Cardiac Slice Contraction-Relaxation Function. Cardiac slices will be created from mammalian left ventricle 100-150 um thick. Prepared slices will be placed between a force transducer and length motor (Figure 1A). Diastolic sarcomere length will be initially established at 2.2 um, and isometric force transients recorded at various sarcomere lengths (Figure 1B). Often, force-length work loops will be recorded at four sarcomere lengths between 1.9-2.3 um, and end-systolic elastance will be calculated as a measure of inherent contractility.
Normally, two slices from each heart and 6-12 hearts per genotype (both male and female) would be used to distinguish the effects of disease and sex. Characteristics reported will include minimum tension (i.e., resting tension as the prescribed sarcomere length), maximum tension development, rates of tension development and tension decline, mechanical work generation, stroke length, and sensitivity of these measures to sarcomere length. Also, end-systolic elastance as a measure of the Frank-Starling response and end-diastolic stiffness as measure of tissue stiffness at rest will be calculated for each slice.
