The early and late effects of surgical closure of ventricular septal defects on pulmonary vascular dynamics

In sixty patients who underwent closure of ventricular septal defect (VSD), cardiac catheterizations were performed before and late after surgery together with pressure measurements immediately after closure of the VSD during surgery. Pulmonary arterial mean pressure (PAm), pulmonary arterial systolic pressure to systemic arterial systolic pressure ratio (Pp/Ps), and pulmonary vascular resistance to systemic vascular resistance ratio (Rp/Rs) were measured and calculated. The patients were classified into 5 groups according to the preoperative Rp/Rs and Qp/Qs as was reported by Nakada: Group A: Rp/Rs less than 0.15, Qp/Qs larger than or equal to 1.8, Group B: Rp/Rs less than 0.15, Qp/Qs less than 1.8, Group C: 0.15 less than or equal to Rp/Rs less than 0.50, Group D: 0.50 less than or equal to Rp/Rs less than 0.85, Group E: 0.85 less than or equal to Rp/Rs. These groups were further divided into 3 groups respectively according to age at operation (less than or equal to 2 years, 3 or 4 years, 5 years less than or equal to). The averages of PAm, Pp/Ps, and Rp/Rs were within the normal range in Group A and B patients (normal pulmonary vascular resistance groups) irrespective to the age at operation except the average of PAm before surgery. In Group C, D and E patients (elevated pulmonary vascular resistance group), these variables decreased immediately after closure of VSD, and further decreases were noted at the time of late catheterization. These variables, however, did not completely normalize even at that time. Among the patients operated upon at 2 years of age or less, the averages of these variables normalized immediately after closure of the VSD. When operated upon at 3 or 4 years of age, these variables decreased but did not normalize immediately after closure of the VSD and were found to be within the normal range at the time of late catheterization. When operated upon at 5 years of age or more, these variables decreased immediately after closure of the VSD, and further decrease was found at the time of late catheterization but mostly remained in the abnormal range even at this time. From the data obtained herein, the factors producing the pulmonary vascular resistances in respective age groups were discussed. The closure of VSD in patients with elevated pulmonary vascular resistance is recommended at the latest 4 years of age and preferably at 2 years of age or less, in order to obtain normal pulmonary circulatory dynamics after surgery.     

Precapillary pulmonary hypertension of uncertain etiology

HISTORY AND CLINICAL FINDINGS: A 39-year-old man was hospitalized for investigation of increasing dyspnoea for 3 month. On admission he was found to have bilateral ankle oedema, an enlarged liver and loud systolic murmur over the lower sternum. INVESTIGATIONS: There were signs of right heart strain/hypertrophy on the chest radiogram and echocardiogram. After treatment of right heart failure cardiac catheterization indicated moderate precapillary pulmonary hypertension (PH) with a mean pulmonary artery pressure (PAPm) of 24 mm Hg and pulmonary vascular resistance (PVR) of 470 dyn.s.cm-5 at rest. All known causes having been excluded, the PH was classified as idiopathic. TREATMENT AND COURSE: Evidence of acute pulmonary vascular reactivity was obtained with nitric oxide (NO) inhalation and oral diltiazem, a calcium-channel blocker. The latter, at a dosage of 3 x 120 mg daily, had after 13 days achieved a persisting reduction of PVR at rest and a reduction in PAP rise during exercise. CONCLUSION: After exclusion of other causes, the acute right heart failure was found to be due to primary pulmonary hypertension. The therapeutic efficacity of diltiazem as a vasodilator can be predicted from the response to inhaled NO.     

Bidirectional shunt flow across a ventricular septal defect: pulsed Doppler echocardiographic analysis

Pulsed Doppler echocardiographic and hemodynamic examinations were performed in 31 patients (mean age 17.8 years) with isolated ventricular septal defect (VSD). Three groups were studied: group I (n = 6) patients had severe pulmonary vascular obstructive disease (PVOD); group II (n = 12) patients had pulmonary hypertension (PH) without severe PVOD; group III (n = 13) patients had no PH. Bidirectional shunting was detected in 9 VSD patients (6 in group I and 3 in group II). Patients with low to moderately elevated right ventricular pressures demonstrated left-to-right shunting across the defect throughout the cardiac cycle. When systolic pressure in the right ventricle reached approximately 60% of the left ventricular pressure, right-to-left shunting occurred across the defect during early and mid diastole. However, in patients with Eisenmenger syndrome (group I) the right-to-left shunting occurred during late systole with continuation during the early and mid diastolic period. The earlier occurrence of right-to-left shunting (index < 0.5 second) signifies the presence of severe PVOD.     

Effects of magnesium sulphate and nitric oxide in pulmonary hypertension induced by hypoxia in newborn piglets

AIM: To examine the haemodynamic effects of intravenous magnesium sulphate on an animal model of neonatal pulmonary hypertension induced by hypoxia. METHODS: The cardiac index (Q), pulmonary arterial pressure (PAP), systemic arterial pressure (SAP), and pulmonary (PVRI) and systemic (SVRI) vascular resistance indices were measured in nine newborn piglets (including three controls). Pulmonary hypertension was induced by lowering the FIO2 to 0.12-0.14, after which there was a significant increase in PAP and PVRI (37% and 142%, respectively; p < 0.01) and a significant fall in SAP and Q (30% and 33%, respectively; p < 0.01). RESULTS: Magnesium sulphate was infused intravenously as four doses of 25 mg/kg, 15 minutes apart, which resulted in a significant mean (SD) increase in serum magnesium (0.83 (0.07) mmol/l to 1.82 (0.19) mmol/l; p < 0.01). After the initial dose SAP, SVRI, PAP and PVRI decreased, but not significantly. Each subsequent dose of (50, 75, 100 mg/kg) was accompanied by further significant reductions in these variables from control baseline (p < 0.05). The PVRI:SVRI ratio remained unchanged throughout. Inhaled nitric oxide (NO) 40 ppm was administered after the last dose of magnesium sulphate. The PVRI:SVRI significantly decreased (p < 0.05), indicating that reversible pulmonary hypertension remained after a maximum dose of magnesium sulphate. CONCLUSIONS: Unlike NO, magnesium sulphate is not a selective pulmonary vasodilator and may lead to deleterious effects on systemic pressures in critically ill newborns.     

Destructive gouty arthritis of the hip

We present a case of a 19-year old female with systemic pulmonary artery (PA) pressure due to a congenital ventricular septal defect (VSD) and atrial septal defect (ASD). She was pink at rest and cyanotic on exercise. Lung biopsy revealed grade IV pulmonary vascular changes. As a preliminary step PA was banded to increase right-to-left shunt and decrease aortic (Ao) saturation with consequent decrease in PA saturation. After one year, when she was no longer cyanotic, even on exercise, lung biopsy revealed total regression of pulmonary vascular changes. As a definitive procedure VSD and ASD were closed and PA was debanded. Cardiac catheterization one week postoperatively showed PA pressure to be 50% of systemic pressure. We postulate that reversal of pulmonary vascular changes were due to lowered PA saturation. We further believe that lower PA pressure could have contributed to this regression of pulmonary vascular changes. We performed the same procedure in six more patients with similar positive clinical response. This new concept brings renewed hope to many children who otherwise are candidates for heart lung transplantation.     

Lung mechanics in congenital heart disease with increased and decreased pulmonary blood flow

Respiratory rate, tidal volume, dynamic lung compliance, functional residual capacity, and pulmonary resistance were measured withim 24 hours of cardiac catheterization in 25 infants, 12 of whom had increased pulmonary blood flow and 13 of whom had decreased PBF. There were no differences in the two groups of patients with respect to VT and FRC. Respiratory rate and pulmonary resistance were higher in infants with increased PBF. Lung compliance was significantly lower in infants with increased PBF (4.9 ml/cm H2O) than in those with decreased PBF (8.9 ml/cm H2O) (P less than 0.01). The decrease in CL in infants with increased PBF significantly correlated with mean pulmonary artery pressure (r = 0.798). No correaltion was found between CL and left atrial pressure or magnitude of the left-to-right shunt. Compliance was normal in patients with increased PBF and normal PAP, suggesting that PAP and not PBF is the primary factor that affects CL in patients with intracardiac left-to-right shunts.     

Paradoxic pulmonary vasoconstriction in response to acetylcholine in patients with primary pulmonary hypertension

Pulmonary vascular reactivity was assessed during diagnostic heart catheterization in two patients with pulmonary hypertension unexplained by pulmonary or cardiac disease and in five patients with atypical chest pain and normal coronary arteriograms. Acetylcholine, an endothelium-dependent vasodilator that also has a direct contracting effect on vascular smooth muscle cells, was infused in the right atrium in a step-wise increasing dose in order to obtain final blood concentrations in the pulmonary circulation ranging from 10(-6) mol/L to 10(-4) mol/L. In the five control patients, acetylcholine induced a dose-related decrease of pulmonary vascular resistance (-52 percent +/- 9 percent). In the patients with primary pulmonary arterial hypertension, however, acetylcholine caused a paradoxic increase of pulmonary arterial pressure and of pulmonary vascular resistance. Thus, it appears that endothelium-dependent vasodilation is impaired in the pulmonary circulation of patients with primary pulmonary arterial hypertension. Endothelial dysfunction in the pulmonary circulation may play a role in the pathophysiology of this disease.     

Hemodynamic effects of vasodilator agents in dogs with experimental ventricular septal defects

The ratio of pulmonary to systemic vascular resistance (Rp/Rs) largely determines the amount of left-to-right shunting and pulmonary to systemic flow rat (Qp/Qs) in the presence of a large isolated ventricular septal defect. The possibility that pharmacologic reduction of systemic vascular resistance with alpha-adrenergic receptor blockade or beta-adrenergic receptor stimulation would increase the ratio Rp/Rs, and therefore reduce the ratio Qp/Qs, was studied in dogs in which ventricular septal defects had been surgically created. Administration of phentolamine and phenoxybenzamine caused a 42% reduction in Rs and no reduction in Rp. Qs was unchanged and Qp declined by 24% and the ratio Qp/Qs fell by 32%. Infusion of the beta-adrenergic receptor stimulant isoproterenol also reduced Qp/Qs. However, this was accomplished as a result of an increase in Qs and at the expense of an increase in heart rate. As a decline in the ratio Qp/Qs has been shown to be beneficial to patients with large left-to-right shunts, pharmacologic reduction of systemic vascular resistance may prove to be helpful in treating congestive heart failure in those patients with large left-to-right shunts at the ventricular level who are refractory to the usual decongestive measures.     

Nitric oxide inhalation: effects on the ovine neonatal pulmonary and systemic circulations

Others have shown that inhaled nitric oxide causes reversal of pulmonary hypertension in anaesthetized perinatal sheep. The present study examined haemodynamic responses to inhaled NO in the normal and constricted pulmonary circulation of unanaesthetized newborn lambs. Three experiments were conducted on each of 7 lambs. First, to determine a minimum concentration of NO which could reverse acute pulmonary hypertension caused by infusion of the thromboxame mimic U46619, the haemodynamic effects of 5 different doses of inhaled NO were examined. Second, the effects of inhaling 80 ppm NO during hypoxic pulmonary vasoconstriction were examined. Finally, to determine if tachyphalaxis occurs during NO inhalation, lambs were exposed to 80 ppm NO for 3 h during which time pulmonary arterial pressure was doubled by infusion of U46619. Breathing NO (80 ppm) caused a slight but significant decrease in pulmonary vascular resistance (PVR) in lambs with normal pulmonary arterial pressure (PAP). Nitric oxide, inhaled at concentrations between 10 and 80 ppm for 6 min (F1O2 = 0.60), caused decreases in PVR when PAP was elevated with U46619. Nitric oxide acted selectively on the pulmonary circulation, i.e. no changes occurred in systemic arterial pressure or any other measured variable. Breathing 80 ppm NO for 6 min reversed hypoxic pulmonary vasoconstriction. In the chronic exposure study, inhaling 80 ppm NO for 3 h completely reversed U46619-induced pulmonary hypertension. Although arterial methaemoglobin increased during the 3-h exposure to 80 ppm NO, there was no indication that this concentration of NO impairs oxygen loading. These data demonstrate that NO, at concentrations as low as 10 ppm, is a potent, rapid-action, and selective pulmonary vasodilator in unanaesthetized newborn lambs with elevated pulmonary tone. Furthermore, these data support the use of inhaled NO for treatment of infants with pulmonary hypertension.     

A survey of diagnostic practices and the use of epoprostenol in patients with primary pulmonary hypertension

STUDY OBJECTIVE: To obtain information about the diagnosis and management of primary pulmonary hypertension (PPH), especially about the use of epoprostenol (Glaxo-Wellcome; Research Triangle Park, NC) in this patient population. BACKGROUND: Long-term IV epoprostenol therapy was approved recently for use in patients with PPH who are unresponsive to conventional therapy. Although epoprostenol represents a major advance in the treatment of PPH, there is no published consensus regarding the optimal use of this therapy. METHODS: A five-page survey was mailed to 23 investigators at medical centers treating five or more patients with PPH with long-term epoprostenol therapy. RESULTS: Nineteen of 23 investigators responded to the survey. During the initial hemodynamic evaluation, 11 investigators used changes in pulmonary vascular resistance (PVR), pulmonary artery pressure (PAP), and cardiac output, 5 investigators considered PVR and PAP only, and 2 investigators analyzed PVR alone to define a short-term vasodilator response. During long-term therapy, two thirds of the investigators increased the dose at scheduled intervals, while all investigators increased the dose in response to worsening symptoms. Epoprostenol doses were reported to range from 0.5 to 270 ng/kg/min. Nine investigators routinely repeated right heart catheterization an average of 7.5+/-3.8 months after starting epoprostenol, and the mean decrease in pulmonary artery pressure was between 15 and 25%. CONCLUSION: This survey indicates that there is wide variation in the evaluation of patients with PPH and in the use of epoprostenol therapy. The lack of consensus suggests the need for multicenter collaborative studies in order to optimize the use of epoprostenol therapy for PPH.     

Predictors of mortality in pulmonary thromboendarterectomy

BACKGROUND: The operative mortality associated with surgical thromboendarterectomy of the pulmonary arteries has decreased at the University of California in San Diego with the application of new techniques. For universal performance of the procedure, however, those factors that contribute to the high operative mortality must be identified. We analyzed our results in 34 consecutive patients undergoing pulmonary thromboendarterectomy to determine those preoperative factors that contribute to operative mortality. METHODS: Since 1983, 34 patients with severe, surgically correctable chronic thromboembolic pulmonary hypertension who were judged to be operable by pulmonary arteriography underwent pulmonary thromboendarterectomy. No patient was excluded because of right ventricular failure or hemodynamic severity of disease; the mean pulmonary artery pressure (PAP) was 54 mm Hg, the mean pulmonary vascular resistance (PVR) was 1,094 dynes.s.cm-5, and all patients were in New York Heart Association functional class III or IV. RESULTS: Postoperative course was characterized either by swift recovery (mean length of stay, 13 days) or by rapid demise resulting from pulmonary or right ventricular failure, or both (overall operative mortality, 23%). In survivors, the mean PAP, PVR, cardiac output, and New York Heart Association functional class were significantly improved (p < 0.05). Patients who died had a significantly greater mean preoperative PAP than did those who survived (62.1 +/- 1.2 versus 49.5 +/- 2.3 mm Hg; p < 0.01) and significantly higher PVR (1,512 +/- 116 versus 949 +/- 85 dynes.s.cm-5; p < 0.01). In addition, both a PVR of more than 1,100 dynes.s.cm-5 and a mean PAP of more than 50 mm Hg could accurately predict operative mortality: operative mortality was six times greater in patients with a preoperative PVR of greater than 1,100 dynes.s.cm-5 (41% versus 5.85%) and almost five times greater in those with a mean PAP of greater than 50 mm Hg (37% versus 8%). No intraoperative factors, including the use or duration of circulatory arrest, affected outcome. CONCLUSIONS: Patients with severe hemodynamic disease (PVR > 1,100 dynes.s.cm-5 and PAP > 50 mm Hg) have a high likelihood of operative mortality and perhaps should not undergo pulmonary thromboendarterectomy, except at institutions where the operation is performed frequently.     

Cardio-pulmonary function during acute unilateral occlusion of the pulmonary artery in broilers fed diets containing normal or high levels of arginine-HCl

Cardio-pulmonary function was measured in male broilers reared on diets formulated to contain 1.5% arginine (NORMAL group) or 2.5% arginine (ARGININE group). A snare placed around the right pulmonary artery permitted acute shunting of the entire cardiac output (CO) through the left pulmonary artery, resulting in sustained increases in blood flow (BF) through the left lung in both groups. The unilateral increase in BF was accompanied by sustained increases in pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in the NORMAL group. However, following initial transient increases in PAP and PVR in the ARGININE group, subsequent pulmonary vasodilation gradually reduced PVR, and thus PAP, in spite of the ongoing elevation of BF through the left lung. The capacity of the pulmonary vasculature in the ARGININE group to accommodate an increased BF at a normal PAP accounts for the previously reported lower incidence of pulmonary hypertension syndrome (PHS, ascites) in cold-stressed broilers fed supplemental dietary arginine. Hypoxemia and respiratory acidosis ensued rapidly in both groups after tightening the pulmonary artery snare, in spite of a compensatory increase in the respiratory rate. The gradual return of PVR and PAP to presnare levels in the ARGININE group did not eliminate the concurrent ventilation-perfusion mismatch caused by the increased rate of BF through the left lung. Tightening the pulmonary artery snare caused mean systemic arterial pressure (MAP) to drop from control levels of approximately 98 mm Hg to sustained hypotensive levels of approximately 65 mm Hg in both groups. This systemic hypotension was caused by decreases in CO and total peripheral resistance (TPR). The reduction in CO were caused by reduction in stroke volume (SV) rather than heart rate (HR), suggesting that acutely tightening the pulmonary artery snare increased PVR sufficiently to impede left ventricular filling. Accordingly, the maximum increment in PAP attainable by the right ventricle during acute increases in PVR apparently was inadequate to propel the entire CO through the pulmonary vasculature, setting the stage for the congestive right-sided pooling of blood routinely associated with PHS in broilers.     

Haemodynamics after Mustard's operation for transposition of the great arteries

Cardiac catheterization data from 54 investigations after Mustard's procedure were examined to study the influence of the operation on pressure events in the atria, great veins, and pulmonary circulation. Systemic venous atrial pressure tracings were characterized by a rapid, sharp 'y' descent. Pressure gradients between the venae cavae and systemic venous atrium were invariable, whether or not vena caval pathway obstruction was present, the 'y' trough and 'a' wave gradients being greater than the mean gradient. Pulmonary venous atrial pressure tracings were not different from normal except when tricuspid regurgitation was present. It is suggested that the baffle effectively reduces the size and compliance of the systemic venous atrium, but influences the pulmonary venous atrium to a lesser degree. The systolic pressure gradient from the left ventricle to pulmonary artery was decreased postoperatively, suggesting that it may be flow-related; the greatest changes were seen in the group with preoperative ventricular septal defect. The ratio of pulmonary: systemic vascular resistance did not change significantly after operation, and it is suggested that both the pre- and postoperative values were higher than normal. Examination of the left ventricular or pulmonary arterial mean pressure postoperatively should raise the suspicion of a complication, e.g. pulmonary venous obstruction or tricuspid regurgitation.     

Inhibition of hypoxic pulmonary hypertension by heparins of differing in vitro antiproliferative potency

Heparin inhibits smooth-muscle cell (SMC) growth in vitro and inhibits the development of hypoxic pulmonary hypertension and vascular remodeling in vivo. We wondered whether preparations of heparin with different antiproliferative potency in vitro would differ in their ability to inhibit the development of hypoxic pulmonary hypertension in vivo. Two such heparins, a weakly antiproliferative lot of Elkins-Sinn (E-S) (% inhibition of SMC growth at 10 micrograms/ml = 13 +/- 9% [mean +/- SEM, n = 24]) and a more active lot from Upjohn (UJ) (% inhibition = 71 +/- 12% [n = 12, p < 0.05 versus E-S]), were infused subcutaneously (300 U.S.P. units/day; E-S 300 versus UJ 300) via an osmotic pump into guinea pigs exposed to hypoxia (10% O2) for 10 d, after which pulmonary artery pressure (PAP; mm Hg) and cardiac index (CI; ml/min/kg) were measured in room air. Hypoxic controls (HC) received saline. PAP increased from 11 +/- 1 mm Hg in normoxic controls (NC) (n = 5) to 24 +/- 1 mm Hg in HC (n = 8, p < 0.05). The PAP was lower in the E-S 300 (21 +/- 1; n = 7, p < 0.05 versus HC and NC) and even lower in the UJ 300-treated group (18 +/- 0.5; n = 7, p < 0.05 versus HC and NC). Total pulmonary vascular resistance (TPR; mm Hg/ml/min/kg) increased significantly from 0.038 +/- 0.002 in NC to 0.076 +/- 0.003 (p < 0.05) in HC. There was no difference in TPR between the HC and the E-S 300-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

An interventricular septal defect, pulmonary stenosis and bicuspid pulmonary valve in a Welsh pony foal

A 6 month Welsh pony filly with an interventricular septal defect in conjunction with a pulmonary stenosis due to a bicuspid pulmonary valve is described. The animal had poor exercise tolerance, a loud pansystolic murmur and a precordial thrill. Blood pressure and oxygen tension values obtained during cardiac catheterization suggested the diagnosis which was confirmed at autopsy.     

Ventilation above closing volume reduces pulmonary vascular resistance hysteresis

The aim of this study was to determine the relationship of pulmonary vascular resistance (PVR) hysteresis and lung volume, with special attention to the effects of ventilation around closing volume (CV). Isolated, blood-perfused canine left lower lung lobes (LLL) were incrementally inflated and deflated. Airway and pulmonary artery pressures (PAP) were recorded after each stepwise volume change. Constant blood flow was provided (600 ml/min) and the pulmonary vein pressure (PVP) was held constant at 5 cm H2O. PAP changes, therefore, were a direct index of PVR changes. Group 1 lobes underwent a full inflation from complete collapse to total lobe capacity (TLC) followed by a full deflation. Group 2 lobes underwent two deflation/inflation cycles, after an initial full inflation. These cycles, both beginning at TLC, had deflation end above and below CV, respectively. Significant PVR hysteresis was noted when the first inflation and deflation were compared. The maximum difference in PAP on deflation was 3.3 cm H2O or 11%. The mean decrease was 2.7 cm H2O for 18 lobes (p < 0.0001). The PAPs on all subsequent inflations or deflations that began above CV remained 9% lower than the initial inflation (n = 9, p < 0.0001), but were not different from each other. However, the final inflation which began from below CV resulted in a 30% return of PVR hysteresis (mean increase in PAP of 0.8 cm H2O, n = 7, p < 0.004). We conclude that there is hysteresis in the PVR response during ventilation, with decreased PVR during deflation relative to the initial inflation, that this hysteresis is absent when lung volume is maintained greater than CV, and that hysteresis returns when inflation occurs after deflation below CV.     

Increased pulmonary vascular resistance with systemic hypertension. Effect of minoxidil and other antihypertensive agents

Recent case reports suggest that pulmonary hypertension could be caused by minoxidil, a new potent vasodilating antihypertensive drug. Therefore, we evaluated the incidence and severity of pulmonary hypertension in 110 patients with systemic hypertension. Fourteen patients were treated with minoxidil for 2 to 35 months (mean 19.9 months), 15 were treated with no drugs, and the remaining 81 patients received conventional antihypertensive agents of several types. Pulmonary vascular resistance correlated positively (P is less than 0.05) with systemic vascular resistance. Minoxidil-treated patients with hypertension previously refractory to conventional therapy had slightly lower pulmonary vascular resistance than other hypertensive subjects. There was no correlation between pulmonary vascular resistance and duration of minoxidil therapy or other types of antihypertensive regimens. The positive correlation between pulmonary and systemic vascular resistance suggests the possibility of a causal hypertension relation in the two vascular beds.     

Radiological evidence of involvement of dust exposure in pathogenesis of pulmonary alveolar proteinosis

A 52-year-old man was admitted because of increasing dyspnea on exersion and presence of pulmonary infiltrates. The patient had pulmonary tuberculosis at the age of 31, which resulted in volume loss and calcified foci in the upper lobe of his left lung. As a construction worker for more than 20 years, he had been exposed to inorganic dusts. Chest radiographs showed a symmetrical consolidation of infiltrates in both lungs with the exception of the left upper lobe, where no apparent infiltrates were shown. A computed tomographic scan of the chest revealed widely panlobular consolidation with the exception of the left upper lobe. A diagnosis of pulmonary alveolar proteinosis (PAP) was established by analysis of bronchoalveolar lavage fluid. Although the patient underwent segmental bronchoalveolar lavage four times under general anesthesia, he suffered frequent pulmonary infection and died two years after the onset his symptoms. Interestingly, the patient had a markedly narrowed orifice in the left upper lobe, as demonstrated by fiberoptic bronchoscopy. Chest radiographs of this lung field revealed no infiltrative shadows. These results suggest that some inhalative agent was involved in the pathogenesis of PAP in this case. In addition, significantly increased levels of KL-6 detected in both serum and bronchoalveolar lavage fluid were attributable to overproduction of KL-6 by Type II pneumocytes that had been stimulated or damaged by PAP.     

Intravascular ultrasonic characteristics and vasoreactivity of the pulmonary vasculature in children with pulmonary hypertension

We sought to describe the morphologic characteristics of pulmonary arteries by intravascular ultrasound (IVUS) in children with and without pulmonary hypertension to compare these anatomic findings with those of pulmonary wedge angiography, and to determine the relation between these structural findings and functional reactivity to pulmonary vasodilators. Direct evaluation of pulmonary vascular structure in children with pulmonary hypertension with current imaging techniques has been limited and little is known about the relation between structural and functional characteristics of the pulmonary vasculature. In 23 children undergoing cardiac catheterization (15 with pulmonary hypertension and 8 controls) we performed IVUS and pulmonary wedge angiography of the distal pulmonary arteries in the same lobe. IVUS was performed in 44 pulmonary arteries measuring 2.5 to 5.0 mm internal diameter with a 3.5Fr 30-MHz IVUS catheter. We assessed vasoreactivity to inhaled nitric oxide (NO) and oxygen in 13 of 15 children with pulmonary hypertension. Baseline pulmonary vascular resistance (PVR) was greater in the 15 children with pulmonary hypertension than in the 8 controls (9.5+/-1.9 vs 1.5+/-0.3 U x m2, p <0.05). NO lowered PVR in patients with pulmonary hypertension (p <0.05). IVUS studies in patients with pulmonary hypertension showed a thicker middle layer, wall thickness ratio, and diminished pulsatility than did those in controls (p <0.05). The inner layer was not visualized by IVUS in any control patient, but was seen in 9 of 15 patients with pulmonary hypertension. Pulmonary artery wedge angiography correlated with baseline mean pulmonary artery pressure and PVR as well as with IVUS findings of wall thickness ratio and inner layer thickness. The inner layer was not visualized by IVUS in any patient with grade 1 wedge angiograms or in 86% of patients with grade 2 wedge angiograms. All patients with grade 4 and 80% of patients with grade 3 wedge angiograms had a visible inner layer. Vasoreactivity to NO and oxygen did not correlate with structural assessment of the pulmonary vasculature by IVUS. Structural changes in the pulmonary arteries in children with pulmonary hypertension can be directly visualized by IVUS, but are not predictive of NO-induced pulmonary vasodilation. IVUS examination of pulmonary arteries may complement current techniques utilized in the evaluation of children with pulmonary hypertension.