Relationship between hemodynamics and hemorrheology in chronic cor pulmonale

Hemodynamics, hemorrheology and blood gases were studied in 20 patients with stable chronic cor pulmonale. Blood viscosity was affected by hematocrit and blood gases, which acted on pulmonary pressure, pulmonary vascular resistance and right cardiac output. Blood viscosity was measured in the shear stress rate of 5.75, 11.5, 23, 46, 115 and 230 s-1. The decrease in plasma pH and PaO2 elevated high shear stress blood viscosity, pulmonary arterial pressure, total pulmonary vascular resistance and decreased right cardiac output, O2 administration decreased in high shear stress blood viscosity, but increased in low shear stress blood viscosity. Blood viscosity was positively correlated with hematocrit, which varied in different shear stress rate, the relative coefficient was the highest when the shear stress rate was in 11.5 s-1 (r = 0.9288 P less than 0.001). Pulmonary arterial pressure and pulmonary vascular resistance were positively correlated with high shear stress blood viscosity but uneffected by low shear stress blood viscosity. The increasing in high shear stress blood viscosity decreased the right cardiac output. Rigidity of red blood cell may play an important role in regulating pulmonary circulation and right heart function.     

Chronic obstructive pulmonary disease and the early stage of cor pulmonale: A perspective in treatment with pulmonary arterial hypertension-approved drugs

Cor pulmonale is right ventricular hypertrophy and/or dilation caused by pulmonary hypertension (PH) due to diseases affecting the lung function and structure. Recently, the definition of PH was revised from a mean pulmonary arterial pressure (mPAP) >25 mmHg to an mPAP >20 mmHg based on the Nice statement; this might expedite the detection of cor pulmonale. However, the only treatment for cor pulmonale for the past 3 decades has been to maintain the lung function and oxygen saturation.Chronic obstructive pulmonary disease (COPD) is the leading cause of cor pulmonale. Cor pulmonale in COPD is generally known to occur due to loss of vascular bed and chronic hypoxic pulmonary vasoconstriction (HPV) due to alveolar wall destruction. However, a recent study suggested that in some patients with COPD, the pulmonary vascular alterations include components that are primary lesions of the pulmonary artery. These alterations may be similar to the remodeling that occurs in pulmonary arterial hypertension (PAH). Although, there is no evidence supporting the treatment of COPD patients with PH using drugs approved for PAH, such drugs may be effective in the treatment of a selected group of COPD patients, whose disease includes PAH-like vascular components.To distinguish these patients, it is necessary to understand the histopathology of COPD and renew our understanding of the concept of cor pulmonale, which treats the heart and lung as a single unit. Herein, we review the recent histopathological concepts of COPD with respect to the progression of cor pulmonale.     

Hemodynamic effects of staged hematocrit reduction in patients with stable cor pulmonale and severely elevated hematocrit levels

Patients with cor pulmonale and high hematocrit levels are often subjected to phlebotomy in the belief that the adverse effects of high viscosity may outweigh the benefit of increased oxygen carrying capacity. To evaluate this, 12 patients with stable cor pulmonale and hematocrit values greater than 55 per cent were studied before and after a series of venesections. Right heart and aortic pressures, cardiac output and blood gases were measured at three mean hematocrit levels, 61 per cent (stage I), 50 per cent (stage II) and 44 per cent (stage III), with blood volume unchanged. From stages I to II, there were significant decreases in both mean pulmonary artery pressure and total pulmonary resistance. Oxygen transport fell but not oxygen consumption. Right ventricular end-diastolic pressure and cardiac output did not change. Right ventricular work either fell or was maintained by increased output. Frank-Starling performance (supine exercise) improved. No significant changes occurred with further reduction in hematocrit to normal levels (stage III). The findings of this study support the concept of overcompensating erythrocytosis in cor pulmonale, and the effects of moderate hematocrit reduction should not be overlooked in these severely ill patients.     

醛固酮与慢性肺源性心脏病肺动脉高压的相关性研究

目的 探讨血浆醛固酮与慢性肺源性心脏病肺动脉高压的关系。方法 选择90例慢性阻塞性肺病（COPD）患者分为COPD合并肺动脉高压组（n=30）、慢性肺源性心脏病肺心功能代偿期组（n=30）、慢性肺源性心脏病肺心功能失代偿期组（n=30）,采用放射免疫分析法测定3组患者的血醛固酮水平、多普勒超声检测肺动脉压力。结果 慢性肺源性心脏病肺心功能失代偿组血浆醛固酮浓度为（124.78±27.64）pg/ml,显著高于COPD合并肺动脉高压组（79.91±20.76）pg/ml及慢性肺源性心脏病肺心功能代偿期组（83.56±28.45）pg/ml,P〈0.05;血浆醛固酮浓度与肺动脉高压呈线性正相关（r=0.514,P〈0.05）,与血氧分压呈负相关（r=-0.248,P=0.019）。结论 醛固酮参与慢性肺源性心脏病患者肺动脉高压的发展。     

Nocturnal pulmonary hypertension in patients with chronic obstructive pulmonary disease.

Oxygen desaturation occurs during sleep in some patients with COPD. To investigate the effects of these hypoxemic episodes on the pulmonary vasculature, we studied four patients with our routine polysomnographic techniques and simultaneously recorded pulmonary artery pressure. In all four subjects, nocturnal episodes of desaturation were accompanied by elevations in the pulmonary artery pressure. Low flow oxygen abolished the drops in arterial oxygen saturation (but not the breathing abnormalities) and no elevations in the PA pressure were observed. We postulate that in some COPD patients these initially transient events may lead to sustained pulmonary hypertension and cor pulmonale. Nocturnal oxygen therapy may be indicated in more patients than previously suspected and may prevent the development of cor pulmonale.     

Serum soluble Fas in patients with Schistosomal cor pulmonale

BACKGROUND: Schistosomal cor pulmonale is considered an important pathological condition in endemic areas. Few recent studies have reported the role of apoptosis in pulmonary hypertension. OBJECTIVES: The aim of this study was to assess serum levels of soluble Fas (sFas), an inhibitor of apoptosis, in patients with schistosomal cor pulmonale as compared to patients with cor pulmonale due to chronic obstructive pulmonary disease (COPD) and normal subjects. METHODS: Serum sFas was assessed in 15 men with schistosomal cor pulmonale (age 32 +/- 10 years), 15 men with chronic cor pulmonale secondary to COPD and 20 healthy men, matched for age. RESULTS: Serum levels of sFas were significantly higher in patients with schistosomal cor pulmonale (74 +/- 80 U/ml) than in patients with cor pulmonale due to COPD (15 +/- 10 U/ml) and normal subjects (19 +/- 11 U/ml, p < 0.001 in both). In patients with schistosomal cor pulmonale, sFas was significantly higher in patients with mean pulmonary artery pressure > 30 mm Hg as compared to patients with pressure < or = 30 mm Hg (109 +/- 97 vs. 34 +/- 20 U/ml, p = 0.01). There was a significant correlation between serum sFas and the mean pulmonary artery pressure in patients with bilharzial cor pulmonale (r = 0.4, p < 0.01), but not in patients with COPD (r = 0.1, p = NS). CONCLUSIONS: Serum sFas levels are elevated in patients with schistosomal cor pulmonale and they are related to the severity of pulmonary hypertension. These findings suggest a role of apoptosis in schistosomal cor pulmonale.     

COPD合并慢性肺源性心脏病与否的肺功能对比分析

目的 通过对单纯COPD与肺心病患者的肺功能进行对比分析,了解COPD合并肺心病与否时的肺功能改变.方法 对所有入选的COPD患者进行肺功能和心脏超声检查,COPD患者GOLD分级为Ⅱ～Ⅳ级.根据有无肺心病将入选患者分为单纯COPD组和COPD合并肺心病组.单纯COPD组37例;COPD合并肺心病组31例.结果 COPD合并肺心病组DLCO% pred显著低于单纯COPD组(P<0.05);两组间FEV1% pred、FVC% pred、FEV1/FVC、RV% pred、TLC% pred、RV/TLC和共振频率无显著差异(P＞0.05).结论 COPD合并肺心病患者较单纯COPD患者肺弥散功能的损害更为显著.     

阿托伐他汀对慢性阻塞性肺疾病合并肺动脉高压患者的影响

目的:评价阿托伐他汀对慢性阻塞性肺疾病(COPD)合并慢性肺源性心脏病(简称肺心病)患者肺动脉高压(PH)的影响。方法:55例COPD合并慢性肺心病、PH患者随机分为2组:阿托伐他汀组(AL组,27例)和常规治疗组(28例)。2组患者均接受常规治疗,阿托伐他汀组口服阿托伐他汀,20mg/d。分别观察阿托伐他汀组及常规治疗组治疗前、治疗后6个月血浆中一氧化氮(nitric oxide,NO)、内皮素I(endothelin-1,ET-1)、超声心动图变化。结果:阿托伐他汀组治疗6个月后ET-1、PH较治疗前和常规治疗组治疗6个月时明显下降(P<0.05)、内源性一氧化氮(NO)明显升高(P<0.05)。常规治疗组治疗前、治疗后6个月上述指标比较差异无统计学意义(P>0.05)。结论:阿托伐他汀可调节NO及ET-1的分泌,有效降低PH。     

Hemodynamic effect of hydralazine in advanced, stable chronic obstructive pulmonary disease with cor pulmonale. Immediate and short-term evaluation at rest and during exercise

Hydralazine was administered to eight patients (mean age, 69 +/- 2 years) who had stable, advanced chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension (mean pulmonary arterial pressure, 31 +/- 3 mm Hg), and cor pulmonale. All of the patients were studied at rest and during exercise. After intravenous administration of hydralazine at rest, there were statistically significant increases in pulmonary arterial pressure (p less than 0.05), cardiac index (p less than 0.005), arterial oxygen saturation (p less than 0.01), and mixed venous saturation (SvO2) (p less than 0.005). Pulmonary vascular resistance did not change, and systemic resistance decreased (p less than 0.005). During exercise, pulmonary arterial pressure increased in all patients, and this increase was not blunted by hydralazine; however, cardiac index (p less than 0.005), arterial oxygen pressure (p less than 0.005), and SvO2 (p less than 0.001) increased further during exercise. The increase in pulmonary vascular resistance was significantly blunted by hydralazine (p less than 0.005). Therapy with the drug was continued orally in seven patients because one patient showed a deleterious response in pulmonary hemodynamics. After seven days of oral hydralazine, pulmonary arterial pressure and pulmonary vascular resistance were not statistically different from control. There were statistically significant increases in cardiac index (p less than 0.005) and SvO2 (p less than 0.05), systemic resistance decreased (p less than 0.01). The same condition was found during exercise; however, only two patients showed pulmonary gas exchange and pulmonary hemodynamic benefit at rest and during exercise with hydralazine therapy. Our results suggest that it is unlikely that vasodilator therapy with hydralazine will be useful in patients with advanced stable COPD and cor pulmonale who seem to have fixed pulmonary vascular disease.     

Repetitive hemodilution in chronic obstructive pulmonary disease and pulmonary hypertension: effects on pulmonary hemodynamics, gas exchange, and exercise capacity.

BACKGROUND: In cor pulmonale associated with severe chronic obstructive pulmonary disease (COPD), disturbances of pulmonary microcirculation may contribute significantly to hypoxemia, pulmonary hypertension, and exercise intolerance. OBJECTIVE: It was tested whether reduction of blood viscosity induced by repetitive hemodilution might improve pulmonary hemodynamics and oxygen uptake. METHODS: Seven patients with stable COPD (forced expiratory volume in 1 s 33 +/- 3 % of predicted, means +/- SE) and pulmonary hypertension were phlebotomized 5-6 times over a period of 3 months with substitution of 6% hydroxyethyl starch (molecular weight 40, 000). This resulted in a stepwise reduction of the hematocrit from 53.3 +/- 2.6 to 45.8 +/- 3.1% and a reduction of whole blood viscosity from 9.8 +/- 0.6 to 8.8 +/- 0.7 mPa x s at a shear rate of 2.0 s-1. Before and after the treatment period, patients underwent cardiopulmonary exercise testing and right heart catheterization. RESULTS: Mean pulmonary artery pressure (PAm) decreased from 30 +/- 3 to 22 +/- 2 mm Hg and arterial oxygen partial pressure (PaO2) increased from 63.2 +/- 2.2 to 71.8 +/- 3.7 mm Hg at rest. During peak exercise, PAm decreased from 59 +/- 7 to 53 +/- 7 mm Hg and PaO2 increased from 54.0 +/- 5.7 to 63.2 +/- 2.4 mm Hg after hemodilution. Peak oxygen consumption rose from 573 +/- 84 to 750 +/- 59 ml x min-1, corresponding to an increase in cardiac index from 4.25 +/- 0.5 to 5.88 +/- 0.76 liters x min-1 x m-2. Pulmonary vascular resistance fell from 345 +/- 53 to 194 +/- 32 dyn x s x cm-5. The patients' peak exercise capacity increased from 9.2 +/- 2. 0 before to 13.5 +/- 3.2 kJ at the end of the study (p < 0.05 for all differences, paired t test). CONCLUSION: The findings suggest that a prolonged improvement of pulmonary microcirculation by reducing blood viscosity may improve pulmonary gas exchange, central hemodynamics, and exercise tolerance in patients with severe COPD and pulmonary hypertension.     

The hemodynamic changes in the course of the development from chronic obstructive pulmonary disease to cor pulmonale

Swan-Ganz catheterization was done in 36 cases of COPD (19 cases) and chronic cor pulmonale (17 cases) patients diagnosed clinically. The results showed that exercise might greatly increase the rate of early diagnosis of chronic cor pulmonale in 47.4%, which is significant in clinical practice, together with gamma-camera, echocardiography and vectorcardiography, it can further increase the early diagnostic rate of cor pulmonale. In these 36 cases, 13 cases had no pulmonary hypertension and in 7 cases of them pulmonary arterial mean pressure were still in normal range even after exercise. If only right heart catheterization was used to diagnose cor-pulmonale without above three noninvasive examinations mentioned above, a high rate of misdiagnosis cor pulmonale would be possible.     

Long-term effects of nitrendipine on hemodynamics and oxygen transport in patients with cor pulmonale

Recent studies have suggested that vasodilators may acutely improve pulmonary hemodynamics in patients with chronic obstructive pulmonary disease and cor pulmonale, but the effects of long-term therapy have not been assessed. We evaluated the hemodynamic and gas exchange effects of nitrendipine, a calcium channel blocker with a cardiovascular profile similar to nifedipine, acutely and after five days and six weeks of therapy in eight patients with stable COPD and cor pulmonale. After six weeks, nitrendipine significantly decreased both mean pulmonary artery pressure (40.4 +/- 10.3 to 31.2 +/- 6.6 mm Hg, p less than 0.01) and pulmonary vascular resistance (6.8 +/- 3.9 to 3.0 +/- 1.1 units, p less than 0.01), while cardiac index increased (2.4 +/- 0.8 to 3.6 +/- 1.0 L/min/m2, p less than 0.001). Despite a fall in arterial PO2 (53.1 +/- 18.7 to 45.5 +/- 11.3 mm Hg, p = NS), systemic oxygen transport increased by over 30 percent (843 +/- 284 to 1,111 +/- 373 ml/min, p less than 0.05). Systemic arterial pressure, pulmonary capillary wedge pressure, and heart rate were unchanged. Despite these hemodynamic changes, three patients died from complications of their underlying disease while receiving long-term therapy after eight, nine, and ten months. These preliminary findings suggest that long-term vasodilator therapy can result in persistent hemodynamic improvement in some patients with cor pulmonale secondary to COPD, although the impact of this form of therapy on survival remains to be clarified.     

The clinical investigation of the pulmonary arterial pressure in stable-stage chronic obstructive pulmonary disease with cor pulmonale]

We measured pulmonary arterial pressure with Swan-Ganz catheters both at rest and after exercise in 21 patients with stable-stage chronic obstructive pulmonary disease (COPD). The results were as follows: pulmonary arterial mean pressure cases (PAPm) increased at rest in 11 cases (PAPm greater than or equal to 2.66kPa); in 6 cases PAPm was normal at rest (PAPm less than 2.66kPa) but increased above the normal level after exercise (PAPm greater than or equal to 3.99 kPa); in 4 cases PAPm was within the normal limit both at rest and after exercise. These results suggest that (1) pulmonary arterial pressure in some patients with COPD and cor pulmonale can return to the normal level; (2) exercise load test can detect early-stage or latent pulmonary hypertension; (3) attention should be paid to the patient selection when long-term vasodilators are administered.     

Hemodynamic changes in patients with chronic cor pulmonale secondary to COPD and effect of sodium nitroprusside administration

Pulmonary hemodynamic changes were studied with Swan-Ganz right heart catheterization in 19 patients with chronic cor pulmonale secondary to COPD. HR, RVP, PAPM, PVR, PCWP, RWI and PaCO2 were significantly higher and PaO2 and PH lower in patients with decompensated than those with compensated heart function. Nitroprusside lowered effectively pulmonary arterial pressure and pulmonary vascular resistance. Meanwhile, the drug also lowered PaO2 when the patient was breathing air but did not so or even increased it when breathing oxygen.     

Measurement of right and left heart function of COPD and cor pulmonale by radionuclide ventriculography]

Non-invasive measurements of right and left ventricular ejection fraction (RVEF, LVEF) by multiple-gated equilibrium radionuclide ventriculography were performed in 19 control subjects, 55 patients with COPD and cor pulmonale, simultaneous right heart catheterizations were performed in 10 patients with cor pulmonale to determine the mean pulmonary artery pressure (mPAP), and then, the acute hemodynamic and functional effects of nifedipine were evaluated. The mean RVEFs are different significantly among the various groups. With the development of the diseases, the RVEFs reduce gradually. The mean LVEF reduces significantly in cor pulmonale patients with heart failure. The RVEF correlated negatively to mPAP (r = -0.7047, P < 0.01). After nifedipine (20mg), the RVEF and mPAP do not change significantly (P > 0.05), but the artery blood pressure reduces significantly. We conclude that the equilibrium radionuclide ventriculography may be a useful and accurate method in diagnosing early cor pulmonale and cor pulmonale with right heart failure, and nifedipine may not be a good vasodilator for pulmonary hypertension.     

Value of plasma BNP levels as a prognostic marker in lung and heart disorders

In this study we included 155 subjects, 35 patients with left heart failure, 49 chronic obstructive pulmonary disease (COPD)-cor pulmonale, 26 COPD, 20 pulmonary embolism and 25 healthy subjects. Plasma BNP level in patient with left heart failure was significantly higher than COPD-cor pulmonale, COPD and control subject in respect 1167 +/- 746, 434 +/- 55, 32 +/- 36 and 32 +/- 12 pg/mL. Plasma BNP in group of cor pulmonale was higher than COPD and control subject 434 +/- 55 vs. 32 +/- 12 pg/mL. There were no difference between COPD and control subject 32 +/- 36 vs. 32 +/- 12 pg/mL. In pulmonary embolism BNP was higher than controls 357 +/- 391 vs. 32 +/- 12 pg/mL and BNP levels of massive pulmonary embolism was higher non-massive embolism 699 +/- 394 vs 166 +/- 213 pg/mL. In this study BNP levels negative correlated with EF and positive correlated with pulmonary artery pressure. We suggest that increased BNP levels are correlated with ventricular failure and BNP is diagnostic and prognostic marker of heart failure and increased right ventricular pressure contributes to elevated BNP in patients with PE.     

Phentolamine infusion in cor pulmonale due to chronic obstructive pulmonary disease.

Continuous phentolamine infusion, produced a marked decrease in pulmonary arterial pressure and pulmonary vascular resistance with an increase in cardiac output, in the majority of a group of 13 patients with chronic obstructive pulmonary disease and cor pulmonale. Changes in vital capacity, forced expiratory volume in one second, arterial blood gas values and peripheral blood pressure were not significant except in one patient. The changes in the pulmonary circulation are probably due to the alpha blocking effect of phentolamine, although a direct effect of the drug on vascular smooth muscle can not be excluded.     

COPD合并肺心病患者的心电图与超声心动图特征比较分析

目的比较慢性阻塞性肺疾病(COPD)合并肺心病患者的心电图与超声心动图特征。 方法回顾性分析我院COPD合并慢性肺源性心脏病患者48例(观察组),无心血管疾病的COPD患者32例(对照组),统计分析入组患者的超声心动图和心电图特征,并比较两种检查对肺心病的诊断价值。 结果2组患者在年龄、性别、病程和吸烟史方面均无统计学差异(P>0.05)。对照组患者心电图异常为房性早搏为(18.75%),右束支传导阻滞、顺钟向转位、肢体导联低电压均为(6.24%),右心室肥大(3.12%),肺型P波、电轴右偏、室上速均未发现;观察组患者心电图异常为房性早搏(33.33%)、电轴右偏(29.64%)、右束支传导阻滞(22.91%)、肢体导联低电压(22.92%)、肺型P波(14.58%)、顺钟向转位(10.41%)、室上速(8.30%),观察组患者心电图异常的发生率均较对照组患者显著的增高(P<0.05)。超声心动图检查显示观察组RA和RV值较对照组亦有显著的增加(P<0.05)。分析发现心电图对肺心病的检出率为54.17%,超声心动图检出率为85.42%,显著高于心电图(P<0.05)。 结论心电图和超声心动图是检测心脏疾病的重要手段,各有优缺点,医生在临床工作中可根据患者病情,同时结合心电图和超声心动图结果,早期发现并诊断COPD发生肺心病,以提高肺心病的诊疗水平。     

低分子肝素联合小剂量洋地黄类药物对于COPD合并慢性肺心病的肺功能及血凝的影响

目的旨在低分子肝素联合小剂量洋地黄类药物对于COPD合并慢性肺心病的肺功能及血凝的影响。方法选取在我院进行治疗的COPD合并慢性肺心病患者96例,将患者分为两组,分别采用一般治疗和低分子肝素联合小剂量洋地黄类药物。结果实验组的血凝和肺功能指标明显优于对照组(P<0.05)。结论低分子肝素联合小剂量洋地黄药物能够显著地改善患者的血凝和肺通气功能。     

Physiopathology and treatment of chronic cor pulmonale due to dysventilation syndrome

133 patients with chronic cor pulmonale due to dysventilation syndrome were studied. Chronic obstructive pulmonary disease (COPD) was found, possibly for the first time in Japan, to be the most common etiological condition, occurring in 54% of the patients. Chronic cor pulmonale was clinically diagnosed as the appearance of right heart failure on admission. Patients were divided into two groups depending on clinical state, compensated and decompensated. There was a marked difference in arterial blood gases and electrocardiographic fluctuations between the states. Serial observations of these parameters and enlarged cardiac silhouette to the left on plain chest film provided diagnostic evidence for development to the decompensated state. Pulmonary artery pressure changes on exercise and during sleep at night has been considered to impair right heart function. Prognosis of chronic cor pulmonale largely depends on the concentrated therapy of the decompensated state. 85% of patients in the current study returned to the compensated state with active intensive therapy. Recent therapeutic progress has made control of this serious disease possible, despite the appearance of right heart failure. Laborious prolonged therapy appears to be essential in order to improve long-term prognosis.