Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH) characterised by preferential remodelling of the pulmonary venules. In the current PH classification, PVOD and pulmonary capillary haemangiomatosis (PCH) are considered to be a common entity and represent varied expressions of the same disease. The recent discovery of biallelic mutations in the EIF2AK4 gene as the cause of heritable PVOD/PCH represents a major milestone in our understanding of the molecular pathogenesis of PVOD. Although PVOD and pulmonary arterial hypertension (PAH) share a similar clinical presentation, with features of severe precapillary PH, it is important to differentiate these two conditions as PVOD carries a worse prognosis and life-threatening pulmonary oedema may occur following the initiation of PAH therapy. An accurate diagnosis of PVOD based on noninvasive investigations is possible utilising oxygen parameters, low diffusing capacity for carbon monoxide and characteristic signs on high-resolution computed tomography of the chest. No evidence-based medical therapy exists for PVOD at present and lung transplantation remains the preferred definitive therapy for eligible patients.

https://erj.ersjournals.com/content/erj/47/5/1518.full.pdf

Pulmonary veno-occlusive disease

Pulmonary hypertension is characterised by the chronic elevation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) leading to right ventricular enlargement and hypertrophy. Pulmonary hypertension may result from respiratory and cardiac diseases, the most severe forms occurring in thromboembolic and primary pulmonary hypertension. Pulmonary hypertension is most often defined as a mean PAP >25 mmHg at rest or >30 mmHg during exercise, the pressure being measured invasively with a pulmonary artery catheter. Doppler echocardiography allows serial, noninvasive follow-up of PAPs and right heart function. When the adaptive mechanisms of right ventricular dilatation and hypertrophy cannot compensate for the haemodynamic burden, right heart failure occurs and is associated with poor prognosis. The haemodynamic profile is the major determinant of prognosis. In both primary and secondary pulmonary hypertension, special attention must be paid to the assessment of pulmonary vascular resistance index (PVRI), right heart function and pulmonary vasodilatory reserve. Recent studies have stressed the prognostic values of exercise capacity (6-min walk test), right atrial pressure, stroke index and vasodilator challenge responses, as well as an interest in new imaging techniques and natriuretic peptide determinations. Overall, careful haemodynamic evaluation may optimise new diagnostic and therapeutic strategies in pulmonary hypertension.

https://erj.ersjournals.com/content/erj/20/5/1314.full.pdf

Haemodynamic evaluation of pulmonary hypertension

Background : In acute lung injury, when pulmonary microvascular permeability is enhanced, transvascular fluid filtration mainly depends on pulmonary capillary pressure. Inhaled nitric oxide has been shown to decrease pulmonary capillary pressure. Therefore, the effect of inhaled nitric oxide at a concentration of 40 ppm on pulmonary transvascular albumin flux was studied in nine patients with acute lung injury. Methods : Transvascular albumin flux was measured by a double radioisotope method using 99m Tc-labeled albumin and 51 Cr-labeled autologous red blood cells. Radioactivity of both isotopes was externally measured over the right lung by a gamma scanner and simultaneously in arterial blood. The normalized ratio of 99m Tc/ 51 Cr lung to 99m Tc/ 51 Cr blood (normalized index) was calculated. The normalized slope index which is the slope of the regression line of the normalized index versus time represents the accumulation rate of albumin in the interstitial space of the lungs. Normalized slope index and pulmonary capillary pressure were determined before, during, and after inhalation of 40 ppm nitric oxide. Pulmonary capillary pressure was estimated using the visual analysis of the pressure decay curve after pulmonary artery occlusion. Results : Normalized slope index decreased from 0.0077 ± 0.0054 min -1 (SD) off nitric oxide to -0.0055 ± 0.0049 min -1 (P < 0.01) during nitric oxide and increased to 0.0041 ± 0.0135 min -1 after nitric oxide. Pulmonary capillary pressure declined from 24 ± 4 mmHg off nitric oxide to 21 ± 4 mmHg during nitric oxide (P < 0.01), whereas pulmonary artery wedge pressure and cardiac output did not change. Conclusions : It is concluded that 40 ppm inhaled nitric oxide decreases pulmonary transvascular albumin flux in patients with acute lung injury. This effect may be the result of the decrease in pulmonary capillary pressure.

Inhaled nitric oxide reduces pulmonary transvascular albumin flux in patients with acute lung injury.

In acute lung injury (ALI), where pulmonary microvascular permeability is increased, transvascular fluid filtration depends mainly on the hydrostatic capillary pressure. In the presence of intrapulmonary vasoconstriction pulmonary capillary pressure (PCP) may increase thereby promoting transvascular fluid filtration and lung oedema formation. We studied the effect of 40 ppm inhaled nitric oxide (NO) on PCP and longitudinal distribution of pulmonary vascular resistance (PVR) in 18 patients with ALI. PCP was estimated by visual analysis of the pressure decay profile following pulmonary artery balloon inflation. Contribution of venous pulmonary resistance to total PVR was calculated as the percentage of the pressure gradient in the pulmonary venous system to the total pressure gradient across the lung. Inhalation of 40 ppm NO produced a prompt decrease in mean pulmonary artery pressure (PAP) from 34.1 +/- 6.8 to 29.6 +/- 5.7 (s.d.) mmHg; (P < 0.0001). PCP declined from 24.8 +/- 6.2 to 21.6 +/- 5.2 mmHg; (P < 0.0001) while pulmonary artery wedge pressure (PAWP) did not change. PVR decreased from 166 +/- 73 to 128 +/- 50 dyn.sec.cm-5; (P < 0.0001). Pulmonary venous resistance (PVRven) decreased to a greater extent (from 76 +/- 41 to 50 +/- 28 dyn.sec.cm-5; (P < 0.001) than pulmonary arterial resistance (PVRart) (from 90 +/- 36 to 79 +/- 29 dyn.sec.cm-5; (P < 0.01). The contribution of PVRven to PVR fell from 44.3 +/- 10.8 to 37.8 +/- 11.9%; (P < 0.01). Cardiac output (CO) remained constant. The findings demonstrate that NO has a predominant vasodilating effect on pulmonary venous vasculature thereby lowering PCP in patients with ALI.

Inhaled nitric oxide lowers pulmonary capillary pressure and changes longitudinal distribution of pulmonary vascular resistance in patients with acute lung injury.

Permeability pulmonary edema following lung resection.

Pulmonary artery catheters are frequently used to measure pulmonary vascular pressures, particularly the pulmonary wedge pressure (Pw), which reflects pulmonary venous and ideally left atrial pressures. However, the pulmonary capillary pressure (Pc) is the major force in the formation of pulmonary edema. Unfortunately, Pw has been interpreted as being identical to Pc. In this study we used 7-Fr pulmonary artery catheters to measure effective Pc in closed-chest animals and patients. The decreasing pressure profile after pulmonary artery occlusion was separated into fast and slow components, with the inflection point between them representing Pc. Pc was also estimated by mathematically analyzing the curves in terms of a precapillary resistance, a large pulmonary capillary capacitor, and a postcapillary resistance. In dogs, Pc was determined after pulmonary vascular resistance had been increased by infusing serotonin and histamine. While Pw remained unchanged, serotonin increased pulmonary artery pressure (Ppa) 52% and Pc 16%, whereas histamine increased Ppa only 25%, but increased Pc by 35%. This is consistent with studies showing that serotonin primarily elevates precapillary resistance, and histamine increases postcapillary resistance. In thoracic surgery patients, Pc was not consistently related to Pw. This measurement was simple, reproducible, and provided a more precise capillary filtration pressure than Pw. It should be clinically useful in monitoring patients with pulmonary hypertension and adult respiratory distress syndrome, especially those with pulmonary artery catheters.

James L. Parmentier

Papers

Measurement of effective pulmonary capillary pressure using the pressure profile after pulmonary artery occlusion.