Lymph Flow Pattern in the Intact Thoracic Duct in Sheep

Abstract

To study the lymph flow dynamics in the intact thoracic duct, we applied an ultrasound transit‐time flow probe in seven anaesthetized and four unanaesthetized adult sheep (.60 kg). In unanaesthetized non‐fasting animals we found that lymph flow in the thoracic duct was always regular pulsatile (pulsation frequency, 5.2 ± 0.8 min−1) with no relation to heart or respiratory activity. At baseline the peak level of the thoracic duct pulse flow was 11.6–20.7 ml min−1 with a nadir of 0–3.6 ml min−1. Mean lymph flow was 5.4 ± 3.1 ml min−1. The flow pattern of lymph in the thoracic duct was essentially the same in the anaesthetized animals. In both the anaesthetized and unanaesthetized animals, the lymph flow response to a stepwise increase in the outflow venous pressure showed interindividual variation. Some were sensitive to any increase in outflow venous pressure, but others were resistant in that lymph flow did not decrease until outflow venous pressure was increased to higher levels. This resistance was also observed in the high lymph flow condition produced by fluid infusion in the anaesthetized animal and mechanical constriction of the caudal vena cava in the unanaesthetized animals. Pulsation frequency of the thoracic duct flow initially increased and then decreased with a stepwise increase in the outflow venous pressure. This initial increase might be a compensatory response to maintain lymph flow against elevated outflow venous pressure. To test the effect of long‐term outflow venous pressure elevation in unanaesthetized sheep, outflow venous pressure was increased by inflation of a cuff around the cranial vena cava for 1, 5 or 25 h. The cuff was inflated to a level where lymph flow was reduced. Lymph flow remained low or decreased further during the entire cuff‐inflation period. We calculated the lymph debt caused by the outflow venous pressure elevation and the amount ‘repaid’ when venous pressure returned to normal. Lymph debt for 25 h was 6400 ml but only 200 ml was repaid. Since we observed no visible oedema formation in the lower body of the sheep, the non‐colloidal components of the lymph must have been reabsorbed into the bloodstream, most likely in the lymph nodes.

Identification of Interstitial Cajal-Like Cells in the Human Thoracic Duct

“…Spontaneous activity independent of heart or respiratory activity, nervous or humoral inputs, or flow and pressure changes has also been observed in animal TD [Reddy and Staub, 1981;Onizuka et al, 1997;Moffatt and Cocks, 2004] and in human TD in situ under anesthesia [Kinmonth and Taylor, 1956;Kinmonth and Sharpey-Schafer, 1959;Edwards et al, 1965] and ex vivo [Sjoberg and Steen, 1991;Telinius et al, 2010]. The cellular mechanism responsible for the spontaneous and autoregulatory activity of the lymphatic vasculature has been debated since the very first experimental observations of this activity in animals.…”

New method for evaluation of lung lymph flow rate with intact lymphatics in anaesthetized sheep

“…The baseline value of LL flow in our model was three‐ to sixfold higher than values obtained in previous studies using the cannulation method (Tables 1–3). Because of the large discrepancy in baseline values between the two methods, we repeated our bench and in situ calibrations (Onizuka et al. 1997) to confirm that our data are reliable.…”

“…The flow probe was connected to an ultrasound transit‐time flow meter (Model H207; Transonic Systems). Calibration procedures of the flowmeter were as reported in our previous study (Onizuka et al. 1997).…”

Advanced drug delivery to the lymphatic system: lipid-based nanoformulations

“…92 Small animals, such as rats, are commonly used, but some larger animals, including sheep, pigs, rabbits, and dogs, have also been used for this model. [92][93][94][95][96][97][98][99][100] Another in vivo model is the lymphatic venous shunt, in which drug concentrations in lymph are measured at fixed time intervals, and lymph is collected over a longer period of time. Further, an indirect method has been used in an oral bioavailability study to evaluate intestinal lymphatic drug transport in both the presence and absence of inhibitors of intestinal chylomicron flow.…”