Chronic propranolol treatment decreases pulmonary artery pressure in conscious dogs

Daily administration of propranolol to 9 chronically instrumented, trained dogs for 2 weeks caused significant (p less than 0.05) decreases in heart rate (70 +/- 8 to 57 +/- 6 beats/min), cardiac output (3.6 +/- 0.3 to 2.9 +/- 0.2 liters/min), pulmonary arterial pressure (15.7 +/- 0.5 to 10.0 +/- 0.5 mm Hg) and total pulmonary vascular resistance (4.6 +/- 0.6 to 3.3 +/- 0.4 units). Nadolol, a structurally dissimilar beta-adrenergic receptor antagonist, caused a similar decrease in total pulmonary resistance. Acute meclofenamate administration did not return to normal pulmonary arterial pressure and resistance in the dogs chronically treated with beta-adrenergic receptor blockers. We therefore conclude that chronic beta-adrenergic receptor blockade lowered pulmonary arterial pressure and resistance by a mechanism independent of cyclooxygenase. In addition, chronic beta-adrenergic receptor blockade did not affect the potential for hypoxic vasoconstriction.     

Changes in lung permeability after chronic pulmonary artery obstruction.

We have shown that left pulmonary artery ligation (LPAL) in mice causes a prompt angiogenic response, with new systemic vessels from intercostal arteries penetrating the pleura within 6 days. Because angiogenic vessels in other organs have been shown to exhibit increased permeability, we studied vascular permeability (Evans blue dye extravasation, lung wet weight-to-dry weight ratio, and lavaged protein) in naive C57BL/6 mice and 4 h, and 14 and 21 days after LPAL (4-6 mice/time point). We also measured radiolabel clearance as an index of functional perfusion after LPAL. Tracer clearance from the left lung was maximal by 6 days after LPAL and not different from right lungs. Thus a functional vasculature is established before 6 days of LPAL that results in normal tracer clearance. By 21 days after LPAL, Evans blue-albumin was significantly increased in the left lung relative to both 4 h (no vasculature) and 14 days after LPAL. Only after 21 days of LPAL was left lung wet weight-to-dry weight ratio significantly different from naive lungs. Additionally, lavaged protein was significantly increased both 4 h and 21 days after LPAL relative to control mice. Thus, using three different methods, results consistently demonstrated increased permeability to protein and water 21 days after LPAL. Although changes in surface area of perfusion might affect the interpretation of these results, blood flow measured with labeled microspheres indicated no change in left lung perfusion between 14 and 21 days of LPAL. Thus the lung vasculature, remodeled as a consequence of chronic pulmonary artery obstruction, demonstrates increased water and protein permeability.     

Acute and chronic pulmonary vasoconstriction after left lung autotransplantation in conscious dogs.

We investigated the acute and chronic effects of left lung autotransplantation (LLA) on the left pulmonary vascular pressure-flow (LP/Q) relationship in conscious dogs. Continuous LP/Q plots were generated in chronically instrumented conscious dogs 2 days, 2 wk, 1 mo, and 2 mo after LLA. Identically instrumented normal conscious dogs were studied at equal time points post-surgery. LLA had little or no effect on baseline systemic hemodynamics or blood gases. In contrast, compared with normal conscious dogs, striking active flow-independent pulmonary vasoconstriction was observed 2 days post-LLA. The slope of the LP/Q relationship was increased from a normal value of 0.275 +/- 0.021 to 0.699 +/- 0.137 mmHg.ml-1.min-1.kg-1 2 days post-LLA. Pulmonary vasoconstriction of similar magnitude was also observed on a chronic basis at 2 wk, 1 mo, and even 2 mo post-LLA. Pulmonary vasoconstriction post-LLA was not due to fixed resistance at the left pulmonary arterial or venous anastomotic sites. Finally, systemic arterial blood gases were unchanged when total pulmonary blood flow was directed to exclusively perfuse the transplanted left lung. Thus, LLA results in both acute and chronic pulmonary vasoconstriction in conscious dogs. LLA should serve as a useful stable experimental model to assess the specific effects of surgical transplantation on pulmonary vascular regulation.     

Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion

Simon, Brett A., Koichi Tsuzaki, and Jose G. Venegas.Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion. J. Appl.Physiol. 82(3): 882-891, 1997.Regionalpneumoconstriction induced by alveolar hypocapnia is an importanthomeostatic mechanism for optimization of ventilation-perfusionmatching. We used positron imaging of ¹³NN-equilibrated lungs to measurethe distribution of regional tidal volume(VT), lung volume(VL), and lung impedance(Z) before and after left (L)pulmonary artery occlusion (PAO) in eight anesthetized, open-chestdogs. Measurements were made during eucapnic sinusoidal ventilation at0.2 Hz with 4-cmH₂O positive end expiratory pressure. Right(R) and L lung impedances(ZRandZL)were determined from carinal pressure and positron imaging of dynamicregional VL. LPAO caused anincrease in|ZL|relative to|ZR|,resulting in a shift in VT awayfrom the PAO side, with a L/R|Z| ratio changing from 1.20 ± 0.07 (mean ± SE) to 2.79 ± 0.85 after LPAO(P < 0.05). Although mean L lungVL decreased slightly, theVL normalized parametersspecific admittance and specific compliance both significantly decreased with PAO. Lung recoil pressure at 50% totallung capacity also increased after PAO. We conclude that PAO results inan increase in regional lung Z thatshifts ventilation away from the affected area at normal breathingfrequencies and that this effect is not due to a change inVL but reflects mechanicalconstriction at the tissue level.

     

Relation of noninvasive parameters and pulmonary artery mean pressure in patients with chronic obstructive lung disease

A series of 31 patients with various degrees of chronic obstructive pulmonary disease (COPD) underwent radionuclide ventriculography with right heart catheterization. The patients were divided into 2 groups on the basis of their reduction in forced expiratory volume in 1 s (FEV1). In patients with FEV1 greater than or equal to 1,300 ml (group 1) the oxygen partial pressure (PaO2) did not significantly change with exercise, while in patients with FEV1 less than or equal to 1,200 ml (group 2) the PaO2 significantly decreased (p less than 0.05) with exercise. The groups were significantly different from each other as to the correlation between hemodynamic and noninvasive parameters. In the resting state, the correlation between pulmonary artery mean pressure (PAP) and both residual volume to total lung capacity (RV/TLC) and PaO2 was close only in group 2. By contrast, the right ventricular end diastolic wall thickness (RWD) correlated closely with PAP in both groups. With exercise close correlations were observed between PAP and the noninvasive parameters: RWD, PaO2 and right ventricular ejection fraction in both groups. Arterial CO2 partial pressure (PaCO2) was only increased (greater than or equal to 45 mm Hg) in group 2. This parameter correlated moderately closely with PAP both in the resting and the exercise state only in group 2. The predictive value of PaCO2 greater than or equal to 45 mm Hg for estimation of PAP greater than 35 mm Hg during exercise was 100%. We conclude that separation of patients with COPD into groups with different impairments of the lung function parameter FEV1 can improve the correlation coefficients between noninvasive and invasive parameters. The exercise values obviously correlate more closely than the resting values. An increased value of echocardiographically determined RWD seems to be a reliable parameter for prediction of PAP.     

Accuracy of Doppler-echocardiographic mean pulmonary artery pressure for diagnosis of pulmonary hypertension

Background

The validity of Doppler echocardiographic (DE) measurement of systolic pulmonary artery pressure (sPAP) has been questioned. Recent studies suggest that mean pulmonary artery pressure (mPAP) might reflect more accurately the invasive pressures.

Methodology/Principal Findings

241 patients were prospectively studied to evaluate the diagnostic accuracy of mPAP for the diagnosis of PH. Right heart catheterization (RHC) and DE were performed in 164 patients mainly for preoperative evaluation of heart valve dysfunction. The correlation between DE and RHC was better when mPAP (r = 0.93) and not sPAP (r = 0.81) was assessed. Bland-Altman analysis revealed a smaller variation of mPAP than sPAP. The following ROC analysis identified that a mPAP≥25.5 mmHg is useful for the diagnosis of PH. This value was validated in an independent cohort of patients (n = 50) with the suspicion of chronic-thromboembolic pulmonary hypertension. The calculated diagnostic accuracy was 98%, based on excellent sensitivity of 98% and specificity of 100%. The corresponding positive and negative predictive values were 100%, respectively 88%.

Conclusion

mPAP has been found to be highly accurate for the initial diagnosis of PH. A cut-off value of 25.5 mmHg might be helpful to avoid unnecessary RHC and select patients in whom RHC might be beneficial.