Effects of tidal volume and respiratory frequency on lung lymph flow

Abstract

Ventilation (V) increases lung lymph flow (Ql), but the separate effects of tidal volume (Vt) and frequency (f) and the role of V-induced changes in edema formation are poorly understood. An isolated, in situ sheep lung preparation was used to examine these effects. In eight sheep with f = 10 min(-1), results obtained during 30-min periods with Vt = 5 or 20 ml/kg were compared with values obtained during bracketed 30-min control periods (Vt = 12.5 ml/kg). Eight other sheep with constant Vt (12.5 ml/kg) were studied at f = 5 or 20 min(-1) and compared with f = 10 min(-1). Three additional groups of six sheep were perfused for 100 min with control V (10 ml/kg, 10 min(-1)). Vt was then kept constant or changed to 20 or 3 ml/kg during a second 100-min period. Increases in Vt or f increased Ql and vice versa, without corresponding effects on the rate of edema formation. For the same change in V, changing Vt had a greater effect on Ql than changing f. The change in Ql caused by an increase in Vt was significantly greater after the accumulation of interstitial edema. The change in Ql caused by a sustained increase in Vt was transient and did not correlate with the rate of edema formation, suggesting that V altered Ql through direct mechanical effects on edema-filled compartments and lymphatic vessels rather than through V-induced changes in fluid filtration.

Lymphatic impairment leads to pulmonary tertiary lymphoid organ formation and alveolar damage

“…Consistent with this role, a hallmark sign of generalized loss of lymphatic function is tissue edema (62), and lymphatic function is required for fluid drainage in the developing lung to enable neonatal lung inflation (2). Although large animal studies using short-term catheter-based approaches have demonstrated that lymphatic flow in the lung may be dynamic (21,22), pulmonary edema can also be considered a consequence of imbalanced Starling forces in the alveolar blood capillaries rather than loss of lung lymphatic function (63). Our studies of CLEC2-deficient lungs provide genetic insight into the long-term role of lymphatic vessels in the management of fluid homeostasis in the mature lung.…”

“…Physiologic studies of collecting lymphatics from the limb and mesentery have demonstrated that active SMC contraction and valve activity are coordinated to create waves of forward movement of lymph (16)(17)(18)(19). In the lung, however, physiologic studies using catheter-based measurement of pulmonary lymph flow in anesthetized large animals have suggested that extrinsic forces such as changes in thoracic pressure associated with respiration may play a more central role (3,4,(20)(21)(22).…”

Short-term hypoxic exposure at rest and during exercise reduces lung water in healthy humans

“…Levine et al (32) have shown that lymph flow increased only 10% with normobaric hypoxia in sheep, whereas Martin et al (35) found that lymph flow was increased by ϳ40% in dogs when exposed to hypoxia. Increases in ventilation are thought to lead to an increase in lung lymph flow (46). In the present study, we were able to monitor changes in ventilation for the entire night of hypoxic exposure using the LifeShirt monitoring system (Vivometrics, Ventura, CA).…”

Hypoxia induced changes in lung fluid balance in humans is associated with beta-2 adrenergic receptor density on lymphocytes

“…Levine et al have shown that lymph flow increased only 10% with normobaric hypoxia in sheep, while Martin et al found that lymph flow was increased by approximately 40% in dogs when exposed to hypoxia (Levine et al, 1988; Martin et al, 1986). Increases in ventilation are also lead to an increase in lung lymph flow (Pearse et al, 2005). And a previous study by our group showed a significant increase in ventilation with exposure to normobaric hypoxia (Snyder et al, 2006a).…”