Response of pulmonary veins to increased intracranial pressure and pulmonary air embolization

Brain compression with subdural air causes pulmonary hypertension and noncardiogenic pulmonary edema (A. B. Malik, J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42: 335-343, 1977). To see whether air emboli to the lungs rather than brain compression caused these findings, anesthetized dogs received intravenous air infusions, subdural air infusions, or brain compression from balloons inflated in the subdural space. Subdural air and intravenous air resulted in similar vascular responses. Pulmonary artery pressure (Ppa) increased 160% (P less than 0.01) and pulmonary venous pressure transiently rose 13 +/- 5 Torr (P less than 0.05) without an increase in left atrial pressure or cardiac output (Q). The end-tidal PCO2 fell 55% (P less than 0.01) and the postmortem weight of the lungs increased 55% (P less than 0.05). Brain compression with a subdural balloon instead of air only caused a 20% rise in Ppa and Q without pulmonary edema. Thus, pulmonary air emboli rather than brain compression accounts for the edema and pulmonary hypertension caused by subdural air. Catheters in pulmonary veins and the left atrium showed that air emboli cause transient pulmonary venous hypertension as well as a reproducible form of noncardiogenic pulmonary endema.     

Elevated intracranial pressure increases pulmonary vascular permeability to protein

The syndrome of neurogenic pulmonary edema raises the question of whether there are neurological influences on pulmonary vascular permeability. Previous experimental models commonly produced severe hemodynamic alterations, complicating the distinction of increased permeability from increased hydrostatic forces in the formation of the pulmonary edema. Accordingly, we employed a milder central nervous system insult and measured the pulmonary vascular protein extravasation rate, which is a sensitive and specific indicator of altered protein permeability. After elevating intracranial pressure via cisternal saline infusion in anesthetized dogs, we used a dual isotope method to measure the protein leak index. This elevated intracranial pressure resulted in a nearly three-fold rise in the protein leak index (54.1 +/- 7.5 vs. 20.2 +/- 0.9). This central nervous system insult was associated with only mild increases in pulmonary arterial pressures and cardiac output. However, when we reproduced these hemodynamic changes with left atrial balloon inflation or isoproterenol infusion, we observed no effect on the protein leak index compared with control. Although the pulmonary arterial wedge pressure with intracranial pressure remained <10 mmHg, increases in the extravascular lung water were demonstrated. The results suggest the existence of neurological influences on pulmonary vascular protein permeability. We conclude that neurological insults result in increase pulmonary vascular permeability to protein and subsequent edema formation, which could not be accounted for by hemodynamic changes alone.     

Vasopressor responses and hypoxemia with acutely increased intracranial pressure

We studied anesthetized dogs subjected to graded increases in intracranial pressure (ICP) to assess the role of the systemic vasopressor (Cushing) response in the arterial hypoxemia associated with increased ICP. The arterial PO2 decrement was significantly greater with rapidly increased ICP compared to slowly increased ICP (P less than 0.01). Systemic vasopressor responses generated in cats by direct electrical stimulation of the vasomotor center resulted in arterial hypoxemia during controlled ventilation. Therefore, arterial hypoxemia was coincident with increased systemic blood pressure produced by either elevation of ICP or electrical stimulation of the vasomotor center.     

Effects of arterial ligation and embolization on pulmonary vascular pressure distribution

The effects of embolization on the longitudinal distribution of pulmonary vascular pressures with respect to vascular compliance were determined by the vascular inflow and outflow occlusion technique in isolated blood-perfused pig lungs treated with papaverine to prevent vasomotor responses. Embolization with microspheres having mean diameters of 75, 200, and 550 microns and with barrier beads (2 X 3 X 3.5 mm) significantly increased the pressure gradient across the relatively compliant middle region (delta Pm) without increasing the gradients across the relatively noncompliant regions on the arterial (delta Pa) or venous (delta Pv) ends of the vasculature. In contrast ligation of several lobar arteries caused delta Pa to increase from 0.9 +/- 0.3 to 5.9 +/- 1.1 mmHg but did not change delta Pm or delta Pv. Assuming that delta Pa and delta Pv measured by vascular occlusion result from cessation of flow through resistances, these data suggest that in isolated pig lungs the vessels at the boundary between the arterial and middle regions defined by the occlusion technique are arteries greater than 2-3 mm diam and smaller than lobar arteries.     

Yarrowia lipolytica lipase production enhanced by increased air pressure

Aims: To study the cellular growth and morphology of Yarrowia lipolytica W29 and its lipase and protease production under increased air pressures. Methods and Results: Batch cultures of the yeast were conducted in a pressurized bioreactor at 4 and 8 bar of air pressure and the cellular behaviour was compared with cultures at atmospheric pressure. No inhibition of cellular growth was observed by the increase of pressure. Moreover, the improvement of the oxygen transfer rate (OTR) from the gas to the culture medium by pressurization enhanced the extracellular lipase activity from 96·6 U l^?1 at 1 bar to 533·5 U l^?1 at 8 bar. The extracellular protease activity was reduced by the air pressure increase, thereby eliciting further lipase productivity. Cell morphology was slightly affected by pressure, particularly at 8 bar, where cells kept the predominant oval form but decreased in size. Conclusions: OTR improvement by total air pressure rise up to 8 bar in a bioreactor can be applied to the enhancement of lipase production by Y. lipolytica. Significance and Impact of the Study: Hyperbaric bioreactors can be successfully applied for yeast cells cultivation, particularly in high‐density cultures used for enzymes production, preventing oxygen limitation and consequently increasing overall productivity.     

Batch and fed-batch growth of Pichia pastoris under increased air pressure

Pichia pastoris CBS 2612 behavior under air pressures of 1, 3 and 5 bar in culture media of glycerol (pure and crude) and methanol was studied. Generally, the increase in oxygen transfer rate due to the increase of total pressure improved cellular growth for all carbon sources and for batch and fed-batch processes with different feeding rate strategies. In batch cultures, 1.4-, 1.2-, and 1.5-fold improvement in biomass production was obtained with the increase of air pressure up to 5 bar, using methanol, pure glycerol, and crude glycerol, respectively. The increase of air pressure to 5 bar using exponential feeding rate led to 1.4-fold improvement in biomass yield per glycerol mass consumed, for crude and pure glycerol. The current low cost of crude glycerol from the biodiesel production together with the present results shows the possibility of improving cell mass production of P. pastoris using increased air pressure.     

Venous occlusion measurement of pulmonary capillary pressure: effects of embolization

The effects of pulmonary arterial embolization on calculated pulmonary capillary pressure as determined by the venous occlusion technique are examined using a simple pressure-flow model for the lung. It is predicted that pulmonary, arterial embolization can induce significant underestimation of pulmonary capillary pressure in flowing vessels. This underestimation is related to the percent of vessels embolized and the caliber of pulmonary arteries that are embolized (i.e., the size of the emboli). Experimental verification of these theoretical findings is necessary before the conclusions can be extended to the interpretation of venous occlusion experiments in the lung.     

Candida utilis metabolism and morphology under increased air pressure up to 12 bar

Batch cultures of Candida utilis CBS 621 were carried out in a pressurized reactor under increased air pressure up to 6 bar. The effect of total air pressure was also investigated in a high cell density fed-batch culture, raising the total air pressure from 1 bar to 12 bar. The results showed that the rise of air pressure, for both operation modes, led to a substantial enhancement of biomass production. Moreover, ethanol formation was significantly reduced at 6 bar and 12 bar air pressure, respectively for batch and fed-batch processes.A method using automatic image analysis for classification of C. utilis cells based on their morphology was developed and applied to experimental data. Morphological parameters such as single and budding cells, cell size and elongation factor, were analyzed to assess the pressure effect on yeast culture. No significant differences were observed in cell size distribution and yeast cells retained the typical oval form, even at 12 bar air pressure.In what biological aspects are concerned, it is possible to state that C. utilis CBS 621 can cope with hyperbaric stress, meaning that the use of increased air pressure is a suitable method for oxygenation enhancement of high-density cultures of this strain.     

Venous occlusion pressure and vascular permeability in the dog lung after air embolization

Pulmonary edema has frequently been associated with air embolization of the lung. In the present study the hemodynamic effects of air emboli (AE) were studied in the isolated mechanically ventilated canine right lower lung lobe (RLL), pump perfused at a constant blood flow. Air was infused via the pulmonary artery (n = 7) at 0.6 ml/min until pulmonary arterial pressure (Pa) rose 250%. While Pa rose from 12.4 +/- 0.6 to 44.6 +/- 2.0 (SE) cmH2O (P less than 0.05), venous occlusion pressure remained constant (7.0 +/- 0.5 to 6.8 +/- 0.6 cmH2O; P greater than 0.05). Lobar vascular resistance (RT) increased from 2.8 +/- 0.3 to 12.1 +/- 0.2 Torr.ml-1.min.10(-2) (P less than 0.05), whereas the venous occlusion technique used to determine the segmental distribution of vascular resistance indicated the increase in RT was confined to vessels upstream to the veins. Control lobes (n = 7) administered saline at a similar rate showed no significant hemodynamic changes. As an index of microvascular injury the pulmonary filtration coefficient (Kf) was obtained by sequential elevations of lobar vascular pressures. The Kf was 0.11 +/- 0.01 and 0.07 +/- 0.01 ml.min-1.Torr-1.100 g RLL-1 in AE and control lobes, respectively (P less than 0.05). Despite a higher Kf in AE lobes, total lobe weight gains did not differ and airway fluid was not seen in the AE group. Although air embolization caused an increase in upstream resistance and vascular permeability, venous occlusion pressure did not increase, and marked edema did not occur.