Incomplete structural reverse remodeling from late-stage left ventricular hypertrophy impedes the recovery of diastolic but not systolic dysfunction in rats

Mihály Ruppert, Sevil Korkmaz-Icöz, Sivakkanan Loganathan, Weipeng Jiang, A. Oláh, Alex Ali Sayour, Bálint András Barta, Christian Karime, B. Merkely, Matthias Karck, T. Radovits, G. Szabó

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: Pressure overload-induced left ventricular myocardial hypertrophy (LVH) regresses after pressure unloading. However, distinct structural alterations become less reversible during the progression of LVH, which might influence the restoration of cardiac function. Here, we investigated how a reverse remodeling process from early versus late-stage LVH affects different aspects of left ventricular function. METHODS: Pressure overload was induced in rats for 6, 12 and 18 weeks. Sham-operated animals were used as controls. Pressure unloading was evoked by removing the aortic constriction at week 6 (early-debanded) and week 12 (late-debanded). Echocardiography and histological analyses were carried out to detect structural alterations. Pressure-volume analysis was performed to assess left ventricular function. Molecular alterations were analyzed by quantitative real-time-PCR, and western blot. RESULTS: Myocardial hypertrophy regressed to a similar degree in early and late-debanded groups. Accordingly, no differences were detected in the extent of regression regarding left ventricular mass, cardiomyocyte diameter, heart weight-to-tibial length ratio and beta-to-alpha myosin heavy chain expression. In contrast, resorption of interstitial and perivascular myocardial fibrosis was only detected in the early-debanded group, whereas it persisted in the late-debanded group. Removing the aortic constriction normalized ventriculo-arterial coupling and increased systolic performance in both debanded groups. However, the residual dysfunction in active relaxation and passive stiffness was more severe in the late-debanded compared to the early-debanded group. CONCLUSION: Early debanding led to complete structural reverse remodeling (reduced hypertrophy and fibrosis) and full restoration of left ventricular function. In contrast, myocardial fibrosis persisted after late debanding, which impeded the normalization of diastolic but not systolic function.

Original languageEnglish
Pages (from-to)1200-1212
Number of pages13
JournalJournal of hypertension
Volume37
Issue number6
DOIs
Publication statusPublished - Jun 1 2019

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Left Ventricular Hypertrophy
Pressure
Left Ventricular Function
Fibrosis
Constriction
Hypertrophy
Ventricular Myosins
Myosin Heavy Chains
Cardiac Myocytes
Echocardiography
Real-Time Polymerase Chain Reaction
Western Blotting
Weights and Measures

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Incomplete structural reverse remodeling from late-stage left ventricular hypertrophy impedes the recovery of diastolic but not systolic dysfunction in rats. / Ruppert, Mihály; Korkmaz-Icöz, Sevil; Loganathan, Sivakkanan; Jiang, Weipeng; Oláh, A.; Sayour, Alex Ali; Barta, Bálint András; Karime, Christian; Merkely, B.; Karck, Matthias; Radovits, T.; Szabó, G.

In: Journal of hypertension, Vol. 37, No. 6, 01.06.2019, p. 1200-1212.

Research output: Contribution to journalArticle

Ruppert, Mihály ; Korkmaz-Icöz, Sevil ; Loganathan, Sivakkanan ; Jiang, Weipeng ; Oláh, A. ; Sayour, Alex Ali ; Barta, Bálint András ; Karime, Christian ; Merkely, B. ; Karck, Matthias ; Radovits, T. ; Szabó, G. / Incomplete structural reverse remodeling from late-stage left ventricular hypertrophy impedes the recovery of diastolic but not systolic dysfunction in rats. In: Journal of hypertension. 2019 ; Vol. 37, No. 6. pp. 1200-1212.
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T1 - Incomplete structural reverse remodeling from late-stage left ventricular hypertrophy impedes the recovery of diastolic but not systolic dysfunction in rats

AU - Ruppert, Mihály

AU - Korkmaz-Icöz, Sevil

AU - Loganathan, Sivakkanan

AU - Jiang, Weipeng

AU - Oláh, A.

AU - Sayour, Alex Ali

AU - Barta, Bálint András

AU - Karime, Christian

AU - Merkely, B.

AU - Karck, Matthias

AU - Radovits, T.

AU - Szabó, G.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - OBJECTIVE: Pressure overload-induced left ventricular myocardial hypertrophy (LVH) regresses after pressure unloading. However, distinct structural alterations become less reversible during the progression of LVH, which might influence the restoration of cardiac function. Here, we investigated how a reverse remodeling process from early versus late-stage LVH affects different aspects of left ventricular function. METHODS: Pressure overload was induced in rats for 6, 12 and 18 weeks. Sham-operated animals were used as controls. Pressure unloading was evoked by removing the aortic constriction at week 6 (early-debanded) and week 12 (late-debanded). Echocardiography and histological analyses were carried out to detect structural alterations. Pressure-volume analysis was performed to assess left ventricular function. Molecular alterations were analyzed by quantitative real-time-PCR, and western blot. RESULTS: Myocardial hypertrophy regressed to a similar degree in early and late-debanded groups. Accordingly, no differences were detected in the extent of regression regarding left ventricular mass, cardiomyocyte diameter, heart weight-to-tibial length ratio and beta-to-alpha myosin heavy chain expression. In contrast, resorption of interstitial and perivascular myocardial fibrosis was only detected in the early-debanded group, whereas it persisted in the late-debanded group. Removing the aortic constriction normalized ventriculo-arterial coupling and increased systolic performance in both debanded groups. However, the residual dysfunction in active relaxation and passive stiffness was more severe in the late-debanded compared to the early-debanded group. CONCLUSION: Early debanding led to complete structural reverse remodeling (reduced hypertrophy and fibrosis) and full restoration of left ventricular function. In contrast, myocardial fibrosis persisted after late debanding, which impeded the normalization of diastolic but not systolic function.

AB - OBJECTIVE: Pressure overload-induced left ventricular myocardial hypertrophy (LVH) regresses after pressure unloading. However, distinct structural alterations become less reversible during the progression of LVH, which might influence the restoration of cardiac function. Here, we investigated how a reverse remodeling process from early versus late-stage LVH affects different aspects of left ventricular function. METHODS: Pressure overload was induced in rats for 6, 12 and 18 weeks. Sham-operated animals were used as controls. Pressure unloading was evoked by removing the aortic constriction at week 6 (early-debanded) and week 12 (late-debanded). Echocardiography and histological analyses were carried out to detect structural alterations. Pressure-volume analysis was performed to assess left ventricular function. Molecular alterations were analyzed by quantitative real-time-PCR, and western blot. RESULTS: Myocardial hypertrophy regressed to a similar degree in early and late-debanded groups. Accordingly, no differences were detected in the extent of regression regarding left ventricular mass, cardiomyocyte diameter, heart weight-to-tibial length ratio and beta-to-alpha myosin heavy chain expression. In contrast, resorption of interstitial and perivascular myocardial fibrosis was only detected in the early-debanded group, whereas it persisted in the late-debanded group. Removing the aortic constriction normalized ventriculo-arterial coupling and increased systolic performance in both debanded groups. However, the residual dysfunction in active relaxation and passive stiffness was more severe in the late-debanded compared to the early-debanded group. CONCLUSION: Early debanding led to complete structural reverse remodeling (reduced hypertrophy and fibrosis) and full restoration of left ventricular function. In contrast, myocardial fibrosis persisted after late debanding, which impeded the normalization of diastolic but not systolic function.

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