Plasma endothelin immunoreactivity in liver disease and the hepatorenal syndrome.

BACKGROUND. Severe renal vasoconstriction is central to the pathogenesis of renal failure in the hepatorenal syndrome. Endothelin-1 and endothelin-3 are potent, long-acting vasoconstrictors, and endothelin-1 has selective potency as a renal vasoconstrictor. These properties suggest a role for endothelins in the hepatorenal syndrome. METHODS. We measured plasma endothelin-1 and endothelin-3 concentrations using specific radioimmunoassays in subjects with hepatorenal syndrome, liver disease but normal renal function, chronic renal failure, acute renal failure, liver dysfunction and renal impairment, or normal liver and kidney function. RESULTS. The patients with the hepatorenal syndrome had markedly elevated mean (+/- SE) plasma concentrations of endothelin-1 (36 +/- 5 ng per liter [14.5 +/- 1.8 pmol per liter]) and endothelin-3 (43 +/- 3 ng per liter [16.3 +/- 1.0 pmol per liter]) as compared with the normal subjects (endothelin-1, 4 +/- 1 ng per liter [1.7 +/- 0.2 pmol per liter]; and endothelin-3, 18 +/- 1 ng per liter [6.8 +/- 0.4 pmol per liter]; P < 0.001) and with the patients in the other four groups (P < 0.001 to P < 0.05). The plasma endothelin-1, but not endothelin-3, concentrations in these four patient groups were significantly higher than in the normal subjects (P < 0.001 to P < 0.05). The concentrations of endothelin-1 in renal arterial plasma and renal venous plasma, measured in five patients with the hepatorenal syndrome and three with chronic liver disease and normal renal function, were 20 +/- 4 ng per liter (7.9 +/- 1.8 pmol per liter) and 24 +/- 4 ng per liter (9.5 +/- 1.5 pmol per liter), respectively (P < 0.05). CONCLUSIONS. The increase in plasma endothelin-1 and endothelin-3 concentrations in patients with the hepatorenal syndrome is consistent with the hypothesis that these substances have a role in the pathogenesis of the disease.     

Gas exchange response to naloxone in chronic obstructive pulmonary disease with hypercapnic respiratory failure

It has been hypothesized that naloxone may alter the ventilation-perfusion relationship in patients with chronic obstructive pulmonary disease (COPD) with associated respiratory failure, through the release of hypoxic pulmonary vasoconstriction. To investigate the effects of naloxone on gas exchange, seven clinically stable patients with severe COPD (type B) (forced expiratory volume in one second/forced vital capacity (FEV1/FVC) 38.3 +/- 4.0%) with hypoxaemia and hypercapnia (PaO2 7.6 +/- 0.4 kPa; PaCO2 6.4 +/- 0.3; pH 7.37 +/- 0.02), aged 59.0 +/- 4.6 yr, were studied. Breathing patterns, haemodynamic and conventional and inert gas exchange measurements were made while breathing room air before, during and 60 min after i.v. naloxone infusion. Naloxone and catecholamine plasma levels were also determined. In three subjects (protocol A), measurements were made using increasing concentrations of naloxone (cumulative dose: 54 mg), while the remaining four patients were studied (protocol B) at a fixed concentration of naloxone (cumulative dose: 38 mg). Despite high levels of naloxone (up to 150 ng.ml-1), no significant differences from baseline were observed in any of the measurements, during or after infusion. It is concluded that i.v. naloxone given as described has no effects on pulmonary gas exchange in clinically stable COPD patients with chronic respiratory failure.     

Effect of nocturnal hypoxia on pulmonary hemodynamics in patients with obstructive sleep apnea

Effects of apnoea induced nocturnal hypoxia on pulmonary haemodynamics (PH) in pts with OSA are still under debate. We studied PH in 67 pts (64 M and 3 F) mean +/- SD: age 45 +/- 8 years, with severe OSA, AHI 62 +/- 22. Patients had normal spirometry: FVC 98 +/- 15% N, FEV1 97 +/- 16% N and arterial blood gases--PaO2 72 +/- 10 mmHg, PaCO2 40 +/- 4 mmHg. PH were studied using Swan-Ganz thermodilution catheter. PH were within normal range: right atrial pressure 4.2 +/- 2.7 mmHg, right ventricular systolic/enddiastolic pressure 28.1 +/- 7.1/5.0 +/- 3.3 mmHg, mean pulmonary artery pressure (PAP) 15.8 +/- 4.6 mmHg, mean pulmonary wedge pressure (PW) 6.8 +/- 3.1 mmHg, cardiac output (CO) 5.6 +/- 2.2 L/min. and pulmonary vascular resistance (PVR) 150 +/- 83 dyn.sec.cm-5. During exercise (44 pts) PAP rose from 15.8 +/- 4.3 to 29.8 +/- 9.4 mmHg, PW rose from 6.8 +/- 3.2 to 12.6 +/- 6.8 mmHg and CO from 4.9 +/- 1.9 to 9.2 +/- 4.2 L/min. All patients presented with nocturnal desaturations. Mean oxygen saturation (SaO2 mean) was: 87.4 +/- 5.4%, minimal saturation (SaO2 min) was 57.4 +/- 15.9%. Time spent in desaturation SaO2 < 90% (T90) was 50.7 +/- 26.5%. Results of PH investigations were related to results of pulse oximetry. Linear regression analysis showed week negative correlations between SaO2 mean and: PAP (r = -0.37 p = 0.003), PVR (r = -0.37 p = 0.007), and positive correlation between T90 and PAP (r = 0.37 p = 0.008). We conclude that there is no diurnal pulmonary hypertension at rest in patients with severe OSA and normal lung function even in the presence of severe overnight nocturnal desaturations. In half of studied patients we observed pulmonary hypertension during exercise.     

Pulmonary hemodynamic effects of intravenous almitrine in patients with chronic bronchitis and respiratory insufficiency

The effects on ventilation, gas exchange and pulmonary haemodynamics of 1 h infusion of 0.5 mg X kg-1 almitrine (Vectarion) were studied in 14 patients with chronic bronchitis, with clear hypoxemia (PaO2 less than 65 mmHg) and hypercapnia (PaCO2 greater than or equal to 45 mmHg). The separate effects of the almitrine solvent and/or the solution were studied in six similar chronic bronchitics. In this latter group, blood gases and haemodynamic values were not significantly altered. In subjects treated with almitrine, PaO2 raised from 51.9 +/- 6.6 (control: T0) to 61.9 +/- 9.9 mmHg at the 60th min (t60) of infusion (p less than 0.001); PaCO2 decreased from 52.8 +/- 6.3 (t0) to 45.7 +/- 5.2 mmHg at t60 (p less than 0.001). The effects on blood gases were still marked 10 min after infusion (t70). The significant increase in PaO2 was faster (10th min) than that of PaCO2 (20th min). The mean pulmonary artery pressure (Ppa) rose appreciably, from 27.8 +/- 11.3 at t0 to 35.5 +/- 12.5 mmHg at t60 (p less than 0.001). This rise was significant from the 10th min (p less than 0.005) and was related to that of pulmonary vascular resistance since on average cardiac output and pulmonary wedge pressure did not change. Ppa came back to its initial value at t70. Thus pulmonary vasoactive effects were at the same time early and transitory. They seemed due to an arterial vasoconstriction (role of chemoreceptors?), which could also explain the perfusion redistribution to the best ventilated areas and the improvement of VA/Q inequalities.     

Glucose-induced insulin release during acute and chronic hypoxia.

Glucose-induced insulin release was studied in young dogs during acute and chronic hypoxia, alone and in combination. Six experimental animals were rendered chronically hypoxic (PaO2, 43.4 +/- 0.5 torr) by creation of a right-to-left shunt at age 6-8 wk. Six control animals underwent sham procedures (PaO2, 85 +/- 2.2 torr) at the same age. During air breathing, glucose-induced plasma insulin increases were similar in chronically hypoxic and control animals. When severe hypoxia was acutely produced by ventilation with low-oxygen mixtures in experimental (PaO2, 23.7 +/- 1.7 torr) and control animals (PaO2, 26.3 +/- 1.0 torr), plasma insulin responses were markedly inhibited in both. On the other hand, acutely lowering oxygen tensions of control animals (PaO2, 37.5 +/- 1.4 torr) to levels close to those of air-breathing chronically hypoxic animals did not affect the insulin responses. These observations suggest that glucose-induced insulin release is inhibited by acute severe hypoxia despite previous chronic oxygen deficiency. In contrast, moderate hypoxia, acute or chronic, does not appear to affect the insulin response to a glucose load.     

Effects of nocturnal desaturation on pulmonary hemodynamics in patients with overlap syndrome (chronic obstructive pulmonary disease and obstructive sleep apnea)

We studied pulmonary haemodynamics and nocturnal desaturation in 17 patients with an overlap syndrome (OS), all males, mean age 51.4 +/- 8.3 years, mean BMI 37 +/- 4.2 kg/m2. Diagnosis of COPD was based on pts history, clinical examination, lung function tests and chest radiography. Spirometry showed: FVC 2.7 +/- 0.7 L (59 +/- 16% N), FEV1 1.5 +/- 0.7 L (43 +/- 16% N), FEV1% FVC 54 +/- 13%, Raw 0.58 +/- 0.4 kP.s/L, RV 3.3 +/- 1.2 L (144 +/- 51% N), TLC 6.6 +/- 1.3 L (100 +/- 14% N) and RV% TLC (49.5 +/- 12.1%. Arterial blood gas values were: PaO2 56.9 +/- 9.5 mmHg, PaCO2 46.9 +/- 9.8 mmHg, pH 7.37 +/- 0.05. Mean apnoea/hypopnoea index (AHI) was 63.9 +/- 18.9. Pulmonary haemodynamics at rest (Swan Ganz thermodilution catheter) were: mean pulmonary artery pressure (PAP-SP) 24.2 +/- 7.4 mmHg, mean pulmonary wedge pressure (PW-SP) was 9.1 +/- 7.3 mmHg, cardiac output (CO-SP) was 5.6 +/- 2.3 L/min. and pulmonary vascular resistance (PVR) was 229 +/- 97 dyn.sec.cm-5. During exercise (40 Watts, 7 mins, in 8 pts) PAP rose from 19 +/- 6 mmHg to 41.2 +/- 15.1 mmHg, PW rose from 7.4 +/- 7.2 mmHg to 11 +/- 10.2 mmHg, CO rose from 5.8 +/- 2.7 L/min to 12.7 +/- 2.4 L/min. Overnight pulse oximetry showed: mean oxygen saturation (SaO2 mean) 80.2 +/- 8.5%, minimal saturation (SaO2 min) was 50.7 +/- 19.7%. Time spent in desaturation SaO2 < 90% (T 90) was 76.9 +/- 25.7%. We conclude that pts with OS have resting pulmonary hypertension and elevated PVR. During low grade exercise the rise in PAP was highly abnormal. Statistical analysis showed no correlations between nocturnal SaO2 and diurnal pulmonary haemodynamics data.     

Influence of recombinant human erythropoietin therapy on plasma endothelin-1 levels during hemodialysis

The correction of anemia with human recombinant erythropoietin (rHuEPO) in end stage renal disease is associated with hypertension in about one third of hemodialysis patients. The pathogenesis of the rHuEPO-induced hypertension is still uncertain, though evidence of the involvement of endothelial cells has emerged. The aim of this study was to determine plasma endothelin-1 during hemodialysis and to compare the endothelin-1 levels in hemodialysis patients with and without rHuEPO substitution. Nineteen stable patients (13 male and 6 female, mean age 62 +/- 11 years) with end stage renal disease were studied. Cuprophan dialysers (GFS 12, Gambro, Lund, Sweden) were used for hemodialysis in all cases. rHuEPO (40 U/kg s.c.) was administered to 10 patients. Blood pressure (BP; RR mmHg) and blood volume changes (deltaBV; hemoglobinometry %) were serially measured. Samples were taken before and every hour during hemodialysis. Plasma endothelin-1 was measured by ELISA (R&D Systems, Minneapolis, USA) and corrected for hemoconcentration. Endothelin-1 concentration was elevated before commencement of hemodialysis (1.16 +/- 0.36 pg/ml) when compared to healthy controls (ref. 0.3-0.9) and increased to 1.47 +/- 0.51 pg/ml by the end of the session (p<0.05). In patients under rHuEPO-substitution plasma endothelin-1 was higher when compared to patients without substitution before (1.25 +/- 0.3 vs. 1.05 +/- 0.3 pg/ml) and at the end of HD (1.62 +/- 0.5 vs. 1.28 +/- 0.3 pg/ml, p<0.05). There was no difference in BP and deltaBV between the two groups during treatment. Plasma endothelin-1 was higher in hemodialysis patients and there was a continuous rise in plasma endothelin-1 during a session. Comparison of two groups of hemodialysis patients with and without s.c. rHuEPO-replacement treatment revealed a significantly higher plasma endothelin-1 concentration in patients with s.c. rHuEPO treatment. However, the elevated endothelin-1 levels were not accompanied by arterial hypertension.     

Elevated plasma amylase levels in advanced chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy: correlation with circulating interleukin-6 activity.

It has been reported that proinflammatory cytokine activation is associated with both mesenteric venous congestion and peripheral tissue underperfusion in advanced chronic heart failure. The aim of our study was to investigate if plasma amylase (as an easily approached marker of a low-grade peripheral organ injury caused by elevated systemic venous pressure and reduced cardiac output) is elevated in severe heart failure and if this elevation is correlated with cytokine and neurohormonal activation in the plasma of heart failure patients. Plasma levels of amylase, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), norepinephrine, and renin activity were measured in 43 severe heart failure patients (ischemic, 28; dilated, 15; left ventricular ejection fraction [LVEF] 27 +/- 3%; New York Heart Association [NYHA] classes III-IV), in 37 mild heart failure patients (ischemic, 26; dilated, 11; LVEF, 33 +/- 5%; NYHA classes I-II), and in 20 age-matched and gender-matched healthy controls. NYHA III-IV heart failure patients exhibited significantly higher plasma levels of amylase (342 +/- 19 vs. 174 +/- 13 U/L, p < 0.01), TNF-alpha (6.2 +/- 0.5 vs. 4.2 +/- 0.3 pg/ml, p < 0.01), IL-6 (5.9 +/- 0.3 vs. 4.4 +/- 0.3 pg/ml, p < 0.05), GM-CSF (21.2 +/- 2.7 vs. 4.1 +/- 0.9 pg/ml, p < 0.001), and neurohormones (both p < 0.001) compared with NYHA I-II heart failure patients and healthy controls (amylase, 165 +/- 11 U/L, p < 0.01; TNF-alpha, 2.7 +/- 0.3 pg/ml, p < 0.001; IL-6, 3.2 +/- 0.2 pg/ml, p < 0.01; GM-CSF, 3.1 +/- 0.7 pg/ml, p < 0.001). Only in NYHA III-IV heart failure patients, plasma amylase levels were significantly correlated with plasma IL-6 activity (r = 0.86, p < 0.001), plasma norepinephrine levels (r = 0.82, p < 0.001) and right atrial pressure (r = 0.52, p < 0.05). Additionally, circulating IL-6 was also significantly correlated with plasma norepinephrine (r = 0.86, p < 0.001) and right atrial pressure (r = 0.57, p < 0.01). In conclusion, plasma amylase levels were elevated in severe heart failure patients and correlated well with circulating IL-6 activation, possibly as a result of both mesenteric venous congestion and impaired peripheral tissue perfusion observed in advanced chronic heart failure. However, the lack of association between plasma IL-6 and amylase levels in mild heart failure patients indicates an independent correlation of each variable with the functional status of the disease.     

肺心病患者血浆CGRP与ET-1的变化

本文通过对35例肺心病患者心导管检查分别于急性发作期和缓解期二次测定血流动力学指标,同时用放免法测定其血浆CGRP、ET-1水平。结果表明,肺心病急性发作期CGRP、ET-1及PAPM、PVR均显著高于缓解期和对照组(p<0,01)。缓解期与对照组比较无明显变化(p>0.05);吸30％氧60分钟,CGRP上升而ET-1下降,并与PAPM,paO_2存在明显相关性。由此推测ET-1水平的升高和CGRP水平的降低可能是肺动脉压力升高的重要原因。因此,积极改善缺氧,降低血浆ET-1水平,提高CGRP水平对防治肺心病肺动脉高压有重要意义。     

Exhaled nitric oxide during normoxic and hypoxic exercise in endurance athletes

Aim: Endogenous nitric oxide (NO) through its relaxing effect on smooth muscle cells may be involved in pulmonary gas exchange as well as in the modulation of the hypoxic pulmonary vasoconstriction. As athletes with exercise-induced hypoxaemia (EIH) present pulmonary gas exchange abnormalities in normoxia that could be even greater in hypoxia, we hypothesized that pulmonary NO may be lower in such athletes with EIH. METHODS: Eleven athletes with EIH [decrease in arterial oxygen blood partial pressure (PaO2) > 12 mmHg] and 9 without EIH (NEIH) exercised at 40%, 60% (10 min) and 90% (5 min) of normoxic maximal power output (Pmax) in normoxia, and at 40% and 60% (10 min) of Pmax in hypoxia (FiO2 = 15%). Exhaled NO concentration during a constant flow exhalation (FENO(0.170)) and arterialized blood gases were measured at every power output. RESULTS: FENO(0.170) decreased from rest to exercise both in normoxia (-27.8 +/- 22.8% at 90% Pmax, P < 0.001) and hypoxia (-23.8 +/- 17.5% at 60% Pmax, P < 0.001). At 90% Pmax in normoxia, EIH athletes showed lower PaO2 (76.7 +/- 5.4 vs. 82.8 +/- 4.4 mmHg, P = 0.013) and greater FENO(0.170) decrement (-37.0 +/- 24.7% vs. -16.6 +/- 14.6%, P = 0.042) than NEIH athletes. During hypoxic exercise, P(a)O(2) and FENO(0.170) decreases were similar in both groups (P > 0.05). CONCLUSION: The present study shows lower pulmonary NO in athletes with gas exchange abnormalities during intense exercise in normoxia, while EIH and NEIH athletes have similar decreases in blood gases and pulmonary NO during hypoxic exercise. Decreased pulmonary NO in such conditions may contribute to ventilation-perfusion inequality and/or increase pulmonary vascular tone in athletes.     

Endothelin-1 in idiopathic pulmonary fibrosis.

AIMS--To evaluate whether endothelin-1 is involved in the pathology of idiopathic pulmonary fibrosis (IPF). METHODS--Plasma endothelin-1 concentrations were evaluated in 37 patients with IPF and 27 normal controls by radioimmunoassay. In addition, expression of endothelin-1 in lung tissue was evaluated in biopsy specimens obtained from four patients with IPF. Three biopsy specimens of normal lung were used as controls. Endothelin-1 immunoreactivity was detected using immunohistochemistry. RESULTS--Elevated endothelin-1 plasma concentrations were found in patients with IPF compared with controls and a positive correlation was found with duration of disease. No significant difference was observed between treated and untreated patients with IPF. Increased endothelin-1 immunoreactivity was found in lungs of three of four patients with IPF. Endothelin-1 positive consisted mainly of small vessel endothelial cells. Some scattered macrophages were also positive. CONCLUSIONS--Elevated plasma concentrations and expression of endothelin-1 in lung tissue are suggestive of increased production of endothelin-1 in at least a proportion of patients with IPF. Consequently, endothelin-1 activity could play a role in the fibrogenic process of the disease.     

缺氧大鼠出、入肺血、肺组织及心室肌降钙素基因相关肽和内皮素-1含量的变化

目的和方法:采用放免法观察常压间断缺氧大鼠出、入肺血和肺及心室肌组织匀浆中降钙素基因相关肽(CGRP)和内皮素-1(ET-1)的含量变化,并分析其与缺氧性肺动脉高压(HPH)和右心肥大间的相关关系。结果:正常大鼠入肺血CGRP含量显著高于出肺血,而ET-1含量和ET-1/CGRP比值则显著低于出肺血(P<0.01);随缺氧时间的延长,缺氧大鼠出肺血CGRP含量显著升高(P<0.05),与其肺动脉平均压(mPAP)呈正相关,而ET-1/CGRP比值则明显降低(P<0.05),与其mPAP呈负相关(r=-0.896,P<0.05);与对照组比较,缺氧大鼠入肺血及肺组织匀浆中CGRP和ET-1的含量及ET-1/CGRP比值均呈现先升高后降低趋势,至缺氧21d时入肺血的3项指标均接近正常水平;缺氧21d大鼠出肺血CGRP含量显著高于其入肺血(P<0.05)。结论:结果提示肺内CGRP和ET水平的失调在慢性HPH和右心肥大发生机制中起重要的作用。     

Pulmonary gas exchange does not worsen during repeat exercise in women

The purposes were to determine (1) if repeat exercise worsens pulmonary gas exchange in women, and, (2) if the level of pulmonary edema obtained in these same women is related to the gas exchange impairment during exercise. Fourteen women (27 +/- 4 yrs; maximal oxygen uptake = 3.12 +/- 0.42 L/min) with minimal arterial PO2 (PaO2) ranging from 76 to 104 mmHg with a maximal alveolar-arterial PO2 difference (AaDO2) ranging from 7 to 35 mmHg performed three bouts of near-maximal exercise on a cycle ergometer (236 +/- 27 W) for 5 min each with 10 min of rest between sets. Cardiorespiratory parameters and oxygenation were measured at rest, throughout exercise and recovery. Chest radiographs were obtained before and 30 min after the interval training session (see Respir Physiol Neurobiol, 153 (2006) 181-190). Repeat exercise did not affect pulmonary gas exchange between sets 1 and 3 (change in PaO2 = 3 +/- 2 mmHg; change in AaDO2 = 1 +/- 2 mmHg P > 0.05). Arterial PCO2 decreased by 4 +/- 2 mmHg (P < 0.05) between sets 1 and 2, which did not reduce further in set 3. The level of PaO2 or AaDO2 was not related to the change in edema score or the post-exercise edema score (P > 0.05). In conclusion, pulmonary gas exchange is not worsened in women during interval training despite the mild edema triggered by exercise.     

慢性肺心病患者血浆脑钠素前体水平及其意义

目的 :选择慢性阻塞性肺疾患和慢性肺心病病人 ,探讨脑钠素前体 (proBNP1 -76)血浆水平与慢性肺心病之间的关系及其意义。方法 :放射免疫分析检测血浆 proBNP1 -76含量 (ng/L)。 结果 :慢性阻塞性肺疾患组的 proBNP1 -76浓度较正常对照组升高 (p <0 0 5 ) ,右下肺动脉横径、右室流出道内径较正常对照组显著增大 (p <0 0 0 1 ) ,右室前壁厚度与proBNP1 -76浓度存在正相关 (r =0 5 4 1 ,p <0 0 1 ) ;慢性肺心病组的proB NP1 -76浓度、右下肺动脉横径、右室流出道内径、右室前壁厚度较正常对照组和慢性阻塞性肺疾患组均显著升高 (p <0 0 0 1 ) ,右室流出道内径与 proBNP1 -76浓度水平存在正相关 (r =0 4 77,p <0 0 5 )。 结论 :测定血浆proBNP1 -76水平对于监测慢性肺心病的发生可以起到一个早期标志物的作用 ,对于临床早期诊断和预防慢性肺心病提供一个有意义的参考指标     

Effect of procaterol on arterial blood gas in asthmatic children

We determined changes in arterial blood gas after the inhalation of procaterol, a highly beta 2-selective and long-acting adrenergic agonist, in 11 asthmatic children. Seven of the patients, with a maximum fall of 14 mmHg (63.6%), showed a decrease in PaO2 (mean +/- SD = -7.1 +/- 4.0 mmHg) and had poorer pulmonary function with a lower initial PaO2 than four subjects who had an increase in PaO2 after inhalation. There was a statistically significant correlation between values of the PaO2 before and after inhalation (P less than .05).     

Actively circulating blood volume in endotoxin shock measured by indicator dilution.

To estimate the size of the actively circulating blood volume of splenectomized dogs during control conditions and after endotoxin infusion, the pattern of concentration changes of 51Cr-labeled erythrocytes and 125I-labeled albumin was monitored. A dual exponential equation was fitted to the data. The total red blood cell and albumin volumes of distribution were determined from the slow exponential disappearance curves. The active red blood cell and albumin volumes were 89.8 +/- 5.3% and 92.0 +/- 2.0% of the total volumes, respectively. After endotoxin shock (mean arterial blood pressure 49.1 +/- 17.8 mmHg) the active volumes fell to only 60.0 +/- 10.3% and 56.2 +/- 20.0% of the total volumes, respectively. The fast-mixing time constants were similar (3.1 +/- 1.4 min and 2.5 +/- 2.7 min, respectively) and did not change significantly during the endotoxin shock, indicating that the albumin tag mixed into its larger volume of distribution as rapidly as the cells mixed into their indicated volume. We conclude that 1) an active blood volume can be distinguished, 2) it decreases for both red blood cells and albumin in endotoxin shock, and 3) a major part of the "extravascular plasma volume," as estimated by albumin dilution, is in the actively circulating circulation.     

肺出血新生儿血中一氧化氮和内皮素-1浓度及血管紧张素转换酶活性变化及意义

目的探讨肺出血新生儿血浆一氧化氮(NO)和内皮素-1及血管紧张素转换酶(ACE)与疾病预后的关系。方法用硝酸还原酶法、放免法及比色法分别测定20例肺出血新生儿极期及恢复期血浆NO、ET-1及ACE水平,并与15例同胎龄正常新生儿比较。结果肺出血组血浆NO浓度明显低于对照组(P<0.05),ET-1浓度明显升高(P<0.01),死亡组ET-1升高尤其显著。肺出血组血NO与ET-1呈显著的负相关,r=-0.79(P<0.01)。肺出血极期血清ACE活性明显高于对照组(P<0.05),死亡组ACE活性最高,恢复期ACE活性接近对照组。结论血管内皮源性因子参与新生儿肺出血的发生,且与病情相关。     

Improvement of gas exchange during inhibition of hypoxic pulmonary vasoconstriction by nitrendipine in piglets

To determine how nitrendipine (N), a calcium antagonist, interferes with haemodynamics and gas exchange during hypoxia, we studied 12 piglets (4-6 weeks, 4.3-9.0 kg) anaesthetized with pentobarbital (20 mg.kg-1 i.p.). Haemodynamics, blood gases and multiple inert gas elimination were measured at the end of three consecutive 30 min periods of spontaneous breathing: room air (RA), 11-12% FIO2 (H) and 11-12% FIO2 with a randomly selected infusion of N (3 micrograms.kg-1.min-1) (HN) or the carrier solution (HP) (6 animals in each group). Pulmonary vascular resistance (Rpv) doubled from 8.7 +/- 2.8 mmHg.min-1.1-1 in RA to 19.5 +/- 10.0 (mean +/- SD) in H while PaO2 fell from 83 +/- 8.3 mmHg to 28.7 +/- 5.2. With N, Rpv fell back to room air value: 8.7 +/- 2.0 (p less than 0.02; comparison H and HN), while PaO2 rose from 29.3 +/- 6.3 mmHg in H to 46.1 +/- 6.1 HN (p less than 0.001) and PaCO2 fell from 33.8 +/- 10 to 23.9 +/- 3.7 mmHg. There was a small non-significant rise in VE. Haemodynamics and blood gases of the placebo group were not statistically different in H and HP. No extrapulmonary shunting was evidenced during any experimental period. The perfusion to lung zones with VA/Q lower than 0.005 rose from 1.1 +/- 2.1% in RA to 8.9 +/- 5.7% in H, but no further increase was obtained with N: 5.1 +/- 2.5%. Overall VA/Q matching did not deteriorate with N during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

慢性阻塞性肺疾病合并慢性缺氧患者肺动脉平滑肌细胞电压门控钾通道亚型基因表达的变化

目的：探讨人肺动脉平滑肌细胞（PASMCs）的几种Kv通道亚型：Kv1.2、 Kv1.3、Kv1.5、Kv2.1、Kv3.1等，在COPD合并慢性缺氧时基因表达的变化。旨在探索预防人类肺源性心脏病的发生和找到新的防治方法提供试验依据。 方法： 从手术室切取人正常肺组织、单纯COPD患者和COPD合并慢性缺氧患者肺组织，将标本分为：①正常对照的PASMCs、单纯COPD和COPD合并慢性缺氧患者的PASMCs；②正常对照的PASMCs和经过慢性缺氧培养的PASMCs。利用半定量RT-PCR技术，分析Kv1.2、Kv1.3、Kv1.5、Kv2.1、Kv3.1等的基因表达。 结果： ①Kv1.2、Kv1.3、Kv1.5、Kv2.1、Kv3.1等基因在正常PASMCs和单纯COPD患者PASMCs中均有表达，而且两者无显著差异；②Kv1.2、Kv1.5、Kv2.1在患者在体慢性缺氧和离体慢性缺氧时的表达均明显降低（P<0.05）；Kv1.3在患者在体慢性缺氧时表达明显降低（P<0.05），而离体慢性缺氧时无显著变化（P>0.05）；Kv3.1在患者在体慢性缺氧和离体慢性缺氧时的表达均无显著变化（P>0.05）；③Kv1.2、Kv1.5、Kv2.1、Kv3.1等基因在单纯COPD时表达显著上调（P<0.05）。 结论： 在慢性缺氧情况下，Kv1.2、Kv1.3、Kv1.5、Kv2.1 4种亚型基因表达明显下降，提示可能在促进人肺动脉高压的形成和发展中起重要作用。而慢性缺氧对Kv3.1基因表达无显著影响，提示它们可能对缺氧不敏感，在人肺动脉高压发生中处于次要地位。至于在单纯COPD时几种亚型的表达上调，原因不清楚，需进一步研究证实。     

Excessive exercise ventilation in moderate left heart dysfunction. Influence of postural changes in central haemodynamics and blood gases.

To evaluate the relative importance of pulmonary congestion and peripheral hypoxia as causes for the excessive exercise ventilation in left heart dysfunction, seven patients with excessive ventilation and distinct left heart dysfunction during moderate exercise (LHD), and seven control patients with essentially normal exertional functions (CTR), had ventilation, central haemodynamics, arterial and mixed venous blood gases examined at rest and exercise, 32 W (25-40) in the LHD group and 44 W (33-49) in the CTR group, in lying and sitting positions. Change from lying to sitting exercise, led to fall in pulmonary artery wedge pressure (PAWP) from 31.0 +/- 5.5 to 8.8 +/- 5.0 mmHg in the LHD group, compared with from 13.7 +/- 1.0 to 2.1 +/- 2.4 mm Hg in the controls, while ventilation/O2 intake ratio (V/VO2) and physiological dead space/tidal volume ratio (VD/VT) showed a tendency to rise, from 36.3 +/- 8.8 to 39.2 +/- 7.4, and from 0.35 +/- 0.11 to 0.39 +/- 0.09, respectively, in the LHD group, and from 27.5 +/- 3.1 to 28.7 +/- 5.3, and from 0.19 +/- 0.09 to 0.21 +/- 0.12 in the controls. Mixed venous O2 tension (PvO2) showed a marked decline from 3.60 +/- 0.33 to 3.26 +/- 0.36 kPa in the LHD group, as compared with from 3.94 +/- 0.28 to 3.71 +/- 0.29 kPa in the controls, while the calculated physiologic shunt (Qs/Qt) suggested improved alveolo-arterial gas exchange. The data fit in with recent studies ascribing the excessive exercise ventilation to a combination of signals from hypoxia-induced changes, particularly in the exercising muscles, and augmented ergoreflex and central and peripheral chemoreceptor activity, partly to changes in the integrated control of ventilation and circulation, not to mechanisms related to pulmonary congestion.