Activation profile of pro-inflammatory cytokines in acute cardiac overload.
BACKGROUND
Pro-inflammatory cytokines have been implicated in ventricular remodeling during heart failure progression. In the present study, we investigated the effects of acute volume and RV pressure overload on biventricular hemodynamics and myocardial gene expression of IL-6 and TNF-alpha.


METHODS
Male Wistar rats (n = 45) instrumented with RV and LV tip micromanometers were randomly assigned to one of three protocols: i) acute RV pressure overload (PrOv) induced by pulmonary trunk banding in order to double RV peak systolic pressure, for 120 or 360 min; ii) acute volume overload (VolOv) induced by dextran40 infusion (5 ml/h), for 120 or 360 min; iii) Sham. Free wall samples from the RV and LV were collected for mRNA quantification.


RESULTS
In the RV, acute overload induced IL-6 and TNF-alpha gene expression, higher in VolOv (IL-6: + 669.7 +/- 263.4%; TNF-alpha: + 5149.9 +/- 1099.0%; 360 min) than in PrOv (IL-6: + 64.9 +/- 44.2%; TNF-alpha: + 628.1 +/- 229.3%; 360 min). In PrOv, TNF-alpha mRNA levels in the LV were increased, in the absence of ventricular overload. IL-6 and TNF-alpha mRNA levels did not correlate in the LV, while in the RV a positive correlation was found (r = 0.574; p < 0.001).


CONCLUSIONS
Acute cardiac overload induces overexpression of pro-inflammatory cytokines. This gene activation is not uniform, being higher in volume overload and involving both load-dependent and load-independent mechanisms.
Roncon-Albuquerque
Roberto Júnior
RJ
Serviço de Fisiologia, Faculdade de Medicina do Porto, Porto, Portugal.
Vasconcelos
Mariana
M
Lourenço
André P
AP
Brandão-Nogueira
Ana
A
Teles
Antónia
A
Faria
Bernardo
B
Henriques-Coelho
Tiago
T
Leite-Moreira
Adelino F
AF
D000818:Animals; D015870:Gene Expression; D006439:Hemodynamics; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D016276:Ventricular Function
D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha