SUMMARY. To investigate the extent to which the properties of the cardiac myofibrils contribute to the length-force relation of cardiac muscle, we determined the sarcomere length-force relations for rat ventricular trabeculae both before and after the muscles were skinned with the detergent Triton X-100 Sarcomere length was measured continuously by laser diffraction. In the unskinned trabeculae stimulated at 0.2 Hz, the relation between active force and sarcomere length at an extracellular calcium concentration of 1.5 HIM was curved away from the sarcomere length axis, with zero force at sarcomere length of 1.5-1.6 firm. At 0 3 rriM calcium, the sarcomere length-force relation was curved toward the sarcomere length axis Chemical skinning of the muscle with 1% Triton X-100 in a "relaxing solution" caused an increase in intensity and decrease in dispersion of the first order diffraction beam, indicating an increased uniformity of sarcomere length in the relaxed muscle During calcium-regulated contractures in the skinned muscles, the central sarcomeres shortened by up to 20%. As the calcium concentration was increased over the range 1-50 /IM, the relation between steady calcium-regulated force and sarcomere length shifted to higher force values and changed in shape in a manner similar to that observed for changes in extracellular calcium concentration before skinning. The sarcomere length-force relations for the intact muscles at an extracellular calcium concentration of 1 5 ITIM were similar to the curves at calcium concentration of 8 9 ^M in the skinned preparations, whereas the curves at an extracellular calcium concentration of 0 3 ITIM in intact muscles fell between the relations at calcium concentrations of 2.7 and 4.3 ^M in the skinned preparations A factor contributing to the shape of the curves in the skinned muscle at submaximal calcium concentrations was that the calcium sensitivity of force production increased with increasing sarcomere length. The calcium concentration required for 50% activation decreased from 7 71 ± 0.52 /IM to 3.77 ± 0.33 MM for an increase of sarcomere length from 1 75 to 2 15 fim. The slope of the force-calcium concentration relation increased from 2.82 to 4.54 with sarcomere length between 1.75 and 2.15 ^m. This change in calcium sensitivity was seen over the entire range of sarcomere lengths corresponding to the ascending limb of the cardiac length-force relation. It is concluded that the properties of the cardiac contractile machinery (including the length-dependence of calcium sensitivity) can account for much of the shape of the ascending limb in intact cardiac muscle (Circ Res 58: 755-768, 1986)

These findings suggest that at peak exercise a non-autonomic mechanism, possibly intrinsic to the heart muscle, may determine heart rate fluctuations in synchrony with ventilation in the intact as well as in the denervated human heart.

OBJECTIVE:To investigate thiamin and its phosphoester content in plasma and erythrocytes for a complete picture of thiamin status in obese individuals. DESIGN: Comparative study of the thiamin status of obese vs normal individuals. SUBJECTS: In all, 10 healthy, overweight, fertile age women (age: 33.175.1 y; BMI: 47.070.2 kg/m 2 ) and 10 normal women (age: 30.173.5 y; BMI: 22.870.2 kg/m 2 ). METHODS: a high-pressure liquid chromatography (HPLC) method for the determination of thiamin and its phosphoesters in the plasma and erythrocytes of the subjects. RESULTS: The major findings were: (1) significant decrease of plasma thiamin, its monophosphate and total thiamin contents in obese vs normal women; (2) significant decrease of thiamin pyrophosphate ester and total thiamin content in obese vs normal women; (3) significant increase in plasma thiamin/thiamin monophosphate ratio (in practice, it was inverted) and corresponding decrease of the plasma thiamin monophosphate/erythrocytes thiamin pyrophosphate ratio in obese vs normal women, where plasma thiamin monophosphate and erythrocytes thiamin pyrophosphate contents are an index of thiamin status. CONCLUSIONS: This study advances the hypothesis that obese women maintain higher levels of thiamin compared to normal weight subjects by storing greater amounts of thiamin in cells through preferential intracellular thiamin recycling to compensate for relatively lower levels of thiamin.

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The effect of hypercapnic acidosis was compared with that of lowering extracellular calcium concentration ([Ca++]o) in rat cardiac trabeculae. The relations between force and sarcomere length and between force and velocity were studied. Sarcomere length was measured by means of laser diffraction techniques and sarcomere shortening velocity by means of isovelocity releases. The curve representing the relation between force and sarcomere length shifted from convex towards the ordinate (pH 7.35) to convex towards the abscissa (pH 6.68) as after [Ca++]o had been reduced from 1.5 to 0.3 mmol X litre-1. Increasing [Ca++]o at low pH from 1.5 to 4.0 mmol X litre-1 allowed the shape of the relation to be restored, but force values failed to return to control values. The relation between force and pH over the range 6.22-7.94 was also tested. During steady low pH maximum unloaded sarcomere shortening velocity was not significantly different from control values whereas it was decreased at low [Ca++]o. Under both conditions maximum isometric tension (Po) was reduced. The results are consistent with the hypothesis that H+ ions cause a shift of the force-p Ca curve to the right at all sarcomere lengths, as a result of competition between Ca++ and H+ ions for binding to the myofilaments.