Premium
Appearance of Local Abnormalities of Left Ventricular Contraction on Top of Global Diastolic Dysfunction in the Hypertensive mRen2 Rat
Author(s) -
Csipo Tamas,
Fulop Gabor Aron,
Bodi Beata,
Fagyas Miklos,
Priksz Daniel,
Juhasz Bela,
Beke Livia,
Hendrik Zoltan,
Mehes Gabor,
Olah Attila,
Radovits Tamas,
Merkely Bela,
Granzier Henk,
Papp Zoltan,
Judit Barta,
Toth Attila,
Kovacs Arpad
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb667
Subject(s) - medicine , cardiology , diastole , interventricular septum , ejection fraction , heart failure , blood pressure , endocrinology , ventricle
Hypertension is a major co‐morbidity of diastolic dysfunction. Appearance of systolic dysfunction on top of diastolic dysfunction further increases the risk of cardiac failure and mortality. We hypothesized that a hypertensive rat model with diastolic dysfunction can give insight into the pathomechanism of progressing human heart failure. To this end we compared 15 weeks old male rats (n=9‐9) with hypertension due to a renin transgene (mRen2, 228.9±4.9 mmHg; P<0.05) with geno‐/phentoype controls (SD, 121.3±4.4 mmHg). Invasive parameters of left ventricular (LV) active relaxation (Tau, mRen2: 16.9±0.8 ms vs. SD: 12.6±0.6 ms; P<0.05) and passive stiffness (slope of EDPVR, mRen2: 0.050±0.004 mmHg/μL vs. SD:0.040±0.002 mmHg/μL; P<0.05) confirmed diastolic dysfunction with preserved ejection fraction (EF, mRen2: 52.5±0.7% vs. SD:53.3±0.7%) in the mRen2 animals. In contrast, regional echocardiography (n=8‐8) and histology (n=5‐5) showed worse Tei index (0.78±0.04; P<0.05) and relatively higher wall thickness (0.74±0.06; P<0.05) of the LV free wall in mRen2 rats than those of the interventricular septum (0.68±0.02 and 0.54±0.03, respectively). At the cellular level, both lower Ca 2+ sensitivity (pCa 50 ) and higher troponin I (cTnI) phosphorylation of LV cardiomyocytes from the free wall and the septum (n=mean of 3‐3/4‐4 rats) suggest abnormal systolic function in the mRen2 group as compared to the control. LV heterogeneity of mRen2 rats is further supported by lower cardiomyocyte maximal Ca 2+ ‐activated force (21.2±1.4 kN/m 2 ), higher Ca 2+ sensitivity (5.85±0.01) and phosphorylation of cTnI at Thr‐144 (1.62±0.19; P<0.05) in the free wall than those in the septum (30.0±0.6 kN/m 2 , 5.76±0.02 and 1.00±0.15, respectively). The local abnormalities of LV contraction on top of global diastolic dysfunction may provide a pathomechanism for the clinical progression with increasing mortality seen in human.