Interpretation of high wedge pressure on exercise in patients with chronic obstructive pulmonary disease.

In a retrospective review of patients subjected to right heart catheterization, case records from 109 consecutive patients with chronic obstructive pulmonary disease (COPD) and wedge pressure > or =15 mm Hg on exercise were analyzed. Patients were separated into group 1, resting wedge pressure (P macro w) <15 mm Hg and difference between P macro w and right atrial pressure (P macro ra) change on exercise <5 mm Hg (n = 54), group 2, same P macro w at rest but increase in macro on exercise > or =5 mm Hg, being higher than that of P macro ra (n = 34), and group 3, P macro w > or =15 mm Hg at rest (n = 21). The occurrence of left heart disease increased from group 1 to group 3 (19, 53 and 71%, respectively), and the slope of the P macro w/stroke index relationship was lowest in group 3. High P macro w on exercise can be explained by the pressure rise in the cardiac fossa associated with lower lobe gas trapping in group 1, which showed the most severe airflow limitation, decreased left ventricular compliance in group 2, and heart failure in group 3.

Role of NO pathway, calcium and potassium channels in the peripheral pulmonary vascular tone in dogs.

Because hypoxic pulmonary vasoconstriction occurs mainly in the small pulmonary arteries, the authors investigated the effects of drugs acting on the nitric oxide (NO) pathway and the calcium and potassium channels in the peripheral pulmonary circulation, without interference with the overall pulmonary or systemic circulation. Mixed venous blood was infused in wedged areas to study the pressure/flow relationship and to compute peripheral pulmonary vascular resistance (PPVR). The authors studied the effects of Nomega-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, sodium nitroprusside (SNP, an NO donor), the calcium channel blockers verapamil, nifedipine and nicardipine, and the potassium channel opener levcromakalim, during normoxia and acute mild normocapnic hypoxia. In the peripheral pulmonary circulation, L-NAME caused an increase in PPVR during normoxia (+95%; p<0.001) and hypoxia (+60%; p<0.01). Following the increase by L-NAME, SNP decreased PPVR during normoxia (-24%; p<0.05) and hypoxia (-23%; p<0.05). Verapamil, nifedipine and nicardipine did not modify PPVR during normoxia but during hypoxia they decreased PPVR (-28%, nonsignificant; -27%, p<0.01 and -33%, p<0.05, respectively). Levcromakalim did not modify PPVR during normoxia or hypoxia. In conclusion, the nitric oxide pathway and voltage-dependent calcium channels, and not adenosine triphosphate sensitive potassium channels, play an important role in the control of peripheral pulmonary circulation in dogs.

Changes in peripheral pulmonary vascular resistance after ioxaglate infusion in anesthetized dogs.

The pulmonary vascular resistance in a peripheral portion of the pulmonary vascular bed can be determined with a catheter wedged in a peripheral branch of the pulmonary artery, from the pressure increase induced by infusion of mixed venous blood at known flow rates. The volume of the wedged vascular bed can be estimated during fluoroscopy, from the volume of a contrast agent infused until the corresponding pulmonary vein can be seen. The present work was undertaken to determine the possible influence of this maneuver on the peripheral pulmonary vascular resistance (PPVR). In anesthetized dogs, after a control flow run, Hexabrix (meglumine ioxaglate and sodium ioxaglate) was infused, then the catheter was flushed with saline, and another flow run was performed. There was no significant difference between two consecutive control runs in the same site (n = 14). Before Hexabrix (n = 23), PPVR was 162 (+/-24) x 10(3) dyn.s.cm-5 (1 dyn = 10 microN) during the control run; it increased to 339 (+/-33) x 10(3) dyn.s.cm-5 after Hexabrix (p < 0.001). These results show that care should be taken to avoid interference between Hexabrix and the results of physiological or pharmacological interventions with this technique.

Effect of acute hypercapnia on alpha atrial natriuretic peptide, renin, angiotensin II, aldosterone, and vasopressin plasma levels in patients with COPD.

Disturbances in hormonal systems involved in sodium and water homeostasis are common during respiratory insufficiency. To investigate the role of hypercapnia, we designed a study to examine the hormonal response to acute hypercapnia induced at constant cardiac filling pressures and without hypoxemia. Seven sedated patients with COPD receiving mechanical ventilation were studied during five successive periods. Hemodynamics, arterial blood gases, and plasma hormone levels (atrial natriuretic peptide, renin, angiotensin II, aldosterone, vasopressin) were measured three times during 60 min of acute hypercapnia (52 +/- 5 mm Hg) and at control periods, before (36 +/- 4 mm Hg) and after (42 +/- 3 mm Hg) acute hypercapnia. During acute hypercapnia, mean pulmonary arterial pressure and cardiac output were increased without variation of other measured cardiorespiratory data and hormonal levels when compared with control values. After acute hypercapnia, cardiorespiratory variables returned to control values without variations of hormonal levels. Our results show that moderate acute hypercapnia does not significantly influence the hormonal levels when cardiac filling pressures and sympathetic tone remain stable. We suggest that changes in those plasma hormones involved in salt and water homeostasis during acute hypercapnia are secondary to hemodynamic changes induced by acute respiratory failure and not to acute hypercapnia per se.

Pulmonary arterial wedge pressure measurement can modify pulmonary haemodynamics in patients with chronic lung disease.

In 20 patients with chronic lung disease in stable condition, haemodynamic values were compared during wedging of a Swan-Ganz catheter, either in a distal branch of the pulmonary artery, or by balloon inflation (with 1 ml) in a proximal branch, mostly excluding right lower lobe perfusion. Average pulmonary arterial wedge pressure, systemic arterial pressure, transcutaneous and mixed venous oxygen saturation, cardiac output and pulmonary blood volume (PBV) were not statistically different during distal and proximal wedging, but systolic pulmonary arterial pressure and pulmonary vascular resistance were slightly higher during balloon inflation (P < 0.05). In four patients, PBV decreased by 20% or more; cardiac output was reduced and mean systemic arterial pressure diminished by 10 mmHg or more in three patients. Of the two patients with the lowest PBV, one did not tolerate the balloon inflation because of dyspnoea, and the other showed dramatically haemodynamic changes. These were more likely to occur when the occlusion lead to the exclusion of a still well perfused area. Our results support optimal matching between ventilation and perfusion in patients with chronic lung disease, although both are inhomogeneous. When pulmonary vascular restriction can be suspected, pressure obtained during catheter wedging by balloon inflation should be interpreted with caution. Monitoring arterial oxygen saturation and systemic arterial pressure before and during the manoeuver could help to diagnose haemodynamic effects of the balloon inflation in a proximal pulmonary artery.

Right ventricular pressure-volume relations in chronic lung disease.

Thirty-four patients with chronic lung disease in stable condition were studied at supine rest (RS), at rest with the legs raised (LR), and during two levels of exercise: E1, 0 or 20 W, E2, 20 or 40 W. Five patients had normal spirometry (group 1), six patients had normal vital capacity but FEV1/VC below 70% (group 2), and 23 patients had VC below 95% of normal and FEV1/VC below 70% (group 3); group 3 was subdivided into group 3a (n = 14) without, and group 3b (n = 9) with a history of right heart failure (RHF). Right ventricular end-diastolic (RVEDV) and end-systolic (RVESV) volumes were computed from stroke volume and right ventricular ejection fraction (RVEF). RVEF at rest was correlated with lung function variables. Changes in RVEF from LR to E2 were normal, i.e. above 0.05, except for in group 3b, where RVEF did not increase with exercise. Relation between RVESV and pressure, and changes in stroke volume with RVEDV from LR to E2 were also abnormal in group 3b. These results show that in patients with chronic lung disease RVEF at rest reflects lung function, whereas its adaptation to exercise is impaired only in patients who have experienced RHF episodes.

Peripheral pulmonary vascular resistance.

The pressure-flow relationship has been studied in a peripheral portion of the lung vasculature in anesthetized dogs with use of a double-lumen catheter wedged in a distal pulmonary artery. One lumen was used to infuse mixed venous blood in the wedged area and the other to measure the corresponding perfusion pressure. Flow ranged from 0 to 9.2 ml/min, and the mean volume of the wedged area (n = 59) was 0.75 +/- 0.05 (SE) ml. In the areas where the distal pulmonary artery was in the same direction as the catheter ("coaxial"), the mean pressure-flow curve showed a negligible gamma-intercept and no significant difference between ascending and descending flow. The slope of the initial part of the ascending limb (peripheral pulmonary vascular resistance) varied from site to site and did not show a significant correlation with the overall pulmonary vascular resistance; it was inversely correlated with the volume of the wedged area (r = -0.35, P < 0.05) and directly, as expected, correlated with the y-intercept (r = 0.78, P < 0.001) and hysteresis (r = 0.48, P < 0.001). The results of two consecutive pressure-flow runs in the same site showed similar results, with no difference exceeding the error of measurement. In contrast, the slope increased by 71% during hypoxia (fraction of inspired O2 was 0.10, n = 5). This procedure seems suitable to determine the effects of physiological or pharmacological interventions on the pulmonary vessels, without interference of the systemic circulation.

[Relationship between right ventricular ejection fraction and pulmonary pressure in man]. / Relation entre fraction d'éjection ventriculaire droite et pression artérielle pulmonaire chez l'homme.

This clinical study analysed the changes in right ventricular ejection fraction induced by changes in right ventricular afterload using a new thermodilution catheter linked to a rapid response computer which allowed instantaneous measurements of the right ventricular ejection fraction. The first group comprised 16 patients referred for coronary angioplasty with single vessel disease (isolated proximal stenosis of one of the two main branches of the left coronary artery) and a normal left ventricular ejection fraction (> or = 55%) and mean pulmonary artery pressure of < 25 mmHg: right ventricular ejection fraction and mean pulmonary artery pressure were measured under basal conditions and after 60 seconds' coronary occlusion with the balloon catheter in order to assess the effects of the reactional increase in afterload on the right ventricular ejection fraction. The second group comprised 11 patients with dilated primary cardiomyopathy with decreased left ventricular ejection fraction (< 50%) and mean pulmonary artery pressure > or = 25 mmHg: the right ventricular ejection fraction and mean pulmonary artery pressure were measured under basal conditions and after intravenous trinitrin (performed to evaluate the pulmonary reaction to vasodilators) in order to analyse the effects of the reduction of afterload on right ventricular ejection fraction. Negative linear correlations were observed between the right ventricular ejection fraction and mean pulmonary artery pressure under basal conditions (r = -0.72; p < 0.005) and between the right ventricular ejection fraction and mean pulmonary artery pressure after changing the conditions of afterload (r = -0.82; p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Pressure/flow relation in the peripheral pulmonary vascular bed in dogs: a preliminary study.

In order to test a technique for the determination of the pressure/flow relationship in the peripheral pulmonary vascular bed, the perfusion pressure changes with increasing and then decreasing flow in a small part of the lung (around 1 ml) were studied in anaesthetized supine dogs, after insertion of a specially designed double distal lumen Swan-Ganz catheter. One lumen was used for the pressure measurement, one for infusion of saline by a pump with variable flow, from 0.1 to 1.0 ml s-1. A conventional thermodilution Swan-Ganz catheter was also advanced in the pulmonary artery, to measure pressures in the pulmonary circulation as well as cardiac output. During infusion in the wedged catheter, right atrial, pulmonary arterial and balloon occlusion wedge pressures did not change. The pressure/flow curve of the occluded vascular bed showed a shape similar to that of collapsible tubes, with a pressure plateau at high flow, but this could also be due to vascular recruitment. The curve exhibited hysteresis, with a lower pressure when flow decreased. The slope of the initial part of the curve increased, on average, from 54 +/- 9 during normoxia to 91 +/- 27 mmHg s ml-1 during hypoxia (FIO2 = 0.10); this difference was not significant, but the perfusion pressure at high flow was significantly higher during hypoxia (P less than 0.05). Using blood instead of saline would allow the determination of the peripheral pulmonary vascular resistance under physiological conditions, and further work is needed to estimate the sensitivity and the reproducibility of this technique.

Pulmonary blood volume and haemodynamic changes with legs raised in chronic lung disease patients.

STUDY OBJECTIVE: The aim was determine the early effect of a posture change from supine (S) to legs raised 30 degrees above the table plane (LR) on haemodynamics in patients with chronic lung disease. STUDY DESIGN: Right heart catheterization was performed as part of a routine evaluation. Pulmonary arterial, pulmonary wedge, right atrial, and systemic arterial pressure were monitored at rest supine and during 8 min (steady values) after LR. Pulmonary blood volume was measured by double dye dilution, at rest S and after 1 and 8 minutes LR, in 14 patients; cardiac output was measured by thermodilution in the remaining 15 subjects, during S and 1, 4, and 8 minutes LR. SUBJECTS: 29 patients with chronic pulmonary disease of various types, mainly chronic bronchitis and emphysema, were studied when in a stable clinical condition, with no signs of heart failure. MEASUREMENTS AND MAIN RESULTS: Raising the legs produced a sharp increase in all the pressures measured, with a subsequent decline towards a steady value slightly higher than during S. Pulmonary blood volume increased in all patients initially, but stayed elevated only in the normocapnic patients; in the patients with hypercapnia it decreased from 1 to 8 min LR. The pulmonary blood volume change showed a significant correlation with PaCO2 (p less than 0.01), and with the VD/VT ratio (p less than 0.01). The relation between the pulmonary blood volume and the distending pressure changes from S to 1 and 8 min LR was linear in the normocapnic group, but not in the hypercapnic group, where it showed a hysteresis. CONCLUSION: In patients with chronic lung disease who are hypercapnic, the volume/pressure relation following leg raising cannot be expressed by a single distensibility coefficient.

One year treatment with almitrine improves hypoxaemia but does not increase pulmonary artery pressure in COPD patients.

Almitrine bismesylate, a chemoreceptor agonist, improves hypoxaemia in a high percentage of chronic obstructive pulmonary disease (COPD) patients and its long-term use may thus be of interest in these patients. The course of pulmonary haemodynamics during a one year treatment was investigated in severe COPD patients (forced expiratory volume in one second FEV1 = 1,040 +/- 80 SEM ml) with persistent hypoxaemia (initial arterial oxygen tension (PaO2) in the range 6.6-8.6 kPa (50-65 mmHg]. Patients were given either almitrine (A, n = 27), 100 mg.day-1, during two consecutive months per quarter followed by a one month wash-out period (intermittent "schedule"), or placebo (P, n = 18) with the same schedule. Eleven patients in group A and 8 in group P could not complete the one year study because of lack of compliance, worsening of respiratory insufficiency, or for other reasons. In the remaining patients, PaO2 significantly increased in group A (n = 16) from 7.6 +/- 0.1 to 8.3 +/- 0.2 kPa (56.9 +/- 1.0 to 62.7 +/- 1.7 mmHg) (p less than 0.001) but not in group P (n = 10) from 7.5 +/- 0.3 to 7.9 +/- 0.3 kPa (56.1 +/- 2.3 to 59.1 +/- 2.1 mmHg). PaCO2 did not significantly change in either group. Pulmonary artery mean pressure (PAP) was stable in both groups: from 26.8 +/- 2.1 to 25.4 +/- 1.9 mmHg in group A, and from 20.6 +/- 1.1 to 20.9 +/- 1.5 mmHg in group P.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects on right ventricular function of transient right, left anterior descending and left circumflex coronary occlusions during percutaneous transluminal coronary angioplasty.

Right ventricular function was studied by means of a thermodilution catheter before, during and after percutaneous transluminal angioplasty of the proximal right (group 1, n = 8), left anterior descending (group 2, n = 8) or left circumflex (group 3, n = 8) coronary artery. All patients had evidence of myocardial ischemia, with single-vessel disease affecting the proximal segment of one of the three major coronary arteries; no patient had had a previous myocardial infarction and all had normal cardiac function at baseline study. Cardiac index decreased during balloon inflation. Mean pulmonary artery pressure was unaffected in group 1 but increased in group 2 (from 19 +/- 5 to 31 +/- 11 mm Hg, p less than 0.01) and in group 3 (from 19 +/- 2 to 22 +/- 5 mm Hg, p less than 0.05). Right ventricular ejection fraction decreased from 62 +/- 9% to 52 +/- 10% (p less than 0.01) in group 1 and from 64 +/- 7% to 44 +/- 10% (p less than 0.005) in group 2, and returned to normal within 2 min after balloon deflation in both groups. In group 3, right ventricular ejection fraction was unchanged during balloon inflation (58 +/- 5% at baseline, 58 +/- 9% at 60 s, p = NS). Therefore, brief occlusion of the proximal segments of the left anterior descending or right coronary artery results in marked alteration of right ventricular performance that is probably caused by right ventricular free wall ischemia in the right coronary group and by the concomitant effects of septal ischemia and increased right ventricular afterload in the left anterior descending artery group.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulatory response to repeated exercise in patients with chronic lung disease.

The pulmonary and systemic circulatory response to repeated exercise has been studied in 24 patients with chronic lung disease, mainly chronic bronchitis. The exercise consisted of supine bicycling at a constant low load (from loadless pedalling to 30 W) for 10 min with a 20 min rest period between exercises. Cardiac output was similar during the first (E1) and the second (E2) exercise periods, as well as pulmonary vascular resistance. Systemic arterial pressure, however, was lower during E2 than during E1, and this difference was significantly correlated with lung function (VC% predicted, FEV1 and FEV1% predicted) and blood gases at rest and during exercise. The patients with PaO2 below 65 mm Hg showed a larger increase in systemic arterial pressure during E1 and a smaller increase during E2 than the others. The larger increase might be due to a vasoconstrictor effect of hypoxemia and/or of the functional residual capacity increase observed in such patients with exercise. Whatever the mechanism involved, these results show that the systemic circulation is modified in patients with chronic lung disease. Results after some intervention have to be interpreted with caution if the protocol includes two exercise periods.

AaDO2 as a predictor of pulmonary hypertension resulting from pulmonary emboli.

The authors examined the records of all patients referred for right heart catheterization between 1963-84 because of persistent dyspnoea after one or more episodes of pulmonary emboli. Patients with a history of congestive heart failure, angina, restrictive or obstructive pulmonary disease that could explain their symptoms were excluded. Catheterization was performed 15.8 +/- 24 months after the first suspected episode of pulmonary embolism. Seven of the 29 patients included had resting pulmonary hypertension (PH). All of these had an alveolo-arterial oxygen difference (AaDO2) greater than 25 mmHg. Twenty patients of the group, taken as a whole, had an AaDO2 greater than 25 mmHg. Information was available from 1 month to 5 years later in 6/9 patients with an AaDO2 less than 25 mmHg. In all of them dyspnoea improved or resolved. Information was available in 15/20 patients with AaDO2 greater than 25 mmHg. Three of 8 patients without PH but with an increased AaDO2 on the initial catheterization developed PH within 2 years. Dyspnoea increased in 1 of the remaining five. Four patients who initially had PH developed right heart failure 6 months-3 years later. In the remaining 3, dyspnoea was stable in 1, increased in 1 and one patient died with autopsy evidence of multiple pulmonary emboli. Abnormal oxygenation predicts the presence or subsequent development of PH in patients who are chronically dyspnoeic after pulmonary embolism.

[Changes in right ventricular ejection fraction in right coronary angioplasty]. / Modifications de la fraction d'éjection ventriculaire droite lors des angioplasties coronaires droites.

In order to analyse the response of the right ventricule (RV) to transient myocardial ischaemia, the RV ejection fraction was measured using a new rapid response thermodilution catheter in 15 patients (14 men and 1 woman: average age 58 +/- 7 years) referred for percutaneous transluminal coronary angioplasty of a dominant right coronary artery. Only patients with single vessel disease with a proximal stenosis of the right coronary without a visible collateral circulation who had no previous history of myocardial infarction were included. Right heart catheterisation was performed with a rapid-response thermodilution catheter which enabled measurement of heart rate, cardiac index, RV end-diastolic and end-systolic volumes and RV ejection fraction. Angioplasty was carried out with the usual steerable balloon catheters. During balloon inflation, there was a slight increase in RV end-diastolic volume (from 78 +/- 11 ml/m2 to 85 +/- 13 ml/m2 at 60 seconds; p less than 0.01) and a large increase in RV end-systolic volume (from 29 +/- 8 ml/m2 to 35 +/- 8 ml/m2 at 30 seconds and 43 +/- 11 ml/m2 at 60 seconds, p less than 0.001) leading to a significant decrease in RV ejection fraction (from 62 +/- 8% to 56 +/- 6% at 30 seconds and 51 +/- 7% at 60 seconds; p less than 0.001). All parameters returned to basal values two minutes after the dilatation. Acute occlusion of the proximal segment of the right coronary artery is therefore associated with a marked change in right ventricular function which rapidly returns to normal after the coronary circulation is restored.

Inter- and intrasubject variability of the thermodilution measurement of right ventricular ejection fraction and volume in patients with chronic obstructive pulmonary disease.

STUDY OBJECTIVE: To determine the spontaneous changes in volumetric indices of right ventricular function assessed by thermodilution. DESIGN: The study involved measurements of inter- and intraindividual variation of right ventricular function in human subjects at rest and at two different levels of low load supine bicycle exercise. SUBJECTS: The subjects were 23 patients with chronic obstructive pulmonary disease, referred for evaluation by right heart catheterisation. Mean (SEM) age was 55.4 (2.2) years and all were in sinus rhythm. MEASUREMENTS AND RESULTS: Successive measurements of ejection fraction and right ventricular end diastolic and end systolic volumes were made by thermodilution with a fast response thermistor mounted in a Swan-Ganz catheter. Five measurements were made at rest (R), and three measurements during each of two levels of exercise (E1, E2). Group average values for each period showed no significant changes with time; interindividual variability was expressed as the coefficient of variation (VC1 = SD/means), intraindividual variability (VC2) as square root of mean value of individual variances. Interindividual variability increased from rest to exercise, while intraindividual variability was lower during exercise, presumably because the variables were more steady. For ejection fraction, VC1, was 23% at rest, 29% for E1 and 32% for E2, while VC2 was 21%, 12% and 15% respectively; for right ventricular end diastolic volume, VC1 was 23% at rest, 29% and 28% during exercise, and VC2 was 17%, 12% and 11% respectively. In some patients cold injection induced bradycardia and spuriously high values of ejection fraction. CONCLUSIONS - It is important to monitor heart rate before and during thermodilution measurements and to take into account only those made with stable heart rate. Injectate temperature should be above 10 degrees C.

Metabolic CO2 removal by dialysis: THAM vs NaOH infusion.

New methods of respiratory support are needed to reduce the high mortality rate of acute respiratory failure. To simplify the procedures of extracorporeal CO2 elimination under apneic oxygenation, one approach is to replace the membrane lung by a hemodialyzer and to administer an alkali, since hemodialysis requires a lower blood flow rate than blood-gas exchange. This study compared the effectiveness of trishydroxymethyl aminomethane (THAM) and NaOH in this procedure. Twelve male Anglo-Poitevin dogs (25 to 33 kg) were anesthetized, curarized and mechanically hypoventilated (VE = 41% of the control value). After not less than 15 min, a venovenous shunt was used for dialysis with blood flow of 7-10 ml. min.-1kg-1 for at least 8 hours. The dialysate contained no acetate, bicarbonate or lactate, but was alkalinized to a pH of 8-9 by the addition of NaOH. A solution of THAM (0.5 N) was infused into the right heart at the rate of 0.30 ml.min.-1kg-1 in six animals, and NaOH (0.15 N) was infused in the other six at the rate of 0.80 ml.min-1kg-1. The injected volumes were compensated for by an equivalent amount of ultrafiltration. Elimination of CO2 (mean TCO2 = 2.3 ml.min.-1kg-1) was the same with both methods and the difference for the electrolytes and acid-base equilibrium was only very small. However, hemolysis was six times greater with NaOH than with THAM. Despite ultrafiltration, a similar marked weight gain was observed from the second hour of the experiment in the NaOH series, but only after 7 hours with THAM. It thus appears that hemodialysis combined with alkalinisation is still too complex a procedure to be safely applied in acute or chronic pulmonary failure.