A careful review of several different organs shows that with the information available today the beginnings of the microlymphatics in the tissue consist of endothelialized tubes only. Lymphatic smooth muscle within the collecting lymphatics appears further downstream, in some organs only outside the parenchyma. This particular anatomic picture has been observed in many different mammalian organs and in humans. The nonmuscular, so-called initial, lymphatics are the site of interstitial fluid absorption that requires only small and transient pressure gradients from the interstitium into the initial lymphatics. A fundamental question concerns the mechanism that causes expansion and compression of the initial lymphatics. I presented several realistic proposals based on information currently on hand relevant to the tissue surrounding the initial lymphatics. To achieve a continuous lymphatic output, periodic (time variant) tissue stresses need to be applied. They include arterial pressure pulsations; arteriolar vasomotion; intestinal smooth muscle contractions and motilities; skeletal muscle contraction; skin tension; and external compression, such as during walking, running, or massage, respiration, bronchiole constriction, periodic tension in tendon, contraction and relaxation of the diaphragm, tension in the pleural space during respiration, and contractions of the heart. The nonmuscular initial lymphatic system drains into a set of contractile collecting lymphatics, which by way of intrinsic smooth muscle propel lymph fluid. The exact transition between noncontractile and contractile lymphatics has been established only in a limited number of organs and requires further exploration. Retrograde flow of lymph fluid is prevented by valves. There are the usual macroscopic bileaflet valves in the initial and collecting lymphatics and also microscopic lymphatic endothelial valves on the wall of the initial lymphatics. The latter appear to prevent convective reflow into the interstitium during lymphatic compression. Many of the lymph pump mechanisms have been proposed in the past, and most authors agree that these mechanisms influence lymph flow. However, the decisive experiments have not been carried out to establish to what degree these mechanisms are sufficient to explain lymph flow rates in vivo. Because individual organs have different extrinsic pumps at the level of the initial lymphatics, future experiments need to be designed such that each pump mechanism is examined individually so as to make it possible to evaluate the additive effect on the resultant whole organ lymph flow. For example, in skeletal muscle, we want to evaluate separately the effects of arteriolar vasomotion (thus general anesthesia should be avoided), pressure pulsations (we need to maintain for different pulse pressures a constant mean arterial pressure at a level compatible with the capillary filtration pressure), and the effect of passive or active skeletal muscle contraction (thus we need to stimulate isometric or isotonic skeletal muscle contractions or induce passive motion) in the presence of continuous capillary filtration. We need to record the resultant lymph flow both under the influence of each individual pump mechanisms and when they are super-imposed on each other. We can then weigh the relative contribution of each lymph pump mechanism to the resultant flow. We need to distinguish between lymph collected from the initial lymphatics and that from the collecting lymphatics. Much research remains to be carried out along these lines, with emphasis on specific organs; no generalizations are justifiable. It would be helpful in this respect if the microarchitecture of lymphatics was further delineated, especially in humans. The ultrastructural studies should be carried out under conditions when the stresses in the lymphatics and surrounding tissue at the moment of fixation are well defined. In solid organs the three-dimensional arrangement should be displayed in conjunction with the microvasculature, the collagen network, nerves, and organ-specific parenchymal cells. Are there human organs with contractile lymphatic endings equipped with a smooth muscle media that are analogous to the lymphatics in the bat wing? If so, what does the surrounding tissue look like and what stresses are applied to such lymphatics. There is a need for basic studies on lymphatic endothelial cell biology and biomechanics, possibly by means of tissue cultures from the central ducts or the microlymphatics. A reliable, preferably noninvasive, technique is needed to measure lymph flow in initial and collecting lymphatics without resorting to cannulation.
