Mechanical and energetic changes in short-term volume and pressure overload of rabbit heart

Abstract

The mechanical and energetic consequences of a short-term volume overload (STVOL) hypertrophy and short-term pressure overload (STPOL) hypertrophy have been investigated in rabbits and compared with short-term sham-operated controls (STSOC). Hypertrophy was induced either by creating an aortocaval shunt (volume overload) or by banding the pulmonary artery (pressure overload). Suitable papillary muscles were excised from the hearts 8-10 days after the surgical procedure. At 27 degrees C and a stimulus frequency of 1.0 Hz, peak stress development of the STVOL preparations was significantly reduced from the control group, whereas no significant difference in peak stress development was evident between the STPOL and STSOC groups. Surprisingly, the STPOL preparations displayed pulsus alternans after only 8-10 days of inducing the overload. At steady-state conditions, the isometric 10%-90% rise times, the 90%-10% relaxation times, and the 1/2-widths were not significantly different between the treated and control groups. In isotonically contracting muscles working against a range of afterloads, the enthalpy (energy) and work output of the STVOL and STPOL preparations were depressed compared to the STSOC preparations; the differences were statistically significant for the STVOL group. Due to the parallel change in work and enthalpy, the mechanical efficiency was unaltered. A force-length-area (FLA) analysis, analogue of the pressure-volume-area (PVA) analysis, was applied to the isotonic data of this study. The isotonic enthalpy at the various load levels was plotted against the measured FLA and the data were fitted by linear regression. It was evident that the FLA correlated closely with the energy used. The STVOL and STPOL mean total energy:FLA regression lines lay parallel to but were below the STSOC line, signifying a drop in the activation heat, although this reduction did not achieve statistical significance. It is concluded that significant mechanical and energetic changes are evident after a short-term volume overload although earlier work has shown that these differences are absent at the later, compensated stage of hypertrophy. Changes associated with the pressure overload model suggest a disturbance in calcium regulation: this effect is also seen in long-term pressure overload.