Mechanisms of hypertension in patients with chronic obstructive pulmonary disease and acute respiratory failure

PURPOSE: To investigate the effects of hypoxemia, hypercapnia, and cardiovascular hormones (norepinephrine, endothelin-1, and atrial natriuretic factor) on blood pressure during acute respiratory failure. PATIENTS AND METHODS: Patients with chronic obstructive pulmonary disease and acute respiratory failure were divided into four groups of 10 patients each: hypoxemia-normocapnia, hypoxemia-hypercapnia, hypoxemia-hypocapnia, and normoxemia-hypercapnia. Plasma norepinephrine levels were determined by high-performance liquid chromatography with electrochemical detection. Plasma endothelin-1 and atrial natriuretic factor levels were radioimmunoassayed after chromatographic preextraction.RESULTS: Systolic blood pressure and cardiovascular hormone levels were greater in patients with hypercapnia (whether or not they also had hypoxemia) than in those with normocapnia and hypoxemia. For example, in patients with hypercapnia and normoxemia, the mean (+/- SD) systolic blood pressure was 183+/-31 mm Hg and the mean norepinephrine level was 494+/-107 pg/mL, as compared with 150+/- 6 mm Hg and 243+/-58 pg/mL in those with normocapnia and hypoxemia (both P<0.05). Similar results were seen for endothelin-1 and atrial natriuretic factor levels, and for the comparisons of hypoxemic patients who were hypercapnic with those who were normocapnic. CONCLUSIONS: These results suggest that blood carbon dioxide levels, rather than oxygen levels, are responsible for hypertension during acute respiratory failure, perhaps as a result of enhanced sympatho-adrenergic activity.     

Evaluation of pulmonary arterial hypertension by Doppler echocardiography in chronic respiratory insufficiency

The usefulness of doppler-echocardiography for the assessment of pulmonary arterial hypertension in patients with chronic respiratory failure was evaluated in 24 consecutive patients with chronic obstructive lung disease. Seventeen of these 24 patients (71 p. 100) who had tricuspid valve regurgitation analysable by the continuous wave doppler technique were selected as study group; they included 15 men and 2 women aged from 33 to 78 years (mean 63 years). The highest maximum velocity value (method A) or the maximum velocity value averaged on several cycles (method B) of the tricuspid regurgitation jet was used to calculate the right ventriculo-atrial pressure gradient, using Bernouilli's equation. Right atrial pressure was determined by three methods: haemodynamic measurement, clinical evaluation or attribution of an arbitrary 10 mmHg value. The pulsed doppler study of the pulmonary ejection flow included measurement of the acceleration time and calculation of the acceleration time/ejection time ratio. The usual echocardiographic parameters were measured. Catheterization was performed 2.5 days on average after the doppler study. Correlations between doppler examination and catheterization to evaluate the right ventricular systolic pressure were significant (p less than 0.001) and better with method B than with method A. Depending on the method employed to evaluate the right atrial pressure, the correlation coefficients obtained with method B were: 0.93 (haemodynamic measurement), 0.91 (clinical evaluation) and 0.88 (arbitrary value of 10 mmHg). The right ventricular systolic pressure evaluated by doppler ultrasound using method B and by clinical evaluation of the right atrial pressure was 47 +/- 12 mmHg (22 to 70 mmHg), as against 51 +/- 13 mmHg (28 to 74 mmHg) measured by catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)     

双水平气道正压对老年急性心源性肺水肿合并呼吸衰竭的疗效观察

目的通过监测双水平气道正压(BiPAP)无创通气对老年急性心源性肺水肿病人的影响,从而评估其临床推广使用的安全性。方法回顾性分析54例常规治疗效果不佳的老年急性心源性肺水肿病人,及时使用BiPAP无创通气并观察治疗效果和血流动力学参数[心率(HR)、平均动脉压(MBP)、中心静脉压(CVP)]、血气[氧合指数(OI)、碳酸氢根离子(HCO3-)]的变化。结果及时使用BiPAP后,患者血流动力学指标(HR)明显缓解(P<0.01);血气分析的数值(OI,HCO3-)明显改善(P<0.05);并且对多巴胺的依赖明显降低(P<0.01);总的治疗有效率高达87%。结论早期使用BiPAP无创通气对老年急性心源性肺水肿合并呼吸衰竭病人具有良好的效果。     

The acute effects of nifedipine on calf and forefoot blood flow in patients with peripheral arterial insufficiency

The calcium-blocking agent nifedipine, which possesses vasodilating potency, was tested in 8 patients with peripheral arterial insufficiency. 10 mg sublingually significantly decreased systolic arm and ankle blood pressure. Neither blood flow nor local peripheral resistance in the calf and the forefoot at rest and the calf during postischemic reactive hyperemia changed significantly. During postischemic hyperemia in the forefoot, the drug significantly reduced peak blood flow and increased local peripheral resistance. The drug-induced reduction in forefoot peak blood flow was correlated to the fall in systolic arm and ankle blood pressure. It is suggested that nifedipine may shorten the claudication distance in patients with peripheral arterial insufficiency.     

Effects of nifedipine on pulmonary hypertension in patients with chronic obstructive pulmonary diseases--a comparison with oxygen administration

We evaluated the effects of the calcium channel blocker nifedipine (Nf) as a vasodilator compared with oxygen administration on pulmonary hypertension and right ventricular performance in 15 patients with COPD. 1. Compared with baseline, sublingual administration of Nf (average dose 39.3mg) decreased mean pulmonary artery pressure (mPAP) and total pulmonary vascular resistance (TPVR) significantly. Cardiac index (CI) and oxygen transport were increased. PaO2 were unchanged and PvO2 were slightly increased after administration of Nf. 2. Compared with oxygen administration, Nf caused significant fall of TPVR. CI and oxygen transport increased. 3. In eleven of 15 patients, continued hourly Nf doses (from 20 to 60mg) produced a significant reduction in mPAP and TPVR. All patients but one did not produce symptomatic systemic hypotension. We considered that higher dose (30mg) of Nf was required to produce marked hemodynamic response in patients with COPD without any side effect.     

粉防己碱与硝苯地平对大鼠肺动脉高压影响对比的实验研究

目的:通过粉防己碱与硝苯地平对比实验研究,探讨粉防己碱与硝苯地平对肺动脉高压的治疗作用及其机制。方法:40只,雄性,Wistar大鼠,随机分为4组,即:模型组、粉防己碱治疗组、硝苯地平治疗组和对照组。采用左全肺切除复合腹腔注射野百合碱建立大鼠肺动脉高压模型,分别应用粉防己碱和硝苯地平按最低安全剂量进行灌胃干预、治疗组。测定大鼠血液中一氧化氮(NO)的含量,血流动力学指标,右心指数,光镜下观察肺小动脉病理变化。结果:两个治疗组肺动脉压力及右心指数均降低,均能够改善肺血管重构,但两者相比差异无统计学意义;血中NO含量粉防己碱组明显高于硝苯地平组,且对大鼠体循环压力影响小,两者相比较差异有统计学意义。结论:粉防已碱和硝苯地平均能够逆转野百合碱所致的大鼠肺动脉高压模型肺血管重建,降低肺动脉压力,但综合比较,前者对于降低肺动脉高压更有优势,可能与NO相关。     

Comparison of patients with pulmonary arterial hypertension with versus without right-sided mechanical alternans

The clinical implications of mechanical alternans in patients with pulmonary arterial hypertension (PAH) remain unknown. In this study, the prevalence, characteristics, and prognostic implications of mechanical alternans in patients with PAH were investigated. Thirty-two consecutive patients with PAH confirmed by cardiac catheterization from 2000 to 2010 were included in this cohort study. During cardiac catheterization, 8 patients (25%) showed mechanical alternans at rest. All alternans were detected in the right ventricle and pulmonary trunk. Serum level of brain natriuretic peptide (584 ± 177 vs 238 ± 252 pg/ml, p = 0.001), World Health Organization functional class (3.5 ± 0.5 vs 2.9 ± 0.4, p = 0.02), mean pulmonary arterial pressure (59 ± 10 vs 47 ± 18 mm Hg, p = 0.03), mean right atrial pressure (10 ± 4 vs 5 ± 4 mm Hg, p = 0.01), right ventricular end-diastolic pressure (15 ± 5 vs 9 ± 5 mm Hg, p = 0.01), and heart rate at catheterization (96 ± 17 vs 70 ± 11 beats/min, p = 0.003) were significantly higher in patients with alternans than in those without. Twelve-month mortality of patients with alternans was higher than in patients without alternans (p = 0.03): the 12-month survival rate after cardiac catheterization was 37% for the alternans group and 75% for the group without alternans. In conclusion, isolated right-sided mechanical alternans is not an uncommon event in patients with PAH. The existence of alternans is associated with the severity of PAH and right ventricular dysfunction and implies a poor prognosis in the short term.     

Central respiratory drive in acute respiratory failure of patients with chronic obstructive pulmonary disease

Control of breathing was studied in patients with chronic obstructive pulmonary disease, both in the chronic state and during acute respiratory failure. The results were compared to those in a group of age-matched normal subjects. In patients breathing air, minute ventilation was not different during acute and chronic states, and was similar to that in normal subjects. The pattern of breathing, however, was different: acutely ill patients took shorter and smaller breaths, with a breathing frequency higher than that of normal subjects. The pattern of the chronic group was intermediate between that of acutely ill patients and that of normal subjects. Mouth occlusion pressure, an index of neuromuscular respiratory drive, was 5 times greater in acutely ill patients than in normal subjects. Administration of O2 at a flow of 5 L/min caused a small (14%), bus significant, decrease in minute ventilation due to decreased respiratory frequency. The tidal volume did not change, so the decrease in minute ventilation was the result of decreased inspiratory flow. This was associated with a decreased mouth occlusion pressure that was still 3 times greater than that of normal subjects. The increase in arterial PCO2, observed after administration of O2 was not correlated with the decrease in ventilation, indicating that other factors must be responsible for the increase in arterial PCO2. We concluded that (1) despite the poor mechanical advantage of the respiratory muscles in acute respiratory failure, the increased drive to breathe results in high mouth occlusion pressure and inspiratory flow, and (2) the increase in arterial PCO2, observed during administration of O2 is not related solely to changes in respiratory drive.     

Comparative study of acute and chronic effects of nifedipine in patients with secondary pulmonary hypertension

The effects of nifedipine in a single dose of 10 mg on the pulmonary circulation and the selected right and left ventricular function indices were studied in a group of 10 patients with secondary pulmonary hypertension (mean systolic pressure 55.2 mm Hg). In 8 patients hemodynamic studies were repeated after seven days treatment (3 x 10 mg). Acute treatment with nifedipine resulted in a reduction in mean systolic arterial pressure by 21.8%, diastolic by 12.2% and systemic resistance by 25.5%, and in an increase in cardiac index by 14.3%. After 7 days a similar pattern of changes was observed, however with less intensity: systolic pressure was reduced by 10.3% diastolic by 5.5%, and systemic resistance by 17.1%. Pulmonary artery wedge pressure did not change after a single dose, and mean pulmonary artery pressures showed a tendency toward lower levels: systolic by 8.9% and diastolic by 8.6%, whereas total pulmonary resistance decreased markedly (by 22.7%), as well as pulmonary vascular resistance. Right ventricular filling pressure was reduced. After chronic treatment we found a further slight fall in the pulmonary arterial pressure. Although per cent changes were similar to those in the arterial pressure, alterations in the mean values were not statistically significant. The total pulmonary resistance remained reduced. While analysing the changes in the pulmonary circulation and right ventricular indices it should be noted that they were less intense and less homogeneous than the left ventricular function parameters. Some of the patients showed certain similarities in the direction and intensity of changes in the hemodynamic indices of the pulmonary circulation in the acute and chronic experiment.     

Beneficial acute effects of rho-kinase inhibitor in patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a poor prognostic disease with limited treatment options. Rho-kinase is involved in the pathophysiology of several diseases underlying smooth muscle hypercontraction, so the purpose of this study was to investigate the efficacy of fasudil, a Rho-kinase inhibitor, in patients with PAH. METHODS AND RESULTS: Fasudil 30 mg was intravenously injected over 30 min in 8 patients (all female, mean +/- SD, 41+/-11 years) with PAH. The lowest total pulmonary resistance (TPR) time was within 30-60 min after administration. Administration of fasudil decreased TPR from 1,069+/-573 dyne . s . cm (-5) to 809+/-416 dyne . s . cm(-5) (p<0.005) and mean pulmonary arterial pressure from 41.3+/-12.8 mmHg to 37.9+/-14.6 mmHg (p<0.05). The cardiac index was increased from 2.42+/-0.73 L . min(-1) . m(-2) to 2.84+/-0.79 L . min(-1) . m(-2) (p<0.02). Systemic vascular resistance and systolic systemic arterial pressure (SAP) were decreased (p<0.005, p=0.09, respectively), but the decrease in SAP was small (-6.4+/-9.1 mmHg). CONCLUSION: These results suggest that Rho-kinase is involved in the pathogenesis of human PAH and that fasudil is a novel therapeutic agent.     

Influence of nebivolol on left ventricular remodeling in patients with arterial hypertension without chronic heart failure

In the recent years the problem of heart remodeling under drugs in patients with arterial hypertension (AH) have been extensively discussed. The beta-blocker of the third generation nebivolol is known as a good antihypertensive agent. The aim of our study was to evaluate effects of nebivolol on structural and functional parameters of cardiac remodeling in patients with AH without heart failure. We examined 28 patients with AH aged 49.99 +/- 5.26 years, with average arterial pressure 154.42 +/- 94.37 mm Hg and ejection fraction (EF) > 60%. All of them underwent routine clinical examination and echocardiography (EchoCG) with calculation of additional indexes, and than were given nebivolol 5 mg. After 3 months and 1 year of treatment with nebivolol we assessed antihypertensive effect and the state of cardiac hemodynamics using EchoCG with calculation of remodeling indexes. After 3 months of therapy myocardial stresses (systolic - MSs and diastolic - MSd) were reduced (from 154.28 +/- 11.65 to 132.77 +/- 11.37 U, p < 0.02, and from 184.17 +/- 14.1 to 159.87 +/- 13.34 U, p < 0.02, respectively), and diastolic function improved. After 1 year of antihypertensive treatment LV diastolic function remained normal, while thickness of LV wall decreased (from 0.41 +/- 0.03 to 0.37 +/- 0.02 U, p=0.01). MS continued to decrease with high degree of significance. At the end of the first year we revealed decrease of MSs/ESVI from 9.66 +/- 1.77 at the start of treatment to 6.1 +/- 0.69 (p < 0.005) and MSd/EDVI from 3.21 +/- 0.4 to 2.57 +/- 0.38 (p < 0,005). Increase of EF/MSs (from 0.47 +/- 0.05 to 0.61 +/- 0.07, p < 0.02) was also revealed after 1 year treatment with nebivolol. There were 32% individuals in the studied group, who had concentric type of LV remodeling at the beginning, after 3 months this number decreased to 16%, and at the end of first year no patients had this type of remodeling. Thus, it was shown that nebivolol is able to interfere with the processes of structural and functional rearrangement of the myocardium, preventing development of systolic and diastolic dysfunction of the heart.     

Effects of digoxin on diaphragmatic strength generation in patients with chronic obstructive pulmonary disease during acute respiratory failure

We studied the effects of digoxin, a compound that has an inotropic effect on the myocardium, on diaphragmatic function in 8 patients with chronic obstructive pulmonary disease. All the patients were in acute respiratory failure and were artificially ventilated. Diaphragmatic strength was assessed by measuring the transdiaphragmatic pressure generated at functional residual capacity during bilateral supramaximal electrical stimulation of the phrenic nerves. The latter were stimulated before and at 45 and 90 min after administration of digoxin (0.02 mg/kg infused for 10 min). In all the patients, cardiac output was measured by the thermodilution technique using a Swan-Ganz catheter placed in the pulmonary artery. Arterial blood gases and pH were maintained within normal range by mechanical ventilation. In all the patients, digoxin plasma levels reached the therapeutic range (mean values, 2.82 +/- 0.17 and 2.90 +/- 0.20 nmol/L at 45 and 90 min, respectively) after digoxin administration. Diaphragmatic strength improves significantly after digoxin administration, the transdiaphragmatic pressure for an identical phrenic stimulation increasing by 19.5% (p less than 0.001) on the average. This increase was noted 45 and 90 min after digoxin administration. We conclude that digoxin has a potent effect on diaphragmatic strength generation that may be beneficial in patients with chronic obstructive pulmonary disease during acute respiratory failure. Furthermore, this inotropic positive effect of digoxin on the diaphragm, as previously observed for the myocardium, emphasizes the similarities between these 2 contractile tissues.