Progressive Cardiac Dysfunction and Fibrosis in the Cardiomyopathic Hamster and Effects of Growth Hormone and Angiotensin-Converting Enzyme Inhibition
| Autor: | Kirk L. Peterson, Ross G. Clark, Yusu Gu, Minoru Hongo, Tsutomu Ryoke, John Ross, Lan Mao |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Cardiac function curve medicine.medical_specialty Transcription Genetic Diastole Angiotensin-Converting Enzyme Inhibitors Blood Pressure Ventricular Function Left Contractility Heart Rate Fibrosis Cricetinae Tetrahydroisoquinolines Physiology (medical) Internal medicine Animals Humans Medicine RNA Messenger Myocardial infarction Mesocricetus biology Human Growth Hormone business.industry Myocardium Hemodynamics Quinapril Heart Angiotensin-converting enzyme Isoquinolines medicine.disease Recombinant Proteins Rats Endocrinology Gene Expression Regulation Echocardiography Heart failure biology.protein Myocardial fibrosis Collagen Cardiomyopathies Cardiology and Cardiovascular Medicine business Atrial Natriuretic Factor |
| Zdroj: | Circulation. 100:1734-1743 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.100.16.1734 |
| Popis: | Background —Growth hormone (GH) improves cardiac function in the rat with myocardial infarction, but its effects in a model of primary dilated cardiomyopathy have not been reported. GH effects were examined at early (4 months) and late (10 months) phases of disease in the cardiomyopathic (CM) hamster, and the combination of GH with chronic ACE inhibition was assessed in late-phase heart failure. Methods and Results —CM hamsters (CHF 147 line) at 4 months showed severe systolic left ventricular (LV) dysfunction with normal LV filling pressure, and at 10 months there was more severe systolic as well as diastolic dysfunction with increasing myocardial fibrosis. Recombinant human GH alone for 3 weeks at age 4 months increased LV wall thickness and reduced systolic wall stress without altering diastolic wall stress, whereas at 10 months, wall stress and fractional shortening did not improve. The LV dP/dt max was enhanced at both ages by GH, which at 4 months reflected increased contractility, but at 10 months was most likely caused by elevation of the LV filling pressure. The increasing degree of fibrosis correlated inversely with LV function but was unaffected by GH. In other CM hamsters, high-dose ACE inhibition alone (quinapril), started at 8 months and continued for 11 weeks, improved LV function and inhibited unfavorable remodeling, but the addition of GH for 3 weeks at age 10 months produced increased wall thickness with little additional functional benefit and increased the LV filling pressure and diastolic wall stress. Conclusions —GH treatment alone improved LV dysfunction at 4 months of age in CM hamsters by increasing contractility and reducing wall stress but had few beneficial effects at 10 months in severe LV failure. After chronic ACE inhibition, addition of GH at 10 months had no additional beneficial effects and further increased LV diastolic pressure. These differing effects of GH may relate to the progressive increase of LV fibrosis in the CM hamster. |
| Databáze: | OpenAIRE |
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