Determinants of pulmonary blood volume. Effects of acute changes in pulmonary vascular pressures and flow

To examine the effects of pulmonary vascular pressures and flow on pulmonary blood volume (PBV), experiments were performed at constant heart rate and zone 3 conditions (mean left atrial pressure (LAP) above airway pressure) in six anesthetized, open-chest dogs. PBV was calculated as the product of electromagnetic aortic flow and pulmonary mean transit time for ascorbate, obtained without blood withdrawal by polarographic recording of aortic ascorbate changes. In three series of experiments LAP was raised similarly in three steps, from 4.5 to 14.8 mmHg: by mitral constriction which reduced pulmonary blood flow, by blood volume expansion which more than doubled pulmonary blood flow, or by a combination of the two procedures which kept pulmonary blood flow constant. In all three series, LAP and mean pulmonary arterial pressure (PAP) rose in proportion, but PBV was better correlated to PAP (r=0.87±0.02) than to LAP (r=0.66±0.09). These experiments suggest that PAP is the most important factor in determining PBV under zone 3 conditions, whether PAP is raised by increasing pulmonary blood flow or by mitral constriction.     

Constrictor response of small pulmonary arteries to acute pulmonary hypertension during left atrial pressure elevation

Acute elevations in left atrial pressure (LAP) were induced by altering the volume of air within a balloon inserted into the left atrium; the changes in internal diameter (ID) of small muscular pulmonary arteries (100-600 microns ID) in response to the associated rises of pulmonary arterial pressure (PAP) were measured using an X-ray TV system on the in vivo cat lung. When LAP was elevated to 14 +/- 1, 24 +/- 1, and 30 +/- 1 mmHg, PAP was increased to 21 +/- 1, 30 +/- 1, and 37 +/- 1 mmHg, respectively. With PAP ranging from 16 (control value) to 21 mmHg the ID did not dilate significantly. With PAP of 30-37 mmHg significant ID dilation occurred. The magnitude of the ID dilation (16%) with PAP of 37 mmHg, however, was significantly smaller than that (20%) with PAP of 30 mmHg despite the greater pressure rise. When the elevated PAP of 30-37 mmHg was quickly returned to the control level by rapid balloon deflation, the ID constricted significantly below the control level. The magnitude of the ID constriction was proportional to the degree of the preceding PAP rise and was maximal in the arteries of 200-400 microns ID. A papaverine hydrochloride injection combined with the balloon deflation completely abolished the ID constriction. A phentolamine injection, on the other hand, significantly attenuated the constriction with approximately half of the constriction persisting. The results indicate that an increase in vascular smooth muscle tone occurred in the small muscular pulmonary arteries, particularly those of 200-400 microns ID, in response to the acute rise of PAP above 30 mmHg during the LAP elevation. In addition, the data suggest the partial participation of catecholamines in the active contraction of vascular smooth muscle. The arterial contraction may serve to protect the pulmonary capillaries from an excessive hydrostatic pressure and pulmonary edema.     

Peripheral and central vascular compliances in conscious normotensive and spontaneously hypertensive rats

Changes of left atrial (LAP) and right atrial pressure (RAP) upon 10% and 20% blood volume expansion were studied in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKR) with intact nervous cardiovascular control. In a separate series the changes of central (CBV) and peripheral (PBV) blood volumes upon similar increases of total blood volume (TBV) were measured as well, throughout using male, adult SHR and WKR in both series. During volume expansion both LAP and RAP increased significantly more in SHR than in WKR, as did CBV, while PBV increased significantly less in SHR than in WKR. Total ‘effective’ vascular compliance, defined as ΔTBV/ΔRAP, was significantly lower in SHR. From the two series of measurements central (CBV/LAP) and peripheral (PBV/RAP) vascular compliances could be separately deduced. Central vascular compliance was nearly 50% lower in SHR than in WKR. However, ‘unstressed’ volume of the peripheral compartment appeared to be rather normal in SHR compared to WKR. It is therefore suggested that the decreased total vascular compliance seen in essential hypertension and in SHR is mainly due to a decreased distensibility of the systemic capacitance vessels.     

The site of action of nerves in the pulmonary vascular bed in the dog

1. The effects of stimulation of the thoracic vagosympathetic nerve or upper thoracic sympathetic chain on the pulmonary vascular resistance have been studied in atropinized, isolated, ventilated lung lobes under various conditions of pulmonary circulation perfusion. Throughout the nerve-stimulation tests bronchial circulation perfusion was maintained or temporarily interrupted.2. The pulmonary vascular resistance increase evoked by nerve stimulation (a) occurred in the absence of tidal air changes; (b) did not consistently differ during predominantly ;sluice' and ;non-sluice' conditions of pulmonary circulation perfusion; (c) was approximately one and a half times greater during constant pressure than during constant volume inflow perfusion of the pulmonary circulation; and (d) was greater during reverse than during forward perfusion.3. In lung lobes perfused in either direction at constant volume inflow nerve stimulation produced an increase in inflow pressure and a diminution in total lung blood volume reflected by a temporary increase in blood outflow.4. In lung lobes in which neither the pulmonary nor the bronchial circulations were perfused and the capillaries were completely blocked by high intratracheal pressures, thus isolating the pulmonary arterial system from the venous system, nerve stimulation produced a diminution in the blood volume of both systems.5. Nerve stimulation produced a rise in bronchial arterial pressure in the absence of pulmonary circulation perfusion.6. Further evidence is adduced that pulmonary vasomotor nerve responses do not depend upon the transfer of transmitter substances from the bronchial to the pulmonary circulation.7. The possible significance of these observations in relation to the site of action of pulmonary vasomotor nerves is discussed.     

Mental stress increases right heart afterload in severe pulmonary hypertension.

Little is known about mental stress effects on the pulmonary circulation in health and disease. The current study was conducted to investigate whether pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) would further increase during standardized mental stress testing in patients with severe pulmonary hypertension. The study was a prospective analysis of seven patients (average age: 40 years, range from 21 to 56 years) with severe pulmonary hypertension (primary: n = 4, secondary forms: n = 3; resting mean pulmonary artery pressure ranged between 48 and 65 mmHg). Right heart catheterization for the determination of PAP, pulmonary capillary wedge pressure (PCW) and cardiac output (CO) was clinically indicated (diagnostic workup, acute drug testing). Patients accomplished a standardized 10 min mental stress test (computer based, adaptive complex reaction-time task). Pulmonary haemodynamics during stress were compared to resting baseline. During mental stress mean PAP (+/- SEM) increased by 9.4 +/- 2.1 mmHg (P < 0.005). Pulmonary vascular resistance increased by 149 +/- 25 dyne s cm-5 (P < 0.001). Stroke volume decreased by 6.6 +/- 2.2 ml (P < 0.03). The data show that moderate mental stress increases right heart afterload in patients with severe pulmonary hypertension owing to elevation of PVR.     

Total body vascular capacitance changes during high intracranial pressure in dogs

The active capacitance response to increased intracranial pressure (Pic) was studied in nine chloralose-anesthetized dogs. The vena cavae were cannulated and drained into a reservoir as blood was pumped at a constant flow (Q) into the right atrium. Central blood volume was determined as Q times the mean transit time of dye from the right atrium to the aortic root. Arterial compliance (Ca) was determined from the monoexponential decay of systemic arterial pressure (SAP) during vagal cardiac arrest to compute changes in arterial volume (delta SAP X Ca). Atropine was administered to prevent bradycardia and dangerous, constant cardiac output-induced increases in pulmonary arterial (PAP) and right and left atrial pressures. Blood volume shifts indicative of active venoconstriction, included changes in reservoir, central, and arterial volumes during Pic of 100-200 mmHg. Raised Pic, after atropine, induced a tachycardia, increased systemic and pulmonary resistances, and increased SAP and PAP. Venoconstriction caused marked blood shifts between 125 and 200 mmHg Pic. The extrapolated response threshold was about 112 mmHg. In the most sensitive range, venoconstriction amounted to 3.9 ml X kg-1 per 25-mmHg change in Pic. These results indicate that intense active capacitance vessel constriction is an important part of cardiovascular hemostasis during rapidly increased intracranial pressure.     

Hemodynamic response to rapidly infused 25% albumin in sheep: blunting the effects with ibuprofen

We document the hemodynamic deterioration in two patients given very rapid intravenous infusions of 25% albumin. We developed an animal model to further elucidate the mechanism involved. Seven sheep were instrumented for the measurement of cardiac index (CI), pulmonary artery pressure (PAP), mean arterial pressure (MAP), left atrial pressure (LAP) and given 0.5 g/kg of Hyland brand 25% albumin over 5 min. Systemic vascular resistance index (SVRI), pulmonary vascular resistance index and left and right ventricular stroke work index were calculated. Equal volumes of normal saline were given to the same sheep as controls. Albumin significantly (p less than 0.05) increased MAP, PAP, LAP and SVRI, while CI decreased over the 3-10-min interval. Ibuprofen (14 mg/kg) intravenously administered 15 min prior to albumin, blunted all the above responses. This implicates a prostanoid as the possible mediator of these changes.     

Constant flow- vs. constant pressure-perfusion for studies of pulmonary vasoactive responses

We have compared the pulmonary vascular responses to a standardized hypoxic vasoconstrictor stimulus (F_1,0,2=0.02) obtained during 1) constant volume inflow, with pulmonary arterial pressure as the dependent variable, and 2) constant inflow pressure, with flow as the dependent variable. Isolated rat lungs were perfused at different baseline transvascular pressures. The experimental arrangement allowed changes between the two types of perfusion. Hypoxia at constant pressure perfusion gave a higher percentage rise in pulmonary vascular resistance (PVR) at all pressure levels. This advantage was however, more than offset by the finding that a) vascular closure (total or partial) often occurred, particularly below arterial pressure of 3 kPa, making detection of graded responses impossible, and b) the control situation was rarely regained. Responses obtained during constant flow were less reduced by elevations in baseline transvascular pressure, and the control situation was rapidly and completely regained. The observation that hypoxic vascular closure may occur in the pulmonary vascular bed supports the hypothesis that high altitude edema is caused by precapillary occlusion of a major part of the vascular bed, thereby subjecting still perfused regions to very high pressures and flow.     

Effect of nocturnal hypoxia on pulmonary hemodynamics in patients with obstructive sleep apnea

Effects of apnoea induced nocturnal hypoxia on pulmonary haemodynamics (PH) in pts with OSA are still under debate. We studied PH in 67 pts (64 M and 3 F) mean +/- SD: age 45 +/- 8 years, with severe OSA, AHI 62 +/- 22. Patients had normal spirometry: FVC 98 +/- 15% N, FEV1 97 +/- 16% N and arterial blood gases--PaO2 72 +/- 10 mmHg, PaCO2 40 +/- 4 mmHg. PH were studied using Swan-Ganz thermodilution catheter. PH were within normal range: right atrial pressure 4.2 +/- 2.7 mmHg, right ventricular systolic/enddiastolic pressure 28.1 +/- 7.1/5.0 +/- 3.3 mmHg, mean pulmonary artery pressure (PAP) 15.8 +/- 4.6 mmHg, mean pulmonary wedge pressure (PW) 6.8 +/- 3.1 mmHg, cardiac output (CO) 5.6 +/- 2.2 L/min. and pulmonary vascular resistance (PVR) 150 +/- 83 dyn.sec.cm-5. During exercise (44 pts) PAP rose from 15.8 +/- 4.3 to 29.8 +/- 9.4 mmHg, PW rose from 6.8 +/- 3.2 to 12.6 +/- 6.8 mmHg and CO from 4.9 +/- 1.9 to 9.2 +/- 4.2 L/min. All patients presented with nocturnal desaturations. Mean oxygen saturation (SaO2 mean) was: 87.4 +/- 5.4%, minimal saturation (SaO2 min) was 57.4 +/- 15.9%. Time spent in desaturation SaO2 < 90% (T90) was 50.7 +/- 26.5%. Results of PH investigations were related to results of pulse oximetry. Linear regression analysis showed week negative correlations between SaO2 mean and: PAP (r = -0.37 p = 0.003), PVR (r = -0.37 p = 0.007), and positive correlation between T90 and PAP (r = 0.37 p = 0.008). We conclude that there is no diurnal pulmonary hypertension at rest in patients with severe OSA and normal lung function even in the presence of severe overnight nocturnal desaturations. In half of studied patients we observed pulmonary hypertension during exercise.     

Hemodynamic differences between the awake and anesthetized conditions in normal calves

There is insufficient information in the literature about baseline circulatory parameters in normal calves in the anesthetized versus postoperative awake conditions under which a large volume of medical research is conducted. Eleven calves (mean body weight, 78.1?±?14.3?kg) were implanted with a flow probe and fluid-filled pressure lines to measure cardiac output (CO), aortic (AoP), central venous (CVP), pulmonary arterial (PAP), and left atrial pressures (LAP). Systemic (SVR) and pulmonary vascular resistance (PVR) were also calculated. We obtained the above hemodynamic data (n?=?11) and epicardial echocardiography (n?=?7) during open-chest surgery under isoflurane anesthesia. After full recovery from surgery, animals were evaluated in the awake condition on postoperative days 6-9 using transthoracic echocardiography (n?=?7) and the hemodynamic monitoring lines and probes noted (n?=?11). CO, AoP, and PAP levels in the anesthetized condition were significantly lower than in the awake condition. Other hemodynamic parameters (CVP, LAP, SVR, and PVR) were not significantly different. In conclusion, data from this study quantify changes in CO, AoP, and PAP in anesthetized calves that may affect the hemodynamic response to experimental therapeutics such as new cardiac assist devices, prosthetic valves, and surgical interventions. Our study also provides baseline data for the translation of the hemodynamic data obtained in acute in vivo calf studies to that of an awake subject.     

Cardiovascular effects of increasing airway pressure in the dog.

In paralyzed anesthetized dogs the cardiovascular effects of increasing positive end-expiratory pressure (PEEP) were explored under two conditions: a) end-expiratory lung volume increasing, b) end-expiratory lung volume kept nearly constant by matching pleural pressure rise to end-expiratory airway pressure rise. Two series of experiments were done: I) xenous return was allowed to fall, II) venous return was kept constant by infusion of volume. Right atrial pressure, pulmonary arterial pressure, and left atrial pressure increased under all conditions when measured relative to atmospheric pressure, but increased relative to pleural pressure only under condition a. The rise in left atrial relative to pleural pressure may indicate a degree of left ventricular dysfunction associated with increasing end-expiratory lung volume. Furthermore, when end-expiratory lung volume increased, inequality of the rise in pulmonary artery wedge pressure exceeded the rise in left atrial pressure in series I. From plots of cardiac output as a function of right atrial pressure it was possible to conclude that the decrease in venous return is partially offset by an increase in mean circulatory pressure.     

Effects of nocturnal desaturation on pulmonary hemodynamics in patients with overlap syndrome (chronic obstructive pulmonary disease and obstructive sleep apnea)

We studied pulmonary haemodynamics and nocturnal desaturation in 17 patients with an overlap syndrome (OS), all males, mean age 51.4 +/- 8.3 years, mean BMI 37 +/- 4.2 kg/m2. Diagnosis of COPD was based on pts history, clinical examination, lung function tests and chest radiography. Spirometry showed: FVC 2.7 +/- 0.7 L (59 +/- 16% N), FEV1 1.5 +/- 0.7 L (43 +/- 16% N), FEV1% FVC 54 +/- 13%, Raw 0.58 +/- 0.4 kP.s/L, RV 3.3 +/- 1.2 L (144 +/- 51% N), TLC 6.6 +/- 1.3 L (100 +/- 14% N) and RV% TLC (49.5 +/- 12.1%. Arterial blood gas values were: PaO2 56.9 +/- 9.5 mmHg, PaCO2 46.9 +/- 9.8 mmHg, pH 7.37 +/- 0.05. Mean apnoea/hypopnoea index (AHI) was 63.9 +/- 18.9. Pulmonary haemodynamics at rest (Swan Ganz thermodilution catheter) were: mean pulmonary artery pressure (PAP-SP) 24.2 +/- 7.4 mmHg, mean pulmonary wedge pressure (PW-SP) was 9.1 +/- 7.3 mmHg, cardiac output (CO-SP) was 5.6 +/- 2.3 L/min. and pulmonary vascular resistance (PVR) was 229 +/- 97 dyn.sec.cm-5. During exercise (40 Watts, 7 mins, in 8 pts) PAP rose from 19 +/- 6 mmHg to 41.2 +/- 15.1 mmHg, PW rose from 7.4 +/- 7.2 mmHg to 11 +/- 10.2 mmHg, CO rose from 5.8 +/- 2.7 L/min to 12.7 +/- 2.4 L/min. Overnight pulse oximetry showed: mean oxygen saturation (SaO2 mean) 80.2 +/- 8.5%, minimal saturation (SaO2 min) was 50.7 +/- 19.7%. Time spent in desaturation SaO2 < 90% (T 90) was 76.9 +/- 25.7%. We conclude that pts with OS have resting pulmonary hypertension and elevated PVR. During low grade exercise the rise in PAP was highly abnormal. Statistical analysis showed no correlations between nocturnal SaO2 and diurnal pulmonary haemodynamics data.     

A single open sea air dive increases pulmonary artery pressure and reduces right ventricular function in professional divers

After decompression from dives, bubbles are frequently observed in the right ventricular outflow tract and may lead to vascular damage, pulmonary arterial hypertension and right ventricular overload. No data exist on the effect of open sea diving on the pulmonary artery pressure (PAP). Eight professional divers performed an open sea air dive to 30 msw. Before and postdive a Doppler echocardiographic study was undertaken. Systolic pulmonary artery pressure (SPAP) was estimated from measurement of peak flow velocity of the tricuspid regurgitant jet; the ratio between pulmonary artery acceleration times (AccT) and right ventricular ejection time (RVET) was used as an estimate of the mean PAP. No evidence of either patent foramen ovale or intra-pulmonary shunt was found in any subject postdive after performing a Valsalva maneuver. SPAP increased from 25 ± 3 to 33 ± 2 mmHg and AccT/RVET ratio decreased from 0.44 ± 0.04 to 0.3 ± 0.02 20 min after the dive, respectively. Pulmonary vascular resistance increased from 1.2 ± 0.1 to 1.4 ± 0.1 Woods Units. Postdive right ventricle end-diastolic and end-systolic volumes were increased for about 19% (P = 0.001) and 33% (P = 0.001) and right ejection fraction decreased about for 6% (P = 0.001). Cardiac output decreased from 4.8 ± 0.9 (l min⁻¹) to 4.0 ± 0.6 at 40 min postdive due to decreases in heart rate and stroke volume. This study shows that a single open sea dive may be associated with right heart overload due to increased pressure in the pulmonary artery.     

Pulmonary haemodynamics in obstructive sleep apnoea

SUMMARY  The time course of right ventricular output (RVO) and transmural pulmonary artery pressure (PAP) changes, detected beat-by-beat, were analysed in a sample of obstructive sleep apnoea (OSA) episodes recorded in six patients with OSA syndrome. RVO showed a trend to a decrease during apnoeas, due to a decrease in heart rate, and decreased further in the immediate post-apnoeic period, due to a decrease in right ventricular stroke volume [post-apnoeic RVO = 82.6 ± 9.3 (SD) % of the value in the immediate pre-apnoeic period; P <0.01]. Both systolic and diastolic transmural PAP showed a progressive increase throughout apnoeas (from 23.7 ± 7.3 to 29 ± 6.9 and from 9.1 ± 4.4 to 14.3 ± 3.3 mmHg, respectively, from early to late apnoeic period; P <0.01), and similarly high values in the late apnoeic and in the immediate post-apnoeic period. Therefore, cardiac output and arterial pressure in the pulmonary circulation undergo simultaneous inverse changes in OSA, similar to what was previously shown in the systemic circulation. Although these data cannot define accurately the behaviour of pulmonary vascular resistance, they suggest that pulmonary vascular resistance could also undergo continuous oscillations in OSA, with recurring peaks detectable between apnoea termination and the immediate post-apnoeic period.     

Reflex responses from the main pulmonary artery and bifurcation in anaesthetised dogs

This study was undertaken to determine the reflex cardiovascular and respiratory responses to discrete stimulation of pulmonary arterial baroreceptors using a preparation in which secondary modulation of responses from other reflexes was prevented. Dogs were anaesthetised with -chloralose, artificially ventilated, the chests widely opened and a cardiopulmonary bypass established. The main pulmonary arterial trunk, bifurcation and extrapulmonary arteries as far as the first lobar arteries on each side were vascularly isolated and perfused through the left pulmonary artery and drained via the right artery through a Starling resistance which controlled pulmonary arterial pressure. Pressures distending systemic baroreceptors and reflexogenic regions in the heart were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a vascularly isolated hind limb and to the remainder of the subdiaphragmatic systemic circulation, both of which were perfused at constant flows. Respiratory responses were assessed from recordings of efferent phrenic nerve activity. Increases in pulmonary arterial pressure consistently evoked increases in both perfusion pressures and in phrenic nerve activity. Both vascular and respiratory responses were obtained when pulmonary arterial pressure was increased to above about 30 mmHg. Responses increased at higher levels of pulmonary arterial pressures. In 13 dogs increases in pulmonary arterial pressure to 45 mmHg increased systemic perfusion pressure by 24 +/- 7 mmHg (mean +/- S.E.M.) from 162 +/- 11 mmHg. Setting carotid sinus pressure at different levels did not influence the vascular response to changes in pulmonary arterial pressure. The presence of a negative intrathoracic pressure of -20 mmHg resulted in larger vascular responses being obtained at lower levels of pulmonary arterial pressure. This indicates that the reflex may be more effective in the intact closed-chest animal. These results demonstrate that stimulation of pulmonary arterial baroreceptors evokes a pressor reflex and augments respiratory drive. This reflex is likely to be elicited in circumstances where pulmonary arterial pressure increases and the negative excursions of intrathoracic pressure become greater. They are likely, therefore, to be involved in the cardio-respiratory response to exercise as well as in pathological states such as pulmonary hypertension or restrictive or obstructive lung disease.     

Responses of C fiber afferents of the rabbit airways and lungs to changes in extra-vascular fluid volume

Effects of changes in extra-vascular fluid volume produced by pulmonary lymphatic obstruction and plasmapheresis on the activities of bronchial and pulmonary C fiber receptors and rapidly adapting receptors (RARs) were investigated in New Zealand White rabbits. In intact rabbits, pulmonary lymphatic obstruction either alone or in combination with plasmapheresis did not stimulate pulmonary C fiber receptors. Only the combined stimulus activated the bronchial C fiber receptors. Bronchial C fiber receptors were also stimulated by graded increases in left atrial pressure (+5 and +10 mmHg). In contrast, RARs were activated by lymphatic obstruction either alone or in combination with plasmapheresis. These procedures increase the extra-vascular fluid volume in the carina and bronchi but not in the lungs (alveoli). In rabbits with chronic pulmonary venous congestion secondary to mitral valve damage, bronchial C fiber receptors were not stimulated by these increments in left atrial pressure which were insufficient to increase the extra vascular fluid content of the airways. However, both pulmonary and bronchial C fiber receptors were stimulated when the left atrial pressure was raised to 25 mmHg in these animals to cause pulmonary edema.     

Measurement of human pulmonary arterial volume in vivo

A method of measuring pulmonary arterial transit time (PATT), from the pulmonary valve to the precapillary vessels, using the gamma-emitting isotope technetium-99m and external counting probes, has been applied in patients coming to cardiac catheterization. The method was successfully applied in 36 of 39 patients. The dose of 99Tc for a single determination was 1 mc. Agreement between right and left lung transit times was good, average difference between the two lungs being less than 7% of mean PATT. Reproducibility between duplicate injections was 9.4 +/- 1.2% (SEM). Pulmonary arterial volume (PAV) was calculated as the product of PATT and flow. In 11 normal patients average PAV was 92 ml . m-2 and constituted 30% of total pulmonary blood volume (PBV). In ten patients with pulmonary hypertension secondary to lung disease average PAV was 129 ml . m-2, constituting 38% of PBV, while, in seven patients with left ventricular disease and a similar degree of pulmonary hypertension, PAV was also 129 ml . m-2, but constituted only 29% of PBV. Thus, in pulmonary hypertension secondary to lung disease the pulmonary arteries are enlarged out of proportion to the remainder of the pulmonary vascular bed. In seven patients with carcinoma of the lung, in whom one main branch of the pulmonary artery was occluded with a balloon catheter, PAV fell significantly less than would be predicted, indicating a distension of the unoccluded portion of the arterial tree. Distensibility in the unoccluded part of the arterial tree was calculated to be 4.5% per cmH2O pressure.     

Spectacularly robust! Tensegrity principle explains the mechanical strength of the avian lung

Among the air-breathing vertebrates, the respiratory system of birds, the lung-air sac system, is remarkably complex and singularly efficient. The most perplexing structural property of the avian lung pertains to its exceptional mechanical strength, especially that of the minuscule terminal respiratory units, the air- and the blood capillaries. In different species of birds, the air capillaries range in diameter from 3 to 20 micro m: the blood capillaries are in all cases relatively smaller. Over and above their capacity to withstand enormous surface tension forces at the air-tissue interface, the air capillaries resist mechanical compression (parabronchial distending pressure) as high as 20 cm H(2)O (2 kPa). The blood capillaries tolerate a pulmonary arterial vascular pressure of 24.1 mmHg (3.2 kPa) and vascular resistance of 22.5 mmHg (3 kPa) without distending. The design of the avian respiratory system fundamentally stems from the rigidity (strength) of the lung. The gas exchanger (the lung) is uncoupled from the ventilator (the air sacs), allowing the lung (the paleopulmonic parabronchi) to be ventilated continuously and unidirectionally by synchronized bellows like action of the air sacs. Since during the ventilation of the lung the air capillaries do not have to be distended (dilated), i.e., surface tension force does not have to be overcome (as would be the case if the lung was compliant), extremely intense subdivision of the exchange tissue was possible. Minuscule terminal respiratory units developed, producing a vast respiratory surface area in a limited lung volume. I make a case that a firm (rigid) rib cage, a lung tightly held by the ribs and the horizontal septum, a lung directly attached to the trunk, specially formed and compactly arranged parabronchi, intertwined atrial muscles, and tightly set air capillaries and blood capillaries form an integrated hierarchy of discrete network system of tension and compression, a tensegrity (tensional integrity) array, which absorbs, transmits, and dissipates stress, stabilizing (strengthening) the lung and its various structural components.     

Inhibition of nitric oxide synthesis potentiates hypoxic vasoconstriction in isolated rat lungs

We have investigated the influence of endogenous nitric oxide (NO) on the vascular resistance of isolated rat lungs by inhibiting its synthesis with the false substrate N-monomethyl-L-arginine (L-NMMA). When perfused with blood at constant flow the addition of L-NMMA (10(-3) M) did not affect pulmonary arterial pressure in hyperoxia but did increase the response to hypoxia (PO2 25-35 mmHg) by 2.5 +/- 0.2 fold (mean +/- S.E.M.). The effect of L-NMMA was reversed by 3 x 10(-3) M-L-arginine, the true substrate for NO synthesis. Thus NO is an important pulmonary vasodilator but hypoxic vasoconstriction does not result from a reduction of its background release.     

Pulmonary hemodynamic effects of intravenous almitrine in patients with chronic bronchitis and respiratory insufficiency

The effects on ventilation, gas exchange and pulmonary haemodynamics of 1 h infusion of 0.5 mg X kg-1 almitrine (Vectarion) were studied in 14 patients with chronic bronchitis, with clear hypoxemia (PaO2 less than 65 mmHg) and hypercapnia (PaCO2 greater than or equal to 45 mmHg). The separate effects of the almitrine solvent and/or the solution were studied in six similar chronic bronchitics. In this latter group, blood gases and haemodynamic values were not significantly altered. In subjects treated with almitrine, PaO2 raised from 51.9 +/- 6.6 (control: T0) to 61.9 +/- 9.9 mmHg at the 60th min (t60) of infusion (p less than 0.001); PaCO2 decreased from 52.8 +/- 6.3 (t0) to 45.7 +/- 5.2 mmHg at t60 (p less than 0.001). The effects on blood gases were still marked 10 min after infusion (t70). The significant increase in PaO2 was faster (10th min) than that of PaCO2 (20th min). The mean pulmonary artery pressure (Ppa) rose appreciably, from 27.8 +/- 11.3 at t0 to 35.5 +/- 12.5 mmHg at t60 (p less than 0.001). This rise was significant from the 10th min (p less than 0.005) and was related to that of pulmonary vascular resistance since on average cardiac output and pulmonary wedge pressure did not change. Ppa came back to its initial value at t70. Thus pulmonary vasoactive effects were at the same time early and transitory. They seemed due to an arterial vasoconstriction (role of chemoreceptors?), which could also explain the perfusion redistribution to the best ventilated areas and the improvement of VA/Q inequalities.