Twelve months of oral sildenafil treatment was well tolerated and appeared to improve exercise capacity, systemic arterial oxygen saturation and haemodynamic parameters in patients with Eisenmenger syndrome.
In Pcells of MI heart, the density and firing rate of Ca2+-release sites were increased by 20% [Normal: 3.0 AE 0.3 sites /25mm (14 scans; 12 cells) vs MI: 3.6 AE 0.2 sites /25mm (9 cells); P < 0.05] and 120% [Normal:0.77 AE 0.10 sparks/s (42 sites, 12 cells) vs MI: 1.74 AE 0.23 sparks /s (40 sites, 9 cells); P < 0.05), respectively. A model fit of Ca2+-waves in MI Pcells revealed 50% increase in amplitude, 25% faster decay, and 35% elevation of Ca2+-uptake rate. No change was observed in CRC expression. However SERCAs redistribution to the cell periphery was detected in all animal MI models and in human heart with large MI. Peripheral protein expression and gene expression of SERCA2 showed 4.5 and 2.3 times increases post MI, respectively. No change was observed in regulatory protein phospholamban. CONCLUSION: Our results strongly suggest that a dramatic increase of SERCA density at the cell periphery accounts for SR Ca2+ overload and pro-arrhythmic spontaneous Ca2+ release in Pcells of post-MI human heart.
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