Está en la página 1de 2

Citation/Abstract

Influence of long-term treatment of imidapril on mortality, cardiac function, and gene


expression in congestive heart failure due to myocardial infarction
Ren, Bin; Shao, Qiming; Ganguly, Pallab K; Tappia, Paramjit S; et al. Canadian Journal of Physiology
and Pharmacology (Dec 2004).

Although it is generally accepted that the efficacy of imidapril, an angiotensin-converting enzyme


inhibitor, in congestive heart failure (CHF) is due to improvement of hemodynamic parameters, the
significance of its effect on gene expression for sarcolemma (SL) and sarcoplasmic reticulum (SR) proteins
has not been fully understood. In this study, we examined the effects of long-term treatment of imidapril on
mortality, cardiac function, and gene expression for SL Na+/K+ ATPase and Na+ -Ca2+ exchanger as well
as SR Ca2+ pump ATPase, Ca2+ release channel (ryanodine receptor), phospholamban, and calsequestrin
in CHF due to myocardial infarction. Heart failure subsequent to myocardial infarction was induced by
occluding the left coronary artery in rats, and treatment with imidapril (1 mg.kg(-1).day(-1)) was started
orally at the end of 3 weeks after surgery and continued for 37 weeks. The animals were assessed
hemodynamically and the heart and lung were examined morphologically. Some hearts were immediately
frozen at -70 degrees C for the isolation of RNA as well as SL and SR membranes. The mortality of
imidapril-treated animals due to heart failure was 31% whereas that of the untreated heart failure group
was 64%. Imidapril treatment improved cardiac performance, attenuated cardiac remodeling, and reduced
morphological changes in the heart and lung. The depressed SL Na+/K+ ATPase and increased SL Na+Ca2+ exchange activities as well as reduced SR Ca2+ pump and SR Ca2+ release activities in the failing
hearts were partially prevented by imidapril. Although changes in gene expression for SL Na+/K+ ATPase
isoforms as well as Na+-Ca2+ exchanger and SR phospholamban were attenuated by treatments with
imidapril, no alterations in mRNA levels for SR Ca2+ pump proteins and Ca2+ release channels were seen
in the untreated or treated rats with heart failure. These results suggest that the beneficial effects of
imidapril in CHF may be due to improvements in cardiac performance and changes in SL gene expression.

Pengaruh pengobatan jangka panjang dari imidapril pada kematian, fungsi jantung, dan
ekspresi
gen
pada
gagal
jantung
kongestif
akibat
infark
miokard
Ren, Bin; Shao, Qiming; Ganguly, Pallab K; Tappia, Paramjit S; et al. Canadian Journal of
Physiology
dan
Farmakologi
(Desember
2004).
Dalam jurnal ini mengatakan meskipun secara umum diterima bahwa khasiat imidapril,
inhibitor enzim angiotensin-converting, pada gagal jantung kongestif (CHF) adalah karena
perbaikan parameter hemodinamik, signifikasi efeknya pada ekspresi gen untuk sarcolemma
(SL) dan retikulum sarkoplasma ( SR) protein belum sepenuhnya dipahami. Dalam studi ini,
meneliti efek dari pengobatan jangka panjang imidapril pada kematian, fungsi jantung, dan
ekspresi gen untuk SL Na + / K + ATPase dan Na + -Ca2 + penukar serta SR Ca2 + pompa
ATPase, Ca2 + channel rilis (reseptor Ryanodine) , fosfolamban, dan calsequestrin di CHF
karena infark miokard. Yang dilakukan pada penelitian ini yaitu gagal jantung setelah infark
miokard diinduksi oleh occluding arteri koroner kiri pada tikus, dan pengobatan dengan
imidapril (1 mg kg (-1) .day (-1)) dimulai secara lisan pada akhir 3 minggu setelah operasi
dan dilanjutkan selama 37 minggu. Hewan-hewan dinilai hemodinamik, jantung dan paruparu diperiksa morfologi. Lalu proses selanjutnya beberapa hati segera dibekukan pada -70
derajat Celcius untuk isolasi RNA serta SL dan membran SR. Mortalitas hewan imidapril
dilakukan karena gagal jantung adalah 31% sedangkan dari kelompok gagal jantung yang
tidak diobati adalah 64%. Pengobatan imidapril meningkatkan kinerja jantung, dilemahkan
remodeling jantung, dan mengurangi perubahan morfologi di jantung dan paru-paru pompa
dan SR kegiatan pelepasan Ca2 + di hati gagal yang sebagian dicegah dengan imidapril.
Meskipun perubahan dalam ekspresi gen untuk SL Na + / K + ATPase isoform serta Na +
-Ca2 + exchanger dan fosfor lamban SR yang dilemahkan oleh pengobatan dengan imidapril,
tidak ada perubahan dalam tingkat mRNA untuk SR Ca2 + pompa protein dan Ca2 +
melepaskan saluran terlihat di diobati atau diobati tikus dengan gagal jantung. Hasil dari
penelitian ini menunjukkan bahwa efek menguntungkan dari imidapril di CHF mungkin
karena perbaikan dalam kinerja jantung dan perubahan dalam ekspresi gen SL.