Mechanical and energetic effects of chronic chagasic patients' antibodies on rat myocardium.
Chagasic (Ch) and nonchagasic (NCh) IgG fraction (20 microg/ml) effects on cardiac performance of adult Wistar rat ventricles were studied with a novel approach applying a microcalorimetric technique. Resting heat (Hr) was significantly decreased by Ch antibodies (DeltaHrCh = 4.8 +/- 0.9 mW/g). Although the Hr decrease can be associated with diminished activity of the Na+/K+ pump, the magnitude of the effect (25% of control Hr) indicates that additional processes may also be affected. Ch antibodies induced an initial increase in developed pressure (P), which was associated with a decreased contractile economy. However, after 30 min of Ch antibody perfusion, P reached a significantly lower level (DeltaPCh = 3.8 +/- 1.2 mN/mm2) without changes in active heat per beat (Ha'). Consequently, Ha'/P ratio increased, indicating that the energetic cost per unit of P was higher. In contrast, P and Ha' were both significantly and reversibly decreased by NCh antibodies (DeltaPNCh = 4.4 +/- 1.2 mN/mm2; DeltaHa'NCh = 9.7 +/- 2.2 mJ/g), but Ha'/P remained unaffected. According to these data, normal hearts exposed to Ch antibodies present a biphasic mechanical response: 1) an initial period of increased contractility (and decreased global muscle economy) consistent with antibodies with beta1-adrenergic activity, such as those used in the present study, and 2) a decrease in P at 30 min of Ch antibody perfusion, which suggests that another Ca(2+)-related mechanism is compromised. These data contribute to redefine the role of antibody-mediated responses in the pathophysiology of chronic chagasic cardiomyopathy as agents of myocardial failure.
Savio-Galimberti
Eleonora
E
Instituto de Investigaciones Cardiológicas, School of Medicine (Universidad de Buenos Aires-Consejo Nacional de Investigaciones Cientificas y Técnicas), Buenos Aires, Argentina. pohornos@mail.retina.ar
Dos Santos Costa
Patrícia
P
Campos De Carvalho
Antônio Carlos
AC
Ponce-Hornos
Jorge Emilio
JE
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D002598:Chagas Cardiomyopathy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D002908:Chronic Disease; D004734:Energy Metabolism / Q000187:drug effects*; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012146:Rest; D016276:Ventricular Function / Q000187:drug effects
D000906:Antibodies; D007074:Immunoglobulin G