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Post-transcriptional alterations in the expression of cardiac Na+ channel subunits in chronic heart failure.

ABSTRACT: Clinical and experimental evidence has recently accumulated about the importance of alterations of Na(+) channel (NaCh) function and slow myocardial conduction for arrhythmias in infarcted and failing hearts (i.e., heart failure, HF). The present study evaluated the molecular mechanisms of local alterations in the expression of NaCh subunits which underlie Na(+) current (I(Na)) density decrease in HF. HF was induced in five dogs by sequential coronary microembolization and developed approximately 3 months after the last embolization (left ventricle (LV), ejection fraction = 27 +/- 7%). Five normal dogs served as a control group. Ventricular cardiomyocytes were isolated enzymatically from LV mid-myocardium and I(Na) was measured by whole-cell patch-clamp. The mRNA encoding the cardiac-specific NaCh alpha-subunit Na(v)1.5, and one of its auxiliary subunits beta 1 (NaCh beta 1), were analyzed by competitive reverse transcription-polymerase chain reaction. Protein levels of Na(v)1.5, NaCh beta 1 and NaCh beta 2 were evaluated by western blotting. The maximum density of I(Na)/C(m) was decreased in HF (n = 5) compared to control hearts (33.2 +/- 4.4 vs. 50.0 +/- 4.9 pA/pF, mean +/- S.E.M., n = 5, P < 0.05). The steady-state inactivation and activation of I(Na) remained unchanged in HF compared to control hearts. The levels of mRNA encoding Na(v)1.5, and NaCh beta 1 were unaltered in FH. However, Na(v)1.5 protein expression was reduced about 30% in HF, while NaCh beta 1 and NaCh beta 2 protein were unchanged. We conclude that experimental HF in dogs results in post-transcriptional changes in cardiac NaCh alpha-subunit expression.

SUBMITTER: Zicha S

PROVIDER: S-EPMC2408747 | biostudies-literature | 2004 Jul

REPOSITORIES: biostudies-literature

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Post-transcriptional alterations in the expression of cardiac Na+ channel subunits in chronic heart failure.

Zicha Stephen S Maltsev Victor A VA Nattel Stanley S Sabbah Hani N HN Undrovinas Albertas I AI

Journal of molecular and cellular cardiology 20040701 1

Clinical and experimental evidence has recently accumulated about the importance of alterations of Na(+) channel (NaCh) function and slow myocardial conduction for arrhythmias in infarcted and failing hearts (i.e., heart failure, HF). The present study evaluated the molecular mechanisms of local alterations in the expression of NaCh subunits which underlie Na(+) current (I(Na)) density decrease in HF. HF was induced in five dogs by sequential coronary microembolization and developed approximatel ...[more]

PMID: 15242739

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Project description:BackgroundThe International Classification of Functioning, Disability, and Health (ICF) is growing in importance in cardiac rehabilitation (CR) as the number of elderly comorbid patients increases.AimTo classify through the ICF framework a group of post-cardiac surgery (CS) and chronic heart failure (CHF) patients undergoing rehabilitation. Then, to compare the two groups and identify possible factors at admission that could affect ICF evaluations at discharge.DesignObservational retrospective real-life study.SettingTwo inpatient CR units.PopulationConsecutive CS and CHF patients admitted for CR (January-December 2019).MethodsClinical, anthropometric data and functional status at admission and discharge were extracted from patient health records. A set of 26 ICF codes regarding body functions (b) and activities (d) was analyzed to identify: 1) the qualifiers attributed (from 0=no impairment to 4=severe impairment) for each code, 2) the percent distribution of qualifiers (0/1/2/3/4) attributed per patient. We then evaluated changes in both (1) and (2 - defined as ICF Delta%) from admission to discharge.ResultsAll patients (55% males; mean age 73±12 years) showed an improvement post-rehabilitation in the ICF qualifiers attributed (P<0.0001 for all codes). CS patients (N.=150) were less functionally impaired at admission than CHF (N.=194) (P<0.05 for all codes), and at discharge showed greater Delta% in the qualifiers 0/1/2 attributed than CHF (P<0.0001 for b codes; P<0.05 for d codes). Delta% for qualifiers 3 and 4 was similar in the two groups. No impairment at admission (qualifier 0), CS group, and presence/complexity of comorbidities were identified as possible covariates influencing ICF qualifiers at discharge, impacting the rate of both no/mild impairment (ICF% aggregate 0+1 - adjusted R2=0.627; P<0.0001) and moderate impairment (ICF% qualifier 2 - adjusted R2=0.507; P<0.0001).ConclusionsCHF patients showed a worse ICF picture at admission and less improvement at discharge than CS. The presence and complexity of comorbidities negatively influenced the ICF classification at discharge, especially in CHF patients.Clinical rehabilitation impactThis study shows the utility of ICF classification in CR as a means for describing, measuring, and comparing patient functioning across the care continuum.

Dataset Information

Post-transcriptional alterations in the expression of cardiac Na+ channel subunits in chronic heart failure.

Publications

Post-transcriptional alterations in the expression of cardiac Na+ channel subunits in chronic heart failure.

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