Differential calcium handling in two canine models of right ventricular pressure overload.
BACKGROUND
The purpose of this investigation was to characterize differential right atrial (RA) and ventricular (RV) molecular changes in Ca(2+)-handling proteins consequent to RV pressure overload and hypertrophy in two common, yet distinct models of pulmonary hypertension: dehydromonocrotaline (DMCT) toxicity and pulmonary artery (PA) banding.


METHODS
A total of 18 dogs underwent sternotomy in four groups: (1) DMCT toxicity (n = 5), (2) mild PA banding over 10 wk to match the RV pressure rise with DMCT (n = 5); (3) progressive PA banding to generate severe RV overload (n = 4); and (4) sternotomy only (n = 4).


RESULTS
In the right ventricle, with DMCT, there was no change in sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) or phospholamban (PLB), but we saw a trend toward down-regulation of phosphorylated PLB at serine-16 (p[Ser-16]PLB) (P = 0.07). Similarly, with mild PA banding, there was no change in SERCA or PLB, but p(Ser-16)PLB was down-regulated by 74% (P < 0.001). With severe PA banding, there was no change in PLB, but SERCA fell by 57% and p(Ser-16)PLB fell by 67% (P < 0.001). In the right atrium, with DMCT, there were no significant changes. With both mild and severe PA banding, p(Ser-16)PLB fell (P < 0.001), but SERCA and PLB did not change.


CONCLUSIONS
Perturbations in Ca(2+)-handling proteins depend on the degree of RV pressure overload and the model used to mimic the RV effects of pulmonary hypertension. They are similar, but blunted, in the atrium compared with the ventricle.
Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, Missouri 63110-1013, USA. moonm@wustl.edu
Marc R
MR
Moon
Abdulhameed
A
Aziz
Anson M
AM
Lee
Cynthia J
CJ
Moon
Shoichi
S
Okada
Evelyn M
EM
Kanter
Kathryn A
KA
Yamada
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000032:analysis; D004195:Disease Models, Animal; D004285:Dogs; D006352:Heart Ventricles / Q000503:physiopathology*; D016686:Monocrotaline / Q000031:analogs & derivatives / Q000633:toxicity; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000032:analysis; D018497:Ventricular Dysfunction, Right / Q000503:physiopathology*; D017725:Ventricular Pressure; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D016686:Monocrotaline; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C014114:monocrotaline pyrrole