Diagnosis of pneumonia in mechanically ventilated patients: clinical judgement or bronchoscopy?
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Bronchoscopy↗
Biomedical subjects
C A Gaillard
Publications and source records attributed to C A Gaillard.
Membranous glomerulonephritis. Towards tailor-made treatment?
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Animals↗
Mechanism of decreased cardiac output during ANP infusion in conscious anephric dogs.
Atrial natriuretic peptide (ANP) may decrease cardiac output (CO) by lowering circulating blood volume (BV) or by altering the vasculature in a manner that would decrease venous return. The purpose of this study was to determine the role of decreased BV in mediating the decrease in CO during acute infusion of ANP. BV was measured by dilution of 51Cr-labeled red blood cells in seven trained conscious splenectomized dogs studied after unilateral (UNX) and total (TNX) nephrectomy. BV, hematocrit (Hct), CO, mean arterial pressure (MAP), and total peripheral resistance (TPR) were determined during a 90-min control period and 270 min of infusion of ANP (20 ng.kg-1.min-1 iv). In UNX dogs, ANP decreased BV from 60.9 +/- 1.4 to 58.6 +/- 1.4 ml/kg and increased Hct from 39.3 +/- 1.8% to 41.1 +/- 1.8% (P less than 0.05). MAP was not changed and CO fell to a low that was 86 +/- 2% of control (P less than 0.05) 240 min after starting ANP. TPR increased significantly during ANP infusion. All variables returned to control after ANP was stopped. In the same dogs studied 24 h after TNX, MAP averaged 111 +/- 5 mmHg during control and did not change during ANP infusion. CO fell to a low of 82 +/- 3% of control (P less than 0.05) after 120 min of infusion and remained reduced until after the ANP was stopped.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The diuretic effect of calcium entry blockade in normals and hypertensive patients.
Calcium entry blockers have been shown to exert hemodynamic and diuretic effects in the kidney. The diuretic effects can be demonstrated most clearly in the isolated perfused kidney, not influenced by compensatory mechanisms such as a lower blood pressure or changes of hormones. However, they can also be shown in vivo in humans. We studied the renal effects of calcium entry blockade after the first dosage and after continued oral dosages of 20 mg nicardipine tid in patients with essential hypertension and in normotensive controls. Renal function was determined during maximal free water clearance, allowing estimation of changes in "proximal" and "distal" tubular sodium reabsorption. Results showed a natriuretic effect. In the control subjects, clearance results were compatible with a decrease of proximal and distal tubular reabsorption, but in the hypertensive group natriuresis was mainly achieved by an increase of the glomerular filtration rate and a decrease of fractional distal reabsorption. In both groups the natriuresis occurred concomitantly with a lower blood pressure. The ratio plasma renin activity/plasma aldosterone concentration increased, although nicardipine did not inhibit the increase of plasma aldosterone during angiotensin II infusion. Pre-treatment with the calcium entry blocker nitrendipine enhanced the natriuretic effect of atrial natriuretic factor (ANF) in sodium replete normal volunteers. Facilitation of sodium excretion by human ANF may be an additional diuretic mechanism of calcium entry blockers.
Calcium Channel Blockers↗
The hemodynamic response to chronic hyperinsulinemia in conscious dogs.
This study describes the hemodynamic effects of chronic hyperinsulinemia in seven normal dogs. Insulin infused at 1 mU/kg/min together with glucose at 14 mg/kg/min for 7 days increased fasting plasma insulin concentration approximately six-fold. Plasma glucose concentration was unchanged on day 1 but was below control on day 6. Mean arterial pressure decreased from 81 +/- 4 mm Hg to 70 +/- 3 mm Hg, while cardiac output increased to 30 +/- 8% above control by day 7. Total peripheral resistance decreased to 69 +/- 5% of control. Urinary sodium excretion was significantly decreased and was accompanied by a 22% increase in extracellular fluid volume with no change in blood volume. All parameters returned to control levels during the recovery period. These data suggest that, in addition to promoting renal sodium retention, insulin may lower blood pressure and increase cardiac output through a peripheral vasodilatory effect.
Animals↗
Acute tumour lysis syndrome in a patient with acute lymphoblastic leukemia after a single dose of prednisone.
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Acute Disease↗
Chronic intrarenal hyperinsulinemia does not cause hypertension.
Hyperinsulinemia has been postulated to link obesity and hypertension via the antinatriuretic actions of insulin. The main goal of this study was to quantitate the importance of the direct intrarenal actions of insulin, independent of systemic effects, in altering blood pressure and renal function. This was accomplished by determining the responses to chronic intrarenal insulin infusion in uninephrectomized, chronically instrumented conscious dogs maintained on a 74 meq/day sodium intake. Insulin was infused at rates calculated to raise intrarenal, but not systemic, insulin to levels similar to those observed in obese hypertensive dogs. Intrarenal insulin infusion (0.6 mU.kg-1.min-1) for 7 days caused transient decreases in sodium excretion but no significant changes in potassium excretion. Mean arterial pressure did not change during 7 days of insulin infusion, averaging 93 +/- 4 mmHg during control and 93 +/- 3 mmHg during insulin infusion. Intrarenal insulin caused small increases in GFR but no significant changes in effective renal plasma flow or renal vascular resistance. These results demonstrate that insulin causes transient decreases in sodium excretion, but chronic intrarenal hyperinsulinemia does not elevate blood pressure in normal dogs. Additional factors other than the direct sodium-retaining effects of insulin may be important in raising blood pressure in obesity-associated hypertension.
Animals↗
Atrial natriuretic peptide induces sustained natriuresis in conscious dogs.
Although acute infusions of atrial natriuretic peptide (ANP) often cause natriuresis, these effects are not sustained, possibly because of reductions in arterial pressure or other compensatory adaptations. The aim of this study was to determine whether physiological increases in intrarenal ANP levels cause sustained natriuresis if changes in arterial pressure and other neurohumoral influences that might obscure the renal responses are controlled. Changes in renal function were quantitated during chronic unilateral renal arterial infusion of ANP at rates of 1, 2, and 4 ng.kg-1.min-1 in conscious dogs (n = 7) with the urinary bladder split to allow continuous measurement of renal excretion in the ANP-infused and contralateral, vehicle-infused kidneys. There was no change in mean arterial pressure at any infusion rate. During 1 ng.kg-1.min-1 infusion of ANP for 5 days, the renal excretory responses were small and variable. However, during 2 and 4 ng.kg-1.min-1 ANP infusion for 7 days, sodium excretion averaged 37.2 +/- 10.0 and 134.8 +/- 19.0% greater, respectively, in the ANP-infused kidneys compared with the vehicle-infused kidneys but there were no changes in glomerular filtration rate or effective renal plasma flow. These results demonstrate that when compensatory changes in arterial pressure and neurohumoral factors are controlled, ANP, at physiological concentrations, causes marked increases in renal excretion. This study supports the concept that ANP's effects to increase renal excretory capability could play a role in long-term control of arterial pressure and body fluid homeostasis.
Aldosterone↗
Intrarenal atrial natriuretic peptide infusion lowers arterial pressure chronically.
Chronic intravenous infusions of atrial natriuretic peptide (ANP) have been shown to lower mean arterial pressure (MAP) in both normal and hypertensive animals. However, the importance of the renal actions of ANP in mediating this hypotension is unknown. This study was designed to determine whether physiological or pathophysiological increases in intrarenal ANP levels influence long-term control of arterial pressure. ANP was infused into the renal artery of seven conscious, uninephrectomized, chronically instrumented dogs at 1, 2, and 4 ng.kg-1.min-1 for 7 days at each dose, followed by a recovery period. Then ANP was infused intravenously following the same protocol. MAP decreased from 88 +/- 3 to 78 +/- 3 mmHg during intrarenal infusion of 1 ng.kg-1.min-1 ANP; increasing the ANP infusion rate did not result in a further reduction in MAP. Systemic arterial plasma ANP concentration did not change from control (15 +/- 5 pg/ml) during 1 or 2 ng.kg-1.min-1 intrarenal ANP infusion but increased slightly during 4 ng.kg-1.min-1 intrarenal ANP infusion, averaging 53 +/- 11 pg/ml. Renal arterial plasma ANP concentrations were calculated to increase to approximately 120 +/- 5, 248 +/- 11, and 484 +/- 22 pg/ml during 1, 2, and 4 ng.kg-1.min-1 intrarenal ANP infusion, respectively. Intravenous ANP infusion did not alter MAP at 1 ng.kg-1.min-1, but MAP was slightly lower than control during 2 and 4 ng.kg-1.min-1 ANP infusion and remained below control during the postinfusion period.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Atrial natriuretic factor and blood pressure control: role of sodium and aldosterone.
This study examined the long-term actions of atrial natriuretic factor (ANF), at physiological levels, on renal function and mean arterial pressure (MAP) and the importance of Na intake and the renin-angiotensin-aldosterone system in modulating those effects. After a control period, ANF was infused intravenously at a rate of 10 ng.kg-1.min-1 for 7 days, followed by 7 days of 20 ng.kg-1.min-1 and 7 days of recovery. After 7 days of ANF at 10 ng.kg-1.min-1, MAP decreased from 87 +/- 3 to 80 +/- 2 mmHg in normal dogs on low sodium intake (LS, 7 meq Na/day) and from 89 +/- 2 to 79 +/- 2 mmHg in adrenalectomized dogs (ADX, 7 meq Na/day) given constant mineralocorticoid replacement. In both groups, no significant change in glomerular filtration rate (GFR) was observed, although sodium excretion increased transiently. ANF failed to cause significant changes in MAP, GFR, or sodium excretion in normal dogs on high sodium intake (HS, 269 meq Na/day). In LS and HS no long-term effects of ANF on plasma renin activity (PRA) and aldosterone were observed. In ADX, as expected, no change in aldosterone was observed. Thus, in normal and adrenalectomized dogs on LS, chronic ANF infusion caused sustained reductions in MAP. HS markedly attenuated the hypotensive effect of ANF. Our data suggest that the long-term effect of ANF is salt sensitive but that decreases in PRA and aldosterone are not essential for the long-term hypotensive effect of ANF.
Adrenalectomy↗
Chronic hyperinsulinemia and blood pressure. Interaction with catecholamines?
Although hyperinsulinemia and increased adrenergic activity have been postulated to be important factors in obesity-associated hypertension, a cause and effect relation between insulin, catecholamines, and hypertension has not been established. The aim of this study was to determine whether chronic hyperinsulinemia, comparable with that found in obese hypertensive patients, causes hypertension in normal dogs, increases plasma catecholamines, or potentiates the blood pressure effects of norepinephrine. In six normal dogs, insulin infusion (1.0 milliunits/kg/min) for 7 days, with euglycemia maintained, increased fasting insulin fourfold to sixfold. However, mean arterial pressure did not increase, averaging 99 +/- 2 mm Hg during the control period and 91 +/- 3 mm Hg during the 7 days of insulin infusion. Insulin did not alter plasma norepinephrine or epinephrine, which averaged 171 +/- 27 and 71 +/- 14 pg/ml, respectively, during the control period and 188 +/- 29 and 45 +/- 12 pg/ml during the 7 days of insulin infusion. In six dogs, norepinephrine was infused (0.2 microgram/kg/min) for 7 days to raise plasma norepinephrine to 2,940 +/- 103 pg/ml. Insulin infusion (1.0 milliunits/kg/min) for 7 days during simultaneous infusion of norepinephrine did not further increase mean arterial pressure, which averaged 101 +/- 3 during norepinephrine and 98 +/- 2 mm Hg during insulin plus norepinephrine infusion. Thus, chronic hyperinsulinemia did not increase mean arterial pressure or plasma catecholamines and did not potentiate the blood pressure actions of norepinephrine. These observations provide no evidence that chronic hyperinsulinemia or interactions between insulin and plasma catecholamines cause hypertension in normal dogs.
Animals↗
Blunted natriuretic response and low blood pressure after atrial natriuretic factor in early cirrhosis.
We compared the natriuretic response to a standard dose of atrial natriuretic factor in nine patients with early cirrhosis (no ascites or edema) with the response in normal subjects displaying a range of baseline sodium excretions due to different sodium intakes (20 mmoles per day, n = 9; 100 mmoles per day, n = 9, and 200 mmoles per day, n = 9). In these normal subjects, sodium output rose, in the same order, from 49 +/- 12 to 177 +/- 26, from 116 +/- 21 to 365 +/- 106 and from 228 +/- 29 to 901 +/- 85 mumoles per min in the first 20 min after 100 micrograms atrial natriuretic factor (human atrial natriuretic factor 99-126). Thus, irrespective of basal excretion, natriuresis rose by at least 2-fold. In the cirrhotic patients, natriuresis rose from 173 +/- 42 to 305 +/- 77 mumoles per min, that is by hardly 1-fold, significantly less than in the normal subjects (p less than 0.01). Renal function studies indicated that atrial natriuretic factor caused less rise in glomerular filtration rate and in fractional sodium excretion. Atrial natriuretic factor induced a fall in blood pressure only in the cirrhotic group, from 130 +/- 4/81 +/- 2 to 108 +/- 4/68 +/- 3 mmHg (p less than 0.001). Plasma atrial natriuretic factor was not low in the cirrhotic patients. Although these data are compatible with a primary disturbance of sodium excretion in early cirrhosis without ascites, such an explanation is complicated by the concomitant drop in blood pressure after atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Renal response to infusion versus repeated bolus injections of atrial natriuretic factor in man.
In 7 healthy humans consuming a 170 mmol sodium diet the effect of the mode of administration of atrial natriuretic factor (human ANF 99-126) on renal function has been investigated, using conventional clearance studies during maximal water diuresis. ANF was administered as four repeated bolus (0.4 microgram/kg) injections and, after a 2-day interval, as a one-hour infusion (0.02 microgram/kg/min) preceded by a 0.4 microgram/kg bolus injection. In the two experiments ANF caused comparable elevations in glomerular filtration rate, free water clearance, and lithium excretion. No change in blood pressure or heart rate was observed in either study, and plasma renin activity and aldosterone fell by a similar extent. As expected, the time course of plasma ANF concentrations was markedly different during the two studies. It is concluded that with those doses of ANF the changes in renal haemodynamics and sodium handling were essentially similar after bolus injections and a constant infusion.
Adult↗
Small intra- and large inter-individual variability in lithium clearance in humans.
We report the inter- and intra-individual variability in fractional lithium clearance (CLi), an alleged quantitative index of Na and water delivery from the proximal tubules, in humans (N = 91). The inter-individual variability was large, the variation coefficients at various Na excretion rates ranging between 11% and 19%. The intra-individual variability was small, the relative intra-individual standard deviation for duplicate measurements (N = 33) being 5%. These observations suggest large inter-individual differences in proximal tubular Na reabsorption. To confirm this, we also studied the inter- and intra-individual variability in the maximum urine flow during water diuresis (Vmax), an index of Na delivery to the diluting segment. They were found to be almost identical to the inter- and intra-individual variability in CLi, and fractional CLi and Vmax correlated strongly (r = 0.83, P less than 0.001). In addition, the inter-individual variability in the fractional clearance of uric acid (CUA), a directional marker of Na reabsorption in the proximal tubules, was large, but the intra-individual variability small. The correlation between fractional CUA and CLi, however, was relatively weak (r = 0.40, P less than 0.01). Although our results do not prove the exact, quantitative validity of the lithium clearance concept, we conclude that the variability in CLi reflects large inter-individual differences in Na handling in the proximal segments of the nephron. Our observations also have implications for the use of the lithium clearance method. The large inter-individual variability in CLi makes the method less suitable to detect subtle differences in CLi in small, unpaired groups of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Role of ANP in natriuresis of head-out immersion in humans.
Atrial natriuretic peptide (ANP) may play a role in the natriuresis after acute circulatory challenges. To assess this role in head-out water immersion (HOI), we compared in clearance studies the effect of 3 h HOI with an equally natriuretic 3-h infusion of ANP [0.01 microgram.kg-1.min-1 human ANP-(99-126)] in seven healthy individuals taking a 100 mmol sodium diet. The studies were repeated after treatment with enalapril (20 mg twice daily), which in previous studies inhibited the natriuresis after ANP. HOI caused a natriuresis equal to that of ANP infusion despite an about five times smaller rise in plasma ANP. HOI increased and ANP decreased estimated renal plasma flow (ERPF). HOI increased maximal free water clearance and decreased fractional lithium reabsorption. ANP did not affect these variables but raised minimal urine osmolality. Enalapril enhanced the fall in ERPF caused by ANP and abolished its natriuretic effect; enalapril did not impair either the natriuresis after HOI or the increase in ERPF and the fall in lithium reabsorption. These data indicate that the low dosage of ANP causes natriuresis by reducing sodium absorption in a distal nephron target segment; enalapril impairs this effect, perhaps by enhancing ANP-induced vasoconstriction, which decreases delivery to this target segment. HOI, by increasing sodium delivery to this segment, is natriuretic despite only a small rise in plasma ANP. Enalapril does not impair these effects. Although a rise in plasma ANP may be one factor in the natriuresis of HOI, the present data speak against an exclusive role. Other factors determine the magnitude of the natriuretic response.
Adult↗
Opposite effects of enalapril and nitrendipine on natriuretic response to atrial natriuretic factor. Renal function evaluated with clearance studies in humans.
In clearance studies, we analyzed the effect of Ca2+ entry blockade with nitrendipine treatment (20 mg b.i.d. for 4 days) and of converting enzyme inhibition with enalapril treatment (20 mg b.i.d. for 4 days) on renal response to atrial natriuretic factor (ANF) (25 micrograms bolus followed by an infusion of 0.03 microgram/kg/min for 90 minutes) in six healthy volunteers who were taking 300 mmol sodium daily. In a control study ANF was administered without Ca2+ entry blockade or converting enzyme inhibition. Natriuresis rose from 239 +/- 38 to 605 +/- 137 mumol/min in the control study (p less than 0.05), from 330 +/- 53 to 943 +/- 152 mumol/min with Ca2+ entry blockade (p less than 0.05), and from 236 +/- 22 to 344 +/- 39 mumol/min with converting enzyme inhibition (NS). ANF induced a rise in maximal free water clearance, inulin clearance, and in the excretion of multiple electrolytes except potassium. Fractional lithium reabsorption fell. In general, these effects were stronger during Ca2+ entry blockade and blunted during converting enzyme inhibition. p-Aminohippurate clearance tended to decrease during the control study (NS), remained constant during Ca2+ entry blockade, and decreased significantly when ANF was infused during converting enzyme inhibition (p less than 0.05 vs. control and vs. Ca2+ entry blockade study). Blood pressure was lowered by Ca2+ entry blockade and, to a somewhat greater extent, by converting enzyme inhibition, but ANF administration induced no additional fall except for a short-term drop during Ca2+ entry blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Lithium clearance during variations in sodium intake in man: effects of sodium restriction and amiloride.
Assuming that lithium is exclusively reabsorbed in the proximal tubules in proportion to sodium and water, the lithium clearance (CLi) has been advanced as an index of filtrate delivery from the proximal tubules. However, studies in the rat and dog showed that CLi drops sharply at fractional sodium excretion rates (FENa) below 0.4% due to lithium reabsorption in the amiloride-sensitive segment of the distal nephron, which disqualified CLi as an index of distal filtrate delivery during sodium restriction in these animals. In order to investigate whether this phenomenon also occurs in man, we studied CLi in 103 normal subjects at varying sodium intakes, including marked sodium restriction. In contrast to findings in the rat and dog, no sharp drop but a gradual fall in CLi was observed at decreasing FENa values down to 0.02%. Maximum urine flow, another index of filtrate delivery from the proximal tubules, decreased proportionally, suggesting that the fall in CLi was due to enhanced proximal and not distal lithium reabsorption. Amiloride (15 mg p.o.) did not affect CLi despite unequivocal effects in the distal nephron in eight normal subjects at a mean FENa of 0.1%. In conclusion, a low FENa due to severe sodium restriction in man is not accompanied by strongly enhanced distal lithium reabsorption sensitive to amiloride. Thus, in contrast to the rat and dog, a low FENa forms no objection to use CLi as an index of sodium and filtrate delivery from the proximal tubules in humans.
Amiloride↗
Enalapril attenuates natriuresis of atrial natriuretic factor in humans.
We studied the effect of converting enzyme inhibition with enalapril on the natriuresis observed after administration of atrial natriuretic factor (human ANF-[99-126], given as a 100-micrograms bolus i.v. injection) in eight healthy humans consuming a 100 mmol sodium diet. Without enalapril, sodium excretion rose from 127 +/- 19 (mean +/- SE) to 437 +/- 103 mumol/min in the first 20 minutes after ANF was administered. Clearance studies performed during maximal water diuresis indicated a rise in glomerular filtration rate (inulin clearance), free water clearance, phosphate, lithium, uric acid, and magnesium excretion. Four days of enalapril (20 mg b.i.d.) increased effective renal plasma flow (p-aminohippurate clearance) and reduced blood pressure (from 114/71 +/- 2/2 to 105/60 +/- 2/1 mm Hg). Under these conditions baseline sodium excretion was not different from the control study, but it rose less after ANF (from 117 +/- 22 to 242 +/- 63 mumol/min), and the increments in glomerular filtration rate, free water clearance, phosphate, lithium, uric acid, and magnesium were all blunted and nonsignificant. In addition, effective renal plasma flow tended to fall; this effect was not observed when ANF was given without enalapril. These results support the notion that the effects of ANF on renal hemodynamics and on tubular sodium handling depend on renal angiotensin II and that blood pressure reduction may interfere with the ANF-induced natriuresis.
Adult↗