A.F. Leite-Moreira

Nonuniform course of left ventricular pressure fall and its regulation by load and contractile state.

BACKGROUND Effects of systolic left ventricular pressure (LVP) on rates of pressure fall remain incompletely understood. This study analyzed phase-plane dP/dt versus LVP plots to differentiate between accelerating and decelerating effects and to investigate the variability in reported load effects on rates of LVP fall. METHODS AND RESULTS Abrupt aortic occlusions were performed by inflating a balloon positioned in the ascending aorta of anesthetized open-chest dogs (n = 17). The occlusions resulted in clamp elevations of systolic LVP. In protocol A, the elevations of systolic LVP induced by total aortic occlusions were timed at early, mid, and late ejection. The magnitude of the elevations was 36.0 +/- 3.6 mm Hg for early, 11.6 +/- 0.6 mm Hg for mid, and negligible for late occlusions. The course of LVP fall appeared to be more complex than previously appreciated. Pressure fall might be subdivided in an initial accelerative phase, an intermediate decelerative phase, and a terminal decelerative phase. The initial phase accelerated with mid and late occlusions. The intermediate phase slowed down with early and to a lesser extent with mid occlusions. The terminal phase was never affected by aortic clamp occlusions. In protocol B, early elevations of systolic LVP were obtained with multiple graded aortic occlusions. The effects of matched LVP elevations of 12 mm Hg on rate of LVP fall were evaluated with the time constant of LVP fall (tau) and showed an interanimal variability ranging from acceleration and a 20% decrease in tau to deceleration and a 35% increase in tau. Changes in tau were moderately correlated with commonly used indexes of contractility (peak +dP/dt, r = -.78; regional fractional shortening, r = -.63). These changes in tau showed a close correlation with the systolic LVP of the test beat, expressed as a percentage of the peak isovolumetric LVP, obtained with total aortic occlusion (r = .984). This suggested that the contraction-relaxation coupling should be analyzed in terms of peak force development rather than contraction velocity or ejection fraction. CONCLUSIONS LVP fall could be subdivided into an initial accelerative phase, an intermediate decelerative phase, and a terminal decelerative phase. Effects of elevations in systolic LVP on rate of LVP fall could be predicted by knowing peak isovolumetric LVP. Nonuniformity of LVP fall and adequate interpretation of load effects should be taken into account when clinical situations or pharmacological interventions are considered. In congestive heart failure, slow LVP fall could mainly reflect working conditions close to isovolumetric rather than relaxation disturbances.

Load dependence of left ventricular contraction and relaxation. Effects of caffeine

Objective: Load dependence of left ventricular (LV) contraction and relaxation was investigated at baseline and after alteration of intracellular calcium handling by caffeine. Methods: Afterload was increased by aortic clamp occlusions (n = 281) in anesthetized open-chest dogs (n = 7). Control and first heartbeat after the intervention were considered for analysis. Results: Caffeine (50 mg/kg, iv) had no inotropic effect. The systolic LV pressure (LVP), developed in response to aortic occlusion, decreased as ejection proceeded and this pressure generating capacity was not affected by caffeine. Late-systolic aortic occlusions induced premature onset and accelerated rate of initial LVP fall at baseline and similarly after caffeine. Graded diastolic aortic occlusions induced systolic LVP elevations of various magnitudes. Smaller LVP elevations prolonged ejection and accelerated LVP fall, while larger elevations had opposite effects. The transition from acceleration to deceleration was observed at 83.1 ± 1.1 % of peak isovolumetric LVP at baseline and at lower loads, at 77.6 ± 1.2 %, after caffeine (p < 0.01). Isovolumetric heartbeats prolonged the time constant τ by 238 ± 70 % at baseline and only by 155 ± 44 % after caffeine (p < 0.01). The relaxation-systolic pressure relation, which describes afterload dependence of relaxation, was also modified by caffeine. Conclusions: Caffeine affected LV relaxation without altering contractility. As a consequence contraction-relaxation coupling was modified by caffeine. These results might help to understand load dependence of relaxation in conditions where intracellular calcium handling is altered.