Browsing by Author "Pereyra, Katherin, V"

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    Carbamylated form of human erythropoietin normalizes cardiorespiratory disorders triggered by intermittent hypoxia mimicking sleep apnea syndrome
    (LIPPINCOTT WILLIAMS & WILKINS, 2021) Andrade, David C.; Toledo, Camilo; Diaz, Hugo S.; Pereyra, Katherin, V; Schwarz, Karla G.; Diaz Jara, Esteban; Melipillan, Claudia; Rios Gallardo, Angelica P.; Uribe Ojeda, Atenea; Alcayaga, Julio; Quintanilla, Rodrigo A.; Iturriaga, Rodrigo; Richalet, Jean Paul; Voituron, Nicolas; Del Rio, Rodrigo
    Background and objective: Chronic intermittent hypoxia (CIH), one of the main features of obstructive sleep apnea (OSA), enhances carotid body-mediated chemoreflex and induces hypertension and breathing disorders. The carbamylated form of erythropoietin (cEpo) may have beneficial effects as it retains its antioxidant/anti-inflammatory and neuroprotective profile without increasing red blood cells number. However, no studies have evaluated the potential therapeutic effect of cEpo on CIH-related cardiorespiratory disorders. We aimed to determine whether cEpo normalized the CIH-enhanced carotid body ventilatory chemoreflex, the hypertension and ventilatory disorders in rats. Methods: Male Sprague-Dawley rats (250 g) were exposed to CIH (5% O-2, 12/h, 8 h/day) for 28 days. cEPO (20 mu g/kg, i.p) was administrated from day 21 every other day for one more week. Cardiovascular and respiratory function were assessed in freely moving animals. Results: Twenty-one days of CIH increased carotid body-mediated chemoreflex responses as evidenced by a significant increase in the hypoxic ventilatory response (FiO2 10%) and triggered irregular eupneic breathing, active expiration, and produced hypertension. cEpo treatment significantly reduced the carotid body--chemoreflex responses, normalizes breathing patterns and the hypertension in CIH. In addition, cEpo treatment effectively normalized carotid body chemosensory responses evoked by acute hypoxic stimulation in CIH rats. Conclusion: Present results strongly support beneficial cardiorespiratory therapeutic effects of cEpo during CIH exposure.
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    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.
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    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.
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    Paraquat herbicide diminishes chemoreflex sensitivity, induces cardiac autonomic imbalance and impair cardiac function in rats
    (2021) Pereyra, Katherin, V; Schwarz, Karla G.; Andrade, David C.; Toledo, Camilo; Rios-Gallardo, Angelica; Diaz-Jara, Esteban; Bastias, Sussy S.; Ortiz, Fernando C.; Ortolani, Domiziana; Del Rio, Rodrigo
    Paraquat (PQT) herbicide is widely used in agricultural practices despite being highly toxic to humans. It has been proposed that PQT exposure may promote cardiorespiratory impairment. However, the physiological mechanisms involved in cardiorespiratory dysfunction following PQT exposure are poorly known. We aimed to determine the effects of PQT on ventilatory chemoreflex control, cardiac autonomic control, and cardiac function in rats. Male Sprague-Dawley rats received two injections/week of PQT (5 mg.kg(-1) ip) for 4 wk. Cardiac function was assessed through echocardiography and pressure-volume loops. Ventilatory function was evaluated using whole body plethysmography. Autonomic control was indirectly evaluated by heart rate variability (HRV). Cardiac electrophysiology (EKG) and exercise capacity were also measured. Four weeks of PQT administration markedly enlarged the heart as evidenced by increases in ventricular volumes and induced cardiac diastolic dysfunction. Indeed, end-diastolic pressure was significantly higher in PQT rats compared with control (2.42 +/- 0.90 vs. 4.01 +/- 0.92 mmHg, PQT vs. control, P < 0.05). In addition, PQT significantly reduced both the hypercapnic and hypoxic ventilatory chemoreflex response and induced irregular breathing. Also, PQT induced autonomic imbalance and reductions in the amplitude of EKG waves. Finally, PQT administration impaired exercise capacity in rats as evidenced by a similar to 2-fold decrease in times-to-fatigue compared with control rats. Our results showed that 4 wk of PQT treatment induces cardiorespiratory dysfunction in rats and suggests that repetitive exposure to PQT may induce harmful mid/long-term cardiovascular, respiratory, and cardiac consequences.