Cardiac-specific norepinephrine mass transport and its relationship to left ventricular size and systolic performance

Abstract

R. Starling. Cardiacspecific norepinephrine mass transport and its relationship to left ventricular size and systolic performance. Am J Physiol Heart Circ Physiol 287: H878 -H888, 2004. First published April 8, 2004 10.1152/ajpheart.00007.2003.-Objectives of this study were to develop a technique for quantifying cardiac-specific norepinephrine (NE) mass transport and determine whether cardiac NE kinetic modeling parameters were related to physiological variables of left ventricular (LV) size and systolic performance in nine patients with chronic mitral regurgitation. Biplane contrast cineventriculograms were used to determine LV size and ejection fraction (EF), micromanometer LV pressures and radionuclide LV volumes from a range of loading conditions to calculate LV end-systolic elastance, and and Ṁ IF u,r,en correlated directly with LV end-systolic volume (r ϭ 0.84, P ϭ 0.005; r ϭ 0.86, P ϭ 0.003); inversely with LV EFs (r ϭ Ϫ0.75, P ϭ 0.02; r ϭ Ϫ0.81, P ϭ 0.008); and inversely with LV end-systolic elastance values, optimally fit by a nonlinear function (r ϭ 0.89, P ϭ 0.04; r ϭ 0.96, P ϭ 0.01). We conclude that total and newly released NE into interstitial fluid of the heart, determined by regional mass transport kinetic model, are specific measures of regional cardiacspecific sympathetic nervous system activity and are strongly related to measures of LV size and systolic performance. These data support the concept that this new model of organ-specific NE kinetics has physiological relevance. mitral regurgitation; left ventricle; ejection fraction; contractility IN CHRONIC MITRAL REGURGITATION (MR), it is known that left ventricular (LV) contractile impairment exists despite the presence of a preserved LV ejection fraction (EF) (32). In an animal model of surgical MR, the sympathetic nervous system (SNS) appears to contribute to this pathophysiological process (25,38). Initially, SNS activation may represent a compensatory mechanism to maintain LV ejection and contractile performance to meet the requirements for tissue perfusion (25). Ultimately, because of the persistent stimulus of the LV volume overload, a positive feedback mechanism may be established, which leads to impaired LV contractility despite the preservation of LV EF due to impaired ␤-adrenergic receptor responsivity and force-frequency relations (24, 34). ␤-Adrenergic blockade results in an improvement of LV contractile dysfunction in animals with MR, lending support for a pathophysiological role for the SNS in the development of impaired LV contractility (25).In patients with chronic MR, we have previously demonstrated that systemic SNS activity is increased, but only weak relationships existed with LV size and EF and no relationship existed with LV contractility (22,23). Given that the SNS is activated in a regional, organ-specific manner, cardiac-specific SNS activity may differ from measures of systemic SNS activity (7,8). Thus systemic SNS activity may not be reflective of the cardiac-specific milieu. Although the systemic SNS has only a wea...

Disruption of desmin-mitochondrial architecture in patients with regurgitant mitral valves and preserved ventricular function

“…These markers of increased oxidative stress are consistent with our previous report of increased xanthine oxidase in patients with isolated MR and LVEF > 60% (9). Human isolated MR has also been associated with upregulation of TNF-alpha expression (28) and increased adrenergic drive (29,30), which are related to severity of LV dilatation and systolic dysfunction. Desmin is a major substrate for the intracellular calcium dependent protease calpain, which is activated during the high intracellular Ca 2+ levels, achieved during ischemia/reperfusion (31,32) but also with increased TNF-alpha and excessive β-adrenergic signaling and oxidative stress (32).…”

Valor de la insuficiencia mitral previa a un primer infarto de miocardio, en el pronóstico clínico y la hemodinámica ventricular

“…Esta puede ser la razón que explicaría por qué la terapia con resincronización ventricular potencialmente podría ser de utilidad para influir en los resultados a largo plazo en este tipo de pacientes, tanto en las miocardiopatías dilatadas de etiología isquémica como en las no Basándonos en la revisión de la bibliografía (245,(273)(274)(275)(276)(277)(278)(279)(280)(281)(282)(283)(284)(285)(286)(287)(288)(289)293) , destacamos el hecho de como la regurgitación mitral crónica promueve el desarrollo de una cascada inflamatoria (273,277,289) , con la expresión de diferentes citoquinas, y una alteración de la función autonómica y de la variabilidad de la frecuencia cardiaca, que en última instancia desencadena un cuadro de insuficiencia cardiaca congestiva.…”

“…La norepinefrina (275,280) liberada en el espacio intersticial del corazón, por el sistema nervioso simpático, está relacionada directamente con el volumen telesistólico e inversamente con la fracción de eyección y los valores de elastancia telesistólicos y el trabajo sistólico. Asimismo, existe una asociación entre los niveles de los péptidos natriuréticos (118,274,284,288) plasmáticos y la severidad de los síntomas originados por la regurgitación mitral.…”

“…Se origina un remodelado ventricular (275,285,286) y una dilatación del ventrículo izquierdo, originando un aumento compensatorio de la masa cardiaca que incrementa el consumo de oxígeno miocárdico. La angiotensina II (289,290,291,292) y la bradiquinina alteran la función endotelial pulmonar y son Este hecho, enfatiza la importancia que tiene la regurgitación mitral previa a un infarto agudo de miocardio como marcador de pronóstico adverso, y sugiere la necesidad de realizar una cautelosa aproximación en el manejo clínico y seguimiento (18,24,25) de este subgrupo de pacientes, especialmente en el periodo posterior al sufrimiento de un evento isquémico de la magnitud de un infarto agudo de miocardio.…”

“…De hecho, la presencia de regurgitación mitral se acompañan de una respuesta neurohormonal (245,(273)(274)(275)(276)(277)(278)(279)(280)(281)(282)(283)(284)(285)(286)(287)(288)(289)293) , que origina proceso fibrótico progresivo, y de reconstrucción vascular. Se originan cambios asociados en pág.…”