Summary
The mechanisms involved in hypertrophy of the left ventricle were studied in Langendorff-perfused rat hearts by measuring the ventricular protein synthesis and its transmural distribution and by differentiating between the effects of changes in mechanical work load, intraventricular and coronary pressures. An increase in the aortic pressure from 7.85 kPa (80 cm of water) to 19.6 kPa (200 cm of water) in beating hearts increased phenylalanine incorporation into left ventricular protein from 1.4 to 2.0 μmol/g protein (p<0.02) during a two-hour perfusion. The protein synthesis was transmurally evenly distributed. A similar elevation in the perfusion pressure in potassium-arrested hearts caused an increase in phenylalanine incorporation from 1.5 to 1.9 μmol/ (p<0.05) when the intraventricular pressure was adjusted to zero, indicating that the increase in aortic (coronary) pressure and not the work loadper se was the reason for increased protein synthesis. Elevation of the end-diastolic pressure from zero to ∼ 2 kPa in beating hearts at an aortic pressure of 7.85 kPa, or from 7.85 kPa to 17.3 kPa in K+-arrested hearts, at an aortic pressure of 19.6 kPa caused a significant reduction in subendocardial protein synthesis, whereas subepicardial phenylalanine incorporation was at most only slightly affected. The energetic parameters, oxygen consumption, output of vasoactive purine compounds and distribution of coronary flow indicate that the increase in protein synthesis via the elevation in aortic pressure was not due to the abolition of partial anoxia, whereas the same parameters indicate that the transmural gradient in protein synthesis observed under certain conditions was due to subendocardial ischemia when the intraventricular pressure approached the aortic pressure in arrested hearts, which are evidently of restricted use for extended periods without special measures to limit the build-up of intraventricular pressure.
Zusammenfassung
Die Mechanismen der Hypertrophie der linken Herzkammer und die Unterschiede zwischen der Wirkung der mechanischen Arbeit, des intraventrikulären und koronararteriellen Druckes wurden in Langendorff-perfundierten Rattenherzen untersucht. Bei einer Erhöhung des Perfusionsdruckes von 7,85 kPA (80 cm Wasser) auf 19,6 kPa (200 cm Wasser) bei schlagenden Herzen vermehrte sich die Inkorporation der Aminosäure Phenylalanin von 1,4 auf 2,0 μmol/g Protein (p<0,02) während einer zweistündigen Perfusion. Die Proteinsynthese zeigte eine gleichmäßige transmurale Verteilung. Eine gleiche Erhöhung des Perfusionsdruckes in mit Kalium stillgestellten Herzen vermehrte die Inkorporation von Phenylalanin von 1,5 auf 1,9 μmol/g (p<0,05) wenn der intraventrikuläre Druck auf Null festgestellt wurde, woraus hervorgeht, daß die Erhöhung des Perfusionsdruckes und nicht die mechanische Arbeit per se die Ursache der vergrößerten Proteinsynthese war. Erhöhung des enddiastolischen Druckes schlagender Herzen von Null auf 2,1 kPa bei einem Perfusionsdruck von 7,85 kPa oder Steigerung des Kammerdrucks K-arretierter Herzen von 7,85 kPa auf 17,3 kPa bei einem Perfusionsdruck von 19,6 kPa verursachte eine wesentliche Verminderung der subendokardialen Proteinsynthese, während sich die subepikardiale Phenylalanininkorporation nur wenig veränderte.
Die Messung der energetischen Parameter, des Sauerstoffverbrauches und der Produktion der vasoaktiven Purinverbindungen sowie der transmuralen Verteilung der Myokarddurchblutung zeigten, daß die von dem erhöhten Perfusionsdruck verursachte Steigerung der Proteinsynthese nicht durch Beseitigung eines partiellen Sauerstoffmangels resultierte. Die gleichen Parameter sprechen andererseits dafür, daß der transmurale Gradient der Proteinsynthese unter bestimmten Bedingungen durch eine subendokardiale Ischämie bedingt war, wenn sich nämlich beim stillstehenden Herzen der Ventrikelinnendruck dem Aortendruck (Perfusionsdruck) nähert; stillstehende Herzen dürfen daher nicht ohne spezielle Regulierung des intraventrikulären Druckes über längere Zeit perfundiert werden.
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Takala, T. Protein synthesis in the isolated perfused rat heart. Basic Res Cardiol 76, 44–61 (1981). https://doi.org/10.1007/BF01908162
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DOI: https://doi.org/10.1007/BF01908162