Luciano Gonçalves Fernandes

On the integration of the baroreflex control mechanism in a heterogeneous model of the cardiovascular system

The aim of the present work is to describe the integration of a mathematical model for the baroreceptor reflex mechanism to provide regulatory action into a dimensionally heterogeneous (3D-1D-0D) closed-loop model of the cardiovascular system. Such heterogeneous model comprises a 1D description of the arterial tree, a 0D network for the venous, cardiac and pulmonary circulations and 3D patient-specific geometries for vascular districts of interest. Thus, the detailed topological description of the arterial network allows us to perform vasomotor control actions in a differentiated way, while gaining insight about the effects of the baroreflex regulation over hemodynamic quantities of interest throughout the entire network. Two examples of application are presented. Firstly, we simulate the hemorrhage in the abdominal aorta artery and analyze the action of the baroreflex over the system. Secondly, the self-regulated closed-loop model is applied to study the influence of the control action in the hemodynamic environment that determines the blood flow pattern in a cerebral aneurism in the presence of a regurgitating aortic valve.

Cardiac autonomic balance in rats submitted to protein restriction after weaning.

1. In the present study, we evaluated the autonomic balance of the heart in protein/energy‐undernourished rats.

Increased activity of the renin-angiotensin and sympathetic nervous systems is required for regulation of the blood pressure in rats fed a low-protein diet.

•  What is the central question of this study? Is the increase in blood pressure observed in rats fed a low protein diet due to overactivation of sympathetic and renin angiontensin systems? •  What is the main finding and its importance? The data show an increase in the expression of angiotensin II type 1 receptors and an incrased sympathetic activity in this experimental model, suggesting that both systems are contributing to the high blood pressure observed in these animals.

Protein malnutrition modifies medullary neuronal recruitment in response to intermittent stimulation of the baroreflex

Protein malnutrition after weaning changes the neurotransmission in neural pathways that organize cardiovascular reflexes in rats. The present study evaluates whether protein malnutrition alters the expression of c-fos protein (immediate-early gene expression) in central areas involved in the control of cardiovascular reflexes after intermittent stimulation of the baroreflex. The main nuclei we focused were paraventricular hypothalamus (PVH); nucleus tract solitarii (NTS); rostral ventromedial medulla (RVMM); rostral (RVLM) and caudal ventrolateral medulla (CVLM). Male Fisher rats at 28 days were submitted to two different isocaloric diets during the subsequent 35 days: control (CT) (15% protein) and malnourished (MN) (6% protein). thirtymin of intermittent (every 3 min) baroreflex stimulation was performed by infusing phenylephrine (Phe-0.25 mM) or, as control, 0.9% NaCl (Sal). Following ninety minutes, animals were anesthetized and perfused. The removed brains were sectioned (35 μm) and used for c-fos immunohistochemistry. Images were analyzed using the software Leica Q Win. Despite not altering the baseline MAP, malnutrition increased baseline HR and expression of c-fos in RVMM. Increases in c-fos expression after intermittent stimulation of baroreflex were evident in the PVH, medial NTS and CVLM in both dietary protocols. Current data further revealed a differential neuronal recruitment to stimulation of baroreflex in the caudal commissural and rostral NTS and RVLM of MN. We conclude that protein malnutrition modifies the cardiovascular control and the pattern of central response to baroreflex stimulation.

Malnutrition affects the pressor response to microinjection of L-glutamate into the RVLM of awake rats

Post-weaning protein malnutrition is often related to the development of cardiovascular and metabolic diseases in humans, as well to changed content of neurotransmitters in the central nervous system under experimental conditions. The rostral ventrolateral medulla (RVLM) is a bulbar region that contains sympathetic premotor neurons; the excitatory amino acid L-glutamate seems to be the main neurotransmitter at this level. The aim of the present study was to evaluate the possible change in the L-glutamate sensitivity of the RVLM neurons of malnourished animals. Male Fischer rats were divided into two groups: control (n = 15) and malnourished (n = 19). Four days before the experiments, guide cannulas were implanted bilaterally in direction of the RVLM for microinjection of L-glutamate. Twenty-four hours before the experiments, the femoral artery was cannulated for cardiovascular recordings. The results showed that the baseline heart rate increased in malnourished compared to control animals (412.18 ± 16.03 bpm vs. 370.74 ± 9.59 bpm, respectively). Malnourished animals presented a dissimilar concentration-dependent pressor response curve to L-glutamate and an attenuated baroreflex gain. Our results suggest that post-weaning protein restriction affects glutamatergic neurotransmission of the baroreflex at the RVLM level.

Bezold–Jarisch reflex in sino-aortic denervated malnourished rats

In this study we assessed the role of Bezold-Jarisch reflex (BJR) in the regulation of blood pressure (BP) of malnourished (MN) and control rats (CN) with sino-aortic denervation (SAD). Fischer rats were fed diets containing either 6% (MN) or 15% (CN) protein for 35 days after weaning. These rats underwent sham or SAD and catheterization of femoral artery and vein for BP measurements and drug injection. Phenylbiguanide (PBG 5 μg/kg, i.v.) for activation BJR, produced bradycardia (-317±22 bpm for CN vs. -372±16 bpm for MN) and hypotension (-57±4 mm Hg for CN vs. -54±6 mm Hg for MN. After SAD, MN rats had reduced hypotensive (-37±7 mm Hg for MN vs. -82±6 mm Hg for CN) and bradycardic (-124±17 for MN vs. -414±20 bpm CN) responses to BJR activation. To evaluate the contribution of the parasympathetic component due to BJR for the fall in BP, methyl atropine bromide, was given between two injections of PBG (5 μg/kg) separated by 10 min each other. Both bradycardic (-216±21 bpm before and -4±3 bpm after for CN -226±43 bpm before and -9±20 bpm after for MN) and hypotensive (-42±4 mm Hg before and -6±1 mm Hg after for CN -33±9 mm Hg before and -5±2 mm Hg after for MN) responses were abolished in CN and MN groups. These data indicate that dietary protein malnutrition changes the relation between baroreflex and BJR required for maintenance of the BP during malnourishment.

Sympathoinhibition to Bezold–Jarisch reflex is attenuated in protein malnourished rats

Malnutrition affects cardiovascular reflexes, including chemoreflex and baroreflex. In this study we assessed the hypothesis that malnourishment changes the responses in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) evoked from Bezold-Jarisch reflex (BJR). Fischer rats were fed diets containing either (6% malnourished or 14% control) protein for 35 days after weaning. There were no differences in baseline MAP (102 ± 4 vs. 95 ± 3 mmHg) whereas higher baseline HR (478 ± 18 vs. 360 ± 11 bpm; P<0.05,) and reduced sympathoinhibition (ΔRSNA=-54 ± 9 vs. -84 ± 7%; P=0.0208) to BJR activation were found in malnourished rats. We conclude that malnutrition affects the sympathetic control of BJR.

Cardiopulmonary reflex is attenuated in iron overload conscious rats

Abstract Increased iron intake can lead to iron accumulation in serum and tissues. Its has been described that serum and tissue iron overload increase reactive oxygen species (ROS) levels and reduce the effectiveness of the cardiovascular neural mechanisms involved in the maintenance of the arterial blood pressure whithin a narrow range of variation, therefore, iron overload may disrupt cardiovascular homeostasis contributing to physiopathological status development. In the present study we evaluated whether iron accumulated in serum or tissue of awake animals affect the cardiovascular homeostasis through changes in the cardiopulmonary reflex (CPR). We observed that the CPR is reduced in both serum and tissue iron overloaded groups, but no changes were found in the left ventricular pressure measurements, suggesting that iron-related effects are restrict to the CPR neural pathways. We also observed that the serum overloaded group presented lower basal heart rate levels, suggesting an increased parasympathetic efferent activity directed to the heart in this group. Taken together, our data suggest an important role for the iron-generated ROS to the cardiovascular homeostasis, especially regarding the CPR in awake animals.

An integrated mathematical model of the cardiovascular and respiratory systems

This study presents a lumped model for the human cardiorespiratory system. Specifically, we incorporate a sophisticated gas dissociation and transport system to a fully integrated cardiovascular and pulmonary model. The model provides physiologically consistent predictions in terms of hemodynamic variables such as pressure, flow rate, gas partial pressures, and pH. We perform numerical simulations to evaluate the behavior of the partial pressures of oxygen and carbon dioxide in different vascular and pulmonary compartments. For this, we design the rest condition with low oxygen requirements and carbon dioxide production and exercise conditions with high oxygen demand and carbon dioxide production. Furthermore, model sensitivity to more relevant model parameters is studied. Copyright