Characterization of intact mesenteric lymphatic pump and its responsiveness to acute edemagenic stress

Abstract

The contractile properties of the mesenteric collecting lymphatics of the rat were analyzed under control conditions and during periods of enhanced lymph formation using in vivo microscopic techniques. Pressure and diameter were simultaneously monitored in microscopic collecting lymphatics, and lymphatic pump function was analyzed in accordance with basic principles of cardiac mechanics. The lymphatic contractile cycle was divided into two phases of systole and four phases of diastole. Under control conditions, lymphatics contracted with a frequency of 6.4 +/- 0.61 beats/min and ejected approximately 67% of their end-diastolic volume. Ten minutes after the rate of lymph formation was elevated by plasma dilution, end-diastolic diameter, contraction frequency, ejection fraction, and stroke volume increased. Pressure in the lymphatic network became less pulsatile in high lymph flow states. Contractility, an index of inotropic changes in lymphatic pump, was unaltered when lymph flow was increased by plasma dilution. Furthermore, the maximal shortening velocity of lymphatic smooth muscle did not change during periods of enhanced lymph flow. Thus it appears that passive increases in the rate of lymph formation exert few, if any, inotropic effects on the lymphatic pump. The augmented stroke volume and contraction frequency appear to result mainly from intrinsic stretch-dependent mechanisms set in motion by elevated preload. These data represent the first comprehensive characterization of both the flow-generating and muscle characteristics of intact collecting lymphatics and provide a basis for future studies on the physiological regulation of lymphatic contraction.

Independent and interactive effects of preload and afterload on the pump function of the isolated lymphangion

“…Our conclusion is consistent with previous studies (3,14,15) of rat mesenteric lymphatics, where calculated pump output was maintained over a pressure range from 1 to 5 cmH 2 O because increases in contraction FREQ counterbalanced decreases in SV; likewise, measurements of SV, EF, and/or flow from bovine and ovine lymphatics suggest that optimal EDP in those vessels is between 2 and 8 cmH 2 O (12,14,15,22,24,26,28,34). An upper end of 8 cmH 2 O is likely to correlate with the diminished pump capacity observed in human peripheral lymphatic vessels during chronic lymphedema (31).…”

“…Rapid, step-wise increases in P in were imposed in ascending order to determine the speed of the adaptation and the time course over which intrinsic, secondary adjustments, if any, occurred. First, cumulative, step-wise increases in Pin from the baseline level to 1,3,5,8,12, and 16 cmH 2O were imposed by the servo controller, with pressure elevation maintained for 1-2 min at each pressure. Second, the same P in levels were tested (either randomized or sequential) but with Pin returned to the baseline level after each step; in these cases, each step and recovery period lasted ϳ5 min.…”

“…Simultaneous increases in preload and afterload simulate changes that might occur during edemagenic stress in vivo (3,18). A slow pressure ramp in both P in and Pout, from baseline pressure to 12 or 16 cmH2O, was imposed.…”

“…First, this is one of only three studies to characterize the relationship between diastolic pressure and function for a single, isolated lymphangion. With the exception of two short reports in untranslated Russian journals (18,27), previous studies (3,12,14,15,26,28) used multiple chains of lymphangions where, due to intrinsic contractile behavior that could be synchronized or nonsynchronized, P in was controlled only for the first segment of the chain and P out only for the last segment. Hence, the results presented here provide insights into the effect of preload on the function of the fundamental pumping unit of the lymphatic system: the lymphangion.…”

“…Notably, two studies have made use of cardiac-style analyses to study lymphatic pump function. Plots of intraluminal pressure (P L ) as a function of volume (calculated from internal diameter measurements) were characterized by counterclockwise loops that shifted to the right after systemic volume expansion (3) or simultaneous elevation of P in and P out (26). While those studies provided valuable information about the adaptation of the intact lymphatic pump to edemagenic loads, the effects of selectively changing preload at low and high levels of afterload were not assessed.…”