Hypoxic pulmonary vasoconstriction in man: effects of hyperventilation.

The pulmonary vasoconstriction response to hypoxia was studied in eight anaesthetized supine subjects. One lung was made hypoxic while the other was ventilated with 100% oxygen. This was achieved by separating the tidal gas-distribution to the lungs by means of a double-lumen tracheal catheter. The hypoxic pulmonary vasoconstriction (HPV) response was estimated from the blood flow diversion away from the hypoxic lung. Blood flow distribution between the lungs was calculated from the regional expired carbon dioxide production, assuming regional carbon dioxide production to be proportional to blood flow. The subjects were studied during six different conditions. Firstly, when ventilated with 100% oxygen to both lungs at a PaCO2 of about 6 kPa. Secondly, with 100% oxygen to the left lung and 5% oxygen in nitrogen to the right (test) lung. The ratio between carbon dioxide output from right and left lung was calculated. These measurements were repeated during two states of hyperventilation (PaCO2 of about 4.5 kPa and 3.5 kPa, respectively) with and without hypoxia (conditions 3-6). During normoventilation, blood flow distribution between the lungs was equal. During hypoxia, blood flow distribution to the hypoxic lung decreased by 35% of the pre-hypoxic value. Furthermore, a decrease in arterial oxygen tension from 51.5 +/- 4.5 to 11.5 +/- 2.1 kPa was observed. During excessive hyperventilation (PaCO2 3.2 +/- 0.2 kPa), blood flow distribution to the hypoxic right lung decreased by only 10% of its pre-hypoxic value. A further decrease in arterial oxygen tension to 8.5 +/- 1.8 kPa was observed. This decrease in PaO2 was possibly due to an increased venous admixture caused by an abolished HPV response. It is concluded that hyperventilation counteracts hypoxic pulmonary vasoconstriction in man.

Hypoxic pulmonary vasoconstriction in the human lung: effect of repeated hypoxic challenges during anesthesia.

Six patients, ages 29-58 yr, were investigated during barbiturate and fentanyl anesthesia. After intubation with a double-lumen bronchial catheter, one lung was ventilated continuously with 100% O2, and the other was rendered hypoxic during three 15-min periods by ventilation with 95% N2 + 5% O2, with intervening 15-min periods of oxygen ventilation. Cardiac output was determined by thermodilution, and the distribution of blood flow between the lungs was assessed from the excretion of a continuously infused poorly soluble gas (SF6). The first hypoxic challenge resulted in a 10% increase in cardiac output (QT) and a reduction in the fractional perfusion of the test lung from 57% to 31% of QT. The pulmonary artery mean pressure increased by 54%, and the vascular resistance of the test lung increased threefold. The venous admixture increased from 19% to 40% of QT, whereas the inert gas shunt remained unaltered at 15% (inert gases also being eliminated by nitrogen-ventilated areas). The arterial oxygen tension decreased from 353 mmHg to 79 mmHg. On resumption of the control state, central hemodynamics and gas exchange returned to the initial values. The second and third hypoxic challenges resulted in reductions in the fractional perfusion of the test lung to 35% and 37% of QT. All other variables were altered to the same degree as during the first challenge. The authors conclude that hypoxic challenge of one lung in an intravenously anesthetized human subject elicits a maximum vasoconstrictor response within the first 15 min, and this response cannot be potentiated by repeated challenges.

Hypoxic pulmonary vasoconstriction in the human lung: the effect of prolonged unilateral hypoxic challenge during anaesthesia.

The influence of time on the pulmonary vasoconstrictor response to hypoxia was studied in six subjects during general anaesthesia and artificial ventilation prior to elective surgery. The lungs were intubated separately with a double-lumen bronchial catheter. After preoxygenation of both lungs for 30 min, the test lung was rendered hypoxic for 60 min by ventilation with 5% O2 in N2, with the control lung still being ventilated with 100% O2. Cardiac output was determined by thermodilution, and the distribution of blood flow between the lungs was assessed from the excretion of a continuously infused poorly soluble gas (SF6). The fractional perfusion of the test lung decreased from 53% to 25% of cardiac output within the first 15 min of unilateral hypoxia. The pulmonary artery mean pressure increased by 14% and the pulmonary vascular resistance (PVR) of the test lung increased by 54%. Venous admixture increased from 21% to 39% of cardiac output, while the "true" shunt was maintained at about 15%. Arterial oxygen tension (Pao2) fell from 45 kPa to 12 kPa. Prolonging the unilateral hypoxic challenge caused no further change in the redistribution of the pulmonary blood flow, but cardiac output and pulmonary artery mean pressure continued to increase to 40%-50% above control values after 1 h of hypoxia. The PVR of the test lung remained unchanged. The findings suggest that there is an immediate vasoconstrictor response to hypoxia in the human lung and that there is no further potentiation or diminution, of the response during a 60-min period of hypoxia.

Ventilation and perfusion of each lung during differential ventilation with selective PEEP.

Lung perfusion was studied in 10 patients (mean age 58 yr) in the lateral position during enflurane anesthesia. They were ventilated through a double-lumen endotracheal catheter: 1) by one ventilator with free distribution of ventilation between the lungs, with no (zero) end-respiratory pressure (ZEEP); 2) as above but with a general positive end-expiratory pressure (PEEP) of 9 cmH2O; or 3) by two ventilators with equal distribution of ventilation between the lungs and with a selective PEEP of 8 cmH2O to the dependent lung only. Total ventilation was on average 8 l/min (BTPS) throughout the study. During the first method, 34% of ventilation was distributed to the dependent and 66% to the nondependent lung. Cardiac output (thermodilution) was 4.5 l/min, 57% being distributed to the dependent lung as assessed by iv boli of Xenon 133. During the second method, ventilation was assumed to be distributed equally between the lungs. Cardiac output was decreased to 3.8 l/min, and the dependent lung received 81% of lung blood flow. During the third method, cardiac output was significantly greater than during the second method (4.1 l/min), 51% passing to the dependent lung. Peak and end-inspiratory airway pressures were 5-18 cm H2O lower during selective than during general PEEP. Arterial oxygen tension was significantly greater during the third method than during either of the other ventilator settings and the alveolar-arterial oxygen tension difference was almost halved compared with the first method. It is concluded that differential ventilation with selective PEEP improves ventilation-perfusion matching and thus oxygenation.

Variations of regional lung function in acute respiratory failure and during anaesthesia.

Acute respiratory failure and anaesthesia impede ventilation of dependent lung units and perfusion of non-dependent ones, creating considerable ventilation-perfusion (V/Q) mismatch. General PEEP can improve V/Q but it cannot restore it to normal. To improve matching, ventilation must be distributed in proportion to regional blood flow. This can be accomplished by (1) placing the subject in the lateral position, (2) ventilating each lung in proportion to its blood flow (differential ventilation), and (3) applying PEEP solely to the dependent lung to ensure even distribution of inspired gas within that lung (selective PEEP). Differential ventilation with equal distribution of the tidal volume between the lungs and a selective PEEP of 10 cm H2O to the dependent lung resulted in equal distribution of perfusion between the lungs in anaesthetized healthy subjects, suggesting "optimum" V/Q matching. Using this ventilator setting as a rule of thumb in patients with acute, severe, bilateral lung disease, arterial oxygen tension was improved by an average of 45% compared with that during general PEEP, with no reduction in cardiac output. It is concluded that differential ventilation with selective PEEP can offer considerable improvement in gas exchange in acute, bilateral lung disease. However, long-term studies are required before a final evaluation can be made.

Selective PEEP in acute bilateral lung disease. Effect on patients in the lateral posture.

Seven patients with acute respiratory failure due to diffuse and fairly uniform lung disease were studied during mechanical ventilation in the lateral decubital position with: (a) zero end-expiratory pressure (ZEEP) through a double-lumen oro-bronchial tube to permit a recording of the ventilation to each lung; (b) bilateral positive end-expiratory pressure (PEEP) of 1.2 kPa, with maintenance of ventilation distribution between lungs as observed during ZEEP; (c) selective PEEP of 1.2 kPa, applied to the dependent lung only, with ventilation as during ZEEP; and (d) conventional PEEP of 1.2 kPa applied to both lungs through a single-lumen tube, with free distribution of ventilation between the lungs. During ZEEP, 69% of ventilation was distributed to the non-dependent and 31% to the dependent lung; cardiac output was 6.51 X min-1, venous admixture (QS/QT) 40% and arterial oxygen tension (PaO2) 8.3 kPa. With bilateral PEEP, functional residual capacity (FRC) increased by 0.331, cardiac output was reduced to 5.11 X min-1 and venous admixture to 32%. PaO2 increased to 10.1 kPa. With selective PEEP the dependent lung FRC increased by 0.211 and the FRC of the non-dependent lung decreased by 0.081. Cardiac output increased to 6.11 X min-1, which was no longer significantly different from that during ZEEP. Venous admixture remained at the same level as with bilateral PEEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential ventilation in acute bilateral lung disease. Influence on gas exchange and central haemodynamics.

Eight patients with acute respiratory failure (ARF) due to diffuse and rather uniform lung disease were intubated with a double-lumen bronchial tube and ventilated in the lateral decubital position by two synchronized ventilators. Ventilation of each lung was individually adjusted to match the expected regional blood flow (differential ventilation). When ventilation with equal volumes (i.e. 50% of tidal volume to each lung) was performed, a 19% reduction of venous admixture (P less than 0.001) and a 22% increment in arterial oxygen tension (P less than 0.001) were seen. Comcomitantly, the cardiac output increased by 17% (P less than 0.001), to which a reduced pulmonary vascular resistance may have contributed. The net result was a 14% increment of the oxygen availability (P less than 0.001). An attempt to go further, giving 2/3 of the tidal ventilation to the dependent lung, was made on six of the patients. However, this ventilatory pattern did not further improve the gas exchange and also had detrimental effects on the haemodynamics. It is concluded that differential ventilation with equal tidal volumes in the lateral position can substantially improve gas exchange and central haemodynamics in patients with ARF due to diffuse lung disease.

Regional differences in lung function during anaesthesia and intensive care: clinical implications.

Anaesthesia and most frequently acute respiratory failure are accompanied by a lowered functional residual capacity (FRC). This lowering promotes airway closure in dependent lung units and forces ventilation to non-dependent regions. Perfusion, on the other hand, is forced towards dependent lung units. A ventilation-perfusion mismatch is created and hypoxaemia may develop. General PEEP counters airway closure, but impedes cardiac output and forces perfusion further to dependent regions. In addition, barotrauma may occur. Improved matching of ventilation and perfusion can be achieved by: (1) positioning the subject in the lateral posture; (2) ventilating each lung separately in proportion to its perfusion (differential ventilation); and (3) applying PEEP only to the dependent lung (selective PEEP). Because of less overall intrathoracic pressure and lung expansion, interference with the total lung blood flow and the danger of barotrauma should be less than with general PEEP. Improved gas exchange with a 50-100% increase in PaO2 has been observed in a limited number of patients with acute bilateral lung disease studied so far during differential ventilation and selective PEEP.

Pressure-volume and airway closure relationships in each lung in anaesthetized man.

Airway closure, functional residual capacity (FRC) and transpulmonary pressure-volume curves were assessed for each lung separately in the anaesthetized subject by means of a double lumen tracheal catheter. In the supine position airway closure occurred synchronously in the two lungs and 0.2-0.31 above FRC. The pressure- volume curves in both lungs were rather similar and critical closing pressure (CP) was approximately 3 cmH2O in each lung. In the left lateral posture, FRC was increased in the non-dependent and reduced in the dependent lung, while closing capacity (CC) remained unaltered. Airway closure was asynchronous and discontinuous between the two lungs. This was caused by the non-linear transpulmonary pressure-volume curve in the lungs, in conjunction with the vertical pleural pressure gradient. An interpulmonary "pendelluft" phenomenon was observed in the left lateral posture, increasing inhomogeneity of ventilation. It may depend on regional differences in compliance.

Ventilation-perfusion distribution during inhalation anaesthesia. Effects of spontaneous breathing, mechanical ventilation and positive end-expiratory pressure.

Ventilation-perfusion (VA/Q) ratios were studied by means of an inert gas elimination technique in healthy subjects with an average age of 51 years in the supine posture (a) when awake, (b) during inhalational anaesthesia, spontaneously breathing, (c) during mechanical ventilation, and (d) when a positive end-expiratory pressure (PEEP) was applied. In the awake subject a bimodal distribution of VA/Q was recovered in most patients, one mode centered around the ratio of 1 and another, smaller mode, within low VA/Q-regions. Any shunt was less than 3% of cardiac output. With anaesthesia and spontaneous breathing, the low VA/Q mode was reduced and the shunt increased to an average of 6.2%. With mechanical ventilation, the major VA/Q mode was widened while the shunt was further increased in 4 of 10 subjects (mean 8.6%). With PEEP, the shunt was reduced and a new mode within high VA/Q-regions appeared. The shunt and low VA/Q-regions appeared. The shunt and low VA/Q-regions may be explained in terms of airway closure while the high VA/Q mode with PEEP may be attributed to the development of a zone I.

Distribution of inspired gas to each lung in anesthetized human subjects.

The distribution of ventilation in man during halothane anesthesia was studied in a two-compartment lung model in which each lung was ventilated separately by means of a double-lumen tracheal tube. Eight subjects were studied prior to scheduled surgery. Tidal volume distribution was even between the lungs in the supine position (horizontal distribution) as was distribution of dynamic lung compliance, resistance and dead space. The vertical distribution was assessed when the patient was in the left lateral position. Dependent dynamic lung compliance and dead space were lower and lung resistance was higher than in the non-dependent lung. These factors favoured a non-dependent lung ventilation and, moreover, caused a re-distribution from dependent to non-dependent lung during an end-inspiratory pause (EIP), thus increasing the inhomogeneity of ventilation. The application of a positive end-expiratory pressure (PEEP) of 10 cmH2O improved dependent ventilation and abolished redistribution between the lungs. In conclusion, uneven distribution of dynamic lung compliance and lung resistance causes inhomogeneous ventilation distribution, favouring the non-dependent lung. An EIP enhances and a PEEP reduces the inhomogeneity of ventilation.

Airway closure in each lung of anesthetized human subjects.

Airway closure and functional residual capacity (FRC) were assessed for each lung separately in the anesthetized subject by means of a double-lumen tracheal catheter. Airway closure was studied by argon-bolus and nitrogen-washout techniques, and FRC was calculated from single-breath nitrogen washout. Recordings were done with subjects in the supine and lateral postures. In the supine position, closing capacity (CC) exceeded FRC in each lung. Airway closure occurred synchronously in the two lungs. Argon CC was 0.05-0.1 liter larger than nitrogen CC of either lung. Minor gas trapping occurred during the vital capacity (VC) maneuver, so that inspired VC exceeded expired VC by 3%. In the left lateral posture, CC remained unaltered in either lung, whereas FRC was markedly increased in the nondependent and reduced in the dependent lung. Airway closure occurred asynchronously in the two lungs, and its distribution was discontinuous between them. Onset of airway closure in the dependent lung caused an early (60% VC) upstroke on the overall tracer gas recording (sampling of mixed expirate at the mouth), whereas onset of airway closure in the nondependent lung caused an additional upstroke at 10% VC. Gas trapping was more marked in the dependent lung than in the supine position, but some gas was released (expired VC greater than inspired VC) n the nondependent lung.

Airway closure during anaesthesia, and its prevention by positive end expiratory pressure.

Airway closure, functional residual capacity (FRC) and the transpulmonary pressure volume relationship of each lung were studied in the anaesthetized subject in the supine and the left lateral positions. In the supine posture, FRC was of approximately the same size in each lung as was closing capacity (CC). CC exceeded FRC in either lung. In the left lateral position, FRC was increased by 0.91 in the non-dependent lung and was reduced by 0.21 in the dependent lung, while CC was unaltered in either lung. Consequently, FRC exceeded CC in the non-dependent lung and was further lowered beneath CC in the dependent lung. Airway closure did not occur in the non-dependent lung until an average of 0.51 of gas had been expelled after the dependent lung had ceased to empty. The addition of positive end-expiratory pressure (PEEP) in the range 0.5-2 kPa, increased FRC more in the non-dependent than the dependent lung. The findings suggest that airway closure is evenly distributed in the horizontal level, while it has a discontinuous distribution between the dependent and non-dependent lung. Moreover, the increase in lung volume caused by PEEP has a distribution that is by no means ideal for the purpose of countering airway closure.

Renal fluoride excretion during and after enflurane anaesthesia: dependency on spontaneous urinary pH-variations.

Renal function, fluoride formation and excretion were studied in seven patients during and after enflurane anaesthesia and surgery. The mean maximal plasma level of fluoride was 17.4 microM. It was reached 2 h after termination of anaesthesia. Pre-operatively, fraction fluoride clearance (CF/CIn) was 0.31. During anaesthesia and surgery it decreased to 0.10 and postoperatively rose to 0.55 and 0.77 during two consecutive measurement periods. There was a highly significant correlation (P less than 0.001) between this increase in CF/CIn and the simultaneous rise in urinary pH between the two periods (r = 0.91).

Renal function and fluoride formation and excretion during enflurane anaesthesia.

Central circulation, renal function, and fluoride formation and excretion were studied in nine patients during enflurane anaesthesia and surgery. Cardiac output and mean systemic arterial pressure remained unchanged compared with preoperative control values. During anaesthesia and surgery, urine flow rate, inulin clearance, PAH clearance and fractional sodium excretion were 60, 65, 55, and 45% of control values, respectively. Mean peak plasma level of fluoride was 20.0 microM. It was reached 4 hours after termination of anaesthesia. Fluoride clearance (CF) decreased from 23.9 ml . min-1 to 2.7 ml . min-1 during anaesthesia. Postoperative, CF increased to 41.6 and 76.0 ml . min-1, respectively, during two consecutive measurement periods. There was no correlation between plasma fluoride levels and depression of any renal function variable.

Airway closure during anesthesia: a comparison between resident-gas and argon-bolus techniques.

Airway closure was measured in awake and then anesthetized supine healthy subjects with the argon-bolus and the resident-gas (nitrogen) techniques simultaneously. The preinspiratory lung volume for the closing volume maneuver was varied from residual volume to closing capacity (CC). Comparative measurements were also performed in the upright and supine positions in awake subjects. Closing volume (CV) was consistently larger with the bolus technique in supine subjects both when awake and when anesthetized (difference between methods 0.1--0.2 l, P less than 0.01), whereas no difference between the methods was noted in upright subjects. The lower "nitrogen CV" in supine subjects may be due to a shorter vertical lung height with a smaller range of nitrogen concentrations, resulting in a less abrupt onset of phase IV (taken to indicate CV). CV was not significantly affected by the preinspiratory lung volume with either technique, and CC was unchanged when anesthesia was instituted. Functional residual capacity (FRC) was reduced with anesthesia (mean reduction: 0.6 l, P less than 0.01) and FRC-CC became negative in all subjects with either technique. This implies intermittent or continuous airway closure during anesthesia and the possibility of increased venous admixture.

Studies on intrapulmonary gas distribution in the normal subject. Influence of anaesthesia and artificial ventilation.

Intrapulmonary gas distribution, assessed by a multiple breath, nitrogen washout technique and expressed by the Fowler index NWOD, was studied in subjects with healthy lungs during spontaneous breathing while awake, and during mechanical ventilation under halothane anaesthesia. The distribution index rose from a mean of 32% awake to 56% during anaesthesia. An attempt was also made to differentiate between the contribution of gravitational (airway closure) and non-gravitational (diffuse airway obstruction) inhomogeneity of ventilation. This was accomplished by measurement of the slope of the alveolar plateau during a sinle breath nitrogen washout. The slope was similar awake and anaesthetized, and it increased equally under both conditions, when preinspiratory lung volume was stepped up from RV to CC, CC being the lung volume at which airways begin to close during expiration. NWOD was significantly correlated to the degree of airway closure, expressed as FRC-CC, and, less so, to inspiratory resistance. It is suggested that a less efficient ventilation distribution in anaesthetized normal subjects, as measured by NWOD, is caused rather by airway closure (gravitational inhomogeneity) than by diffuse airway obstruction (non-gravitational inhomogeneity of ventilation).