Measurements of membrane diffusing capacity and pulmonary capillary blood volume in normal subjects and patients with mild emphysema

OBJECTIVE: To establish predicted values of membrane diffusing capacity (Dm) and pulmonary capacity blood volume (Vc), to compare the predicted values from our equations with those for Caucasians, to determine whether there are changes initially in Dm or Vc in patients with mild emphysema. PATIENTS AND METHODS: Diffusing capacity for carbon monoxide (DLco), Dm and Vc were determined in 86 normal subjects and 16 patients using the single-breath diffusing capacity for carbon monoxide (DLcosB) with two different alveolar concentrations of oxygen. RESULTS: The predicted equations are as follows. For males, DLco (ml/min/mm Hg) = 0.37H-0.19A-27.8; Dm (ml/min/mm Hg) = 0.65H-0.24A-53.7; Vc(ml) = 0.88H-78.9. For females, DLco = 0.28H-22.7; Dm = 0.59H-53.6; Vc = 66.6-0.36A. DLco and Vc are lower in Chinese than Caucasians while Dm is similar in Chinese and Caucasians. Eleven of 16 patients had a low DLco (< 80% predicted value), 12 had a low Dm and 5 had a low Vc. Eight of 12 patients with a low Dm also had a low DLco, but in 4 the DLco was normal. Nine of 12 with low Dm had a normal Vc. CONCLUSIONS: This study provides prediction equations of Dm and Vc. Chinese have a low DLco because their Vc is lower than Caucasians. The DLco and Dm are abnormal in a comparable percentage of patients. In patients with mild emphysema, the Dm becomes abnormal before the Vc.     

Changes of vasoactive peptides and effects of inhaled nitric oxide after pneumonectomy

To clarify the role of vasoactive peptides in the physiologic response to pneumonectomy, we investigated the changes of atrial (A-type) natriuretic peptide (ANP). C-type natriuretic peptide (CNP), and endothelin-1 (ET-1) levels in the lung and blood after pneumonectomy and the effects of inhaled nitric oxide (NO; 5 ppm) after pneumonectomy in beagle dogs. The concentrations of these peptides in the lung and blood were measured by radioimmunoassay. The dogs in group A (n = 10) were observed without NO inhaling after right pneumonectomy, and the dogs in group B (n = 5) were observed with NO inhaling from 120 to 180 min after right pneumonectomy. After the thoracotomy, right lung tissue was resected for the pre-operative histological control. Tissue from the left lung was obtained at 120 min (5 dogs in group A), at 180 min (5 dogs in group A), and after 60 min of NO inhalation (group B) for the post-operative histological material. Peripheral blood was collected from the femoral artery. The pulmonary arterial pressure (PAP) was significantly increased after pneumonectomy, but rapidly decreased to the same level as the pre-operative stage after NO inhalation. Increases of plasma ANP, lung ANP and lung CNP levels occurred after pneumonectomy, while the ET-1 level was unchanged. Inhaled NO rapidly reduced the plasma ANP, lung ANP and lung CNP. These results indicate that both ANP and CNP act to maintain normotensive homeostatic balance in the pulmonary circulation.     

Effects of sensor selection on exercise stroke volume in pacemaker dependent patients

The effects of sensor selection and sensor blending on the cardiovascular response to graded exercise was evaluated in 10 patients (age 74 +/- 2 yrs; 7 men and 3 women) implanted with a dual sensor rate adaptive VVIR pacemaker (Vitatron Topaz model 515). Patients underwent three graded exercise tests (GXT) with sensor programming randomly assigned. For a given graded exercise text the pacemaker was programmed into activity sensing (ACT), QT sensing, or dual sensing (ACT = QT). Data were recorded at rest and during each stage of the graded exercise text. Oxygen uptake (VO2) was measured continuously using a Q Plex I system. Heart rate (HR), stroke volume (SV), and cardiac output (Qc) were measured by impedance cardiography. Systolic time intervals were calculated from simultaneous recordings of the ECG, phonocardiogram, and the impedance cardiogram. In response to the GXT no differences in peak VO2 were observed across the three sensor settings. Regardless of the sensor setting Qc increased linearly with each increment in VO2. The HR response to ACT only pacing was significantly higher than in the other two pacing conditions. During ACT only pacing SV failed to rise in response to exercise. The increased exercise Qc during QT and ACT = QT pacing were mediated by significant increases in both HR and SV. The QT and dual pacing conditions were also associated with longer diastolic filling times. The data indicate that the mechanisms responsible for the increase Qc during exercise were different for ACT versus ACT = QT or QT sensor-driven pacing.     

Gas exchange during exercise in healthy people II. Venous admixture

1. Venous admixture/cardiac output ratio (Qva/Qt) has been measured in twenty-four healthy volunteer subjects of both sexes aged 20-71 years, at rest and during the steady state of treadmill exercise at two rates of work, and breathing air and breathing oxygen. 2. With oxygen breathing, Qva/Qt was considerably less during exercise than during the time subjects were taking either normal or deep breaths of oxygen at rest, and did not significantly increase with the intensity of exercise. It is postulated that the increase in ventilation during exercise opens most or all of those alveoli which, during oxygen breathing at rest, close because of critically low ventilation/perfusion (V/Q) ratios. 3. With air breathing, Qva/Qt fell from rest to exercise (especially in older subjects), presumably due to improved ventilation of alveoli at the lung bases. With an increase in work rate Qva/Qt increased in all age groups. This increase was not due to increase in the shunt fraction (Qs/Qt), nor to limitation of diffusing capacity; it arose from an increase in V/Q variance. 4. Equations have been derived for the prediction of normal Qva/Qt during exercise, with or without correction for the effects of increasing pulmonary capillary temperature. These effects do not materially influence the accuracy of prediction, but may be relevant to some of the interpretations. In particular, they provide a further indication that Qs/Qt probably cannot be measured by breathing oxygen at rest, even in deep breathing.     

Role of reaction resistance in limiting carbon monoxide uptake in rabbit lungs

The contribution of reaction resistance to overall resistance to pulmonary carbon monoxide (CO) uptake [DLCO/(ThetaCO . Vc), where DLCO is lung CO diffusing capacity, ThetaCO is CO uptake conductance of erythrocytes, and Vc is pulmonary capillary blood volume] was determined in 10 anesthetized, paralyzed, and artificially ventilated rabbits. On the basis of the classical double-reciprocal equation of F. G. W. Roughton and R. E. Forster (J. Appl. Physiol. 11: 290-302, 1957), DLCO/(ThetaCO . Vc) was obtained by solving the relation DLCO/(ThetaCO . Vc) = 1 - 2/(DLNO/DLCO), where DLNO/DLCO represents the ratio between the respective single-breath diffusing capacities (DL) of nitric oxide (NO) and CO pulmonary capillary blood. The lungs of eight rabbits were inflated, starting from residual volume, by using 55 ml of indicator gas mixture (0.2% CO and 0.05% NO in nitrogen). DL values were calculated by taking the end-tidal partial pressures of CO and NO as analyzed by using a respiratory mass spectrometer. The overall value was DLCO/(ThetaCO . Vc) = 0.4 +/- 0.025 (mean +/- SD). Because of the use of O2-free indicator gas mixtures, the end-tidal O2 partial pressures were approximately 21 Torr. In one other rabbit, the application of 0.2% CO and 0.001% NO yielded DLCO/(ThetaCO . Vc) = 0.39; in the tenth rabbit, however, inspiratory volume was varied, and an identical value was found at functional residual capacity. We conclude that the contribution of reaction resistance to overall resistance to pulmonary CO uptake is independent of the inspiratory NO concentration used, including, with respect to the pertinent literature, the conclusion that in rabbits, dogs, and humans this contribution amounts to 40% when determined at functional residual capacity.     

Clinical correlates of an elevated diffusing capacity for carbon monoxide corrected for alveolar volume

The diffusing capacity for carbon monoxide is partially dependent on lung volume at which it is measured. As a consequence, the diffusing capacity for carbon monoxide is often indexed to the simultaneously measured lung volume (VA), giving rise to the term DL/VA. This reflects the diffusing capacity of carbon monoxide per unit area of lung parenchyma. The authors investigated the pulmonary function of 18 patients who had an elevated DL/VA in order to identify factors that could account for this abnormality. Sixteen of the 18 had a reduction in vital capacity. The vital capacity was reduced because of obesity, pleural disease, and diaphragmatic dysfunction. Eight of nine patients with a body mass index > 30 kg/m2 had a reduction in vital capacity. On the basis of these findings, we believe that an elevated DL/VA should alert the physician to the possibility of 1) an increase in pulmonary capillary blood volume (Vc) (obesity, polycythemia, negative pleural pressure), and 2) reduced VA that does not directly affect the pulmonary capillary bed (pleural disease, neuromuscular disease).     

Blood flow in different adipose tissue depots during prolonged exercise in dogs

Adipose tissue blood flow was measured by the microsphere technique in all major adipose tissue depots in dogs during exercise. The measurements were done during rest, after 1 and 2 h of exercise and after a postexercise rest period. It was found that the blood flow to the inguinal, subcutaneous adipose tissue increased from about 6 ml/(100 g . min) during rest to about 10 ml/(100 g.min) during exercise. This increase in flow was significantly smaller than the increase found in the perirenal, the mesenteric and the pericardial depots. In these depots the resting blood flow was about 10 ml/(100 g . min) increasing to about 30 ml/(100 g . min) during exercise. It is concluded that the increase in adipose tissue blood flow during exercise is a general phenomenon for all major adipose tissue depots. The increase in flow in the inguinal, subcutaneous fat pad was comparable to the previously described increase in flow in abdominal, subcutaneous tissue in man. Blood flow to abdominal skin was constant during exercise, while the flow in tissues from the gastrointestinal canal and in the kidneys decreased. The flow in the tongue and in the Achilles tendon significantly increased during exercise.     

Age alters regional distribution of blood flow during moderate-intensity exercise

During dynamic exercise in warm environments, requisite increases in skin and active muscle blood flows are supported by increasing cardiac output (Qc) and redistributing flow away from splanchnic and renal circulations. To examine the effect of age on these responses, six young (Y; 26 +/- 2 yr) and six older (O; 64 +/- 2 yr) men performed upright cycle exercise at 35 and 60% of peak O2 consumption (VO2peak) in 22 and 36 degrees C environments. To further isolate age, the two age groups were closely matched for VO2peak, weight, surface area, and body composition. Measurements included heart rate, Qc (CO2 rebreathing), skin blood flow (from increases in forearm blood flow (venous occlusion plethysmography), splanchnic blood flow (indocyanine green dilution), renal blood flow (p-amino-hippurate clearance), and plasma norepinephrine concentration. There were no significant age differences in Qc; however, in both environments the O group maintained Qc at a higher stroke volume and lower heart rate. At 60% VO2peak, forearm blood flow was significantly lower in the O subjects in each environment. Splanchnic blood flow fell (by 12-14% in both groups) at the lower intensity, then decreased to a greater extent at 60% VO2peak in Y than in O subjects (e.g., -45 +/- 2 vs. -33 +/- 3% for the hot environment, P < 0.01). Renal blood flow was lower at rest in the O group, remained relatively constant at 35% VO2peak, then decreased by 20-25% in both groups at 60% VO2peak. At 60% VO2peak, 27 and 37% more total blood flow was redistributed away from these two circulations in the Y than in the O group at 22 and 36 degrees, respectively. It was concluded that the greater increase in skin blood flow in Y subjects is partially supported by a greater redistribution of blood flow away from splanchnic and renal vascular beds.     

Lung-heart ratio in stress thallium myocardial perfusion imaging in patients with a history of a previous pneumonectomy

Increased TI-201 lung-heart ratio after treadmill exercise or pharmacologic stress is an indicator of left ventricular dysfunction. After pneumonectomy, it is not reliable because of increased pulmonary circulation in the remaining lung. The authors present an example of normal stress TI-201 myocardial perfusion imaging with an increased lung-heart ratio of TI-201 uptake.     

Distance and the presentation of visual stimuli to birds

Hemodynamic factors have profound influences on blood vessels. To test the hypothesis that hemodynamic conditions modify the pattern of remodeling in response to injury, monocrotaline (MCT) injury in Sprague-Dawley rats was followed 1 week later by left pneumonectomy to increase blood flow to the right lung. Right pulmonary artery remodeling in these MCT plus pneumonectomy animals was compared with animals receiving MCT or pneumonectomy alone. Neointimal changes developed in more than 90% of all right lung intra-acinar vessels 5 weeks after MCT injury (4 weeks after pneumonectomy). Neointimal lesions did not develop in untreated animals or in animals receiving MCT or pneumonectomy only. Animals with a neointimal pattern of remodeling developed severe right ventricular hypertrophy (RVH) whereas animals with a medial hypertrophy pattern of remodeling (MCT only) developed moderate RVH compared with control animals. Neointimal lesions and RVH were similar whether injury preceded pneumonectomy or vice versa. To exclude the possibility that neointimal lesions resulted from injury plus post-pneumonectomy compensatory lung growth, rather than injury plus increased flow, a left subclavian-pulmonary artery anastomosis was substituted for pneumonectomy. Neointimal lesions and severe RVH developed in these animals but were not seen in animals receiving either MCT or anastomosis only. These studies demonstrate an important role for hemodynamics in determining the pattern of pulmonary vascular remodeling after injury.     

Natriuretic peptides in the lung modulated by pneumonectomy

BACKGROUND: Natriuretic peptides are vasodilator hormones involved in the regulation of blood pressure and volume homeostasis. However, the mechanism of these peptides after pneumonectomy remains obscure. METHODS: We investigated changes in the pulmonary arterial pressure and the localization and changes in the atrial (A-type) natriuretic peptide (ANP) and the C-type natriuretic peptide (CNP) in the lung, using immunohistochemistry and radioimmunoassay (RIA) in anesthetized dogs. Furthermore, we examined guanosine 3', 5'-monophosphate (cGMP) levels in plasma and in the contralateral lung. RESULTS: Pulmonary arterial pressure was significantly increased after pneumonectomy. The immunoreactivities of both ANP and CNP were detected in the endothelium of the pulmonary artery. In the contralateral lung, the concentrations of ANP and CNP were both significantly increased. In plasma, only ANP levels were significantly increased. In contrast, the plasma and lung cGMP levels were significantly reduced after pneumonectomy. CONCLUSIONS: We postulate that the processes from secretion in the vascular endothelial cells to the action via ANP and CNP receptors are effected in the contralateral lung tissue at the acute stage of pneumonectomy.     

Prospective evaluation for pneumonectomy using the 99mtechnetium quantitative perfusion lung scan

We evaluated 33 high-risk patients before pneumonectomy, all of whom had a forced expiratory volume in one second (FEV1) of less than 2.0 L before surgery. A quantitative perfusion lung scan was used to assess the right-left distribution of blood flow. A predicted postoperative FEV1 was calculated from the information on the lung scan and the preoperative FEV1. If this calculated value exceeded 800 ml, the patient was physiologically cleared for surgery up to and including a pneumonectomy. Surgery was otherwise believed to be contraindicated in the absence of studies using balloon occlusion. Perioperative mortality (less than or equal to 30 days after surgery) was found to be 15 percent (5/33). In surgery of this magnitude, we find this to be an acceptable percentage of mortality and have continued to use these simple physiologic criteria to determine whether a patient can tolerate pneumonectomy.     

Cardiopulmonary function at rest and during exercise after resection for bronchial carcinoma

BACKGROUND: Measurements of postoperative spirometric values after pneumonectomy and lobectomy vary considerably, and few researchers have studied the changes in exercise capacity during maximal work after lung resection. The purpose of this study was to describe the postoperative alterations in cardiopulmonary function. METHODS: Ninety-seven consecutive patients with lung malignancy were prospectively examined with maximal exercise test, spirometry, and arterial gas tensions. Fifty-seven patients were reinvestigated 6 months postoperatively. RESULTS: In patients having lobectomy, forced expiratory volume in 1 second decreased 8%, and exercise capacity, expressed by maximal oxygen uptake and maximal work rate, significantly decreased 13%. In patients having pneumonectomy forced expiratory volume in 1 second significantly decreased 23%, but the loss in lung volume was partly compensated as measured by exercise capacity, which decreased only 16%. Generally patients with the smallest preoperative forced vital capacity had the smallest postoperative deterioration expressed in percentages. We found a weak correlation between alterations in maximal oxygen uptake and lung function after resection. CONCLUSIONS: Lobectomy is associated with only minor deterioration of lung function and exercise capacity. Pneumonectomy causes a decrease in pulmonary volumes to about 75% of the preoperative values, partly compensated in better oxygen uptake, which postoperatively was about 85% of the preoperative values. Alteration in forced expiratory volume in 1 second is a poor predictor of change in exercise capacity after pulmonary resection.     

Invasive exercise testing in the evaluation of patients at high-risk for lung resection

The aim of this study was to investigate whether invasive exercise testing with gas exchange and pulmonary haemodynamic measurements could contribute to the preoperative assessment of patients with lung cancer at a high-risk for lung resection. Sixty-five patients scheduled for thoracotomy (aged 66+/-8 yrs (mean+/-SD), 64 males, forced expiratory volume in one second (FEV1) 54+/-13% predicted) were studied prospectively. High risk was defined on the basis of predicted postpneumonectomy (PPN) FEV1 and/or carbon monoxide diffusing capacity of the lung (DL,CO) <40% pred. Arterial blood gas measurements were performed in all patients at rest and during exercise. In 46 patients, pulmonary haemodynamic measurements were also performed at rest and during exercise. Predicted postoperative (PPO) values for FEV1 and DL,CO were calculated according to quantitative lung scanning and the amount of resected parenchyma. There were four postoperative deaths (6.2% mortality rate) and postoperative cardiorespiratory complications developed in 31 (47.7%) patients. Patients with respiratory complications only differed from patients without or with minimal (arrhythmia) complications in FEV1,PPO. Peak O2 uptake and haemodynamic variables were similar in both groups. The four patients who died had a lower FEV1,PPO, a lower DL,CO,PPO and a greater decrease in arterial oxygen tension during exercise, compared with the remaining patients. In conclusion, the forced expiratory volume in one second, together with the extent of parenchymal resection and perfusion of the affected lung, are useful parameters to identify patients at greatest risk of postoperative complications among those at a high-risk for lung resection. In these patients, pulmonary haemodynamic measurements appear to have no discriminatory value, whereas gas exchange measurements during exercise may help to identify patients with higher mortality risk.     

A modified rebreathing technique using an infrared gas analyzer

To lower the cost and improve accessibility of the rebreathing technique for measuring cardiopulmonary function during exercise, we implemented a fast-response infrared (IR) gas-analyzer system to simultaneously measure lung diffusing capacity, cardiac output lung tissue volume, and lung volume by a rebreathing technique in five healthy subjects at rest and during steady-state exercise. Interferences by water vapor and CO2 on the analyzer were determined and corrected for. During rebreathing, a gas mixture of 0.4% C2H2-0.3% CH4-9% He-30% O2, and either 0.3% C18O or 0.3% C16O in a balance of N2 was simultaneously sampled by both a mass spectrometer and the IR analyzer, permitting paired comparisons. Measurements obtained by the two devices were not significantly different. We conclude that this modified rebreathing technique using the IR analyzer is accurate for the measurement of cardiopulmonary function at rest and during exercise.     

Mechanics of breathing in patients with atrial septal defect

Mechanics of breathing and pulmonary diffusing properties were investigated in 24 adult patients with atrial septal defect. The patients were divided into 3 groups according to mean pulmonary artery pressure: less than 19 mm Hg (group I), 20 to 24 mm Hg (group II), and greater than 25 mm Hg (group III). The only change observed in group I was a marked increase in diffusing capacity. Patients of group II showed not only an increase in diffusing capacity, but also an overt decrease in maximal expiratory flow at all lung volumes and at any given driving pressure. For these two groups, a highly significant inverse correlation was found between changes in diffusing and elastic lung properties (r = -0.71; P less than 0.001). In patients of group III, the expiratory flow remained clearly decreased; furthermore, lung compliance and lung volumes were sharply reduced, airway resistance was elevated, and diffusing capacity was normal. Finally, from group I to group III, the lung elastic recoil became progressively diminished at small lung volumes. These results suggest that an increased pulmonary blood volume induces an increase in diffusing capacity and a slight decrease in lung compliance. Simultaneous existance of high intravascular pressure strengthens the effects of increased pulmonary blood volume on lung mechanics and results in significant abnormalities in the lung mechanical behavior. It is postulated that these effects are due to a competition for space between vessels and airways within the bronchovascular sheaths, with a subsequent compression of small airways.     

Site of action of inhaled 6 per cent carbon dioxide in the lungs of asthmatic subjects before and after exercise

We studied 10 nonsmoking young adults before and after inducing asthmatic attacks by treadmill exercise. We used body plethysmography, flow-volume curves with air and a mixture of 80% helium and 20% oxygen, pressure-volume diagrams, and arterial blood gas analyses to characterize the effects of exercise and acute inhalation of 6% CO2. Even when exercise produced no change in arterial CO2 tension, inhalation of 6% CO2 relieved obstruction to airflow. It also altered the volume-pressure ralationship of the lungs so that total lung capacity was reduced within minutes, and elastic recoil was increased at fixed lung volume. A large increase in density dependence of airflow was seen in some cases, suggesting relief of obstruction in peripheral airways. Atropine sulfate did not prevent obstruction after exercise and did not prevent relief during CO2 inhalation. We concluded that CO2 inhalation can relax both central and peripheral airways in young asthmatic adults, both at rest and after exercise, and that both total lung capacity and density dependence of airflow can change acutely in these subjects.     

The effect of exercise intensity on lipid peroxidation

This study characterizes exercise-induced lipid peroxidation during graded aerobic exercise in seven healthy men and women (36.4 +/- 3 yr). Levels of ethane and pentane in expired breath during cardiopulmonary exercise stress testing were measured at rest, lactic acidosis threshold (LAT), maximal exercise (VO2max), and recovery. Serum malonaldehyde (MDA) levels were measured at rest before exercise and 5 min after maximal exercise. Expired ethane and pentane flux levels were increased above resting levels at LAT, continued to rise at VO2max, then declined during recovery. Serum MDA levels were not significantly different before and after maximal exercise. Substantial exercise-induced lipid peroxidation (by expired ethane and pentane) apparently occurred in healthy individuals at LAT and continued to increase at VO2max, yet rapidly attenuated during post-exercise recovery. These findings indicate that in healthy individuals physical exercise induced lipid peroxidation transiently and that there was a removal of lipid peroxidation byproducts during recovery.     

Adipose tissue blood flow during prolonged, heavy exercise

Subcutaneous adipose tissue blood flow (ATBF) was examined in 8 subjects during 6 h exercise on a bicycle ergometer. The initial work load was 118 W corresponding to about 50% of maximal work capacity. The oxygen uptake increased from 0.261 - min-1 at rest to about 1.61-min-1 during work. In 7 subjects ATBF increased, in 1 it remained constant. After 3 h exercise ATBF at an average reached values 3--4 times the control value. This increase was maintained for the remaining work periods. The increase was significant at the 5% level. Plasma free fatty acids increased 7-, plasma glycerol 10-fold during work.     

Two-level spinal stenosis in minipigs. Hemodynamic effects of exercise

STUDY DESIGN: Twenty-two G?ttingen minipigs were trained to run on a treadmill. Two-level lumbar spinal stenosis was created in 12 pigs, 10 were unoperated control subjects. Blood flow of the spinal cord and nerve roots was determined with microspheres at rest, during exercise, and after exercise. OBJECTIVES: To study the effect of lumbar spinal stenosis and exercise on blood flow of spinal neural tissue. SUMMARY OF BACKGROUND DATA: Neurogenic claudication, the key symptom of lumbar spinal stenosis, may be caused by vascular impairment or mechanical distress of neural tissue during exercise. Experimental compression of the cauda equina causes reversible nerve root edema, stasis, blood flow decrease, and compromised neural function. The vascular pathophysiology of spinal stenosis during exercise has not been studied previously. METHODS: Pigs were trained daily for 3 months. Two-level 25% lumbar spinal stenosis was introduced by placement of stenosing bands around the dural sac. Neurologic function was monitored before surgery by evoked potentials and after surgery by the Tarlov score. Regional blood flow in lumbosacral neural tissue was measured 3 days after chronic catheterization using microspheres at rest, during exercise at 3 km/h for 15 minutes, and at rest 30 minutes after exercise. RESULTS: Blood flow of grey and white matter increased during exercise in both groups, with no differences between groups. slight hyperemia prevailed after exercise in white matter of the stenotic area but not in grey matter. Nerve root blood flow was largely unchanged in control subjects during exercise but was reduced in spinal stenosis at rest, further depressed during exercise, and normalized after exercise. Dural blood flow was elevated throughout. CONCLUSION: The study suggests that exercise-induced impairment of spinal nerve root blood flow plays a role in the pathophysiology of neurogenic claudication.