Protein synthesis in the isolated perfused rat heart. Effects of mechanical work load, diastolic ventricular pressure and coronary pressure on amino acid incorporation and its transmural distribution into left ventricular protein.

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 mumol/g protein (p less than 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 mumol/ (p less than 0.05) when the intraventricular pressure was adjusted to zero, indicating that the increase in aortic (coronary) pressure and not the work load per se was the reason for increased protein synthesis. Elevation of the end-diastolic pressure from zero to approximately 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.