Experimental Subproject 3: Investigation of the physiopathological cardiocirculatory and inflammatory mechanisms in rats with stomatitis.

• Grant number: 24/01181-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2024
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Helio Cesar Salgado
• Grantee: Beatriz Magalhães Oliveira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 20/06043-7 - Autonomic (sympathetic and parasympathetic) modulation of cardiovascular and inflammatory responses under physiopathological clinical and experimental conditions, AP.TEM

Abstract

Rationale. The increase in the prevalence of cardiovascular diseases has motivated the scientific community to seek new approaches for assessing cardiocirculatory performance, mainly associated with Autonomic Regulation (Sympathetic and Parasympathetic). Among these approaches, we highlight the study of the variability of cardiovascular parameters, especially Arterial Pressure and Heart Rate (HRV). Several factors, including The Immune System, can affect the autonomic balance. The presence of Oral Inflammation has recently been related to the pathophysiology of several systemic conditions, including cardiovascular diseases. The impact of Periodontitis (chronic inflammation of the tissues surrounding the teeth) associated to cardiovascular risk has been significantly studied in patients with oral disease. On the other hand, the impact of Stomatitis (a specific inflammatory process of the oral and oropharyngeal mucous membrane), both from a clinical and experimental point of view, has received much less attention, especially concerning cardiovascular risk. Stomatitis is highly prevalent in patients with a dental prosthesis, also known as prosthesis-related stomatitis, whose main etiological factor is the infection by Candida albicans. Experimental studies have shown that the Experimental Stomatitis Model, obtained through oral inoculation with Candida albicans, has clinical and histological aspects, similar to those observed in humans.Objectives. To evaluate the Cardiovascular Autonomic Modulation (Sympathetic and Parasympathetic) through Arterial Pressure and Heart Rate Variability, Hemodynamic Responses (arterial pressure and heart rate), Cardiac Function (through echocardiography and cannulation of the left ventricle by the Millar catheter), and the Inflammatory Responses (Cytokine Dosage in plasma, heart, kidney, and spleen) in the Experimental Model of Stomatitis, in Sprague - Dawley rats, infected orally with Candida albicans.Methods. Sprague - Dawley rats will receive Tetracycline Hydrochloride seven days before and during the period (three days) of inoculation of the Candida albicans suspension. For the inoculation of this suspension, the rats will be anesthetized with Ketamine associated with Xylazine, whose procedure will be repeated for three consecutive days. Five days after the last inoculation with Candida albicans, a polyethylene catheter will be implanted into the femoral artery. After twenty-four hours, i.e., six days after the end of the inoculation of Candida albicans, the animals will be submitted to basal Arterial Pressure (AP) recordings. The AP records will be used to generate time series of systolic AP and pulse interval (PI) values for the calculation of AP and HR variability indices in the time and frequency domains, as well as by non-linear approaches. After the AP recording, the animals will be anesthetized with isoflurane (5%) for the study of Cardiac Function (echocardiography and cannulation of the left ventricle by the Millar catheter), Tissue Collection (palate, oral mucosa, and tongue) to demonstrate the presence of Stomatitis, and Cytokines Dosage (plasma, heart, kidney, and spleen). Moreover, a new protocol will be carried out to assess the neuroinflammation and neurodegeneration in the Central Nervous System (Nucleus Tractus Solitarius - NTS; Rostral Ventrolateral Medulla - RVLM; and the Paraventricular Nucleus of the Hypothalamus - PVN).