Therefore, differences do exist between species, for in particular baroreflex evoked cholinoceptor effects in the mammalian coronary circulation. They are vasoconstrictor in sheep, and vasodilator in the dog. These species differences specify successful alternatives in the evolution of reflex systems to meet the demand for coronary blood flow.

Large inter-individual differences exist in the degree of bradycardia induced by breath-hold facial immersion. The purpose of this study was to examine baroreceptor sensitivity in subjects who exhibit a strong response and in those who exhibit a minimal response. Thirty-nine healthy volunteers. were screened with three trials of breath-hold facial immersion during mild steady-state cycling. The six subjects displaying the greatest bradycardia were selected as responders and the six showing the least as non-responders. Baroreceptor sensitivity was estimated in each subject by examination of the heart rate and blood pressure responses to a controlled Valsalva manoeuvre and to isometric handgrip exercise. Regression lines for changes in systolic blood pressure over time showed a flatter response in the responders both during isometric handgrip exercise (p<.05) and over the 25 s immediately following release (p<.01). One interpretation of these findings is that the non-responders are less able to maintain a resting level of arterial blood pressure. As well, regression lines for the change in diastolic blood pressure over the period 25 to 55 s post-release of isometric handgrip exercise had different slopes in the two groups (p<.05). A positive mean slope calculated for the responders and a negative mean slope calculated for the non-responders, when plotted with the average intercepts, suggested an undershoot in diastolic blood pressure upon release in the responders. This may represent an attempt to regain resting levels of arterial blood pressure through peripheral vasodilitation. Direct measures by arterial catheter, in a sub-sample of four subjects, suggested that the blood pressure overshoot during the recovery phase of the Valsalva manoeuvre may not have been large enough to demonstrate group differences in baroreceptor sensitivity. / Thesis / Master of Science (MS)

Master of Science / Department of Kinesiology / Carl Ade / Background – Chemotherapy-induced left ventricular cardiotoxicity is associated with many cancer treatments; however, what is less known is how these treatments affect vascular health and autonomic control of blood pressure. Arterial stiffness and cardiovagal baroreflex sensitivity (BRS) are indicators of cardiovascular health and may provide insight into the adverse effects of anti-cancer chemotherapy. Therefore, the primary aims of the present study were to evaluate carotid artery stiffness and arterial BRS in cancer patients currently being treated with adjuvant chemotherapy. Methods – We performed a cross-sectional, case-control study involving 9 cancer patients and 9 age- and sex-matched controls. Carotid artery stiffness was assess via 2D ultrasonography. Cardiovagal BRS was assessed from the spontaneous changes in beat-to-beat time series of R-R interval and systolic blood pressure via the cross correlation technique. Results – Our findings indicated a significant decrease in cardiovagal BRS in cancer patients compared to controls (4.7 ± 0.6 vs 9.2 ± 1.7 msec mmHg⁻¹ respectively, P = 0.02). Carotid artery β-Stiffness was significantly higher in the cancer patients compared to control participants (9.2 ± 1.2 vs 6.6 ± 0.74 U respectively, P = 0.05). Conclusions – These data suggest that anti-cancer chemotherapy elicits significant decreases in the autonomic control of blood pressure and arterial stiffness, leaving cancer survivors with an increased risk of future cardiovascular disease.

Reports indicate that postexercise heat loss is modulated by baroreceptor input; however, the mechanisms remain unknown. We examined the time-dependent involvement of adenosine receptors, noradrenergic transmitters, and nitric oxide (NO) in modulating baroreceptor-mediated changes in postexercise heat loss. Eight males performed two 15-min cycling bouts (85% VO2max) each followed by a 45-min recovery in the heat (35°C). Lower body positive (LBPP), negative (LBNP), or no (Control) pressure was applied in three separate sessions during the final 30-min of each recovery. Four microdialysis fibres in the forearm skin were perfused with: 1) lactated Ringer’s (Ringer’s); 2) 4mM Theophylline (inhibits adenosine receptors); 3) 10mM Bretylium (inhibits noradrenergic transmitter release); or 4) 10mM L-NAME (inhibits NO synthase). We measured cutaneous vascular conductance (CVC; percentage of maximum) calculated as perfusion units divided by mean arterial pressure, and local sweat rate. Compared to Control, LBPP did not influence CVC at L-NAME, Theophylline or Bretylium during either recovery (P>0.07); however, CVC at Ringer’s was increased by ~5-8% throughout 30 min of LBPP during Recovery 1 (all P<0.02). In fact, CVC at Ringer’s was similar to Theophylline and Bretylium during LBPP. Conversely, LBNP reduced CVC at all microdialysis sites by ~7-10% in the last 15 min of Recovery 2 (all P<0.05). Local sweat rate was similar at all treatment sites as a function of pressure condition (P>0.10). We show that baroreceptor input modulates postexercise CVC to some extent via adenosine receptors, noradrenergic vasoconstriction, and NO whereas no influence was observed for postexercise sweating.

Indiana University-Purdue University Indianapolis (IUPUI) / Autonomic control of the heart results in variations in the intervals between heart beats, known as heart rate variability. One of the defining components of autonomic control is the baroreflex, a negative feedback controller that balances heart rate and blood pressure. The baroreflex is under constant command from the branches of the autonomic nervous system. To better understand how the autonomic nervous system commands the baroreflex, a baroreflex reflexogenic animal protocol was carried out. Heart rate variability analysis and baroreflex sensitivity were used to quantify the neural control of the heart. This thesis reconfirmed the existence of sexually dimorphic properties in the baroreflex through the use of heart rate variability analysis and baroreflex sensitivity. It was discovered that there are many caveats to utilizing heart rate variability analysis, which have to be addressed both in the experimental protocol and the signal processing technique. Furthermore, it was suggested that the slope method for quantifying baroreflex sensitivity also has many caveats, and that other baroreflex sensitivity methods are likely more optimal for quantifying sustained activation of the baroreflex. By utilizing various heart rate variability signal processing algorithms to assess autonomic tone in Sprague-Dawley rats during rest and sustained electrical activation of the baroreflex, the null hypothesis was rejected.

Diss. (sammanfattning) Göteborg : Univ. , 2009. / Härtill 3 uppsatser.

Acute (~2 min) baroreceptor unloading was reported to modulate metaboreflex control of postexercise cutaneous blood flow, but not sweating. We examined whether sustained changes in baroreceptor loading status during prolonged postexercise recovery can alter the metaboreceptors’ influence on heat loss. Thirteen young males performed a 1-min isometric handgrip exercise (IHG) at 60% maximal voluntary contraction followed by 2-min of forearm ischemia (to activate metaboreceptors) before and 15, 30, 45 and 60-min after a 15-min intense treadmill running exercise (>90% maximal heart rate) in the heat (35°C). This procedure was repeated on three separate days with the application of lower-body positive (LBPP, +40 mmHg), negative (LBNP, -20 mmHg), or no pressure (Control) postexercise. Sweat rate (ventilated capsule; forearm, chest, upper back) and cutaneous vascular conductance (CVC; forearm, upper back) were measured. Relative to pre-IHG levels, sweating at all sites increased during IHG and remained elevated during ischemia at baseline and similarly at 30, 45, and 60-min postexercise (site average sweat rate increase during ischemia: Control, 0.13±0.02; LBPP, 0.12±0.02; LBNP, 0.15±0.02 mg·min-1·cm-2; all P<0.01), but not at 15-min (all P>0.10). LBPP and LBNP application did not modulate the pattern of sweating to IHG and ischemia (all P>0.05). At 15-min postexercise, forearm CVC was reduced from pre-IHG levels during both IHG and ischemia under LBNP only (ischemia: 3.9±0.8 %CVCmax; P<0.02). Therefore, we show metaboreceptors modulate postexercise sweating in the mid-to-late stages (30-60 min) of recovery, independent of baroreceptor loading status and similarly between skin sites. In contrast, metaboreflex modulation of forearm but not upper back CVC occurs only in the early stages of recovery (15 min) and depends upon baroreceptor unloading.

Interoception, the perception of the body's physiological state, is often studied in relation to emotion processing. Particularly, cardioception has been largely implicated in anxiety. Three related but distinct dimensions of interoception have recently emerged in the literature: sensibility (IS), accuracy (IAC), and awareness (IAW). Divergent findings regarding interoception and anxiety may result from lacking appreciation for interoceptive dimensions. Additionally, the role of cardiovascular afferent feedback in anxiety and interoception is largely unknown. Baroreflex sensitivity (BRS) has been implicated in interoceptive processes yet no known research directly measures this in relation to multidimensional cardioception. The present study aimed to assess the degree to which IS, IAC, IAW, and BRS predict trait anxiety at rest and during anticipatory anxiety. Results partially suggest increased IAC and BRS, but more variable IS and IAW in relation to trait anxiety. Overall, results show complex associations among factors, suggesting increased specificity among the constructs. Results highlight the importance of attention to construct validity and method variance in the study of interoceptive subdomains. Finally, the present study helps to pave the way for continued investigations concerning cardioception in enduring anxiety and the related role of the baroreflex in cardiac afferent processes. / PHD / Interoception, the perception of the body’s physiological state, is often studied in relation to emotion processing. Particularly, cardioception (the sense of cardiac activity, such as the perception of a racing heart) has been largely implicated in anxiety. Three related but distinct dimensions of interoception have recently emerged in the literature: sensibility (IS), accuracy (IAC), and awareness (IAW). Divergent findings regarding interoception and anxiety may result from lacking appreciation for interoceptive dimensions. Additionally, the role of cardiovascular feedback to the brain in anxiety and interoception is largely unknown. The baroreflex system rapidly modulates activity of the heart in accordance with short-term blood pressure changes. The sensitivity of this homeostatic baroreflex system (BRS) also plays a role in interoceptive processes, yet no known research directly measures this in relation to multidimensional cardioception. The present study aimed to assess the degree to which IS, IAC, IAW, and BRS predict dispositional anxiety at rest and during anticipatory anxiety. Results partially suggest increased IAC and BRS, but more variable IS and IAW in relation to dispositional anxiety. Overall, results show complex associations among factors, suggesting increased specificity among the variables. Results highlight the importance of attention to measurement precision and various ways to assess the dimensions of interoception. Finally, the present study helps to pave the way for continued research concerning perception of the heart’s activity in enduring anxiety and the related role of cardiovascular activity at various levels of conscious awareness. Ultimately, research on this topic is highly important for the eventual improvement of existing therapeutics for individuals regularly experiencing severe anxiety.

Anesthesia affects the central nervous system and can suppress cardiovascular activity. In this study, we compared two anesthetics, urethane and alpha-chloralose, to better understand their effect on sympathetic control of blood pressure, as well as how they would affect baroreceptor response and blood pressure in adult rats. To do this we performed baroreceptor tests in adult rats under isoflurane anesthesia and then either urethane (I.V. 1.25 g/kg, n=2) or alpha-chloralose (100 mg/kg, n=2). We found that baroreceptor responses were not significantly different between urethane or alpha-chloralose anesthesia. However, significant depression of baseline blood pressure occurred under alpha-chloralose anesthesia compared with urethane. Additionally, we observed significant elevation of baseline renal sympathetic nerve activity (RSNA) occurred under urethane anesthesia. Ultimately, our findings suggest that both urethane and alpha-chloralose provided sufficient induction of anesthesia without significantly modifying baroreceptor response. However, since urethane significantly raised baseline sympathetic nerve activity, it should be avoided in studies where raised sympathetic activity could confound with the test results. alpha-chloralose significantly lowered baseline blood pressure by nearly 30%, and its use should be avoided in studies where lowered blood pressure may confound the results.