Preload-induced changes in systolic and diastolic performance in the aged and young murine heart

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] The aged heart exhibits modifications limiting cardiac performance. The purpose of this study was to test the hypothesis that aged hearts exhibit impaired systolic and diastolic function in response to elevated preload. To test this, hearts of Young (3-6 month) and Aged (22-27 month) C57Bl/6 mice were excised and cannulated via aorta and left atrium. In working heart mode (8 Hz stimulation), defined preloads were applied via atrial cannula while peak pressure (mmHg), rate of pressure development (+dP/dt), and rate of pressure decay (-dP/dt) were monitored via intraventricular pressure catheter. Hearts underwent progressive preload increases from 5-20 mmHg, followed by preload challenge (30 mmHg, 20 minutes). Young hearts (6/6) responded to greater preloads (5-20 mm Hg) with increased pressure (from 73+4 to 96+7 mmHg), rate of development (from 2542+247 to 3628+328 mmHg/s), and rate of decay (from -2194+290 to -3370+368 mmHg/s). In contrast, divergent responses were observed in Aged, one population (5/9) increasing in peak pressure (from 67+5 to 109+8 mmHg) and rates (+dP/dt 2384+184 to 4317+347 mmHg/s, -dP/dt -1476+244 mmHg/s to -3783+275 mmHg/s)(i.e., positive responsive) and a second population (4/9) decreasing in peak pressure (from 81+10 to 75+9 mmHg) and rates (+dP/dt 2653+295 to 2378+378 mmHg/s, -dP/dt -1972+462 to -1914+716 mmHg/s)(i.e., negative responsive). Interestingly, during sustained preload challenge, positive responsive Aged exhibited greater decline in rate of decay (-3402+510 initial to -2457+336 mmHg/s final) compared to Young ( -3023+328 initial to -2758+362 mmHg/s final) and negative responsive Aged (-1450+532 initial to -1325+433 mmHg/s final). In summary, our data suggest the Aged heart manifests two forms of diastolic dysfunction; one characterized by an inability to respond to preload and a second by the capacity to respond to preload with augmented hemodynamics but inability to sustain diastolic function.