Effect of alveolar hypoxia on pulmonary fluid filtration in in situ dog lungs

We have studied the effect of alveolar hypoxia on fluid filtration characteristics of the pulmonary microcirculation in an in situ left upper lobe preparation with near static flow conditions (20 ml/min). In six dogs (group 1), rate of edema formation (delta W/delta t, where W is weight and t is time) was assessed over a wide range of vascular pressures under two inspired O2 fraction (FIO2) conditions (0.95 and 0.0 with 5% CO2-balance N2 in both cases). delta W/delta t was plotted against vascular pressure, and the best-fit linear regression was obtained. There was no significant difference (paired t test) in either threshold pressure for edema formation [18.3 +/- 1.8 and 17.1 +/- 1.2 (SE) mmHg, respectively] or the slopes (0.067 +/- 0.008 and 0.073 +/- 0.017 g.min-1. mmHg-1.100g-1, respectively). In another seven dogs (group 2), delta W/delta t was obtained at a constant vascular pressure of 40 mmHg under four FIO2 conditions (0.95, 0.21, 0.05, and 0.0, with 5% CO2-balance N2). Delta W/delta t for the four conditions averaged 0.60 +/- 0.11, 0.61 +/- 0.11, 0.61 +/- 0.10, and 0.61 +/- 0.10 (SE) g.min-1.mmHg-1.100g-1, respectively. No significant differences (ANOVA for repeated measures) were noted. We conclude that alveolar hypoxia does not alter the threshold for edema formation or delta W/delta t at a given microvascular pressure.     

Hypoxic exposure and activation of the afterdischarge mechanism in conscious humans

After voluntary hyperventilation, normal humans do not develop a significant ventilatory depression despite low arterial CO2 tension, a phenomenon attributed to activation of a brain stem mechanism referred to as the "afterdischarge." Afterdischarge is one of the factors that promote ventilatory stability. It is not known whether physiological stimuli, such as hypoxia, are able to activate the afterdischarge in humans. To test this, breath-by-breath ventilation (VI) was measured in nine young adults during and immediately after a brief period (35-51 s) of acute hypoxia (end-tidal O2 tension 55 Torr). Hypoxia was terminated by switching to 100% O2 (end-tidal O2 tension of first posthypoxic breath greater than 100 Torr). Brief hypoxia increased VI and decreased end-tidal CO2 tension. In all subjects, termination of hypoxia was followed by a gradual ventilatory decay; hyperoxic VI remained higher than the normoxic baseline for several breaths and, despite the negative chemical stimulus of hyperoxia and hypocapnia, reached a new steady state without an apparent undershoot. We conclude that brief hypoxia is able to activate the afterdischarge mechanism in conscious humans. This contrasts sharply with the ventilatory undershoot that follows relief of sustained hypoxia, thereby suggesting that sustained hypoxia inactivates the afterdischarge mechanism. The present findings are of relevance to the pathogenesis of periodic breathing in a hypoxic environment. Furthermore, brief exposure to hypoxia might be useful for evaluation of the role of afterdischarge in other disorders associated with unstable breathing.     

Arterial occlusion versus isofiltration pulmonary capillary pressures during very high flow

Pressure in the compliant middle segment of the pulmonary vascular bed (PM), as determined by arterial occlusion, was compared with pressure at the filtration site (effective filtration pressure, EFP), determined by the isofiltration technique, at very high (7-10 times normal) pulmonary flow in six in situ perfused canine left upper lobes. At these flow rates inflow and left atrial pressures averaged 41.9 +/- 1.3 and 2.5 +/- 0.5 (SE) mmHg, respectively. PM was 30.9 +/- 1.6 mmHg, and EFP was 32.3 +/- 1.9 mmHg with no significant difference between the two measurements by paired t test. The results indicate that the arterial occlusion technique yields a pressure that is equivalent to EFP even during very high pulmonary blood flow where the longitudinal distribution of resistance is quite different from that obtained during normal flow.     

Distensibility and pressure-flow relationship of the pulmonary circulation. I. Single-vessel model

To ascertain the relative contributions of vascular distensibility and nonhomogeneous behavior within the pulmonary circulation to the distinctive nonlinear relationship between inflow pressure (Pin) and flow [pressure-flow (P-F) relationship] and between Pin and outflow pressure (Pout) at constant flow (Pin-Pout relationship), we developed a multibranched model in which the elastic behavior of, and forces acting on, individual branches can be varied independently. The response of the multibranched model is described in the companion article (J. Appl. Physiol. 68: 1514-1527, 1990). Here we describe the methods used and the responses of single components of the larger model. Perivascular pressure is modeled as a function of intravascular and transpulmonary pressures (Pv and Ptp, respectively) and vessel length as a function of lung volume. These and the relationship between vascular area (A) and transmural pressure (Ptm) were modeled primarily from the dog data of Smith and Mitzner (J. Appl. Physiol. 48: 450-467, 1980). Vasomotor tone is modeled as a radial collapsing pressure (Pt) in the same plane as Ptm. In view of lack of information about the relationship between Pt and A for a given active state, different patterns were assumed that span a wide range of possible relationships. The P-F and Pin-Pout relationships of single vessels were very similar to those reported for the entire intact circulation. Of note, the slope of the Pin-Pout relationship in the low Pout range (0-5 Torr) was very low (less than 0.25) and increased gradually with Pout toward unity. Vasomotor tone caused an apparent parallel shift in the P-F relationship in the physiological flow range of the dog (2-8 l/min) regardless of the pattern used to model the Pt vs. A relationship; different patterns affected the P-F relationship only over the low flow range before the parallel shift was established.     

Longitudinal distribution of pulmonary vascular resistance with very high pulmonary blood flow

Dog left upper lobes (LUL) were perfused in situ via the left lower lobe artery. Lobe weight was continuously monitored. Increasing lobar flow from normal to 10 times normal had little effect on left atrial pressure, which ranged from 1 to 5 mmHg. There was a flow threshold (Qth) below which lobar weight was stable. Qth ranged from 1.1 to 1.55 l/min (mean 1.27) corresponding to four times normal LUL blood flow. Above Qth, step increases in lobar flow resulted in progressive weight gain at a constant rate that was proportional to flow. The effective pressure at the filtration site (EFP) at different flow rates was estimated from the static vascular pressure that resulted in the same rate of weight gain. From this value and from mean pulmonary arterial (PA) and left atrial (LA) pressures, we calculated resistance upstream (Rus) and downstream (Rds) from filtration site. At Qth, Rds accounted for 60% of total resistance. This fraction increased progressively with flow, reaching 83% at Q of 10 times normal. We conclude that during high pulmonary blood flow EFP is closer to PA pressure than it is to LA pressure, and that this becomes progressively more so as a function of flow. As a result, the lung accumulates water at flow rates in excess of four times normal despite a normal left atrial pressure.     

Distensibility and pressure-flow relationship of the pulmonary circulation. II. Multibranched model

The contribution of distensibility and recruitment to the distinctive behavior of the pulmonary circulation is not known. To examine this question we developed a multibranched model in which an arterial vascular bed bifurcates sequentially up to 8 parallel channels that converge and reunite at the venous side to end in the left atrium. Eight resistors representing the capillary bed separate the arterial and venous beds. The elastic behavior of capillaries and extra-alveolar vessels was modeled after Fung and Sobin (Circ. Res. 30: 451-490, 1972) and Smith and Mitzner (J. Appl. Physiol. 48: 450-467, 1980), respectively. Forces acting on each component are modified and calculated individually, thus enabling the user to explore the effects of parallel and longitudinal heterogeneities in applied forces (e.g., gravity, vasomotor tone). Model predictions indicate that the contribution of distensibility to nonlinearities in the pressure-flow (P-F) and atrial-pulmonary arterial pressure (Pla-Ppa) relationships is substantial, whereas gravity-related recruitment contributes very little to these relationships. In addition, Pla-Ppa relationships, obtained at a constant flow, have no discriminating ability in identifying the presence or absence of a waterfall along the circulation. The P-F relationship is routinely shifted in a parallel fashion, within the physiological flow range, whenever extra forces (e.g., lung volume, tone) are applied uniformly at one or more branching levels, regardless of whether a waterfall is created. For a given applied force, the magnitude of parallel shift varies with proportion of the circulation subjected to the added force and with Pla.