"Natural history" of pulmonary hypertension in a series of 131 patients with chronic obstructive lung disease.

The prognostic value and the evolution of pulmonary hypertension (PH) in patients with markedly hypoxemic chronic obstructive pulmonary disease (COPD), treated or not with long-term oxygen therapy (LTOT), has been extensively investigated. However, little is known in patients with mildly or moderately hypoxemic COPD not requiring LTOT. Therefore, we assessed the evolution of pulmonary hemodynamics in 131 patients with stable COPD by performing two right heart catheterizations at a mean (+/- SD) time interval of 6.8 +/- 2.9 yr. At inclusion (T0), no patient had PH (i.e., the mean pulmonary artery pressure [Ppa] at rest was < 20 mm Hg). Group 1 included 55 patients without exercising PH and group 2 included 76 patients with exercising PH, defined by a pulmonary arterial pressure (Ppa) > 30 mm Hg during a steady-state 40-W exercise. Group 2 patients compared with group 1 patients had a significantly higher resting Ppa (16 +/- 3 mm Hg versus 14 +/- 2 mm Hg, p = 0.001). At the second catheterization, 33 (25%) patients (9 of 55 in group 1, 24 of 76 in group 2, p = 0.048) showed a resting Ppa > 20 mm Hg, but PH was generally mild, ranging from 20 to 42.5 mm Hg. The mean Ppa at second evaluation was 16 +/- 5 mm Hg in group 1 and 19 +/- 7 mm Hg in group 2 (p = 0.01). The patients who developed resting PH at the second catheterization (T1) had higher resting and exercising Ppa (p = 0.001 and p = 0.002, respectively), and significantly lower resting and exercising Pa(O(2)) (p = 0.005 and p = 0.012, respectively) at T0. Logistic regression analysis showed that resting and exercising Ppa were independent predictors (at T0) for the subsequent development of PH (p = 0.029 and p = 0.027, respectively). The patients who developed resting PH (T1) had a significantly worsening of Pa(O(2)) (from 63.5 mm Hg at T0 to 60 mm Hg at T1, p = 0.047), whereas the Pa(O(2)) as a mean was stable in the remainder (69.5 mm Hg at T0 and T1). These results show the following. The progression of Ppa over time in patients with COPD with mild to moderate hypoxemia is rather slow, the average change for the group as a whole being of + 0.4 mm Hg/yr. Only about 25% of patients with COPD with mild to moderate hypoxemia and without resting PH at the onset will develop PH during a 6-yr follow-up. The patients with exercising PH at the onset have a significantly increased risk of developing PH over time. Only resting and exercising Ppa at the onset are independently related to the subsequent development of PH. However, in individual cases, the models of linear or logistic regression do not allow a pertinent prediction of the level of Ppa or the presence of PH at the second right heart catheterization.     

Daytime pulmonary hypertension in patients with obstructive sleep apnea: the effect of continuous positive airway pressure on pulmonary hemodynamics.

BACKGROUND: Limited information exists regarding the development of pulmonary hypertension in patients with obstructive sleep apnea (OSA) in the absence of lung and heart comorbidity. OBJECTIVES: The aims of this study were to investigate whether OSA patients without any other cardiac or lung disease develop pulmonary hypertension, and to assess the effect of continuous positive airway pressure (CPAP) treatment on pulmonary artery pressure (P(PA)). METHODS: Twenty-nine patients aged 51 +/- 10 years with OSA and 12 control subjects were studied with pulsed-wave Doppler echocardiography for estimation of P(PA) before and after 6-month effective treatment with CPAP. RESULTS: A significantly higher mean P(PA) was found in OSA patients as compared to control subjects (17.2 +/- 5.2 vs. 12.1 +/- 1.9 mm Hg, p < 0.001). Six out of the 29 OSA patients had mild pulmonary hypertension (P(PA) > or = 20 mm Hg). Significant differences were observed between pulmonary hypertensive and normotensive OSA patients with respect to age (62 +/- 4 vs. 48 +/- 15 years, respectively, p < 0.05), body mass index (41 +/- 7 vs. 32 +/- 4 kg/m(2), p < 0.02) and daytime P(a)O(2) (81 +/- 9 vs. 92 +/- 9 mm Hg, p < 0.05). CPAP treatment was effective in reducing mean P(PA) in both groups of pulmonary hypertensive and normotensive OSA patients (decreases in P(PA) from 25.6 +/- 4.0 to 19.5 +/- 1.5 mm Hg, p < 0.001; from 14.9 +/- 2.2 to 11.5 +/- 2.0 mm Hg, respectively, p < 0.001). CONCLUSIONS: A proportion (20.7%) of OSA patients without any other lung or heart disease and characterized by older age, greater obesity and lower daytime oxygenation develop mild pulmonary hypertension which has been partially or completely reversed after 6-month CPAP treatment. In conclusion, OSA alone constitutes an independent risk factor for the development of pulmonary hypertension.     

Pulmonary vascular pressure-flow characteristics. Effects of dopamine before and after pulmonary embolism.

We compared the general hemodynamic effects of dopamine and dobutamine in dogs with acute pulmonary hypertension complicated by a decrease in cardiac output (CO). The pulmonary hypertension was induced by injection of autologous blood clot. Emboli markedly increased mean pulmonary artery pressure (Ppa) and decreased CO (both p < 0.001). Both dopamine and dobutamine increased CO 50% (p < 0.05) and decreased pulmonary vascular resistance (PVR) (p < 0.05), calculated as (PAP - left ventricular end diastolic pressure)/CO. Mean PVR (mm Hg/L/min) decreased from 16.1 to 12.4 with dopamine and from 16. to 11.9 with dobutamine, both p < 0.05. Ventricular filling pressures were not affected. In another 12 dogs we investigated the effects of both drugs on pulmonary pressure-flow (P-Q) characteristics. P-Q characteristics were determined in dogs with normal Ppa values and in those with embolic pulmonary hypertension. The slope of the P-Q relationship defines the incremental vascular resistance and the extrapolated pressure intercept, the effective vascular outflow pressure. All P-Q relationships were described well by a linear equation. Despite significant systemic effects in both groups and despite a decrease in PVR with both drugs in embolized dogs, neither drug significantly affected pulmonary P-Q characteristics. The discrepancy between PVR and incremental resistance is explained by an incorrect assumption in PVR that the left ventricular filling pressure is the effective vascular outflow pressure. We conclude that both before and after the induction of pulmonary hypertension, both dopamine and dobutamine improve CO without affecting pulmonary vascular tone.     

Pulmonary hypertension in obstructive sleep apnoea: effects of continuous positive airway pressure: a randomized, controlled cross-over study.

AIMS: We tested the hypothesis that: (i) obstructive sleep apnoea (OSA) by itself originates pulmonary hypertension (PH); and (ii) the application of continuous positive airway pressure (CPAP) can reduce pulmonary pressure. METHODS AND RESULTS: In this randomized and cross-over trial, 23 middle-aged OSA (apnoea-hypopnoea index, 44.1 +/- 29.3 h(-1)) and otherwise healthy patients and 10 control subjects were included. OSA patients randomly received either sham or effective CPAP for 12 weeks. Echocardiographic parameters, blood pressure recordings, and urinary catecholamine levels were obtained at baseline and after both treatment modalities. At baseline, OSA patients had higher pulmonary artery systolic pressure than control subjects (29.8 +/- 8.8 vs. 23.4 +/- 4.1 mmHg, respectively, P = 0.036). Ten out of 23 patients [43%, (95% CI: 23-64%)] and none of the control subjects had PH at baseline (P = 0.012). Two patients were removed from the study because of inadequate CPAP compliance. Effective CPAP induced a significant reduction in the values for pulmonary systolic pressure (from 28.9 +/- 8.6 to 24.0 +/- 5.8 mmHg, P < 0.0001). The reduction was greatest in patients with either PH or left ventricular diastolic dysfunction at baseline. CONCLUSION: Severe OSA is independently associated with PH in direct relationship with disease severity and presence of diastolic dysfunction. Application of CPAP reduces pulmonary systolic pressure levels.     

Daytime pulmonary hypertension in patients with obstructive sleep apnea syndrome

The frequency of daytime pulmonary hypertension (PH) in patients with obstructive sleep apnea syndrome (OSAS) has not been well established and its mechanisms are still under debate. We have thus performed right heart catheterization, in addition to standard spirography and arterial blood gas measurements, in a series of 46 consecutive patients in whom OSAS was firmly diagnosed by whole-night polysomnography. Only 9 of the 46 patients (20%) had PH defined by a mean resting pulmonary arterial pressure (Ppa) greater than or equal to 20 mm Hg. Among the patients without resting PH, 14 had exercising PH (defined by a Ppa greater than 30 mm Hg during 40-watt, steady-state exercise). Patients with resting PH differed from the others by a lower daytime PaO2 (60.8 +/- 7.6 versus 76.2 +/- 9.4 mm Hg; p less than 0.001), a higher daytime PaCO2 (44.6 +/- 4.2 versus 38.0 +/- 4.0 mm Hg; p less than 0.001), and lower VC and FEV1 (p less than 0.001). There was no difference between the 2 groups with regard to apnea index (62 +/- 34 versus 65 +/- 40) or the lowest sleep SaO2 (59 +/- 21 versus 66 +/- 18%) or the time spent in apnea. For the group as a whole, there was a good correlation between Ppa and daytime PaO2 (r = -0.61; p less than 0.001), PaCO2 (r = 0.55; p less than 0.001), and FEV1 (r = -0.52; p less than 0.001), but there was no significant correlation between Ppa and the apnea index, the lowest sleep SaO2, or the time spent in apnea.(ABSTRACT TRUNCATED AT 250 WORDS)     

40-O-(2-hydroxyethyl)-rapamycin attenuates pulmonary arterial hypertension and neointimal formation in rats

Pneumonectomized rats develop pulmonary hypertension (PH) and pulmonary vascular neointimal formation 4 wk after monocrotaline (MCT) administration. Male Sprague-Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Three groups (n = 5) received 40-O-(2-hydroxyethyl)-rapamycin (RAD, 2.5 mg/kg/d, by gavage): Group PMR(5-35) from Day 5 to Day 35, Group PMR5-14 from Day 5 to Day 14, and Group PMR15-35 from Day 15 to Day 35. By Day 35, rats that received vehicle had higher mean pulmonary arterial pressures (Ppa = 41 +/- 3 mm Hg) (p < 0.001), right ventricular systolic pressures (Prv,s = 45 +/- 2 mm Hg) (p < 0.01), and right ventricle/(left ventricle plus septum) (0.55 +/- 0.05) (p = 0.028) than rats in Groups PMR5-35 (Ppa = 25 +/- 3 mm Hg, Prv,s = 32 +/- 7 mm Hg, RV/LV&S = 0.42 +/- 0.06) and PMR5-14 (Ppa = 29 +/- 4 mm Hg, Prv,s = 30 +/- 5 mm Hg, RV/LV&S = 0.43 +/- 0.07). Pulmonary arterial neointimal formation (quantified by a vascular occlusion score) was more severe in vehicle-treated rats (1.93 +/- 0.03) than in Groups PMR5-14 (1.56 +/- 0.27) and PMR(5-35) (1.57 +/- 0.1) (p < 0.01). RAD attenuates the development of MCT-induced pulmonary arterial hypertension in the pneumonectomized rat.     

Dibutyryl cyclic AMP inhibits acute hypoxic pulmonary vasoconstriction in conscious sheep

We examined the effects of cell-permeable dibutyryl cyclic AMP (DBcAMP) on acute hypoxic pulmonary vasoconstriction (HPV) in conscious sheep. Mean left and right atrial, pulmonary, and systemic pressures (Pla, Pra, Ppa, and Psa, mm Hg), cardiac output (CO, L/min), and heart rate were measured continuously. Systemic (SVR) and pulmonary vascular resistances (PVR) were calculated by (Psa-Pra)/CO and (Ppa-Pla)/CO, respectively. Five groups of experiments were performed using the same sheep (n = 6). After a 30-min baseline period, sheep inhaled a hypoxic gas mixture (O2:N2 = 1:9) for 40 min. Pretreatment with DBcAMP (200 micrograms/kg/min) inhibited HPV (Ppa, 12.0 +/- 2.3 to 20.0 +/- 2.3 versus 13.2 +/- 2.5 to 14.3 +/- 1.4 mm Hg, p less than 0.01; PVR, 2.61 +/- 0.81 to 4.15 +/- 1.14 versus 2.30 +/- 0.87 to 2.52 +/- 0.59 mm Hg/L/min, p less than 0.01). DBcAMP treatment (200 micrograms/kg/min) after induction of HPV also significantly attenuated hypoxic pulmonary response (Ppa, 19.0 +/- 1.7 to 14.2 +/- 2.3 mm Hg, p less than 0.01; PVR, 3.92 +/- 0.39 to 2.34 +/- 0.34 mm Hg/L/min, p less than 0.01) without significant decreases in Psa and SVR. Pretreatment with DBcAMP (200 micrograms/kg/min) did not significantly alter pulmonary pressor responses to bolus injections of prostaglandin F2 alpha (PGF2 alpha) (10 micrograms/kg) and norepinephrine (4 micrograms/kg). These results may suggest that intracellular augmentation of cyclic AMP plays a crucial role in modulating HPV.     

Obstructive sleep apnea syndrome: more insights on structural and functional cardiac alterations, and the effects of treatment with continuous positive airway pressure.

OBJECTIVES: We studied structural and functional cardiac alterations in obstructive sleep apnea (OSA), their relationship to the severity of OSA, and the effects of treatment with continuous positive airway pressure (CPAP). BACKGROUND: Obstructive sleep apnea may influence the cardiac function by several mechanisms in the awake patient. METHODS: Left and right ventricular morphology and function were studied using echocardiography before and after treatment with CPAP in symptomatic patients (Epworth sleepiness score, 10 +/- 4.8) with severe OSA (apnea-hypopnea index [AHI], 42 +/- 24). The patients (n = 43, 32 men) had no known cardiac disease and were obese (body mass index, 31.6 +/- 5.4 kg/m2). The same echocardiographic parameters were studied in age-matched overweight patients (n = 40; body mass index, 26.4 +/- 2.3 kg/m2). RESULTS: The patients were hypertensive (systolic blood pressure, 153 +/- 25 mm Hg), with a higher resting heart rate (77 +/- 10 beats/min, p = 0.008) compared with age-matched control patients (n = 40). There was right ventricular dilatation, hypertrophic interventricular septum, reduced left ventricular stroke volume, tissue Doppler-determined systolic and diastolic velocities of the left and right ventricle, and normal pulmonary artery pressure. The structural and functional parameters were significantly associated with AHI (p < 0.004). Multiple stepwise regression showed the interventricular septum thickness, right ventricular free wall, and mitral annulus tissue Doppler systolic velocities to be predictive of a higher AHI (p < 0.001). Six months after treatment with CPAP, significant improvements were observed in the symptoms and hemodynamics, as well as left and right ventricular morphology and function. CONCLUSIONS: The structural and functional consequences of OSA on the heart are influenced by the severity of AHI. These effects are reversible if the apneic episodes are abolished.     

Pulmonary hypertension and sleep-related breathing disorders

Pulmonary hypertension (PH), i. e. an increase of mean pulmonary artery pressure above 20 mm Hg under resting conditions, can be observed in different forms of sleep-disordered breathing (SDB). In obstructive sleep apnea (OSA) the apnea-associated triggers of hypoxia and intrathoracic pressure swings lead to repetitive rises of pulmonary artery pressure during sleep. In 20 - 30 % of these patients daytime PH occurs. PH in the setting of OSA is usually mild and rarely causes clinically evident cor pulmonale. Effective CPAP therapy has a beneficial influence on pulmonary hemodynamics in OSA. Severe congestive heart failure (i. e. with a LVEF < 40 %) might provoke pulmonary venous hypertension and thereby stimulation of pulmonary stretch and irritant receptors. The ensuing hyperventilation leads to a decrease of pCO (2) levels below the apneic threshold and thus contributes to the emergence of Cheyne Stokes respiration (CSR) in up to one half of the affected patients. Patients suffering from advanced idiopathic pulmonary arterial hypertension (IPAH) might show a similar breathing pattern while asleep. Possible pathogenetic factors of the nocturnal periodic breathing occurring in end-stage IPAH are prolonged circulation times and hypocapnia. In conclusion, SDB might cause PH (OSA-associated PH). On the other hand, PH might lead to the development of SDB (CSR in congestive heart failure, periodic breathing in IPAH).     

Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure

OBJECTIVES: This study was designed to determine whether reductions in morning systolic blood pressure (BP) elicited by treatment of moderate to severe obstructive sleep apnea (OSA) in heart failure (HF) patients are associated with a reduction in sympathetic vasoconstrictor tone. BACKGROUND: Daytime muscle sympathetic nerve activity (MSNA) is elevated in HF patients with coexisting OSA. In our recent randomized trial in HF, abolition of OSA by continuous positive airway pressure (CPAP) increased left ventricular ejection fraction (LVEF) and lowered morning systolic BP. METHODS: Muscle sympathetic nerve activity, BP, and heart rate (HR) of medically treated HF patients (EF <45%) and OSA (apnea-hypopnea index > or =20/h of sleep) were recorded on the morning after overnight polysomnography, and again one month after patients were randomly allocated nocturnal CPAP treatment or no CPAP (control). RESULTS: In nine control patients, there were no significant changes in the severity of OSA, MSNA, systolic BP, or HR. In contrast, in the 8 CPAP-treated patients, OSA was attenuated, and there were significant reductions in daytime MSNA (from 58 +/- 4 bursts/min to 48 +/- 5 bursts/min; 84 +/- 4 bursts/100 heart beats to 72 +/- 5 bursts/100 heart beats; p < 0.001 and p = 0.003, respectively), systolic BP (from 135 +/- 5 mm Hg to 120 +/- 6 mm Hg, p = 0.03), and HR (from 69 +/- 2 min(-1) to 66 +/- 2 min(-1); p = 0.013). CONCLUSIONS: Treatment of coexisting OSA by CPAP in HF patients lowers daytime MSNA, systolic BP, and HR. Inhibition of increased central sympathetic vasoconstrictor outflow is one mechanism by which nocturnal CPAP reduces awake BP in HF patients with moderate to severe OSA.     

Vascular remodeling in experimentally induced subacute canine pulmonary hypertension

We quantified in vivo pulmonary vascular remodeling in a large animal model of pulmonary hypertension (PH). In group PH (n = 6), 3 mg/kg dehydromonocrotaline (DHMC) was administered to 12-week-old beagles via a right atrial injection. Eight weeks after DHMC in group PH, pulmonary artery pressure increased significantly (P < .05) from 18 +/- 2 mm Hg at baseline to 30 +/- 4 mm Hg. Medial wall thickness and medial wall area as a percentage of total vessel diameter or area was significantly higher (P < .05) in group PH (29 +/- 9% and 48 +/- 12%) than in a control group (n = 5) (7 +/- 1% and 14 +/- 1%). Neointimal proliferation was observed in 42% of pulmonary arterioles in the PH group but never in the control group. We conclude that a single injection of DHMC in young beagles, in addition to the development of moderate degrees of PH after 8 weeks, causes significant pulmonary vascular remodeling, with features similar to those observed in patients with primary PH.     

Hemodynamic effects of inhaled nitric oxide in women with mitral stenosis and pulmonary hypertension

Mitral stenosis (MS) is associated with elevated left atrial pressure, increased pulmonary vascular resistance (PVR), and pulmonary hypertension (PH). The hemodynamic effects of inhaled nitric oxide (NO) in adults with MS are unknown. We sought to determine the acute hemodynamic effects of inhaled NO in adults with MS and PH. Eighteen consecutive women (mean age 58 +/- 15 years) with MS and PH underwent heart catheterization. Hemodynamic measurements were recorded at baseline, after NO inhalation at 80 ppm, and after percutaneous balloon valvuloplasty (n = 10). NO reduced pulmonary artery systolic pressure (62 +/- 14 mm Hg [baseline] vs 54 +/- 15 mm Hg [NO]; p <0.001) and PVR (3.7 +/- 2.5 Wood U [baseline] vs 2.2 +/- 1.4 Wood U [NO]; p <0.001). NO had no effect on mean aortic pressure, left ventricular end-diastolic pressure, left atrial pressure, cardiac output, or systemic vascular resistance. Mitral valve area increased after valvuloplasty (0.9 +/- 0.2 cm2 [baseline] vs 1.6 +/- 0.3 cm2 [postvalvuloplasty]; p <0.001). A decrease in left atrial pressure (25 +/- 4 mm Hg [baseline] vs 17 +/- 4 mm Hg [after valvuloplasty]; p <0.001) and pulmonary artery systolic pressure (58 +/- 12 mm Hg [baseline] vs 45 +/- 8 mm Hg [after valvuloplasty]; p <0.001) was observed after valvuloplasty. No change in cardiac output or PVR was observed. Thus inhaled NO, but not balloon valvuloplasty, acutely reduced PVR in women with MS and PH. This suggests that a reversible, endothelium-dependent regulatory abnormality of vascular tone is an important mechanism of elevated PVR in MS.     

Systemic and coronary effects of intravenous milrinone and dobutamine in congestive heart failure

The effects of dobutamine and intravenous milrinone on systemic hemodynamics, coronary blood flow and myocardial metabolism were studied in 11 patients with severe congestive heart failure. Although milrinone and dobutamine similarly increased cardiac index from 1.9 +/- 0.4 to 2.5 +/- 0.4 liters/min per m2 (p less than 0.001) and from 1.9 +/- 0.4 to 2.8 +/- 0.8 liters/min per m2 (p less than 0.001), respectively, milrinone decreased left ventricular end-diastolic pressure to a greater extent than dobutamine, that is, from 26 +/- 6 to 12 +/- 8 mm Hg (p less than 0.001) versus 26 +/- 8 to 20 +/- 8 mm Hg (p less than 0.001). In contrast to dobutamine, milrinone significantly reduced mean systemic arterial and right atrial pressures. Dobutamine increased the first derivative of left ventricular pressure (dP/dt) from 1,013 +/- 309 to 1,360 +/- 538 mm Hg/s (p less than 0.01) but milrinone did not. Similarly, blood flow and myocardial oxygen consumption were increased by dobutamine from 152 +/- 87 to 187 +/- 118 ml/min (p less than 0.05) and from 17.7 +/- 10.9 to 21.5 +/- 14.9 ml O2/min (p less than 0.05), respectively, but were unchanged by milrinone. Both drugs significantly decreased coronary vascular resistance and myocardial oxygen extraction but did not change myocardial lactate extraction. Thus, dobutamine and milrinone produce similar improvement in cardiac index. However, dobutamine increases myocardial oxygen consumption, whereas milrinone does not. This difference can probably be explained by the substantial vasodilating properties of milrinone.     

The effects of controlled oxygen therapy on ventricular function in patients with stable and decompensated cor pulmonale

We made simultaneous measurements of pulmonary hemodynamics, cardiac output, and right ventricular ejection fraction (RVEF) to assess the right ventricular function in 14 patients with pulmonary arterial hypertension as a result of chronic obstructive pulmonary disease (COPD). From these measurements, the right ventricular end-systolic pressure/volume relationship could be calculated and used to assess right ventricular contractility. Eight of the patients were clinically stable, without edema, and 6 presented acutely with gross edema, indicating decompensated cor pulmonale. Measurements were made at rest, while breathing air and oxygen. Although mean pulmonary arterial pressure (Ppa) was similar in those with (Ppa = 33 +/- 6 mm Hg) and without edema (Ppa = 30 +/- 8 mm Hg, p greater than 0.05), RVEF was lower in edematous (RVEF = 0.23 +/- 0.11) compared with non-edematous patients (RVEF = 0.47 +/- 0.04, p less than 0.01). Cardiac output was normal in both groups. The mean right ventricular end-systolic pressure/volume ratio (P/V) was lower in those patients with edema (P/V = 0.41 +/- 0.27), as compared with those without edema (P/V = 1.69 +/- 0.35, p less than 0.05), as a result of an increase in right ventricular end-systolic volume index. Similarly, left ventricular end-systolic volumes were higher in edematous than in non-edematous patients. Breathing 1 to 3 L/min of oxygen for 30 min decreased total pulmonary vascular resistance (p less than 0.05) in those patients without edema, but not in patients with edema. Oxygen did not change RVEF, left ventricular ejection fraction (LVEF), or the ventricular end-systolic P/V relationships.(ABSTRACT TRUNCATED AT 250 WORDS)     

Partitioning of Pulmonary Vascular Resistance in Primary Pulmonary Hypertension

Objectives. This study sought to determine the site of increased pulmonary vascular resistance (PVR) in primary pulmonary hypertension by standard bedside hemodynamic evaluation.Background. The measurement of pulmonary vascular pressures at several levels of flow (Q) allows the discrimination between active and passive, flow-dependent changes in mean pulmonary artery pressure (Ppa), and may detect the presence of an increased pulmonary vascular closing pressure. The determination of a capillary pressure (Pc′) from the analysis of a Ppa decay curve after balloon occlusion allows the partitioning of PVR in an arterial and a (capillary + venous) segment. These approaches have not been reported in primary pulmonary hypertension.Methods. Ppa and Pc′ were measured at baseline and after an increase in Q induced either by exercise or by an infusion of dobutamine, at a dosage up to 8 μg/kg body weight per min, in 11 patients with primary pulmonary hypertension. Reversibility of pulmonary hypertension was assessed by the inhalation of 20 ppm nitric oxide (NO), and, in 6 patients, by an infusion of prostacyclin.Results. At baseline, Ppa was 52 ± 3 mm Hg (mean value ± SE), Q 2.2 ± 0.2 liters/min per m², and Pc′ 29 ± 3 mm Hg. Dobutamine did not affect Pc′ and allowed the calculation of an averaged extrapolated pressure intercept of Ppa/Q plots of 34 mm Hg. Inhaled NO had no effect. Prostacyclin decreased Pc′ and PVR. Exercise increased Pc′ to 40 ± 3 mm Hg but did not affect PVR.Conclusions. These findings are compatible with a major increase of resistance and reactivity at the periphery of the pulmonary arterial tree.     

Upper airway sensation in snoring and obstructive sleep apnea.

Previous studies indicate that upper airway (UA) sensory receptors play a role in the maintenance of UA patency and contribute to arousal in response to airway occlusion. An impairment of UA sensory function could therefore predispose to UA obstruction during sleep. We hypothesized that UA sensation is impaired in obstructive sleep apnea (OSA), and that sensation improves after treatment with nasal continuous positive airway pressure (CPAP). We measured two-point discrimination (2PD) and vibratory sensation thresholds (VT) in 37 patients with OSA (mean [+/- SE] apnea- hypopnea index [AHI] = 39 +/- 5 events/h), 12 nonapneic snorers (SN), and 15 control subjects (CL). Sensory thresholds were determined in the UA and on the lip and hand as control sites. Both 2PD and VT were similar among the three groups at the lip and hand sites but were significantly reduced in the UA of OSA and SN subjects versus CL (p < 0.05). Values for 2PD and VT in the UA of OSA versus SN were not significantly different. Sensory measures were repeated after 6 mo in 23 OSA patients treated with CPAP as well as in 18 untreated patients. Thresholds for 2PD and VT at control sites remained identical in both groups, as did 2PD for the UA. However, VT in the UA showed a significant improvement in treated (4.4 +/- 0.2 pre-CPAP versus 3.8 +/- 0.2 mm post-CPAP, p < 0.05) but not untreated patients. These findings indicate the presence of a selective impairment in the detection of mechanical stimuli in the UA of patients with OSA and SN, which is partially reversible after treatment with nasal CPAP in patients with OSA.     

Mechanisms of hypoxemia in chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension is characterized by widespread central obstruction of the pulmonary arteries with organized thrombus and thereby differs substantially from other forms of pulmonary hypertension. We studied 25 patients using the multiple inert gas elimination technique to identify and quantitate the physiologic mechanisms of hypoxemia in this disorder. All patients had chronic obstruction of the central pulmonary arteries, which was demonstrated angiographically and later surgically confirmed. All patients but one were hypoxemic (PaO2 = 65 +/- 11 mm Hg, PaCO2 = 32 +/- 4 mm Hg, AaPO2 = 45 +/- 14 mm Hg), and all patients had pulmonary hypertension (mean Ppa = 45 +/- 11 mm Hg) with an elevated pulmonary vascular resistance (mean PVR = 1,000 +/- 791 dyne/s/cm5, normal less than 300). The cardiac index was reduced (1.7 +/- 0.6 L/min/m2), as was the P-vO2 (31 +/- 5 mm Hg). Inert gas studies revealed widened unimodal Va/Q distributions in 20 of 25 subjects, with a log standard deviation of 1.01 +/- 0.32 (upper limit of normal, 0.6; ages 20 to 40), shunt = 0.03 +/- 0.05 of cardiac output, and dead space of 3.4 +/- 1.1 ml/kg (upper limit of normal, 2.9). The VD/VT ratio was 0.51 +/- 0.10. No low (VA/Q less than 0.1) or high (VA/Q greater than 10.0) regions were present, and no evidence for diffusion limitation of O2 transfer at rest was found. The low cardiac output and resulting low P-VO2 were responsible for approximately 33% of the increased AaPO2. The magnitude of the VA/Q abnormality correlated poorly with the PVR, the mean Ppa, or the magnitude of vascular obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)     

The differential effects of positive inotropic and vasodilator therapy on diastolic properties in patients with congestive cardiomyopathy

Symptoms of congestive heart failure frequently reflect abnormalities in both systolic and diastolic performance. While much work has been reported regarding the mechanisms by which positive inotropic and vasodilator therapy affect systolic performance, little is known about their effect on diastolic function. In 12 patients with diffuse congestive cardiomyopathy micromanometer left ventricular and aortic pressure measurements were recorded simultaneously with two-dimensionally targeted M mode echocardiograms and thermodilution-determined cardiac output. Each patient received dopamine (2, 4, and 6 micrograms/kg/min), and dobutamine (2, 6, and 10 micrograms/kg/min), and 10 received nitroprusside (0.125 to 2.0 micrograms/kg/min). Baseline hemodynamics were characterized by low cardiac index (2.1 +/- 0.7 liter/min/m2, mean +/- SD), high left ventricular end-diastolic pressure (24 +/- 10 mm Hg), and increased end-diastolic (6.8 +/- 1.0 cm) and end-systolic dimensions (6.0 +/- 1.0 cm). All patients had abnormal left ventricular pressure decay with a prolonged time constant (67 +/- 20 msec) and reduced peak diastolic lengthening rates. Dopamine and dobutamine decreased the time constant of relaxation and increased the peak lengthening rate. Dobutamine also reduced the minimum diastolic pressure from 14 +/- 7 to 10 +/- 9 mm Hg (p less than .01); neither drug reduced end-diastolic pressure. In fact, dopamine elevated end-diastolic pressures in seven patients, despite more rapid pressure decay. Diastolic pressure-dimension relations after dopamine and dobutamine showed a leftward shift with a reduced end-systolic chamber size, but no significant changes in passive chamber stiffness. Nitroprusside decreased left ventricular minimum diastolic pressure by 4 +/- 2 mm Hg and end-diastolic pressure by 7 +/- 4 mm Hg (p less than .01). It did not consistently accelerate left ventricular pressure decay at the doses tested. The decreased end-diastolic pressure with nitroprusside was due to a reduced end-diastolic dimension in five patients. In the other patients, all of whom had elevated right atrial pressures, diastolic pressure-dimension relations showed a parallel downward shift after nitroprusside. Thus, positive inotropic therapy with beta 1-adrenoceptor agonists enhances early diastolic distensibility by accelerating relaxation, augmenting filling, and reducing end-systolic chamber size. Vasodilator therapy is much more effective in lowering diastolic pressures.(ABSTRACT TRUNCATED AT 400 WORDS)     

持续气道正压通气对急性心源性肺水肿犬呼吸及循环功能的影响

目的研究持续气道正压(CPAP)通气对急性心源性肺水肿(ACPE)犬呼吸及循环功能的影响。方法分别监测10条犬健康状态及ACPE发生后自主呼吸、5cmH2O(1cmH2O=0.098kPa)、10cmH2O、15cmH2OCPAP时的胸腔负压(Pt)、中心静脉压(CVP)、心输出量(CO)、平均动脉压(BPm)、肺动脉楔压(PAWP)。结果与健康状态相比,ACPE犬呼吸增强、增快,Pt由-(4.90±0.09)cmH2O上升至-(10.90±0.75)cmH2O,CVP由(10.1±0.4)mmHg下降至(8.0±0.7)mmHg,CO由(1.52±0.13)L/min下降至(0.85±0.09)L/min,PAWP升高(P均<0.05)。CVP与Pt变化呈正相关(r=0.78,P<0.01)。5及10cmH2OCPAP时Pt值恢复至-(6.53±0.11)cmH2O和-(5.14±0.25)cmH2O,呼吸形式基本恢复正常,CVP升至(11.6±0.7)mmHg和(14.2±0.2)mmHg,CO增加至(1.45±0.11)L/min和(1.24±0.11)L/min,其中5cmH2OCPAP组PAWP下降(P均<0.05)。15cmH2OCPAP时,呼吸浅快,Pt为-(0.82±0.37)cmH2O,CO为(0.82±0.07)L/min,其他血流动力学指标皆恶化(P均<0.05)。结论犬ACPE发生时,呼吸运动显著增强,Pt升高,并导致CVP和CO的下降;适当CPAP通过改善呼吸功能,调节Pt改善ACPE犬的心功能。     

The effects of prostaglandin E1 on lung injury complicating hyperdynamic sepsis in sheep

We examined the hypothesis that PGE1 would reduce the severity of lung injury in sheep rendered septic by cecal ligation and perforation (CLP). Twenty-four to 30 h after CLP, septic lung injury was documented in 37 sheep because pulmonary lymph flow (Qlym) was increased above the baseline, nonseptic study (delta = +7.38 +/- 5.1 ml/h; p less than 0.05), whereas the lymph-to-plasma total protein ratios remained unchanged. During a subsequent 24-h "septic treatment" study period, Qlym continued to increase in an untreated study group (septic treatment minus septic delta = +10.24 +/- 4.9 ml/h; p less than 0.05), but not in sheep treated with PGE1 by continuous infusion at two doses, 1 micrograms/kg/h ("low-dose": delta Qlym = -0.04 +/- 6.1 ml/h; p = NS) and 1 microgram/kg/min ("high-dose": delta Qlym = -0.04 +/- 6.1 ml/h; p = NS. Mean pulmonary artery pressures (Ppa) increased in the untreated group during the septic treatment period (delta = +3.74 +/- 4.8 mm Hg; p less than 0.01), but not during PGE1 infusion in either of the low-dose (delta Ppa = -4.1 +/- 5.7 mm Hg; p less than 0.04) or the high-dose (delta Ppa = -0.1 +/- 6.2 mm Hg; P = NS) groups. Unlike other study groups, the PaO2 fell in the high-dose PGE1 group during the septic treatment study (delta PaO2 = -15.0 +/- 9.6 mm Hg; p less than 0.01). During a study period of drug withdrawal 24 h after the septic-treatment period, Qlym again increased in the low-dose PGE1 group such that the untreated and PGE1 groups were no longer dissimilar.(ABSTRACT TRUNCATED AT 250 WORDS)