Browsing by Author "Marcus, Noah J."

Now showing 1 - 14 of 14
  • Thumbnail Image
    Item
    Ablation of brainstem C1 neurons improves cardiac function in volume overload heart failure
    (2019) Andrade Andrade, David Cristóbal; Toledo, Camilo; Díaz, Hugo S.; Lucero, Claudia; Arce Álvarez, Alexis; Oliveira, Luis M.; Takakura, Ana C.; Moreira, Thiago S.; Schultz, Harold D.; Del Rio, Rodrigo; Marcus, Noah J.; Alcayaga Urbina, Julio Andrés
  • No Thumbnail Available
    Item
    Cardiorespiratory alterations following intermittent photostimulation of RVLM C1 neurons: Implications for long-term blood pressure, breathing and sleep regulation in freely moving rats
    (2022) Toledo, Camilo; Andrade, David C.; Diaz-Jara, Esteban; Ortolani, Domiziana; Bernal-Santander, Ignacio; Schwarz, Karla G.; Ortiz, Fernando C.; Marcus, Noah J.; Oliveira, Luiz M.; Takakura, Ana C.; Moreira, Thiago S.; Del Rio, Rodrigo
    Aim Sympathoexcitation and sleep-disordered breathing are common contributors for disease progression. Catecholaminergic neurons from the rostral ventrolateral medulla (RVLM-C1) modulate sympathetic outflow and have anatomical projections to respiratory neurons; however, the contribution of highly selective activation of RVLM-C1 neurons on long-term autonomic and breathing (dys)regulation remains to be understood. Methods To explore this relationship, a lentiviral vector carrying the light-sensitive cation channel channelrhodopsin-2 (LVV-PRSX8-ChR2-YFP) was unilaterally injected into the RVLM of healthy rats. On the contralateral side, LVV-PRSX8-ChR2-YFP was co-injected with a specific immunotoxin (D beta H-SAP) targeted to eliminate C1 neurons. Results Intermittent photostimulation of RVLM-C1 in vivo, in unrestrained freely moving rats, elicited long-term facilitation of the sympathetic drive, a rise in blood pressure and sympatho-respiratory coupling. In addition, photoactivation of RVLM-C1 induced long-lasting ventilatory instability, characterized by oscillations in tidal volume and increased breathing variability, but only during non-rapid eye movement sleep. These effects were not observed when photostimulation of the RVLM was performed in the presence of D beta H-SAP toxin. Conclusions The finding that intermittent activation of RVLM-C1 neurons induces autonomic and breathing dysfunction suggest that episodic stimulation of RVLM-C1 may serve as a pathological substrate for the long-term development of cardiorespiratory disorders.
  • No Thumbnail Available
    Item
    Cardiovascular and autonomic dysfunction in long-COVID syndrome and the potential role of non-invasive therapeutic strategies on cardiovascular outcomes
    (2023) Allendes, Francisca J.; Diaz, Hugo S.; Ortiz, Fernando C.; Marcus, Noah J.; Quintanilla, Rodrigo; Inestrosa, Nibaldo C.; Del Rio, Rodrigo
    A significant percentage of COVID-19 survivors develop long-lasting cardiovascular sequelae linked to autonomic nervous system dysfunction, including fatigue, arrhythmias, and hypertension. This post-COVID-19 cardiovascular syndrome is one facet of "long-COVID," generally defined as long-term health problems persisting/appearing after the typical recovery period of COVID-19. Despite the fact that this syndrome is not fully understood, it is urgent to develop strategies for diagnosing/managing long-COVID due to the immense potential for future disease burden. New diagnostic/therapeutic tools should provide health personnel with the ability to manage the consequences of long-COVID and preserve/improve patient quality of life. It has been shown that cardiovascular rehabilitation programs (CRPs) stimulate the parasympathetic nervous system, improve cardiorespiratory fitness (CRF), and reduce cardiovascular risk factors, hospitalization rates, and cognitive impairment in patients suffering from cardiovascular diseases. Given their efficacy in improving patient outcomes, CRPs may have salutary potential for the treatment of cardiovascular sequelae of long-COVID. Indeed, there are several public and private initiatives testing the potential of CRPs in treating fatigue and dysautonomia in long-COVID subjects. The application of these established rehabilitation techniques to COVID-19 cardiovascular syndrome represents a promising approach to improving functional capacity and quality of life. In this brief review, we will focus on the long-lasting cardiovascular and autonomic sequelae occurring after COVID-19 infection, as well as exploring the potential of classic and novel CRPs for managing COVID-19 cardiovascular syndrome. Finally, we expect this review will encourage health care professionals and private/public health organizations to evaluate/implement non-invasive techniques for the management of COVID-19 cardiovascular sequalae.
  • No Thumbnail Available
    Item
    Chronic intermittent hypoxia promotes glomerular hyperfiltration and potentiates hypoxia-evoked decreases in renal perfusion and PO2
    (2023) Kious, Kiefer W.; Savage, Kalie A.; Twohey, Stephanie C. E.; Highum, Aubrey F.; Philipose, Andrew; Diaz, Hugo S.; Del Rio, Rodrigo; Lang, James A. A.; Clayton, Sarah C.; Marcus, Noah J.
    Introduction: Sleep apnea (SA) is highly prevalent in patients with chronic kidney disease and may contribute to the development and/or progression of this condition. Previous studies suggest that dysregulation of renal hemodynamics and oxygen flux may play a key role in this process. The present study sought to determine how chronic intermittent hypoxia (CIH) associated with SA affects regulation of renal artery blood flow (RBF), renal microcirculatory perfusion (RP), glomerular filtration rate (GFR), and cortical and medullary tissue PO2 as well as expression of genes that could contribute to renal injury. We hypothesized that normoxic RBF and tissue PO2 would be reduced after CIH, but that GFR would be increased relative to baseline, and that RBF, RP, and tissue PO2 would be decreased to a greater extent in CIH vs. sham during exposure to intermittent asphyxia (IA, FiO2 0.10/FiCO2 0.03). Additionally, we hypothesized that gene programs promoting oxidative stress and fibrosis would be activated by CIH in renal tissue.Methods: All physiological variables were measured at baseline (FiO2 0.21) and during exposure to 10 episodes of IA (excluding GFR).Results: GFR was higher in CIH-conditioned vs. sham (p < 0.05), whereas normoxic RBF and renal tissue PO2 were significantly lower in CIH vs. sham (p < 0.05). Reductions in RBF, RP, and renal tissue PO2 during IA occurred in both groups but to a greater extent in CIH (p < 0.05). Pro-oxidative and pro-fibrotic gene programs were activated in renal tissue from CIH but not sham.Conclusion: CIH adversely affects renal hemodynamic regulation and oxygen flux during both normoxia and IA and results in changes in renal tissue gene expression.
  • No Thumbnail Available
    Item
    Exercise intolerance in volume overload heart failure is associated with low carotid body mediated chemoreflex drive
    (2021) Andrade, David C.; Diaz-Jara, Esteban; Toledo, Camilo; Schwarz, Karla G.; Pereyra, Katherin V.; Diaz, Hugo S.; Marcus, Noah J.; Ortiz, Fernando C.; Rios-Gallardo, Angelica P.; Ortolani, Domiziana; Del Rio, Rodrigo
    Mounting an appropriate ventilatory response to exercise is crucial to meeting metabolic demands, and abnormal ventilatory responses may contribute to exercise-intolerance (EX-inT) in heart failure (HF) patients. We sought to determine if abnormal ventilatory chemoreflex control contributes to EX-inT in volume-overload HF rats. Cardiac function, hypercapnic (HCVR) and hypoxic (HVR) ventilatory responses, and exercise tolerance were assessed at the end of a 6 week exercise training program. At the conclusion of the training program, exercise tolerant HF rats (HF+EX-T) exhibited improvements in cardiac systolic function and reductions in HCVR, sympathetic tone, and arrhythmias. In contrast, HF rats that were exercise intolerant (HF+EX-inT) exhibited worse diastolic dysfunction, and showed no improvements in cardiac systolic function, HCVR, sympathetic tone, or arrhythmias at the conclusion of the training program. In addition, HF+EX-inT rats had impaired HVR which was associated with increased arrhythmia susceptibility and mortality during hypoxic challenges (similar to 60% survival). Finally, we observed that exercise tolerance in HF rats was related to carotid body (CB) function as CB ablation resulted in impaired exercise capacity in HF+EX-T rats. Our results indicate that: (i) exercise may have detrimental effects on cardiac function in HF-EX-inT, and (ii) loss of CB chemoreflex sensitivity contributes to EX-inT in HF.
  • Thumbnail Image
    Item
    Exercise training improves cardiac autonomic control, cardiac function, and arrhythmogenesis in rats with preserved-ejection fraction heart failure
    (2017) Andrade Andrade, David Cristóbal; Arce-Alvarez Alexis; Toledo, Camilo; Díaz, Hugo S.; Lucero, Claudia; Schultz, Harold D.; Marcus, Noah J.; Del Rio, Rodrigo
  • Thumbnail Image
    Item
    Heart rate and cardiac autonomic responses to concomitant deep breathing, hand grip exercise, and circulatory occlusion in healthy young adult men and women
    (2021) Andrade Andrade, David Cristóbal; Melipillan, Claudia; Toledo, Camilo; Rios-Gallardo, Angélica; Marcus, Noah J.; Ortiz, Fernando C.; Martinez, Gonzalo; Muñoz Venturelli, Paula; Río Troncoso, Rodrigo Andre del
    Background: Deep breathing (DB) and handgrip (HG) exercise -with and without circulatory occlusion (OC) in muscle-, have been shown to have beneficial effects on cardiovascular function; however, the combination of these maneuvers on heart rate (HR) and cardiac sympathovagal balance have not been previously investigated. Therefore, the aim of the present study was to evaluate the effect of simultaneous DB, HG, and OC maneuvers on the sympathovagal balance in healthy women and men subjects. Methods and results: Electrocardiogram and ventilation were measured in 20 healthy subjects (Women: n = 10; age = 27 ± 4 years; weight = 67.1 ± 8.4 kg; and height = 1.6 ± 0.1 m. Men: n = 10; age = 27 ± 3 years; weight = 77.5 ± 10.1 kg; and height = 1.7 ± 0.1 m) at baseline and during DB, DB + HG, or DB + HG + OC protocols. Heart rate (HR) and respiratory rate were continuously recorded, and spectral analysis of heart rate variability (HRV) were calculated to indirectly estimate cardiac autonomic function. Men and women showed similar HR responses to DB, DB + HG and DB + HG + OC. Men exhibited a significant HR decrease following DB + HG + OC protocol which was accompanied by an improvement in cardiac autonomic control evidenced by spectral changes in HRV towards parasympathetic predominance (HRV High frequency: 83.95 ± 1.45 vs. 81.87 ± 1.50 n.u., DB + HG + OC vs. baseline; p < 0.05). In women, there was a marked decrease in HR after completion of both DB + HG and DB + HG + OC tests which was accompanied by a significant increase in cardiac vagal tone (HRV High frequency: 85.29 ± 1.19 vs. 77.93 ± 0.92 n.u., DB + HG vs. baseline; p < 0.05). No adverse effects or discomfort were reported by men or women during experimental procedures. Independent of sex, combination of DB, HG, and OC was tolerable and resulted in decreases in resting HR and elevations in cardiac parasympathetic tone. Conclusions: These data indicate that combined DB, HG and OC are effective in altering cardiac sympathovagal balance and reducing resting HR in healthy men and women.
  • No Thumbnail Available
    Item
    Inhibition of Brainstem Endoplasmic Reticulum Stress Rescues Cardiorespiratory Dysfunction in High Output Heart Failure
    (2021) Diaz, Hugo S.; Andrade, David C.; Toledo, Camilo; Schwarz, Karla G.; Pereyra, Katherin, V; Diaz-Jara, Esteban; Marcus, Noah J.; Del Rio, Rodrigo
    Recent evidence shows that chronic activation of catecholaminergic neurons of the rostral ventrolateral medulla is crucial in promoting autonomic imbalance and cardiorespiratory dysfunction in high output heart failure (HF). Brainstem endoplasmic reticulum stress (ERS) is known to promote cardiovascular dysfunction; however, no studies have addressed the potential role of brainstem ERS in cardiorespiratory dysfunction in high output HF. In this study, we assessed the presence of brainstem ERS and its potential role in cardiorespiratory dysfunction in an experimental model of HF induced by volume overload. High output HF was surgically induced via creation of an arterio-venous fistula in adult male Sprague-Dawley rats. Tauroursodeoxycholic acid (TUDCA), an inhibitor of ERS, or vehicle was administered intracerebroventricularly for 4 weeks post-HF induction. Compared with vehicle treatment, TUDCA improved cardiac autonomic balance (LFHRV/HFHRV ratio, 3.02 +/- 0.29 versus 1.14 +/- 0.24), reduced cardiac arrhythmia incidence (141.5 +/- 26.7 versus 35.67 +/- 12.5 events/h), and reduced abnormal respiratory patterns (Apneas: 11.83 +/- 2.26 versus 4.33 +/- 1.80 events/h). TUDCA administration (HF+Veh versus HF+TUDCA, P<0.05) attenuated cardiac hypertrophy (HW/BW 4.4 +/- 0.3 versus 4.0 +/- 0.1 mg/g) and diastolic dysfunction. Analysis of rostral ventrolateral medulla gene expression confirmed the presence of ERS, inflammation, and activation of renin-angiotensin system pathways in high output HF and showed that TUDCA treatment completely abolished ERS and ERS-related signaling. Taken together, these results support the notion that ERS plays a role in cardiorespiratory dysfunction in high output HF and more importantly that reducing brain ERS with TUDCA treatment has a potent salutary effect on cardiac function in this model.
  • No Thumbnail Available
    Item
    Medullary astrocytes mediate irregular breathing patterns generation in chronic heart failure through purinergic P2X7 receptor signalling
    (2022) Toledo, Camilo; Diaz-Jara, Esteban; Diaz, Hugo S.; Schwarz, Karla G.; Pereyra, Katherin, V; Las Heras, Alexandra; Rios-Gallardo, Angelica; Andrade, David C.; Moreira, Thiago; Takakura, Ana; Marcus, Noah J.; Del Rio, Rodrigo
    Background Breathing disorders (BD) (apnoeas/hypopneas, periodic breathing) are highly prevalent in chronic heart failure (CHF) and are associated with altered central respiratory control. Ample evidence identifies the retrotrapezoid nucleus (RTN) as an important chemosensitivity region for ventilatory control and generation of BD in CHF, however little is known about the cellular mechanisms underlying the RTN/BD relationship. Within the RTN, astrocyte-mediated purinergic signalling modulates respiration, but the potential contribution of RTN astrocytes to BD in CHF has not been explored.
  • No Thumbnail Available
    Item
    Peripheral chemoreflex modulation of renal hemodynamics and renal tissue PO2 in chronic heart failure with reduced ejection fraction
    (2022) Kious, Kiefer W.; Philipose, Andrew; Smith, Luke J.; Kemble, Jayson P.; Twohey, Stephanie C. E.; Savage, Kalie; Diaz, Hugo S.; Del Rio, Rodrigo; Marcus, Noah J.
    Aberrant carotid body chemoreceptor (CBC) function contributes to increased sympathetic nerve activity (SNA) and reduced renal blood flow (RBF) in chronic heart failure (CHF). Intermittent asphyxia (IA) mimicking sleep apnea is associated with additional increases in SNA and may worsen reductions in RBF and renal PO2 (RPO2) in CHF. The combined effects of decreased RBF and RPO2 may contribute to biochemical changes precipitating renal injury. This study sought to determine the role of CBC activity on glomerular filtration rate (GFR), RBF and RPO2 in CHF, and to assess the additive effects of IA. Furthermore, we sought to identify changes in gene expression that might contribute to renal injury. We hypothesized that GFR, RBF, and RPO2 would be reduced in CHF, that decreases in RBF and RPO2 would be worsened by IA, and that these changes would be ameliorated by CBC ablation (CBD). Finally, we hypothesized that CHF would be associated with pro-oxidative pro-fibrotic changes in renal gene expression that would be ameliorated by CBD. CHF was induced in adult male Sprague Dawley rats using coronary artery ligation (CAL). Carotid body denervation was performed by cryogenic ablation. GFR was assessed in conscious animals at the beginning and end of the experimental period. At 8-weeks post-CAL, cardiac function was assessed via echocardiography, and GFR, baseline and IA RBF and RPO2 were measured. Renal gene expression was measured using qRT-PCR. GFR was lower in CHF compared to sham (p < 0.05) but CBD had no salutary effect. RBF and RPO2 were decreased in CHF compared to sham (p < 0.05), and this effect was attenuated by CBD (p < 0.05). RBF and RPO2 were reduced to a greater extent in CHF vs. sham during exposure to IA (p < 0.05), and this effect was attenuated by CBD for RBF (p < 0.05). Downregulation of antioxidant defense and fibrosis-suppressing genes was observed in CHF vs. sham however CBD had no salutary effect. These results suggest that aberrant CBC function in CHF has a clear modulatory effect on RBF during normoxia and during IA simulating central sleep apnea.
  • Thumbnail Image
    Item
    Revisiting the physiological effects of exercise training on autonomic regulation and chemoreflex control in heart failure : does ejection fraction matter?
    (2018) Andrade Andrade, David Cristóbal; Arce Alvarez, Alexis; Toledo, Camilo; Díaz, Hugo S.; Lucero, Claudia; Quintanilla, Rodrigo A.; Schultz, Harold D.; Marcus, Noah J.; Amann, Markus; Del Río, Rodrigo
  • No Thumbnail Available
    Item
    Rostral ventrolateral medullary catecholaminergic neurones mediate irregular breathing pattern in volume overload heart failure rats
    (2019) Toledo, Camilo; Andrade, David C.; Diaz, Hugo S.; Pereyra, Katherin V.; Schwarz, Karla G.; Diaz-Jara, Esteban; Oliveira, Luiz M.; Takakura, Ana C.; Moreira, Thiago S.; Schultz, Harold D.; Marcus, Noah J.; Del Rio, Rodrigo
    Key points
  • Thumbnail Image
    Item
    Topical Application of Connexin43 Hemichannel Blocker Reduces Carotid Body-Mediated Chemoreflex Drive in Rats
    (2018) Andrade Andrade, David Cristóbal; Iturriaga Agüera, Rodrigo; Toledo, Camilo; Lucero, Claudia M.; Diaz, Hugo S.; Arce-Alvarez, Alexis; Retamal, Mauricio A.; Marcus, Noah J.; Alcayaga Urbina, Julio Andrés; Del Rio, Rodrigo
  • Thumbnail Image
    Item
    Ventilatory and Autonomic Regulation in Sleep Apnea Syndrome: A Potential Protective Role for Erythropoietin?
    (2018) Andrade Andrade, David Cristóbal; Haine, Liasmine; Toledo, Camilo; Diaz, Hugo S.; Quintanilla, Rodrigo A.; Marcus, Noah J.; Iturriaga Agüera, Rodrigo; Richalet, Jean-Paul; Voituron, Nicolas; Del Rio, Rodrigo