Adaptive and Pathological Alterations in Experimental Cardiac Hypertrophy

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135

The distribution of cardiac myosin isoenzymes is altered as a result of pressure overload and physical training. Using polyacrylamide gel electrophoresis in sodium pyrophosphate, it was found that myosin from left ventricles of adult rats exists in three polymorphic forms, V1, V2 and V3. Cardiac hypertrophy due to renal hypertension (Goldblatt II) led to a shift of the isoenzymes towards V3, whereas swimming training resulted in an opposite redistribution. The isoenzyme V1 predominated, only traces of V2 and V3 were detectable. The changes in the isoenzyme distribution were reflected in an altered ATPase activity of myofibrils. In a representative sample of the Goldblatt rats, the activity was reduced by 11%, and the swimming training led to an increase by 10%. Changes in myofibrillar ATPase can, therefore, be traced to alterations in the isoenzyme pattern of myosin. The polymorphism of myosin has a two-faced aspect as regards cardiac performance. For example, a shift towards V3 is expected to increase the economy for tension development during isovolumetric contraction at the expense of a reduced maximum speed of ventricular contraction.

Section: The Myosin Isoenzyme Pattern and Myocardial Energeticsmentioning

confidence: 95%

The adaptive changes in the isoenzyme pattern of myosin from hypertrophied rat myocardium as a result of pressure overload and physical training

Rupp

1981

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135

“…The functional changes which t~upp, Polymorphic myosin as the common determinant occur in whole heart haemodynamics and the mechanics of isolated native muscle fibres are well documented (1,2). Some of these adaptive alterations originate from a change in myocardial morphology.…”

Section: Introductionmentioning

confidence: 96%

“…Such a change in gene expression has been demonstrated for myosin comprising the thick filament of muscle fibres (3)(4)(5)(6). Pressure overload induced by aortic stenosis (7) or renal hypertension (2,8,9) of the rat led to a redistribution of the myosin isoenzymes towards myosin V3, the isoenzyme of low electrophoretic mobility and ATPase activity. By contrast, endurance training in the form of swimming exercise of rats induced synthesis of the isoenzyme V1 of high electrophoretic mobility and high ATPase activity (2,8,9).…”

Section: Introductionmentioning

confidence: 99%

“…Pressure overload induced by aortic stenosis (7) or renal hypertension (2,8,9) of the rat led to a redistribution of the myosin isoenzymes towards myosin V3, the isoenzyme of low electrophoretic mobility and ATPase activity. By contrast, endurance training in the form of swimming exercise of rats induced synthesis of the isoenzyme V1 of high electrophoretic mobility and high ATPase activity (2,8,9). Beside haemodynamic load, thyroid hormone state influences the isoenzyme pattern (4).…”

Section: Introductionmentioning

confidence: 99%

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Polymorphic myosin as the common determinant of myofibrillar ATPase in different haemodynamic and thyroid states

Rupp

1982

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SummaryChronic alterations in haemodynamic load or thyroid state affect the ATPase activity of myofibrils from the rat heart. In order to determine the limits of such an adaptational reaction, the Ca2+-dependent activation of myofibrils containing only myosin V1 or V 3 was investigated. These limiting states were achieved by changes in the thyroid state, i.e., myosin V 1 myofibrils were obtained from 5-week-old rats, and myosin V 3 myofibrils from hypothyroid rats. Analysis of the activation of myofibrillar ATPase by Ca 2+ using the model-independent Hill equation showed that transition of the myosin isoenzymes neither affected Ca 2+ sensitivity (pCas0 % = 6.52) nor positive co-operativity (n = 2.4). The ATPase activity at saturating Ca 2+ concentrations was 192 nMole Pmg -1 rain -1 in myosin Vl-myofibrils and was reduced to 131 nMole Pmg -~ min -1 in the case of myosin V3-myofibrils. Beside changes in the thyroid hormone state, polymorphic myosin is also influenced by chronic pressure overload and endurance training of a swimming routine. Such haemodynamically induced changes in myofibrillar ATPase were accounted for on the basis of the altered myosin isoenzyme pattern and the ATPase activities of isoenzymatically homogeneous myofibrils obtained by changes in the thyroid state. It can therefore be concluded that both haemodynamic load and thyroid state affect myofibrillar ATPase by a common mechanism, namely, by inducing a change in the isoenzyme pattern of myosin due to a redirected expression of myosin genes. Myosins from other mammals were compared with rat myosin on pyrophosphate gels. The Ca 2+-dependent activation of myofibrillar ATPase from euthyroid and hypothyroid adult mice suggested the existence of a polymorphic myosin which was verified by the pyrophosphate gel technique. The mouse myosin isoenzymes were, however, less separated on pyrophosphate gels when compared with the rat myosins. It therefore seems advisable to consider both the activation properties of myofibrillar ATPase, as well as electrophoretie properties, for defining the adaptational state of myocardium of higher mammalian species.

“…Such loading conditions appear to be superior to an abrupt increase as is utilized to redevelop the myocardium of the low pressure ventricle as preparation for anatomic correction of simple transposition of the great arteries (2,9,14,(34)(35)(36). Rapid excessive increase of pressure loading leads to degenerative alterations of the myocardium (11). A newly developed device (17), which produces a slow progressive stenosis of the pulmonary artery was used to raise RV pressure to systemic levels in young pigs within 4 to 5 weeks.…”

Section: Introductionmentioning

confidence: 97%

Response of the right ventricle to progressive pressure loading in pigs

Lange¹,

Nürnberg²,

Sievers

et al. 1985

The purpose of this study was to determine the speed and duration of progressive pressure loading of the right ventricle to systemic pressure levels, which allows right ventricular adaptation without myocardial impairment at rest. In 8 pigs with an average weight of 22 kg progressive right ventricular pressure loading of different speeds and durations was induced with a newly developed constrictor. Pressures in the right atrium, right ventricle, and pulmonary artery as well as angiocardiographic volume parameters of the right ventricle were determined weekly over a period of 4 to 7 weeks. A fast progressive right ventricular pressure increase of 3.4 mm Hg/day during 3 weeks was associated with a 20-30% reduction of ejection fraction and a 100% increase of the end-systolic volume. Increase of end-diastolic pressure was 3 to 5 fold. A slow progressive pressure increase of 1.5 to 2.2 mm Hg/day to 100 mm Hg within 4 to 5 weeks was associated with an increase of the end-diastolic pressure to a level observed in systemic ventricles, while change of ejection fraction and end-systolic volume was minimal. The faster the increase of right ventricular pressure the flatter was the peak systolic pressure/end-systolic volume relationship. It is concluded that in contrast to sudden and fast progressive increase of afterload slow progressive increase of afterload to systemic levels does not impair right ventricular myocardial function.