Diferencia venoarterial de Pco2 como predictor de disfunción miocárdica en niños con sepsis severa y choque séptico.

Introducción: La sepsis es una de las principales causas de morbilidad y mortalidad en la población pediátrica a nivel mundial, siendo la disminución del gasto cardiaco uno de los principales factores asociados a mortalidad. Se ha planteado la diferencia venoarterial de pCO2 como predictor de la función miocárdica en pacientes con sepsis, sin embargo hasta el momento no hay estudios en la población pediátrica que lo evalúen. Objetivo: Determinar la capacidad predictora y las características operativas de la diferencia venoarterial de pCO2, como predictor de disfunción miocárdica en pacientes pediátricos con sepsis severa y choque séptico. Métodos: Para alcanzar los objetivos del estudio, se llevo a cabo un estudio prospectivo de pruebas diagnósticas. Se realizó ecocardiograma y diferencia venoarterial de pCO2 en cada paciente, posteriormente se calculó las características operativas de la diferencia venoarterial de pCO2 para determinar su utilidad. Resultados: Se incluyeron 71 pacientes. La mediana de la diferencia venoarterial de pCO2 no fue significativamente mayor en los pacientes que tuvieron disfunción cardiaca en el ecocardiograma en comparación con los que no tuvieron disfunción. Se encontró una relación estadísticamente significativa de valores de 1,5 a 2,1 mmHg, como predictor negativo de disfunción miocárdica con una sensibilidad de 100% y una especificidad de 88%. Conclusiones: La diferencia venoarterial de pCO2 requiere de estudios mas extensos para determinar la probabilidad como predictor de disfunción miocárdica en pacientes pediátricos con sepsis severa y choque séptico, incluso cuando otros biomarcadores se encuentran dentro de límites normales.

Diferencia venoarterial de PCO2 como predictor de disfunción miocárdica en pacientes pediátricos con sepsis severa y choque séptico

El objetivo de este estudio, es determinar la capacidad de la diferencia venoarterial de de pCO2, como predictor de disfunción miocárdica en pacientes pediátricos con sepsis severa y choque séptico en la Unidad de Cuidado Intensivo Pediátrico de la Fundación Cardio Infantil. El documento eviado corresponde a un informe parcial de un estudio en curso en la Fundación CardioInfantil.

[Myocardial dysfunction in sepsis]

Myocardial dysfunction appears in 25% of patients with severe sepsis and in 50% of patients with septic shock, even in the presence of hyper dynamic states. It is characterized by a reduction in left ventricle ejection fraction, that reverts at the seventh to tenth day of evolution. Right ventricular dysfunction and diastolic left ventricular dysfunction can also appear. There is no consensus if an increase in end diastolic volume is part of the syndrome. High troponin or brain natriuretic peptide levels are associated with myocardial dysfunction and a higher mortality. The pathogenesis of myocardial dysfunction is related to micro and macro circulatory changes, inflammatory response, oxidative stress, intracellular calcium management disturbances, metabolic changes, autonomic dysfunction, activation of apoptosis, mitochondrial abnormalities and a derangement in catecholaminergic stimulation. Since there is no specific treatment for myocardial dysfunction, its management requires an adequate multi systemic support to maintain perfusion pressures and systemic flows sufficient for the regional and global demands.

Rutin administration attenuates myocardial dysfunction in diabetic rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Platelet-derived exosomes from septic shock patients induce myocardial dysfunction

Abstract Introduction Mechanisms underlying inotropic failure in septic shock are incompletely understood. We previously identified the presence of exosomes in the plasma of septic shock patients. These exosomes are released mainly by platelets, produce superoxide, and induce apoptosis in vascular cells by a redox-dependent pathway. We hypothesized that circulating platelet-derived exosomes could contribute to inotropic dysfunction of sepsis. Methods We collected blood samples from 55 patients with septic shock and 12 healthy volunteers for exosome separation. Exosomes from septic patients and healthy individuals were investigated concerning their myocardial depressant effect in isolated heart and papillary muscle preparations. Results Exosomes from the plasma of septic patients significantly decreased positive and negative derivatives of left ventricular pressure in isolated rabbit hearts or developed tension and its first positive derivative in papillary muscles. Exosomes from healthy individuals decreased these variables non-significantly. In hearts from rabbits previously exposed to endotoxin, septic exosomes decreased positive and negative derivatives of ventricular pressure. This negative inotropic effect was fully reversible upon withdrawal of exosomes. Nitric oxide (NO) production from exosomes derived from septic shock patients was demonstrated by fluorescence. Also, there was an increase in myocardial nitrate content after exposure to septic exosomes. Conclusion Circulating platelet-derived exosomes from septic patients induced myocardial dysfunction in isolated heart and papillary muscle preparations, a phenomenon enhanced by previous in vivo exposure to lipopolysaccharide. The generation of NO by septic exosomes and the increased myocardial nitrate content after incubation with exosomes from septic patients suggest an NO-dependent mechanism that may contribute to myocardial dysfunction of sepsis.

Eosinophilic heart: Marked left ventricular wall thickening and myocardial dysfunction improving with corticosteroid therapy

We report a case of a 34-year-old male with acute severe heart failure associated with marked concentric left ventricular wall thickening and biopsy evidence of eosinophilic myocardial infiltrate. This appears to be an unusual description of this degree of concentric myocardial thickening in eosinophilic myocarditis coupled with Doppler tissue echocardiography. Following high-dose corticosteroid treatment, wall thickness, systolic and diastolic left ventricular function normalized and the patient experienced a dramatic clinical improvement. (ECHOCARDIOGRAPHY, Volume 20, May 2003).

Reperfusion-induced myocardial dysfunction is prevented by endogenous annexin-A1 and its N-terminal-derived peptide Ac-ANX-A12-26

BACKGROUND AND PURPOSE : Annexin-A1 (ANX-A1) is an endogenous, glucocorticoid-regulated anti-inflammatory protein. The N-terminal-derived peptide Ac-ANX-A12–26 preserves cardiomyocyte viability, but the impact of ANX-A1-peptides on cardiac contractility is unknown. We now test the hypothesis that ANX-A1 preserves post-ischaemic recovery of left ventricular (LV) function.

EXPERIMENTAL APPROACH : Ac-ANX-A12–26 was administered on reperfusion, to adult rat cardiomyocytes as well as hearts isolated from rats, wild-type mice and mice deficient in endogenous ANX-A1 (ANX-A1–/–). Myocardial viability and recovery of LV function were determined.

KEY RESULTS: Ischaemia–reperfusion markedly impaired both cardiomyocyte viability and recovery of LV function by 60%. Treatment with exogenous Ac-ANX-A12–26 at the onset of reperfusion prevented cardiomyocyte injury and significantly improved recovery of LV function, in both intact rat and wild-type mouse hearts. Ac-ANX-A12–26 cardioprotection was abolished by either formyl peptide receptor (FPR)-nonselective or FPR1-selective antagonists, Boc2 and cyclosporin H, but was relatively insensitive to the FPR2-selective antagonist QuinC7. ANX-A1-induced cardioprotection was associated with increased phosphorylation of the cell survival kinase Akt. ANX-A1−/− exaggerated impairment of post-ischaemic recovery of LV function, in addition to selective LV FPR1 down-regulation.

CONCLUSIONS AND IMPLICATIONS : These data represent the first evidence that ANX-A1 affects myocardial function. Our findings suggest ANX-A1 is an endogenous regulator of post-ischaemic recovery of LV function. Furthermore, the ANX-A1-derived peptide Ac-ANX-A12–26 on reperfusion rescues LV function, probably via activation of FPR1. ANX-A1-based therapies may thus represent a novel clinical approach for the prevention and treatment of myocardial reperfusion injury.

Myocardial dysfunction with increased ventricular compliance in volume overload hypertrophy

The aim this study was to evaluate systolic and diastolic function in volume overload induced myocardial hypertrophy in rats.Volume overload myocardial hypertrophy was induced in thirteen male Wistar rats by creating infrarenal arteriovenous fistula (AVF). The results were compared with a SHAM operated group (n = 11). Eight weeks after surgery, tail-cuff blood pressure was recorded, then rats were sacrificed for isolated heart studies using Langendorffs preparation.AVF rats presented increased left and right ventricular weights, compared to controls. The increased normalized ventricular volume (V0/LVW, 0.141 +/- 0.035 mL/g vs. 0.267 +/- 0.071 mL/g, P < 0.001) in the AVF group indicated chamber dilation. Myocardial hydroxyproline concentration remained unchanged. There was a significant decrease in +dP/dt (3318 +/- 352 mm Hg s(-1) vs. 2769 +/- 399 mm Hg s(-1); P=0,002), end-systolic pressure-volume relation (246 +/- 56 mm Hg mL(-1) vs. 114 +/- 63 mm Hg mL(-1);, P < 0,001), and -dP/dt (1746 +/- 240 min Hg s(-1) vs. 1361 +/- 217 mm Hg s(-1), P < 0.001) in the AVF group, which presented increased ventricular compliance (Delta V-25: SHAM=0.172 +/- 0.05 mL vs. AVF=0.321 +/- 0.072 mL, P < 0.001) with preserved myocardial passive stiffness (Strain(25): SHAM=13.5 +/- 3.0% vs. AVF=12.3 +/- 1.9%, P > 0.05).We conclude that volume-overload induced hypertrophy causes myocardial systolic and diastolic dysfunction with increased ventricular compliance. These haemodynamic features help to explain the long-term compensatory phase of chronic volume overload before transition to overt congestive heart failure. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Involvement of L-Type Calcium Channel and SERCA2a in Myocardial Dysfunction Induced by Obesity

Obesity has been shown to impair myocardial performance. Nevertheless, the mechanisms underlying the participation of calcium (Ca2+) handling on cardiac dysfunction in obesity models remain unknown. L-type Ca2+ channels and sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), may contribute to the cardiac dysfunction induced by obesity. The purpose of this study was to investigate whether myocardial dysfunction in obese rats is related to decreased activity and/or expression of L-type Ca2+ channels and SERCA2a. Male 30-day-old Wistar rats were fed standard (C) and alternately four palatable high-fat diets (Ob) for 15 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. L-type Ca2+ channels and SERCA2a activity were determined using specific blockers, while changes in the amount of channels were evaluated by Western blot analysis. Phospholamban (PLB) protein expression and the SERCA2a/PLB ratio were also determined. Compared with C rats, the Ob rats had increased body fat, adiposity index and several comorbidities. The Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca2+ was compromised. The diltiazem promoted higher inhibition on developed tension in obese rats. In addition, there were no changes in the L-type Ca2+ channel protein content and SERCA2a behavior (activity and expression). In conclusion, the myocardial dysfunction caused by obesity is related to L-type Ca2+ channel activity impairment without significant changes in SERCA2a expression and function as well as L-type Ca2+ protein levels. J. Cell. Physiol. 226: 2934-2942, 2011. (C) 2011 Wiley-Liss, Inc.

Myocardial dysfunction induced by food restriction is related to morphological damage in normotensive middle-aged rats

Previous works from our laboratory have revealed that food restriction (FR) promotes discrete myocardial dysfunction in young rats. We examined the effects of FR on cardiac function, in vivo and in vitro, and ultrastructural changes in the heart of middle-aged rats. Twelve-month-old Wistar- Kyoto rats were fed a control (C) or restricted diet (daily intake reduced to 50% of the control group) for 90 days. Cardiac performance was studied by echocardiogram and in isolated left ventricular (LV) papillary muscle by isometric contraction in basal condition, after calcium chloride (5.2 mM) and beta- adrenergic stimulation with isoproterenol (10(-6) M). FR did not change left ventricular function, but increased time to peak tension, and decreased maximum rate of papillary muscle tension development. Inotropic maneuvers promoted similar effects in both groups. Ultrastructural alterations were seen in most FR rat muscle fibers and included, absence and/or disorganization of myofilaments and Z line, hyper-contracted myofibrils, polymorphic and swollen mitochondria with disorganized cristae, and a great quantity of collagen fibrils. In conclusion, cardiac muscle sensitivity to isoproterenol and elevation of extracellular calcium concentration is preserved in middle-aged FR rats. The intrinsic muscle performance depression might be related to morphological damage.

Myocardial dysfunction induced by food restriction is related to calcium cycling and beta-adrenergic system changes

Food restriction (FR) has been shown to promote myocardial dysfunction in rats. The aim of this study was to verify the participation of calcium and beta-adrenergic system on myocardial mechanical alteration in rats submitted to FR. Myocardial performance was studied in isolated left ventricular papillar muscle from young Wistar-Kyoto rats (WKY) submitted to FR or to control diet. The groups subjected to FR were fed 50% less food than the control group for 90 days. Mechanical function was studied in isometric contraction at post-rest contraction of 30 seconds (PRC), calcium chloride concentration 5.20 mM, and beta-adrenergic stimulation with isoproterenol 10(-6) M. FR decreased the body weight, and left and right ventricular weight. In basal condition (1.25 MM of calcium) time to peak tension (TPT) and time from peak tension to 50% relaxation (RT50) were greater in the FR group. Muscle function was. The same in both PRC groups. TPT decrease in both high calcium groups, more in FR rats; RT50 dropped only in FR animals. TPT decreased in both Isoproterenol groups, more intensely in the FR group. This result suggests that food restriction impairs myocardial performance and these changes may be attributed to alterations in the intracellular calcium cycling and beta-adrenergic system. (C) 2003 Elsevier B.V. All rights reserved.

Severe food restriction induces myocardial dysfunction related to SERCA2 activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ventricular remodeling and diastolic myocardial dysfunction in rats submitted to protein-calorie malnutrition

The effects of protein-calorie malnutrition (PCM) on heart structure and function are not completely understood. We studied heart morphometric, functional, and biochemical characteristics in undernourished young Wistar rats. They were submitted to PCM from birth (undernourished group, UG). After 10 wk, left ventricle function was studied using a Langendorff preparation. The results were compared with age-matched rats fed ad libitum (control group, CG). The UG rats achieved 47% of the body weight and 44% of the left ventricular weight (LVW) of the CG. LVW-to-ventricular volume ratio was smaller and myocardial hydroxyproline concentration was higher in the UG. Left ventricular systolic function was not affected by the PCM protocol. The myocardial stiffness constant was greater in the UG, whereas the end-diastolic pressure-volume relationship was not altered. In conclusion, the heart is not spared from the adverse effects of PCM. There is a geometric alteration in the left ventricle with preserved ventricular compliance despite the increased passive myocardial stiffness. The systolic function is preserved.