Functional lung unit in the pig

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Abstract

To study the size of the vessels supplying the functional lung unit, polystyrene beads of uniform diameter were injected intravenously in anaesthetised pigs and subsequent gas exchange abnormalities were studied using the multiple inert gas elimination technique. Beads of different sizes, ranging from 63 to 262 μm, were used, each pig receiving beads of only one size. Successive 0.25 g boli of beads (cumulative dose 1.0–1.5 g) increased shunt (from 3% baseline to 20% of cardiac output) and pulmonary artery mean pressure (from 26 to 45 mmHg) and decreased arterial PO2 (from 96 to 43 mmHg) and cardiac output from 2.8 to 2.2 L min−1 with no differences according to bead sizes. The dispersion of the ventilation dist ribution (log SDV), normal at 0.39 before beads, increased progressively with bead size from 0.48 (63 μm to 0.91 (262 μm). The 63 μm beads were lodged in vessels associated with respiratory bronchioles and smaller airways, whereas larger beads were positioned in vessels associated with non-respiratory airways. A linear correlation analysis between log SDV and bead size showed that 59 μm beads produce a log SDV that is 2 SEM above mean baseline log SDV. These findings suggest that the functional lung unit in this species (with no collateral ventilation) is smaller than in a species of the same size and with collateral ventilation (dog) in whom occlusion of 124 μm or larger diameter vessels is required to increase log SDV.

Introduction

Pulmonary vascular emboli may reduce or eliminate gas exchange in the affected lung region by obstructing blood flow to that region. However, this requires that the embolus be larger than a certain minimum size. Thus, small emboli lodging peripherally within the respiratory zone may not increase physiological dead space or cause a disturbance in ventilation-perfusion (V̇a/Q̇) relationships because alveolar gas mixing and rich capillary interconnections will allow continued perfusion and gas exchange of the tissue distal to the site of obstruction. Using the multiple inert gas elimination technique, it has been shown that 150 μm (or larger) diameter beads injected into the pulmonary arterial tree in dogs produced regions with high V̇a/Q̇ ratios, whereas beads of 100 μm or smaller diameter caused no increase in dead space or any development of high V̇a/Q̇ regions (Young et al., 1980). A similar interpretation (cessation of gas exchange) was proposed by (Swinburne et al., 1982) on the observation of erroneously small lung water determinations, using inhaled C15O2, after injection of 175 μm spheres but not after 50 μm spheres. These findings suggest that the functional gas exchanging lung unit in the dog was supplied by a pulmonary arteriole of between 100 and 150 μm in diameter.

Another species that is frequently used for circulatory and respiratory studies is the pig. However, there are differences in lung morphology that may affect pulmonary gas exchange. One difference is that the muscle layer of the pulmonary artery is thicker in the pig than in the dog, and that the hypoxic pulmonary vasoconstrictor response is stronger (Tucker et al., 1975, Rendas et al., 1978). Another is that the pig lung has well-developed interlobular fibrous septa, not seen in the dog. This allows the dog to have collateral ventilation (Van Allen et al., 1931), mainly by communications between respiratory bronchioles (Martin, 1966), whereas the pig is devoid of such ventilation (Woolcock and Macklem, 1971, Sylvester et al., 1975). These collaterals enable gas mixing between units, which have no blood supply, e.g. after micro-embobilisation, and adjacent normal units. Thus, to impair gas exchange, a vessel must be obstructed that supplies all alveoli that can exchange gas via the collaterals (the ‘functional unit’). If there is no collateral ventilation, occlusion of a smaller vessel should suffice to produce a measurable gas exchange impairment. Pigs complete their pulmonary alveolarisation and growth of the pulmonary circulation in the first 8–12 weeks after birth (Hislop and Reid, 1977). Also, 2–3 month old pigs weigh ±20 kg and are similar in size to the dogs in previous studies of the functional lung unit (Young et al., 1980, Swinburne et al., 1982).

Accordingly, the purpose of the present study was to compare the size of the vessel supplying the functional lung unit in the pig with that in the dog of the same size, and to relate the findings to vascular dimensions and the presence or absence of collateral ventilation.

Section snippets

Preparation of animals

Twenty-two pigs (age 2–3 months, average weight of 20.5 kg) were studied in the supine position. All animals were initially anaesthetised with an i.m. injection of 1.5 ml Innovar Vet, 2.5 ml ketamine and 4 ml atropine. They were then brought to the laboratory where they received 300 mg pentobarbital i.v. and were intubated and connected to a Harvard ventilator. All were ventilated with air throughout the study at a respiratory frequency of 12 breaths min−1 and a tidal volume of ≈20 ml kg−1,

Baseline measurements

Cardiac output, pulmonary artery mean pressure and pulmonary vascular resistance were comparable to previously published data in normal pigs (Fredén et al., 1995) (Fig. 1). In all pigs, baseline ventilation-perfusion distributions measured before bead injection contained virtually all of the perfusion and most of the ventilation in a single narrow mode centred on a V̇a/Q̇ ratio of 1. The dispersion of the perfusion and ventilation distributions against V̇a/Q̇ ratios (log SDQ, log SDV) was 0.54

Discussion

This study suggests that the functional lung unit in the 20 kg pig is supplied by a vessel that is smaller by a factor of two than in the dog of similar size. Thus, the dispersion of the ventilation distribution, which is particularly sensitive to reduction in regional lung blood flow causing areas of greater than average V̇a/Q̇ ratio, increased with increasing size of beads injected into the pulmonary vasculature at and above bead sizes of 92 μm. Linear interpolation of data (Fig. 4) suggests

Acknowledgements

This study was supported by National Heart, Lung and Blood Institute grant HL-17731, the Swedish Medical Research Council (5315) and the Swedish Heart–Lung Fund.

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