Cardiac Impairment Evaluated by Transesophageal Echocardiography and Invasive Measurements in Rats Undergoing Sinoaortic Denervation

Background: Sympathetic hyperactivity may be related to left ventricular (LV) dysfunction and baro- and chemoreflex impairment in hypertension. However, cardiac function, regarding the association of hypertension and baroreflex dysfunction, has not been previously evaluated by transesophageal echocardiography (TEE) using intracardiac echocardiographic catheter.Methods and Results: We evaluated exercise tests, baroreflex sensitivity and cardiovascular autonomic control, cardiac function, and biventricular invasive pressures in rats 10 weeks after sinoaortic denervation (SAD). the rats (n = 32) were divided into 4 groups: 16 Wistar (W) with (n = 8) or without SAD (n = 8) and 16 spontaneously hypertensive rats (SHR) with (n = 8) or without SAD (SHRSAD) (n = 8). Blood pressure (BP) and heart rate (HR) did not change between the groups with or without SAD; however, compared to W, SHR groups had higher BP levels and BP variability was increased. Exercise testing showed that SHR had better functional capacity compared to SAD and SHRSAD. Echocardiography showed left ventricular (LV) concentric hypertrophy; segmental systolic and diastolic biventricular dysfunction; indirect signals of pulmonary arterial hypertension, mostly evident in SHRSAD. the end-diastolic right ventricular (RV) pressure increased in all groups compared to W, and the end-diastolic LV pressure increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD.Conclusions: Our results suggest that baroreflex dysfunction impairs cardiac function, and increases pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of hypertensive cardiac disease. Moreover, TEE is a useful and feasible noninvasive technique that allows the assessment of cardiac function, particularly RV indices in this model of cardiac disease.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Fac Med, Cardiomyopathy Unit, Heart Inst InCor,Hosp Clin, São Paulo, BrazilUniv São Paulo, Fac Med, Hypertens Unit, Heart Inst InCor,Hosp Clin, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biosci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biosci, São Paulo, BrazilWeb of Scienc

Brabykinin B1 Receptor Antagonism Is Beneficial in Renal Ischemia-Reperfusion Injury

Previously we have demonstrated that bradykinin B1 receptor deficient mice (B1KO) were protected against renal ischemia and reperfusion injury (IRI). Here, we aimed to analyze the effect of B1 antagonism on renal IRI and to study whether B1R knockout or antagonism could modulate the renal expression of pro and anti-inflammatory molecules. To this end, mice were subjected to 45 minutes ischemia and reperfused at 4, 24, 48 and 120 hours. Wild-type mice were treated intra-peritoneally with antagonists of either B1 (R-954, 200 µg/kg) or B2 receptor (HOE140, 200 µg/kg) 30 minutes prior to ischemia. Blood samples were collected to ascertain serum creatinine level, and kidneys were harvested for gene transcript analyses by real-time PCR. Herein, B1R antagonism (R-954) was able to decrease serum creatinine levels, whereas B2R antagonism had no effect. The protection seen under B1R deletion or antagonism was associated with an increased expression of GATA-3, IL-4 and IL-10 and a decreased T-bet and IL-1β transcription. Moreover, treatment with R-954 resulted in lower MCP-1, and higher HO-1 expression. Our results demonstrated that bradykinin B1R antagonism is beneficial in renal IRI

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Tissue Doppler imaging data of mitral and tricuspid annulus data obtained by transesophageal echocardiography.

<p>Va1ues are mean ± SD.</p><p>W = Wistar; SAD = sinoaortic denervation; SHR = spontaneously hypertensive rats; SHRSAD = spontaneously hypertensive rats with sinoaortic denervation.</p><p>S’ = peak velocity of systolic velocity obtained by tissue Doppler imaging; E’ = peak velocity of early diastolic velocity obtained by tissue Doppler imaging; A’ = peak velocity of late diastolic velocity obtained by tissue Doppler imaging.</p>a<p>p<0.05 vs. W, ^bp<0.05 vs. SAD, and ^cp<0.05 vs. SHR.</p

Blood pressure, heart rate, baroreflex sensitivity and cardiovascular autonomic modulation of normotensive and hypertensive groups.

<p>Va1ues are mean ± SD.</p><p>W = Wistar; SAD = sinoaortic denervation; SHR = spontaneously hypertensive rats; SHRSAD = spontaneously hypertensive rats with sinoaortic denervation.</p><p>HR = heart rate; PI = pulse interval; SD PI = standard deviation of pulse interval; SBP = systolic blood pressure; SD SBP = standard deviation of systolic blood pressure; PIV = pulse interval variance; LF (ms²) = low-frequency band of heart rate variability; HF (ms²) = high-frequency band of heart rate variability; LF band (%) = low-frequency band of heart rate variability; HF band (%) = high-frequency band of heart rate variability; SBPV = SBP variability; LF SBP (mmHg²) = low frequency band of SBPV; BRI = bradycardic response index; TRI = tachycardic response index;</p>a<p>p<0.05 vs. W, ^bp<0.05 vs. SAD, and ^cp<0.05 vs. SHR.</p

Volumes and ejection fraction of the right ventricle, and biventricular diastolic function data obtained by transesophageal echocardiography.

<p>Va1ues are mean ± SD.</p><p>W = Wistar; SAD = sinoaortic denervation; SHR = spontaneously hypertensive rats; SHRSAD = spontaneously hypertensive rats with sinoaortic denervation.</p><p>FE VD = right ventricular ejection fraction; E/A = ratio of peak velocity of E and A waves of mitral or tricuspid inflow; DT = deceleration time of E wave; IVRT = isovolumic relaxation time of LV; AFF = atrial filling fraction.</p>a<p>p<0.05 vs. W, ^bp<0.05 vs. SAD and ^cp<0.05 vs. SHR.</p

Correlations between invasive and noninvasive data in all animals.

<p>Values are mean ± SD.</p><p>AFF = atrial filling fraction; LV = left ventricle; AcT TTE = aceleration time of right ventricular outflow (transthoracic echocardiography); AcT TEE = aceleration time of right ventricular outflow (transesophageal echocardiography); TT = time from the beginning to the end of right ventricular outflow; CI = cardiac index; LVMass = left ventricular mass; MPI = myocardial performance index; EF = ejection fraction; E/E’ =  ratio of peak velocity of E wave of mitral inflow and peak velocity of early diastolic velocity obtained by tissue Doppler imaging; EDP = end-diastolic pressure.</p

Transesophageal echocardiography of spontaneously hypertensive rats showing right ventricle (RV) (A), tricuspid inflow (B) and tissue Doppler imaging of the tricuspid annulus (C).

<p>Transesophageal echocardiography of spontaneously hypertensive rats showing right ventricle (RV) (A), tricuspid inflow (B) and tissue Doppler imaging of the tricuspid annulus (C).</p