Diastolic Dysfunction of the Heart. Pharmacological Strategies for Modulating Calcium Sequestration of the Sarcoplasmic Reticulum

Rupp, Heinz

doi:10.1007/978-1-4615-3090-9_19

Cited by 3 publications

(1 citation statement)

References 113 publications

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“…In previous experimental studies we have been able to demonstrate that the development of myocardial fibrosis and not muscle mass per se is the major determinant of myocardial diastolic stiffness in hypertensive heart disease [8] besides relevant phenotype changes of cardiac myocytes, e.g., isomyosin pattern or sarcoplasmatic ATPase function [32]. This has now been confirmed in patients with primary hypertension where myocardial stiffness, measured by the stiffness constant k of the left ventricle, showed a significant correlation with the amount of myocardial fibrosis morphometrically determined by CVF of LV endomyocardial biopsies while no correlation was found between myocardial stiffness and myocyte hypertrophy.…”

Section: Functional Consequences Of Myocardial Fibrosismentioning

confidence: 99%

Effects of ACE Inhibition versus Non-ACE Inhibitor Antihypertensive Treatment on Myocardial Fibrosis in Patients with Arterial Hypertension

Brilla

Rupp

Maisch

2003

Herz

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Section: Functional Consequences Of Myocardial Fibrosismentioning

confidence: 99%

Effects of ACE Inhibition versus Non-ACE Inhibitor Antihypertensive Treatment on Myocardial Fibrosis in Patients with Arterial Hypertension

Brilla

Rupp

Maisch

2003

Herz

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Gene Expression of Cardiac Myocytes: A Pharmacologic Target for the Failing Heart?

Rupp¹,

Turcani²,

Maisch³

et al. 1996

Developments in Cardiovascular Medicine

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Advanced Hypertensive Heart Disease in Spontaneously Hypertensive Rats

1996

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Left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR) is accompanied by a structural remodeling of the myocardium that includes myocyte hypertrophy and interstitial and perivascular fibrosis of intramyocardial coronary arteries. The structural abnormalities related to fibrous tissue accumulation lead to increased myocardial diastolic stiffness and ultimately impaired systolic function of the left ventricle. It has been shown in 14-week-old SHR with early hypertensive heart disease that myocardial fibrosis could be reversed and myocardial diastolic stiffness normalized by 12-week treatment with the angiotensin-converting enzyme inhibitor lisinopril. Whether such functional defects of the myocardium, based on adverse structural changes, are also reversible in advanced hypertensive heart disease has been questioned. Therefore, we treated 78-week-old male SHR that had chronic hypertension and advanced LVH with severe myocardial fibrosis and age- and sex-matched normotensive Wistar-Kyoto rats (WKY) with 20 mg/kg per day oral lisinopril for 8 months. Compared with untreated SHR or WKY, we found the following: (1) Systolic arterial pressure was normalized (P < .025) and LVH completely reversed (P < .025) in SHR, with no significant reduction in systolic arterial pressure or left ventricular mass in WKY; (2) morphometrically determined myocardial fibrosis in SHR was significantly reversed (P < .025) and associated with improved diastolic stiffness (P < .05), which was measured in the isolated heart by calculation of the stiffness constant of the myocardium; no significant changes occurred in WKY; (3) reversal of myocardial fibrosis was accompanied by an increase (P < .025) in myocardial matrix metalloproteinase 1 activity determined by degradation of [14C]collagen with myocardial tissue extracts after trypsin activation of myocardial promatrix metalloproteinase 1; matrix metalloproteinase 1 activity remained unchanged in WKY treated with lisinopril; and (4) systolic dysfunction, measured by a significantly (P < .025) diminished slope of the systolic stress-strain relation under isovolumic conditions of the left ventricle, was found in 110-week-old SHR, and it could be prevented by lisinopril treatment. Thus, long-term angiotensin-converting enzyme inhibition with lisinopril normalized arterial pressure and LVH, reversed myocardial fibrosis, and improved abnormal myocardial diastolic stiffness in advanced hypertensive heart disease in SHR. In addition, systolic dysfunction of the left ventricle could be prevented. The fibrolytic response to lisinopril was at least partly due to enhanced collagen degradation by activation of tissue matrix metalloproteinase 1.

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Diastolic Dysfunction of the Heart. Pharmacological Strategies for Modulating Calcium Sequestration of the Sarcoplasmic Reticulum

Cited by 3 publications

References 113 publications

Effects of ACE Inhibition versus Non-ACE Inhibitor Antihypertensive Treatment on Myocardial Fibrosis in Patients with Arterial Hypertension

Effects of ACE Inhibition versus Non-ACE Inhibitor Antihypertensive Treatment on Myocardial Fibrosis in Patients with Arterial Hypertension

Gene Expression of Cardiac Myocytes: A Pharmacologic Target for the Failing Heart?

Advanced Hypertensive Heart Disease in Spontaneously Hypertensive Rats

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