Changes in atrial natriuretic peptide concentrations during intravenous saline infusion in hypoxic cor pulmonale.

BACKGROUND: The pathogenesis of oedema in hypoxic cor pulmonale is poorly understood. One possibility is a failure of atrial natriuretic peptide release, leading to salt and water retention. This hypothesis was tested by observing the response to an intravenous saline challenge in patients with and without cor pulmonale. METHODS: Plasma atrial natriuretic peptide concentrations were measured before and for three hours after an intravenous saline load (0.1 ml 2.7% saline/kg/min for 60 minutes) in 20 patients with chronic obstructive airways disease. Ten patients with cor pulmonale, as judged clinically by the presence of peripheral oedema with a previously documented increase in the jugular venous pressure or pleural effusions during an acute exacerbation of airway obstruction (mean (SE) age 67 (3) years, FEV1 0.73 (0.08) 1, arterial oxygen tension (PaO2) 6.4 (0.4) kPa, and arterial carbon dioxide tension (PaCO2) 6.7 (0.3) kPa), were compared with 10 patients with hypoxic chronic obstructive airways disease who had never had oedema (mean age 63 (1) years, FEV1 1.07 (0.09) 1, PaO2 8.6 (0.4) kPa, and PaCO2 5.3 (0.2) kPa). All patients were studied fasting and after diuretics had been stopped for three days. No supplemental oxygen was given. RESULTS: The mean four hourly urine sodium excretion was less in the patients who had oedema (27 (4.6) mmol, 13% of the intravenous load) than in those without oedema (82 (15.5) mmol, 43% of the load). Initial mean plasma atrial natriuretic peptide values were significantly higher in the patients with cor pulmonale (19.1 (1.6) compared with 10.2 (0.7) pmol/l) and the mean peak rise in atrial natriuretic peptide after the intravenous saline load had been given was 13 (8.0) pmol/l in the patients with cor pulmonale and 5.5 (2.3) pmol/l in the controls. There were no significant differences in plasma and urinary osmolality, blood pressure, or creatinine clearance between the groups. CONCLUSION: Patients with chronic obstructive airways disease and cor pulmonale have an impaired ability to excrete a hypertonic intravenous saline load despite a normal physiological release of plasma atrial natriuretic peptide.     

Endocrine and metabolic studies in unstable cor pulmonale

Serum testosterone, follicle-stimulating hormone, luteinising hormone, and dihydro-epiandrosterone concentrations rose significantly in seven men studied during recovery from a severe exacerbation of chronic obstructive airways disease. Urinary 17-ketosteroids also rose significantly though serum androstenedione and prolactin concentrations did not. Our findings suggest that hypoxia in this condition suppresses the hypothalamus or pituitary or both and that such suppression is reversible. In view of previous reports of increase in total body potassium and intracellular water with recovery from cor pulmonale, we also carried out metabolic studies on our patients. Low body potassium concentrations in cor pulmonale fell further with recovery, in part reflecting a fall in lean body tissue. Intracellular water appeared to increase on recovery despite a fall in other lean body mass indices (the simplest and most reliable being skinfold thickness). We suspect this result to be spurious and due to problems with equilibration in isotope dilution. Alternatively it may reflect waterlogging of cells. A false figure for intracellular water could be responsible for an unexpectedly low estimated intracellular potassium concentration on recovery. Our results cast doubt on isotope dilution methods for measuring body water compartments in disease states likely to cause changes in cell permeability.     

Total body potassium in cor pulmonale.

Total body potassium was measured in 12 patients with cor pulmonale, by determination of potassium-40, a naturally occurring radioisotope. In all subjects the observed value of total body potassium showed no significant depletion when compared with that predicted from height and age. All previous studies in similar groups of patients have been confined to the estimation of exchangeable potassium by the technique of isotope dilution. Results using the latter technique have shown gross potassium depletion. It is suggested that the apparent disparity between total body potassium and exchangeable potassium could be explained by the requirement for a longer equilibration period when using isotope dilution techniques in patients who are in chronic hypoxaemic state.     

Short term effect of oxygen on renal haemodynamics in patients with hypoxaemic chronic obstructive airways disease.

BACKGROUND: Oxygen therapy is effective in the prevention and treatment of oedematous exacerbations of cor pulmonale. As renal blood flow is reduced in cor pulmonale a study was designed to investigate whether one of the beneficial effects of oxygen was to increase renal blood flow. The effect of oxygen therapy on renal haemodynamics measured noninvasively was examined in patients with chronic obstructive airways disease and previous episodes of oedema. METHODS: Renal blood flow waveforms were recorded in a single vessel by colour flow Doppler ultrasound in nine hypoxaemic patients (PaO2) (arterial oxygen tension < 8 kPa while they were breathing air) with chronic obstructive airways disease and previous oedema and eight age matched normoxaemic volunteers (arterial oxygen saturation (SaO2) 97% or more when breathing air) while they were breathing air and oxygen. SaO2 and transcutaneous PaO2 (TcPO2) and PaCO2 (TcPCO2) were monitored. Five renal velocity profile recordings were made from the same segmental vessel with the patient breathing room air for one hour followed by oxygen titrated to achieve an oxygen saturation of 95% or more without a rise in TcPCO2 for 15 minutes. Control subjects breathed 35% oxygen. RESULTS: No significant change in the pulsatility index (a measure of distal vascular resistance) or mean height of the waveform (Tamx, a measure of renal blood flow) occurred in the control subjects while they were breathing air or oxygen. The pulsatility index of the patients with chronic obstructive airways disease was significantly greater than that in the control subjects breathing air (1.44 (SD 0.28) v 1.03 (0.14). Breathing oxygen was associated with an increase in TcPO2 in the patients (from 6.9 (1.9) to 11.5 (0.7) kPa), a fall in pulsatility index (from 1.44 (0.28) to 1.26 (0.14) and an increase in Tamx (from 0.187 (0.055) to 0.234 (0.087) m/s). CONCLUSIONS: The results suggest that renal vascular resistance is increased in patients with chronic obstructive airways disease and hypoxaemia and that short term oxygen therapy reduces renal vascular resistance and increases blood flow. Some of the benefits of oxygen therapy in cor pulmonale may be due to improvements in renal haemodynamics.     

Postmortem assessment of chronic airways obstruction by tantalum bronchography.

Tantalum bronchography was performed on 22 left lungs obtained at necropsy. Seven were from patients dying in cor pulmonale as a result of chronic airways obstruction and 15 were from unselected necropsies. Of the latter group, nine had no evidence of respiratory disease and six had pathological changes of emphysema and bronchial mucous gland enlargement when the lungs were examined following formalin fixation. A range of changes in the bronchographic appearances from the normal to the groosly abnormal is illustrated. The main changes in severely diseases lungs were: irregularity of the bronchial walls, failure of the walls to taper towards the periphery, areas of narrowing and dilatation, and 'pooling' of tantalum at the ends of airways. A count was made of the numbers of small airway branches in the most distal 4 cm of the lung and also of the number of airways of less than 1 mm in diameter. Patients dying in cor pulmonale had a significantly reduced total number of patent small airways in the area measured and also fewer patent airways of less than 1 mm diameter compared to both the other groups. Histological study of four of the lungs in greater detail revealed that the reduction in small airways filling was the result of a combination of obliteration and obstruction of the lumen by pus. Tantalum bronchography provides a good indication of the state of the bronchial tree at the time of death, and the changes seen are the result of both acute and chronic disease processes.     

Diet, absorption, and hormone studies in relation to body weight in obstructive airways disease.

Sixteen male patients with stable chronic obstructive airways disease were separated into two groups of eight according to arterial carbon dioxide tensions. Hypercapnia was associated with lower arterial oxygen tensions, higher red cell volume, and increased weight, while normocapnic subjects were decidedly thin. The considerable difference in body weight between the two groups could not be explained by variation in caloric intake, and malabsorption was excluded as a cause of weight loss in the underweight subjects. Serum tri-iodothyronine, thyroxine, cortisol, and oestradiol concentrations were similar and normal in each group, but both groups had significantly low testosterone values as compared with controls, values in the hypercapnic being appreciably lower than in the normocapnic group. The adrenal androgen dehydroepiandrosterone was significantly high in the normocapnic group and low in the hypercapnic group compared with controls. Serum pituitary luteinising and follicle stimulating hormones were normal, but three hypercapnic individuals had high serum prolactin values. Early morning urinary aldosterone values were significantly higher in the hypercapnic than in the normocapnic group. Such hormone comparisons have not previously been made in subjects with chronic obstructive airways disease grouped according to arterial blood gas values, and it is concluded that major alterations in adrenal and testicular function may occur, possibly due to pituitary suppression from hypoxia. Such hormonal changes might in part account for the contrasting alterations in body habitus found in this condition.     

Assessment by radionuclide angiography of right and left ventricular function in chronic bronchitis and emphysema

Non-invasive measurements of right and left ventricular ejection fraction (RVEF, LVEF) by multiple-gated equilibrium radionuclide ventriculography were performed in 18 control subjects, 16 patients with angina pectoris, and 45 patients with hypoxic chronic bronchitis and emphysema. The mean RVEF in the control subjects was 0.62 +/- 0.09 (SD), which was not significantly different from the mean RVEF in the patients with angina (0.60 +/- 0.09), but was significantly higher (p less than 0.01) than the mean value in patients with chronic bronchitis and emphysema (0.45 +/- 0.11). LVEF was not significantly different in the groups studied. There was a significant correlation between LVEF and RVEF only in patients with chronic bronchitis and emphysema (p less than 0.001). Those patients with chronic bronchitis and emphysema who had clinical evidence of cor pulmonale at the time of the study had significantly lower values of RVEF and LVEF (p less than 0.001) than patients with no previous cor pulmonale or those who had had cor pulmonale in the past. There was a significant correlation between RVEF and arterial oxygen (p less than 0.01) and carbon dioxide tensions (p less than 0.05). Reduced RVEF in patients with chronic bronchitis and emphysema may be an early indicator of the development of cor pulmonale and may be useful as a non-invasive method of assessing the effects of therapeutic interventions.     

Twelve year clinical study of patients with hypoxic cor pulmonale given long term domiciliary oxygen therapy.

Patients presenting with chronic obstructive airways disease and hypoxic cor pulmonale were assessed during a period of clinical stability. Seventy two patients (53 male) with a mean age of 60 years were selected for long term oxygen therapy. Mean FEV1 was 0.78 l and forced vital capacity 1.9 l. The mean arterial oxygen tension (PaO2) was 6.1 kPa (46 mm Hg) and the mean arterial carbon dioxide tension (PCO2) 6.9 kPa (52 mm Hg). All patients had a PaO2 of less than 8.0 kPa (60 mm Hg) and 57 patients had a PCO2 of more than 6.0 kPa (45 mm Hg). Pulmonary haemodynamics were measured in 45 patients yielding the following mean values: pulmonary artery pressure 28.3 mm Hg; cardiac output 5.9 l min-1; total pulmonary vascular resistance 59.2 kPa l-1 S. Oxygen delivery systems, including 23 oxygen concentrators, were installed in the patients' homes. Flow rates were adjusted to raise PaO2 to more than 8.0 kPa (60 mm Hg) for at least 15 hours each day and close supervision was maintained. Overall five year survival was 62%, which is better than previously reported for this type of patient; but the 10 year survival was only 26% owing to an observed acceleration in death rate at about this time. Progressive disturbances of the pulmonary circulation were arrested. Mortality was associated with the severity of airflow obstruction, reflecting a continuing pathological process affecting the airways.     

Oral almitrine in treatment of acute respiratory failure and cor pulmonale in patients with an exacerbation of chronic obstructive airways disease.

The effects of oral almitrine bismesylate, a respiratory stimulant that acts on peripheral arterial chemoreceptors, was studied in patients with chronic obstructive airways disease and hypoxaemic cor pulmonale. Twenty three patients admitted to hospital with an acute exacerbation of ventilatory failure were randomised to receive either almitrine 100 mg twice a day reducing to 50 mg twice a day over 48 hours or placebo in addition to conventional treatment. On admission the mean (SE) values for blood gas tensions were PaO2 4.8 (0.3) and PaCO2 7.7 (0.3) kPa in the 12 patients who received almitrine and PaO2 4.9 (0.1) and PaCO2 7.6 (0.3) kPa in the 11 who received placebo. After three hours of oxygen therapy at 1 1/min there was a similar rise in PaO2 in both groups, 6.4 (0.2) kPa in those receiving almitrine and 6.6 (0.4) kPa in those receiving placebo. After 24 hours of oxygen therapy values of PaO2 were again similar at 6.3 (0.8) kPa and 6.7 (2.2) kPa respectively. Arterial blood gas tensions improved during the study in those who survived but no significant differences were apparent between the two groups. There were six deaths, five in the almitrine group and one in the placebo group. There were no differences between the groups in respiratory rate, results of spirometry, oxygen requirement, or degree of dyspnoea (on visual analogue scale). The results did not show any benefit from oral almitrine in patients with acute respiratory failure secondary to chronic obstructive airways disease. Plasma almitrine concentrations, however, were often below the optimum therapeutic range, suggesting impaired drug absorption.     

Prevalence of chronic bronchitis in a rural community of the Hill Region of Nepal.

A house to house survey of everyone aged 20 years and above living in a rural community in the Hill Region of Nepal, situated about 16 km outside Kathmandu city, was conducted to determine the prevalence of chronic bronchitis and cor pulmonale. Of the total eligible population, 2826 (95.5%) were interviewed. Chronic bronchitis was diagnosed according to the British Medical Research Council criteria, and emphysema and cor pulmonale according to the World Health Organisation expert committee criteria. The crude prevalence of chronic bronchitis was found to be 18.3%. The prevalence rate of chronic bronchitis was similar in men and women, whereas in most parts of the world much lower rates have been recorded in women. Study of a random sample of 85 individuals with chronic bronchitis showed that 57.4% had evidence of airways obstruction, whereas 15.8% of a representative sample (n = 111) of the surveyed population (excluding those with chronic bronchitis) showed evidence of airway obstruction. Of 516 subjects diagnosed as having chronic bronchitis, 382 were subsequently investigated in hospital, 134 having declined further investigation. The diagnosis was confirmed in most of the patients (93.2%) who were investigated. Other diseases played an insignificant part in the production of the observed high prevalence rates of chronic bronchitis. Of the 382 patients studied in hospital, 87 had emphysema and 42 had cor pulmonale, yielding overall prevalence rates for these two conditions of at least 3.1% and at least 1.5% respectively.     

Total body potassium, acid-base status and serum electrolytes in acute diarrhoeal disease.

Total body potassium (TBK), acid-base status and serum electrolyte concentrations were measured in 49 children suffering from acute diarrhoeal disease, on admission and after rehydration. The TBK was usually low and the lowest values were found in those with the lowest pH. There was no relationship between TBK and serum sodium or potassium concentrations. Hyponatraemia was common as would be expected in a series containing many underweight children.     

Does right ventricular function predict survival in patients with chronic obstructive lung disease?

Non-invasive measurements of the right ventricular ejection fraction by radionuclide ventriculography were made in 115 patients with chronic obstructive lung disease. Survival was assessed over a mean period of 918 days. The right ventricular ejection fraction was reasonably normal in most patients (mean 0.42, range 0.10-0.66) but was lower in those with peripheral oedema, indicating cor pulmonale (mean 0.31 (SD 0.07); p less than 0.0001). Right ventricular ejection fraction was related to survival, but the relationship was weak (p = 0.03) by comparison with the association between the arterial oxygen and carbon dioxide tensions and survival (both p less than 0.0001). It is concluded that, although right ventricular function is predictive of survival in patients with chronic obstructive lung disease, it is probably a reflection of severity of disease and does not directly affect the prognosis.     

Potassium retention in acute diarrhoeal disease.

Most children suffering from severe acute diarrhoeal disease had a low total body potassium (TBK) or admission to hospital. TBK fell even lower during the first 5 - 9 days in hospital, and returned to normal levels during the next 8 - 12 days. There was good correlation between potassium retention and stool weight. An increase in the potassium intake had little effect on the rate of potassium repletion.     

Total body and exchangeable potassium in chronic airways obstruction: a controversial area?

Potassium deficiency is an important complication in the treatment of heart disease. However, there is a serious dichotomy in the literature. Severe potassium depletion has been reported in this condition when exchangeable potassium was measured whereas normal levels or marginal depletion were found in measurements of total body potassium. To clarify this situation, simultaneous measurements of total body potassium by whole-body counting, and of exchangeable potassium by isotope dilution using 43K, were made in 10 male subjects with established airways obstruction. Sequential determinations showed that exchangeable potassium increased up to 68 hours after administration, and values obtained at only 24 hours would have been a substantial underestimate. In this group of subjects neither total body nor exchangeable potassium at 48 hours was significantly different from the expected normal value.     

Long-term changes in body composition after pancreaticoduodenectomy

Background: The Whipple's procedure (WP) is a major operation that adds a further demand on the body's nutritional reserves and therefore body composition after the effect of pancreatic cancer. The aim was to document changes in body composition changes that occur during the first six months after a WP for a pancreatic cancer malignancy. Methods: Twenty‐seven (14 males, 13 females) consecutive WP patients had body composition measured at baseline and then at 2, 5, 14 and 26 weeks after surgery. These included; anthropometric measure (weight, skin folds and arm muscle area (AMA)), total body measures of protein (TBP), potassium (TBK), water (TBW) and fat mass (FM). Changes were compared using repeated measures analysis of variance. Results: Hospital nutritional care maintained TBP and TBK but at 2 weeks there was a loss of FM (P= 0.037). The nadir of weight loss (P < 0.001) occurred at 5 weeks because of losses of protein (P= 0.007), fat (P < 0.001) and potassium (P= 0.045) but not water. Although weight and FM were still significantly less than baseline measures at 26 weeks weight, TBP, TBK and AMA were not significantly different to preoperative values. Conclusions: Although at 6 months, important measures of the metabolically functioning tissue, TBP and TBK, have returned to preoperative values significant losses occurred during the first 3 weeks after discharge from hospital and FM did not return to preoperative values. These results suggest the need to improve post‐discharge nutritional care.     

Total body potassium in Bartter's syndrome before and during treatment with enalapril

Total Body Potassium (TBK) was measured by whole body counting of 40K in 3 patients with Bartter's syndrome before, after 3 months and after 1 year of treatment with enalapril. In 2 patients TBK was found to be decreased before treatment, whereas TBK was within the normal range in the 3rd. During treatment serum potassium concentration and TBK increased in each subject and symptoms of fatigue and tetany disappeared. Enalapril is shown to be an effective treatment in Bartter's syndrome as it improves serum potassium, TBK and complaints.     

Bioelectrical impedance analysis in the measurement of the body composition of surgical patients.

The evaluation of nutritional status in surgical patients remains a difficult problem. Bioelectrical impedance analysis (BIA) is a new method of body composition analysis which is easily performed at the bedside. This study determined the accuracy of BIA in the measurement of total body water (TBW) and potassium (TBK) in a heterogeneous group of surgical patients. The resistance and reactance components of impedance were measured with a whole body impedance analyser. Tritiated water dilution and whole body monitoring were the reference methods for TBW and TBK analysis. With the BIA technique the coefficient of variation for the estimation of TBW was 8.1 per cent and for TBK was 6.4 per cent. Allowing for the errors of the reference methods these results show that BIA is of limited value in the estimation of TBW but may provide a useful index of TBK.     

Screening older patients for obstructive airways disease in a semi-rural practice

BACKGROUND: Obstructive airways disease in older patients is reported to be not only common, but frequently overlooked and untreated by general practitioners. This study examines the value of screening elderly patients in a large semi-rural general practice for potentially treatable asthma and chronic obstructive pulmonary disease (COPD). METHODS: A random sample of 353 patients aged 60-75 years attended a nurse run screening clinic for pulmonary function testing, serial peak flow recording, and completion of a symptom questionnaire. Patients with a low forced expiratory volume in one second (below the fifth centile of their predicted value) or >15% mean diurnal variation in peak flow were referred to a doctor's clinic for further diagnostic assessment and/or to discuss possible treatment where appropriate. RESULTS: Fifty eight patients (16.4%) had obstructive airways disease, the prevalence of asthma being 6.5% and that of COPD 9.9%. Of these, 30 had no previous diagnosis of airways disease and were not on treatment; eight of them had significant airways reversibility and 10 were current smokers. No newly diagnosed patients had severe disease as measured by pulmonary function or quality of life assessment, and six patients accepted treatment. CONCLUSION: Few older patients benefited from a screening programme for obstructive airways disease in a semi-rural general practice.     

Total body potassium depletion and the need for preoperative nutritional support in Chrohn's disease.

Significant intracellular potassium depletion was documented in 57 patients with Crohn's disease by measurements of total body potassium, body water compartments, and red cell Na,K-ATPase units. Total body potassium deficits paralleled the activity of illness, but were not correlated to serum potassium levels. Treatment before surgery to improve individual body potassium content resulted in a reduced surgical mortality and complication rate compared with a retrospective series of 56 patients in whom pretreatment had simply been aimed at normalizing serum albumin and other standard serum parameters. In conclusion, preoperative nutritional support in Crohn's disease is recommended for patients with a total body potassium level less than 70% of normal. If whole body counting for direct measurement of total body potassium is not available, a Crohn's Disease Activity Index above 225 is proposed as the deciding level, and the parenteral administration of a standardized regimen consisting of 150 to 200 mval potassium plus 2500 to 3000 kcal daily for a two-week period is recommended.     

Body composition in the cirrhotic patient with ascites: assessment of total exchangeable sodium and potassium with simultaneous serum electrolyte determination

The precise mechanism of initiation and maintenance of the disturbed fluid and electrolyte balance in cirrhotic patients remains unclear. Measurement of total exchangeable potassium in 11 cirrhotic patients with ascites revealed marked depletion compared to 9 healthy volunteers. Total exchangeable potassium was 50.8 +/- 5.1 m moles/L TBW in the patient group compared to 75.2 +/- 3.4 m moles/L TBW in the control group (P less than 0.01, Mann-Whitney U Test). Total body exchangeable sodium measured 80.1 +/- 3.7 m mole/L TBW in the cirrhotic group, which is not significantly elevated compared to the value in healthy volunteers of 74.1 +/- 1.9 m mole/L TBW. Serum sodium was low in four of the cirrhotic patients (129-133 mEq/L); exchangeable sodium was low in only one of these four (53.4 m mole/L TBW). Serum potassium was low in two of the cirrhotics (2.6-2.9 mEq/L); total body potassium was depressed in both of these patients (43.5-50.1 m mole/L TBW). An additional three patients had a low total body potassium (29.6-48.9 m mole/L TBW) with normal serum levels (4.0-4.2 mEq/L). There was no correlation between serum and total exchangeable electrolyte levels (Pearson's regression, r = 0.16 and 0.23). This work confirms that serum levels are not reliable indicators of true body sodium and potassium stores. The decreased total exchangeable potassium appears to be related to loss of body cell mass rather than intracellular potassium depletion.(ABSTRACT TRUNCATED AT 250 WORDS)