Evaluation of cellular viability by quantitative autoradiographic study of myocardial uptake of a fatty acid analogue in isoproterenol-induced focal rat heart necrosis

1991 ◽  
Vol 18 (11) ◽  
pp. 870-878 ◽  
Author(s):  
Thierry Humbert ◽  
Cuong Luu-Duc ◽  
Michel Comet ◽  
Pierre Demenge
1994 ◽  
Vol 72 (10) ◽  
pp. 1120-1126 ◽  
Author(s):  
Catherine Communal ◽  
Jean Verdetti ◽  
Colette Estrade ◽  
Thierry Humbert ◽  
Pierre Demenge

The aim of this study was to determine the extent and location of damaged myocardial areas in senescent rats. The viability of myocardial cells was evaluated in virgin young (4 months old) and aged (29 months old) female Wistar rats by analysing the uptake of a slowly metabolisable radiolabelled fatty acid analogue, 15-p-iodophenyl-β-methylpentadecanoic acid (IMPPA). The biodistribution of IMPPA was measured in various organs, and regional myocardial uptake was specifically assessed using quantitative autoradiography. Myocardial enzymatic activity and DNA content were also evaluated with nitro blue tetrazolium (NBT) and propidium iodide (PÏ) staining, respectively. In senescent rats, cardiac and renal IMPPA uptake showed a significant (50%) reduction compared with young adult rats and the uptake was not significantly changed in the liver, spleen, lungs, and skeletal muscle. Total ventricular NBT staining and IMPPA uptake were almost homogeneous in young adult rats, whereas they were very heterogeneous in aged rats. In the latter, approximately 11% of the total ventricular volume showed a significantly decreased (by 60% or more) IMPPA uptake compared with normal values, and this reduction was greater in ventricle base than in apex. The myocardial areas unlabelled or poorly labelled by IMPPA represented 4, 5, 6, and 21% of the right ventricular, left ventricular epicardial, septal, and left ventricular endocardial volume, respectively, and were poorly stained with NBT. In some of these areas, PI staining indicated the presence of living cells unable to pick up NBT staining. In conclusion, in young adult rats, no myocardial lesions were observed using three different labelling techniques. However, important and significant myocardial lesioned areas were detected in senescent rats and were located preferentially in the left ventricular endocardium, as shown by a decrease in NBT staining and IMPPA uptake. These likely corresponded to a reduced number of cardiomyocytes and (or) a reduced aerobic substrate utilization, along with the development of fibrosis.Key words: senescent female rats, fatty acid analogue uptake, myocyte loss, lesioned and borderline areas.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Sara I Liin ◽  
Johan E Larsson ◽  
Rene Barro-Soria ◽  
Bo Hjorth Bentzen ◽  
H Peter Larsson

About 300 loss-of-function mutations in the IKs channel have been identified in patients with Long QT syndrome and cardiac arrhythmia. How specific mutations cause arrhythmia is largely unknown and there are no approved IKs channel activators for treatment of these arrhythmias. We find that several Long QT syndrome-associated IKs channel mutations shift channel voltage dependence and accelerate channel closing. Voltage-clamp fluorometry experiments and kinetic modeling suggest that similar mutation-induced alterations in IKs channel currents may be caused by different molecular mechanisms. Finally, we find that the fatty acid analogue N-arachidonoyl taurine restores channel gating of many different mutant channels, even though the mutations are in different domains of the IKs channel and affect the channel by different molecular mechanisms. N-arachidonoyl taurine is therefore an interesting prototype compound that may inspire development of future IKs channel activators to treat Long QT syndrome caused by diverse IKs channel mutations.


2019 ◽  
Vol 27 (18) ◽  
pp. 4059-4068 ◽  
Author(s):  
Henriette Arnesen ◽  
Nadia Nabil Haj-Yasein ◽  
Jørn E. Tungen ◽  
Helen Soedling ◽  
Jason Matthews ◽  
...  

1996 ◽  
Vol 23 (3) ◽  
pp. 272-279 ◽  
Author(s):  
Nagara Tamaki ◽  
Eiji Tadamura ◽  
Takashi Kudoh ◽  
Naoya Hattori ◽  
Yoshiharu Yonekura ◽  
...  

1988 ◽  
Vol 63 (4) ◽  
pp. 681-692 ◽  
Author(s):  
D D Miller ◽  
J B Gill ◽  
E Livni ◽  
D R Elmaleh ◽  
T Aretz ◽  
...  

2001 ◽  
Vol 38 (7) ◽  
pp. 1888-1894 ◽  
Author(s):  
Yuko Kawai ◽  
Eriko Tsukamoto ◽  
Yoichi Nozaki ◽  
Koichi Morita ◽  
Masayuki Sakurai ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document