Effect of measurement conditions on measured levels of peak exhaled nitric oxide.

BACKGROUND: It is possible to measure nitric oxide (NO) levels in exhaled air. The absolute concentrations of exhaled NO obtained by separate workers in similar patient groups and normal subjects with apparently similar techniques have been very different. A study was undertaken to determine whether changes in measurement conditions alter the concentration of exhaled NO. METHOD: NO concentrations measured by a chemiluminescence analyser (Dasibi Environmental Corporation) and carbon dioxide (CO2) measured by a Morgan capnograph were analysed in single exhalations from total lung capacity in healthy volunteers (mean age 35.9 years). Ten subjects performed five exhalations at four different expiratory flow rates, at four different expiratory mouth pressures, and before and after drinking hot (n = 5) or cold (n = 5) water. Three subjects performed five exhalations on a day of high background NO (mean NO level 134 ppb) before and after a set of five exhalations made while both the subject and analysers were sampling from a low NO/NO-free reservoir system. RESULTS: The mean peak concentration of NO decreased by 35 ppb (95% CI 25.7 to 43.4) from a mean (SE) of 79.0 (15.5) ppb at an expiratory flow rate of 250 ml/min to 54.1 (10.7) ppb at 1100 ml/min. The mean peak concentration of NO did not change significantly with change in mouth pressure. The mean (SE) peak NO concentration decreased from 94.4 (20.8) ppb to 70.8 (16.5) ppb (p = 0.002, 95% CI 12.9 to 33.1) with water consumption. The mean NO concentration with machine and subject sampling from the low NO reservoir was 123.1 (19.4) ppb, an increase from results obtained before (81.9 (10.2) ppb, p = 0.001, 95% CI -19.9 to -62.7) and after (94.2 (18.3) ppb, p = 0.017, 95% CI 6.0 to 51.8) sampling with high ambient NO. CONCLUSIONS: The measurement of exhaled NO must be performed in a carefully standardised manner to enable different teams of investigators to compare results.

Is nitric oxide in exhaled air produced at airway or alveolar level?

The aim of this study was to determine whether the nitric oxide (NO) measured in exhaled air is produced at airway or alveolar level. Exhaled NO was measured using a chemiluminescence analyser, and carbon dioxide (CO2 concentration using a Morgan capnograph in single exhalations in 12 healthy subjects (mean age 32 yrs; 6 males and 6 females). For each subject, five exhalations were made directly into the NO analyser and five were made through a T-piece system, which allowed measurement of expiratory flow rate. The peak NO levels measured via the T-piece system were 41.2 (SEM 10.8) parts per billion (ppb), significantly lower than direct levels 84.8 (14.0) ppb (p<0.001). The levels of NO tended to rise to an early peak and plateau, while the CO2 levels continued to rise to peak late in the exhalation. The mean times to reach peak NO levels were 32.2 s (direct) and 23.1 s (T-piece), which were significantly different from that of peak CO2 levels 50.5 s (direct) and 51.4 s (T-piece) (p<0.001). At peak NO level, the simultaneous CO2 level mean 4.9% (SEM 0.14)%, was significantly lower than the peak CO2 reached, 5.8 (0.21)% (p<0.001). We conclude that peak nitric oxide levels are dependent on measurement conditions. There are significant differences between the time to peak of carbon dioxide and nitric oxide. Therefore, most nitric oxide, unlike carbon dioxide, is produced in airways and not at alveolar level.

A new device for ambulatory cough recording.

Nocturnal cough reporting on diary cards has been shown to be unreliable and inconsistent. Whether subjective reporting of daytime cough is equally unreliable remains unknown. We have, therefore, developed a new and easily portable device (RBC-7) that records electromyographic (EMG) and audio cough signals for at least a 24-hr period, with a capacity of over 48 hr. Additional information is obtained from electrocardiographic (ECG) signals, and from an accelerometer indicating the level of the subject's activity. The RBC-7 can be set up with the aid of a notebook computer at the subjects home, school or workplace. Initial studies utilizing a prototype device were performed to determine the optimal position of the EMG leads and the microphone. The optimal position for the EMG leads was determined as the positive electrode in the sixth intercostal space (ICS) in the midclavicular line on the left, the negative electrode in the same position on the right, and the reference electrode in the midline over the abdomen. This position was shown to give the highest EMG voltages and the greatest difference in voltages between cough and other signals. The optimal microphone position for signal strength and comfort was over the first ICS, either right or left, close to the sternum. Recordings were performed simultaneously in 20 subjects with conventional tape recorders and the multiparametric cough monitoring system (RBC-7). Conventional tape recordings limited the duration of the studies due to the inherent restrictions. No significant difference in the number of single coughs recorded by each system was detected (correlation coefficient = 0.996). The RBC-7 offers a unique opportunity to obtain objective information on cough in ambulatory subjects over at least a 24-hr period, and to relate cough to time, activity and heart rate, while normal activities are pursued.

Coughing frequency in patients with persistent cough: assessment using a 24 hour ambulatory recorder.

Cough is an important symptom of many respiratory disorders. We determined the frequency and diurnal variation of cough in normal subjects and in patients with asthma or with persistent cough of unknown cause. We used a portable, solid-state, multiple-channel recorder to record cough sounds over a 24 h period. The audio-signal was recorded from a unidirectional microphone strapped over the chest wall, and electromyographic (EMG) signals from the lower respiratory muscles were simultaneously registered with surface electrodes. The recorded digital data were examined on an IBM-compatible computer, and the typical signals induced by cough (as assessed by voluntary or experimentally-induced cough) were counted. In 12 normal subjects, only 0-16 coughs were recorded over 24 h. In 21 stable asthmatics with a history of chronic cough ("asthma") the median number was 282 (ranges: 45-1,577), and in 14 patients with the predominant symptom of daily dry coughs ("chronic coughers") the median number was 794 (64-3,639). In both groups of patients, there was a diurnal variation of coughs, such that the least numbers occurred between 2 and 5 a.m. (< 3% of total). In the asthma group, there was no significant correlation between forced expiratory volume in one second (FEV1) (% predicted) or diurnal variation of peak expiratory flow and cough frequency. In the chronic coughers, there was a significant correlation between daytime cough numbers and daytime cough symptoms scores but not for the night-time values. Our data show that cough frequency is not determined by the severity of asthma in relatively stable asthmatics on inhaled steroids, and is reduced during sleep in both asthmatics and chronic cough patients. This portable cough recorder may be useful in the assessment of drug therapy for chronic cough.

Exercise capacity after complete repair of tetralogy of Fallot: deleterious effects of residual pulmonary regurgitation.

OBJECTIVE: To determine the effects of residual pulmonary regurgitation on exercise tolerance after complete repair of tetralogy of Fallot. DESIGN: Prospective study of symptom free patients more than five years after complete repair. Graded exercise performance was measured with standard Bruce protocol. Maximal oxygen uptake and ventilatory anaerobic threshold were measured by respiratory mass spectrometry. Measurement of pulmonary regurgitant fraction was from pressure-volume loops constructed from measurements of right ventricular volume obtained from biplane angiograms and simultaneous pressures measured with a micromanometer. SETTING: Tertiary referral centre. PATIENTS: 16 patients were studied. Two patients had been excluded because of residual cardiac lesions or inadequate data from cardiac catheterisation. Four were later excluded because they failed to reach a respiratory quotient of greater than 1.0 during graded exercise. RESULTS: There was a significant negative correlation between the degree of residual regurgitation and both total duration of exercise and maximal heart rate achieved. Maximal heart rate and total duration of exercise were significantly lower in the patients than in normal controls. Patients with an abnormal maximal oxygen uptake (less than 85% of the predicted normal value) had significantly greater residual pulmonary regurgitation than those in whom oxygen uptake was normal. CONCLUSIONS: Impaired exercise capacity after complete repair of tetralogy of Fallot is directly related to the degree of residual pulmonary regurgitation. These data should be taken into account when deciding the optimal timing and nature of corrective surgery.

Exercise ability after Mustard's operation.

Twenty children who were well six to 12 years after undergoing Mustard's operation for transposition of the great arteries were studied. Each child performed a graded maximal treadmill test with measurements of gas exchange and oxygen saturation, and had electrocardiography carried out. Nineteen were also catheterised, and oxygen consumption was measured so that pulmonary and systemic flow could be calculated. Compared with 20 age and size matched controls, seven of the patients had normal exercise tolerance (as judged by a maximal oxygen consumption of greater than 40 ml/kg/min), 10 showed a moderate reduction (30-39 ml/kg/min), and three were more seriously limited. None of the patients with normal exercise tolerance had obstruction of venous return but six of those with mild impairment of exercise ability had partial or complete obstruction of one or both of the vena cavas. More severe limitation was associated with pulmonary vascular disease and fixed ventricular outflow tract obstruction. Formal exercise testing of apparently well children who have undergone Mustard's operation identifies those with haemodynamic abnormalities that may require intervention.

Changes in pulmonary circulation in severe bronchopulmonary dysplasia.

Eight patients with severe bronchopulmonary dysplasia underwent cardiac catheterisation. Seven had a pulmonary vascular resistance greater than 3 mm Hg.l-1 min.m2 (mean 8.9, range 2.2-13.8). All had raised intrapulmonary shunts (mean 25.6%, range 5.4-50%, normal less than 5%). Two had a high alveolar dead space, and two had unsuspected congenital heart disease. Epoprostenol (prostacyclin), but not 100% oxygen, caused a significant fall in pulmonary vascular resistance. Death was associated with a high pulmonary vascular resistance and a high shunt. Morphometric studies in three cases showed normal numbers of airways, but increased thickness of bronchial muscle. The numbers of alveoli were reduced and the walls thickened. There was increased medial thickness in small pulmonary arteries with distal extension of muscle. In the oldest child some vessels were obliterated by fibrosis. We speculate that measurements of pulmonary vascular resistance and shunt may have prognostic value; that a trial of pulmonary vasodilators other than oxygen might be worthwhile in patients with poor prognosis; and that abnormalities of the pulmonary circulation contribute to the difficulties of managing patients with bronchopulmonary dysplasia.

Preoperative measurement of pulmonary vascular resistance in complete transposition of the great arteries.

Transposition of the great arteries is frequently complicated by the early onset of pulmonary vascular disease. It is difficult to measure pulmonary blood flow by the Fick principle because the pulmonary arteriovenous oxygen content difference is small and bronchial blood flow is increased in this condition. In eight patients (mean age 7.7 years, range 3 months to 29 years) with transposition of the great arteries mass spectrometry was used to measure oxygen uptake and predict pulmonary end capillary blood oxygen content. The effects of the bronchial circulation were studied by computer modelling. There was close agreement between pulmonary end capillary and pulmonary vein blood oxygen contents but the resultant percentage difference in arteriovenous content difference was significant (mean (SE of difference)) (14.5(3.8)%). The effect of the bronchial circulation was to give spuriously high estimates of pulmonary blood flow. The error was greatest when oxygen consumption was low and aortic blood was very desaturated.

Do asymptomatic school children have normal haemodynamics 6-13 years after Mustard's operation?

Twenty asymptomatic school children who had undergone Mustard's operation for simple complete transposition (concordant atrioventricular and discordant ventriculo-arterial connexions) were catheterised electively 6-13 years later. The studies were carried out under general anaesthesia in air and in 100% O2. Oxygen consumption was measured and end-tidal gases were monitored using respiratory mass spectrometry. There was significant left ventricular outflow tract obstruction in 2 patients. Cardiac output in air was normal in 15 and decreased in 5 patients. The pulmonary vascular resistance was normal in 18 of 19 cases, but grossly elevated in one patient. Baffle dysfunction was present in 11 patients: 10 with important gradients between the venous pathways and the systemic venous atrium, and 5 with a leak identified either by a left-to-right shunt or by the course of the catheter. Balloon dilatation was attempted in the inferior caval venous channel in 6 and in the superior caval venous channel in 2. Mean gradient before the dilatation fell after the procedure. No pulmonary venous obstruction was identified. Even in this group of children selected as asymptomatic, approximately half had a detectable haemodynamic abnormality.

Interactions between alveolar hypercapnia and epoprostenol on the pulmonary circulation: clinical and pharmacological implications.

Hypoxic vasoconstriction has been the subject of many studies, but little is known about the interaction of hypercapnia and the pulmonary circulation. We performed two haemodynamic studies on each of three patients with pulmonary vascular disease secondary to congenital heart disease. On the first occasion ventilation was inadequate due to technical problems, and the patients were therefore hypercapnic (arterial pCO2 greater than 5.3 kPa). On the second occasion, they were normocapnic. Pulmonary vascular resistance was measured on each occasion while the patients were breathing 100% oxygen (alveolar hyperoxia) and while epoprostenol (prostacyclin) was infused at doses of 5-20 ng/kg/min. Pulmonary vascular resistance was elevated in the presence of hypercapnia and, despite oxygen and epoprostenol, could not be reduced to the levels observed in the normocapnic study. We conclude that hypercapnia causes significant vasoconstriction in infants; and that epoprostenol is a relatively ineffective pulmonary vasodilator in infants who are hypercapnic due to inadequate ventilation. Where possible, respiratory acidosis should be corrected before using oxygen or epoprostenol as a pulmonary vasodilator.

Comparison of the cardiovascular and pulmonary effects of oral celiprolol, propranolol and placebo in normal volunteers.

1. The effects on heart rate, blood pressure and pulmonary function of single oral doses of celiprolol hydrochloride (400 mg), and propranolol (40 mg) were compared with placebo in 12 healthy volunteers, in a double-blind three-period crossover study. 2. Celiprolol had no effect on heart rate while propranolol caused a significant reduction compared with placebo. Systolic blood pressure was reduced by propranolol but not celiprolol, whereas standing diastolic blood pressure was lowered by both drugs. 3. The maximal expiratory flow at 50% vital capacity (MEF.50), was significantly lower after propranolol compared with placebo and celiprolol. Celiprolol had no effect on the flow-volume loop parameters. 4. Effective pulmonary blood flow was significantly increased by celiprolol, but reduced by propranolol. 5. A high incidence of subjective side-effects were experienced on celiprolol (10/12; particularly unpleasant in 5). Side-effects were experienced to a lesser extent on placebo (8/12). Only one volunteer experienced a side-effect on propranolol. 6. Oral celiprolol exerts its hypotensive effect by vasodilatation without reflex tachycardia. It does not cause airways obstruction in healthy subjects.

Multiple pulmonary arteriovenous fistulas in childhood.

Three cases of multiple pulmonary arteriovenous fistulas are described in children who presented at five months, two and nine years of age. Mass spectrometry was used to measure pulmonary blood flow and, in two cases, the intrapulmonary right-to-left shunt. The shunt fractions were 51% and 35%, with no significant change on breathing 100% oxygen. In one case, effective pulmonary blood flow was measured during cardiac catheterisation by the argon-freon rebreathing method and agreed closely with that found from the Fick, principle with measured oxygen consumption. Treatment consisted of surgical ligation of a lower lobe pulmonary artery in the youngest child, balloon embolisation in the second, and initial surgical oversewing of a single large fistula followed twenty months later by steel coil embolisation in the third. The last and oldest child is well and no longer cyanosed. The first two children died seven months after treatment with evidence of progression of their pulmonary arteriovenous fistulas. The first of these, who also had an atrial septal defect and discordant thoraco-abdominal arrangement, died of heart failure. Autopsies on both children confirmed extensive involvement of both lungs by arteriovenous fistulas. In one case who had a diffuse, telangiectatic form of pulmonary arteriovenous fistulas, microscopic serial reconstructions of lung tissue revealed that anastomoses occurred between arteries accompanying terminal bronchioles and intra-acinar arteries and adjacent veins. Occlusion of the pulmonary arteries supplying the fistulas led to extensive fibrosis within them, and was associated with enlargement of the corresponding bronchial arterial circulation.

Effect of infused adenosine on cardiac output and systemic resistance in normal subjects.

1. The purine nucleoside adenosine relaxes smooth muscle in vitro and is a vasodilator in animals, but its effects on cardiac output and systemic vascular resistance have not been measured in normal conscious human subjects. 2. We have studied the effects of infused adenosine in doses of 0.005, 0.03 and 0.07 mg kg-1 min-1 on pulmonary blood flow and systemic vascular resistance in eight healthy volunteers, using a non-invasive, inert gas method and mass spectrometry. 3. At a dose of 0.07 mg kg-1 min-1, there was a rise in effective pulmonary blood flow (which is approximately equivalent to cardiac output) of 0.52 +/- 0.08 l min-1 m-2 (mean +/- s.e. mean) and a fall in estimated systemic vascular resistance of 357 +/- 44 dyn s cm-5. Despite this marked systemic vasodilation, there was no significant change in mean heart rate. 4. The effects of this dose of adenosine were maximal 2 min after starting the infusion, and had disappeared within 5 min of stopping it. 5. Adenosine may be therapeutically useful in the reduction of left ventricular afterload, where the absence of reflex tachycardia may be advantageous. We suggest that adenosine in doses of 0.03 mg kg-1 min-1 should be evaluated as a selective pulmonary vasodilator.

Effects of infusion of prostacyclin on anatomical intrapulmonary right to left shunt: a useful model of human hypoxic vasoconstriction?

1. Eleven infants and children (mean age 4.3 years, range 0.2-12 years) with pulmonary vascular disease secondary to congenital cardiac anomalies (n = 6) or bronchopulmonary dysplasia (n = 5), were studied during cardiac catheterization while ventilated on 100% oxygen. 2. All had a raised pulmonary vascular resistance (mean 11.8 units, range 4.1-26.0 units, normal value less than 3 units) and a raised anatomical intrapulmonary right to left shunt (mean 22%, range 8-50%, normal value less than 5%). The elevated shunt was attributed to the effects of 100% oxygen and general anaesthesia causing alveolar collapse, with only partial compensation for impairment of gas exchange by compensatory local hypoxic vasoconstriction. 3. When prostacyclin was infused, pulmonary vascular resistance fell by 3.2 +/- 1.8 units (mmHg litre-1 min m2), and pulmonary blood flow rose by 1.0 +/- 0.7 litre min-1 m-2 (mean +/- 95% confidence intervals). 4. Intrapulmonary right to left shunt fraction increased in eight of 11 patients, with a maximal rise for the group of 5.9 +/- 4.6% (mean +/- 95% confidence intervals). However, even at doses of prostacyclin sufficient to cause systemic vasodilatation and tachycardia, there was no evidence for a selective increase in shunt fraction. 5. We suggest that studying the effects of therapeutic interventions on intrapulmonary shunt fraction may be a useful model in vivo of human hypoxic pulmonary vasoconstriction.

Comparison of the haemodynamic effects of epoprostenol (prostacyclin) and tolazoline.

The haemodynamic effects of infusion of epoprostenol (prostacyclin) and bolus injection of tolazoline were compared in a crossover study in 11 children with pulmonary hypertension caused by pulmonary vascular disease. The children were studied during cardiac catheterisation, while they were anaesthetised, paralysed, and ventilated with 100% oxygen. The order of drug administration was not randomised because tolazoline has a half life of hours whereas epoprostenol has a half life of a few minutes. Both drugs caused pulmonary and systemic vasodilatation, and there were no significant differences between the two. The 95% confidence intervals suggest that tolazoline did not have a clinically important haemodynamic advantage over epoprostenol. Previous reports suggest that serious side effects are common when tolazoline is used in repeated doses; epoprostenol has only a few minor side effects that are rapidly reversible when the infusion is stopped. Epoprostenol is more expensive than tolazoline but this study suggests that epoprostenol is a more suitable pulmonary vasodilator if more than a single dose is required.

Rebreathing method for the simultaneous measurement of oxygen consumption and effective pulmonary blood flow during exercise.

This paper describes a rebreathing method for the simultaneous measurement of oxygen consumption (VO2) and effective pulmonary blood flow (QP. eff) at rest and during exercise. Subjects rebreathed a test gas consisting of 35% oxygen, 3.5% chlorodifluoromethane (freon-22), and 10% argon in nitrogen for 30 seconds or until the respired oxygen tension fell to below 13.3 kPa. Sixty normal subjects were studied on a motorized treadmill, the Bruce protocol being used. The rebreathing manoeuvre was performed at three minute intervals, and was initially practised sitting down. Measurements were then made with the subjects standing at rest, and subsequently during the last minute of each stage of the Bruce exercise protocol until the subjects were exhausted. Heart rate was recorded from the electrocardiogram. Oxygen uptake plotted against calculated power (watts) showed a discontinuity between resting and exercise values, probably because power output during treadmill exercise is underestimated. The arbitrary addition of 30 watts to the exercise power output abolished this discontinuity. There was good agreement between rebreathing estimates of oxygen consumption and values measured during a second exercise test by the conventional open circuit argon dilution method. Coefficients of variation of oxygen consumption and effective pulmonary blood flow measured by rebreathing were usually less than 10% even during maximal exertion. At rest mean (SD) effective pulmonary blood flow corrected for body surface area was 2.2 (0.46) l/min/m2. Effective pulmonary blood flow rose linearly with oxygen consumption. At rest the arteriovenous oxygen content difference for pulmonary blood (VO2/QP eff) was 9.1 (1.6) ml/dl, rising to a maximum of 16.4 (1.8) ml/dl. The stroke volume index was 27.5 (6.8) ml/m2, rising to a maximum of 46.5 (7.1) ml/m2 during exertion.

Cardiovascular function at rest and on exercise in patients with cryptogenic fibrosing alveolitis.

Cardiovascular complications are common in fibrosing alveolitis, but there have been few physiological studies of the pulmonary circulation in this condition, and those that have been carried out have usually depended on right heart catheterisation. This paper reports non-invasive measurements of effective pulmonary blood flow, oxygen uptake, pulmonary arteriovenous oxygen content differences, and estimates of mixed venous oxygen saturation in 20 patients with histologically proved cryptogenic fibrosing alveolitis at rest and while exercising on a motorized treadmill. Results were compared with those of 20 age and sex matched normal subjects, at rest and at an arbitrarily chosen oxygen uptake of 0.75 l/min. The latter results were obtained by linear interpolation. Effective pulmonary blood flow was normal at rest, but oxygen dispatch to the tissues (blood flow x blood oxygen content) was significantly reduced at rest (mean reduction 190 (SD 68) ml/l/min; p less than 0.01) and at an oxygen uptake of 0.75 l/min (mean reduction 128 (50) ml/l/min; p less than 0.02), reflecting the presence of systemic arterial hypoxaemia. Pulmonary arteriovenous oxygen content differences were similar in patients and normal subjects, but mixed venous saturation was lower in the patients at rest (mean % reduction 6.8 (2.6); p less than 0.02) and at an oxygen uptake of 0.75 l/min (mean % reduction 9.6 (2.9); p less than 0.002). It is concluded that the supply of oxygen potentially available to the tissues is reduced at rest and during exercise in patients with fibrosing alveolitis and hence, by analogy with normal people exercising under hypoxic conditions, that pulmonary blood flow is inappropriately low in this condition. The low mixed venous oxygen saturation may contribute to the development of pulmonary hypertension in some patients. The rebreathing technique used in this study may be of use in monitoring treatment; it could be applied many times to the same patient, and might be a suitable way of following the response to pulmonary vasodilators.

Correlations of lung morphology, pulmonary vascular resistance, and outcome in children with congenital heart disease.

Pulmonary vascular resistance was measured in air, oxygen, and after administration of vasodilators in 14 children with pulmonary hypertension and congenital heart disease. Lung morphology was examined by light microscopy and assessed quantitatively. In this selected group of patients (a) medial muscle thickness of greater than 20% in the intra-acinar arteries and Heath-Edwards changes of I or II were significantly associated with perioperative death from pulmonary complications after cardiac surgery; (b) children with lower percentage medial muscle thickness had a higher baseline resistance (r = -0.84) associated with Heath-Edwards grade III or higher changes (most of these patients were not offered corrective surgery); (c) when the lowest pulmonary vascular resistance was less than 3 units, Heath-Edwards grading was I or II (n = 4). When the pulmonary vascular resistance was greater than 6 units, however, there was no direct correlation with Heath-Edwards grading (n = 9). Four patients with a resistance of greater than 6 units had only grade I or II changes. Three had a medial muscle thickness above 20%, and were among those who died at or soon after operation. It is concluded that (a) patients with a lowest pulmonary vascular resistance of greater than 6 units have a bad prognosis whatever their lung morphology; and (b) some patients with Heath-Edwards grade I or II will have a high resistance (this group has a high medial muscle mass and a poor prognosis and would not be detected by Heath-Edwards grading alone).

Time course of the effects of epoprostenol on effective pulmonary blood flow in normal volunteers.

1. Epoprostenol (prostacyclin) has been widely used as a vasodilator, but its effects on cardiac output are controversial and the time course of its effects little studied. 2. We report its cardiovascular effects in doses of 5 and 10 ng kg-1 min-1 in six healthy volunteers. 3. Each of the two doses caused a mean 20% rise in effective pulmonary blood flow and a 15% rise in heart rate. These effects appeared to reach a maximum within 10 min of starting or increasing the rate of infusion, with no evidence of a rebound effect. 4. When the dose was reduced, heart rate and effective pulmonary blood flow appeared to reach a new steady state within 5 min of reducing or stopping the infusion. Only minor side-effects were encountered, and they were rapidly reversed on stopping the drug. 5. These results should be applied to the therapeutic use of epoprostenol as a vasodilator, particularly when titrating the optimum dose for a given individual.

Modification of pulmonary hypertension secondary to congenital heart disease by prostacyclin therapy.

We have shown that PGI2 is a powerful but not selective pulmonary vasodilator, and we believe that there is a role for PGI2 in pulmonary vascular disease secondary to congenital heart disease, but much work remains to be done, including comparisons of PGI2 with other vasodilators. The role of PGI2 in altering the cellular and chemical events producing pulmonary vascular disease secondary to congenital heart disease, and any role in long-term treatment, is largely unexplored.