Resumo (PT):
Recently, we demonstrated a transient LV systolic dysfunction and a sustained RV
and LV diastolic dysfunction with a change of the genetic expression of remote
non-ischemic myocardium, after 120 min of LAD occlusion. Gene expression of
NCX and SERCA2a were decreased and Phospholamban (PLB) mRNA was increased
only in the LV; BNP, IGF-1, HIF-1a and inflammatory mediators as IL-6
and iNOS were increased in both ventricles. The objectives of the present study
were to determine the precocity of the genetic changes of remote myocardium
and to understand the distinct genetic modulation of each ventricle after a period
of 30 min of ischemia.
Wistar rats instrumented with RV and LV tip micromanometers randomly underwent
either LAD coronary artery ligation (n=7) or sham procedures (n=7) during
30 min. Hemodynamic parameters were recorded continuosly and transmural
samples of RV and LV remote myocardium were collected for relative quantification
of mRNA of ET-1, IGF-1, NCX, SERCA2a, PLB, NHE, HIF-1a, BNP, IL-6,
iNOS and TNF-a by real-time RT-PCR.
Evan’s blue infusion after LAD occlusion in 5 additional rats revealed reproducible
areas of antero-apical LV and left IV septal ischemia (41±5.4% of LV+IV septum
weight). In remote myocardium we observed an increase of genetic expression
of: (I) IGF-1 (LV: 567±192% and RV: 59±18%) and HIF-1a (LV: 190±94% and
RV: 63±25%) in both ventricles; (II) BNP (567±192%) e IL-6 (977±568%) only in
the LV; and (III) iNOS (256±88%) only in the RV. We still observed a significantly
decrease in mRNA of NHE (79±5%) in the RV and a tendency to a decrease of
expression of calcium regulatory protein SERCA2a (44±10%, p=0,10) in the LV.
The genetic changes in remote non-ischemic myocardium observed after 120
min of LAD occlusion, as well as, the distinct modulation of each ventricle are
already present at 30 min. This very acute genetic modulation after LV ischemia
takes place not only in the LV but also in the non-ischemic RV. This modulation
assumes distinct features in the two ventricles possibly due to distinct mechanical
and inflammatory stresses, as well as, to intrinsic myocardial properties of the
RV and the LV. The remarkable activation of cytokines and growth factors may
contribute to the functional disturbances in this setting.
Language:
English
Type (Professor's evaluation):
Scientific
Notes:
27th Congress of the European-Society-of-Cardiology, published in journal, European Heart Journal. 2005; Vol.26(Abstract.851)(Suppl1):119-119.