Peripheral chemoreceptor insensitivity in chronic severe anaemia

Ventilatory response to central and peripheral chemoreceptor stimulation by carbon dioxide was assessed in 15 severely and chronically anaemic subjects before and after the correction of anaemia. Whereas the central CO2 responsiveness was found to be normal in the anaemic state, the peripheral response to CO2 was remarkably depressed. This blunted peripheral response to CO2 was restored to normal with the correction of anaemia.     

Pathogenesis of oedema in chronic severe anaemia: studies of body water and sodium, renal function, haemodynamic variables, and plasma hormones.

BACKGROUND--Patients with chronic severe anaemia often retain salt and water. Fluid retention in these patients is not caused by heart failure and the exact mechanisms remain unclear. This study was designed to examine some of the possible mechanisms. METHODS AND RESULTS--Haemodynamic variables, body fluid compartments, renal function, and plasma hormones were measured in four patients with oedema caused by chronic severe anaemia (mean (SE) haematocrit 13 (1.7)) who had never received any treatment. Cardiac output was increased (6.1 (0.6) l/min/m2) and right atrial (7.8 (1) mm Hg), mean pulmonary arterial (20.5 (2.0) mm Hg), and mean pulmonary arterial wedge (13 (2.7) mm Hg) pressures were slightly increased. The mean systemic arterial pressure (81 (1.3) mm Hg) and systemic vascular resistance (12.3 (1.1) mm Hg x min x m2/l were low. There were significant increases in total body water (+14%), extracellular volume (+32%), plasma volume (+70%), and total body exchangeable sodium (+30%). Renal blood flow was moderately decreased (-46%) and the glomerular filtration rate was slightly reduced (-24%). There were significant increases in plasma noradrenaline (2.1-fold), renin activity (15-fold), aldosterone (3.2-fold), growth hormone (6.3-fold), and atrial natriuretic peptide (12-fold). CONCLUSION--In patients with oedema caused by chronic severe anaemia there is retention of salt and water, reduction of renal blood flow and glomerular filtration rate, and neurohormonal activation similar to that seen in patients with oedema caused by myocardial disease. However, unlike patients with myocardial disease, patients with anaemia have a high cardiac output and a low systemic vascular resistance and blood pressure. It is suggested that the low concentration of haemoglobin in patients with anaemia causes a reduced inhibition of basal endothelium-derived relaxing factor activity and leads to generalised vasodilatation. The consequent low blood pressure may be the stimulus for neurohormonal activation and salt and water retention.     

Haemodynamic changes with blood transfusion in chronic severe anaemia.

Circulatory behavior in chronic, severely anaemic patients on volume loading is not precisely known. Twenty young male subjets with hook-worm anaemia, (Hb 2 to 5 gm %), without any complications were transfused with 300 or 600 ml of whole blood at 3 6 or ml/mt. Haemodynamic study was done before and immediately after. Blood volume was low, intracardiac pressures normal or minimally abnormal, cardiac output raised and vascular resistances low. After transfusion, there was a small but significant rise in arterial and mixed venous oxygen content, oxygen transport, heart rate, pulmonary wedge and mean polmonary arterial pressures and fall in % coeffcient of oxygen utilisation. Central venous pressures rose only with bigger transfusion. Change in cardiac output was related to the output before transfusion. Three subjects with cardiac index above 7 1/min had a fall and 6 of 7 below 7 1/min. a rise. Fall is perhaps related to the rise in blood oxygen content. It is argued that it is not an index of cardiac failure, as is often believed. Changes in pulmonary pressures are more sensitive than central venous pressure. One of our subjects died suddenly a day after uneventful study. Existing knowledge of haemodynamic status in severe anaemia and the change on transfusion helps little in explaining such deaths and others due to pulmonary oedema during or shortly after small to large transfusions. Further work in this field aiming to study changes in myocardial function and dynamic pressure volume relation in the vascular system is required.     

Additive haemodynamic effects of piroximone and prostacyclin in severe chronic heart failure

This study was undertaken to assess the haemodynamic effectsof the combined infusion of prostacyclin and piroximone, a phosphodiesteraseinhibitor, in 18 patients with severe congestive heart failure.Right heart catheterization was performed with a Swan-Ganz thermodilutioncatheter and arterial blood pressure was monitored using a radialline. After baseline haemodynamic measurements, prostacyclinwas administered in all patients at the incremental infusionrate of 2, 4, 6 and 8 and 10 ng. kg^–1. min^–1 during15min each. After recovery of baseline haemodynamics, patientswere randomly assigned to the piroximone infusion rate of 5or 10µg. kg^–1. min^–1 or placebo. After 24h piroximone or placebo infusion, the same prostacyclin protocolwas applied. Prostacyclin infusion added to piroximone resultedin a significant improvement in haemodynamics, as compared tothe group receiving prostacyclin added to placebo. As comparedto the curve observed with the placebo infusion, 10 ng. kg^–1.min^–1 prostacyclin infusion resulted in a further increasein cardiac index, by 41 and 38% (P<0·01) at the piroximone-infusionrates of 5 and 10 ng. kg^–1. min^–1, respectively,whereas systemic vascular resistance decreased by 25 and 21%,respectively (P<0·01). Additionally, a further decreasein pulmonary capillary wedge pressure by 13 and 11% (P<0·05)and in pulmonary vascular resistance by 21 and 19% (P<0·05)was observed at the piroximone-infusion rates of 5 and 10µig.Kg^–1. min^–1, respectively. Consequently, strokework index increased significantly, as compared to the groupreceiving prostacyclin added to placebo. This haemodynamic improvementoccurred without significant changes in heart rate and meanarterial pressure. Thus, this study shows that in patients withsevere congestive heart failure, short-term infusion of prostacyclinis safe and has additive haemodynamic effects on phosphodiesteraseinhibitors.     

Effect of treatment on pulmonary functions in chronic severe anaemia.

Pulmonary functions were measured in 15 patients with severe chronic anaemia (haemoglobin level < 5 g/dl). The measurements were repeated after correction of anaemia (Hb > 10 g/dl). Twenty age and sex matched, asymptomatic, non-smoker subjects served as controls. There was 80-100% improvement in various lung functions after correction of anaemia. Effort dependent parameters, viz FVC, ERV, IC, MVV were low in anaemic patients which improved with the rise of haemoglobin. The TLCO, DM, VC, KCO were not significantly influenced during anaemic state. FEV1, PEFR, RV/TLC were essentially normal. We conclude that the observed changes produced in lung functions during anaemic state are fully reversible after its correction.     

The anaemia of chronic renal failure in sheep: studies in vitro

S ummary . The presence of inhibitors which accumulate during uraemia has been postulated as a significant factor in the development of anaemia in chronic renal failure (CRF). To determine whether factors in uraemic serum depress erythropoiesis, samples were obtained from sheep prior to and after surgical induction of CRF. The sera were tested in vitro for their effect on erythroid colony growth. The sheep sera were substituted for fetal calf serum (30% concentration) in cultures of serotype-matched or autologous sheep marrow cells at optimal doses of erythropoietin (Ep). Forty-two paired sera from five animals were tested against normal (22) and uraemic marrow (20). In 7/42 random pairs, erythroid colony growth was decreased by 20% in the presence of uraemic serum when compared to a normal sample from the same animal. In the remainder of the cultures, uraemic sera stimulated or supported erythroid colony growth as well as normal sera. When the results were analysed individually, serum from only one of five animals showed minimal (10%) in vitro inhibition of erythroid colony growth. This study, performed in a prospective manner utilizing compatible target cells, disputes the hypothesis that uraemic toxins significantly inhibit in vitro erythropoiesis. These data correlate with the in vivo response to Ep in this sheep model, and suggest Ep would be effective in treating the anaemia of CRF.     

Renal haemodynamic studies in obesity hypertension

Previous investigations have reported the systemic haemodynamic characteristics of obese hypertensive patients; however, their renal haemodynamics have not been explored. This report compares the renal and systemic haemodynamic findings in obese and lean normotensive and hypertensive patients. Our results demonstrate that both normotensive and hypertensive obese subjects had an increased renal blood flow, total blood volume and cardiac output, with decreased total peripheral and renal vascular resistances in comparison with lean normotensive and hypertensive patients. Body weight correlated directly and significantly with total blood volume, cardiac output and renal blood flow but indirectly with total peripheral resistance. Therefore, the elevated cardiac output and volume expansion found in obese patients were associated with increased renal perfusion; this increased renal blood flow accounts for the reduced renal vascular resistance in patients with obesity hypertension. Thus, we suggest that this effect of volume expansion in obesity could counteract the opposing effect of active vasoconstriction produced by the hypertensive disease and may account for the difference in prognosis of obese and lean hypertensive patients.     

Systolic time intervals in chronic severe anaemia and effect of diuretic and digitalis.

Systolic time intervals were measured from simultaneous high speed recordings of the electrocardiogram, phonocardiogram, and carotid artery pulse in 15 men with chronic severe anaemia not in heart failure and with a normal heart size, and in 15 normal men. Heart rates, electromechanical systole (QS2), pre-ejection period index (PEPI), left ventricular ejection time index (LVETI), and the ratio of pre-ejection period to left ventricular ejection time (PEP/LVET) did not differ significantly in the two groups. After the intravenous administration of frusemide in 10 of the anaemic patients, the pre-ejection period index was prolonged, the PEP/LVET ratio increased, heart rate increased, and the left ventricular ejection time index shortened. Intravenous digoxin did not alter the QS2 interval and heart rate significantly in the anaemic subjects. Left ventricular function in chronic severe anaemia as measured by systolic time intervals does not differ from that of normal controls. The effect of frusemide on the systolic time intervals is explained as an effect of the fall in preload, bringing cardiac function further down on the ascending limb of the Frank-Starling curve. Other related studies are discussed.     

Pulmonary haemodynamic changes in patients with severe COPD

Worsening gas exchange during exercise and during exacerbations of COPD contributes to systemic hypoxaemia and reduces quality of life. However, pulmonary haemodynamic changes under such conditions are not well understood. Right heart catheterization was performed in six patients with severe COPD (%FEV(1) < 50%) during rest, exercise and during an exacerbation. Pulmonary artery pressure (Ppa) was slightly elevated at rest. The Ppa, as well as pulmonary artery wedge pressure (Pawp) and cardiac index were significantly increased during bicycle ergometer exercise. In contrast, pulmonary vascular resistance increased significantly during an exacerbation accompanied by a slightly increased Ppa. Supplemental oxygen resulted in significant decreases in Ppa and Pawp during exercise and Ppa during exacerbations. In patients with COPD, haemodynamic changes in the pulmonary circulation may differ during exercise and with exacerbations. Supplementary oxygen is beneficial and associated with reductions in pulmonary arterial pressures.