The external work–pressure time integral relationships and the afterload dependence of Frank–Starling mechanism

The mechanisms underlying the Frank–Starling Law of the heart are elusive and the prevalent notion suggests that it is afterload independent. However, isolated fiber studies reveal that the afterload determines cardiac function through cross-bridge dependent mechanisms. The study explores the roles of the afterload, in situ. The LV was exposed by left-thoracotomy in adult sheep (72.6 ± 8.2 kg, n = 8). Pressure transducers were inserted into the LV and aorta, a flowmeter was placed around the aortic root, and the LV volume was assessed by sonocrystals. Occluders around the aorta and the inferior vena cava enabled control of the afterload and preload. Different afterloads were imposed by partial aortic occlusions. Transient inferior vena cava occlusions (IVCOs) were preformed whenever the afterload was steady. A highly linear relationship was found between the external work (EW) and pressure time integral (PTI) (R2 = 0.98 ± 0.01) during each transient IVCO (n = 48). The slope of the EW–PTI relationship (WPTiR) was preload independent since, for any given afterload, the EW and PTI lay on a straight line. Interestingly, the slope of the WPTiR was afterload dependant: The slope was 33.3 ± 4.1 mJ/mmHg·s at baselines and decreased by 1.0 ± 0.50 mJ/mmHg·s with every 1 mmHg·min/L increase in the peripheral resistance. A unique WPTiR was obtained during both the occlusion and release phases of each IVCO, while two distinct EW–preload or PTI–preload relationships were observed. The novel WPTiR ties the Frank (pressure development) and Starling (EW production) phenomena together. The dependence of the WPTiR on the afterload highlights the adaptive control of the Frank–Starling mechanisms to changes in the afterload.