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The new guidelines addressing the management of patients with acute coronary syndromes have recently been published.1,2These guidelines are the first in Europe after the redefinition of acute myocardial infarction (AMI). Treatment strategies in the early phase of AMI have changed dramatically during the last 10–15 years. However, the evidence that confirms a prognostic benefit of β-blockade in AMI was obtained in the 1980s. Only one randomized, post-AMI trial addresses the effects of β-blockade in the era of ACE-inhibitors, statins, anti-platelet therapy, fibrinolytic treatment or early coronary revascularization.3This study, however, excluded patients with a LVEF >40%. Do we really have data that justify recommendation of β-blockers to …

To elucidate and to try to reverse the antinatriuretic mechanisms in liver cirrhosis, atrial natriuretic peptide (ANP) was given as a pharmacological bolus dose (2 micrograms per kg body weight) to 14 cirrhotic patients, and as a control to 14 healthy subjects. The nine patients with ascites had baseline values of glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and blood pressure (BP) similar to controls. Their distal tubular fractional reabsorption of sodium (DFRNa), estimated by the lithium clearance technique, was higher than in controls, and so were plasma values of aldosterone (564 vs. 119 pmol l-1 medians), endothelin (1.23 vs. 0.63 pmol l-1), ANP (7.5 vs. 3.6 pmol l-1) and cyclic GMP (8.8 vs. 4.6 nmol l-1); p0.01 for all. The five patients without ascites had higher GFR and ERPF, and lower plasma angiotensin II than controls. After ANP injection, similar plasma levels of ANP and cyclic GMP were reached in all groups. Urinary sodium excretion rate increased in controls (0.23 to 0.52 mmol min-1, p0.01), while GFR increased (108 to 117 ml min-1, p0.05), and DFRNa decreased (93 to 89%, p0.01). In cirrhotics with ascites sodium excretion was unaltered (0.12 to 0.11 mmol min-1), and so was GFR (84 to 83 ml min-1). Proximal tubular fractional reabsorption of sodium increased after 90 min, whereas DFRNa decreased immediately (97 to 96%, p0.01) though less markedly than in controls. Sodium excretion increased in four of five patients without ascites (0.23 to 0.27 mmol min-1, medians). In patients with ascites, endothelin in plasma decreased after ANP (p0.05). Plasma levels of angiotensin II, aldosterone and vasopressin were unchanged in all groups. In conclusion, although hyper-reabsorption of sodium occurred in the distal rather than the proximal part of the nephron in cirrhotic patients with ascites, ANP had no natriuretic effect. This was most probably due primarily to the lack of increase of GFR and blunted inhibition of DFRNa, attributed to high aldosterone. The effect of ANP in suppressing the high endothelin did not seem to improve sodium excretion.

To evaluate therapeutic and side effects, atrial natriuretic peptide (ANP) was administered as a pharmacological bolus dose (2 micrograms/kg body weight) to 7 patients with nephrotic syndrome and to 13 age- and gender-matched control subjects. The basal glomerular filtration rate was similar, but the blood pressure was slightly higher in the patients than in the controls. Injection of ANP induced a significant increase of sodium excretion in controls (from 0.21 to 0.52 mmol/min, medians, p0.01), but not in nephrotics (from 0.21 to 0.32 mmol/min). Urinary output and free water clearance after ANP had been given were also lower in the patients. The natriuretic effect was mediated through inhibition of distal tubular fractional sodium reabsorption, as estimated by the lithium clearance technique, and through an increase of glomerular filtration rate, both effects only significant in the healthy subjects. The blood pressure was reduced to the same extent in the two groups. Although similar levels of ANP were reached in the groups after injection, cyclic guanosine monophosphate (GMP)/ANP was less in the patients, both basally and after ANP injection, and the urinary excretion of cyclic GMP did not increase in the nephrotics (from 478 to 1,220 pmol/min, ns) as in the controls (from 389 to 2,500 pmol/min, p0.01). The urinary albumin excretion rate increased significantly in patients, whereas the prostaglandin E2 excretion increased after ANP administration only in controls. Endothelin, angiotensin II, aldosterone, and arginine vasopressin were unchanged in the two groups. Basal aldosterone was lower and ANP higher in patients than in controls. In conclusion, the natriuretic effect of ANP was reduced in nephrotic patients. This could not be attributed to counterregulatory haemodynamic or hormonal factors, but probably to reduced second messenger cyclic GMP.

on post transplant survival of patients (pts) bridged to transplant. Methods and Materials: 490 pts were implanted with HeartMate II LVAD in the multicenter BTT clinical trial. 416/490 (85%) had TPG data available for analysis. TPG was calculated as the difference between mean pulmonary arterial pressure and pulmonary capillary wedge. Pts were divided into two groups based on the median TPG value. Results: The median TPG of all pts was 10 mmHg. Pts age (50 13 vs. 51 12), sex, co morbidities, renal and hepatic function, and pre-HTX LVAD support times (239 264 days vs. 262 264 days) did not differ between groups. Overall, there were no differences in LVAD outcomes (Recovery, HTX, or ongoing support) for pts below median TPG ( 10 mmHg) and those above median TPG ( 10 mmHg). However, one year post HTX survival for pts with TPG below the median value ( 10 mmHg) was significantly higher (94%) than for those patients with TPG 10 mmHg (82%) (p 0.006). Analysis based on median PVR of 2.69 or upper quartile PVR of 3.8 did not reveal any differences between LVAD outcome of the groups or their post HTX survival. (91% vs 86% p 0.308, and 90% vs 84% p 0.3 respectively). Conclusions: Elevated TPG prior to LVAD implantation rather than high PVR, is associated with worse 1-year survival in HTX recipients. Elevated TPG appears as an important risk factor for post HTX mortality and therefore should be taken into consideration when contemplating heart transplant versus LVAD destination therapy in patients with advanced CHF.

Objective. To examine whether the effect of atrial natriuretic peptide (ANP) on renal glomerular and tubular segmental handling of sodium in patients with essential hypertension is pressure dependent. Design.Part 1. The renal effects of a low-dose continuous infusion (10 ng kg−1 min−1) with ANP for 1 h were compared in 10 untreated essential hypertensives (EH) and 13 normotensive control subjects (CS). Part 2. The hypertensives were studied on another day with ANP infusion during preceding acute BP reduction with sodium nitroprusside infusion (NP). The results were compared with those obtained during infusion with ANP + placebo (Part 1). Methods. Lithium clearance was used to estimate the proximal tubular reabsorption of sodium. Results.Part 1. Atrial natriuretic peptide caused an exaggerated increase in urinary sodium excretion (+ 102 vs. + 38%; P < 0.05), fractional excretion of sodium (+ 80 vs. + 37%; P < 0.05), and urinary output (+ 56 vs. + 8.3%; P < 0.05) in EH compared with CS. Glomerular filtration rate and filtration fraction increased to the same degree in both groups. Absolute lithium clearance (CL1) increased and FEL1 tended to increase (P = 0.061) in EH, but these were unchanged in CS. The increase in plasma cyclic guanosine 5′-phosphate (cGMP) and urinary excretion of cGMP and the decrease in plasma aldosterone during ANP infusion were the same in the two groups. Part 2. During NP infusion the natriuresis caused by ANP in EH was reduced (+ 51 vs. +99%; P

Immunoreactive endothelin (ir-ET) was measured in peripheral venous plasma in 12 patients with renovascular hypertension (RVH) due to unilateral renal arterial stenosis, in 12 patients with essential hypertension (EH), and in 12 control subjects (C). In the patients with RVH, ir-ET was also measured in the aorta and in both renal veins before and 1 h after 25 mg of captopril was given orally. In peripheral venous plasma, ir-ET was the same in RVH (median 1.02 pmol/l (range 0.53-1.65)) as in EH (0.96 pmol/l (0.76-1.32)) and in C (1.00 pmol/l (0.77-1.16)). In RVH, the concentrations of ir-ET decrease from the aorta to the renal vein of both the affected (0.88 pmol/l (0.54-1.28) vs 0.68 (0.51-1.24), p0.01) and in the unaffected kidney (0.85 pmol/l (0.62-1.38) vs 0.78 pmol/l (0.36-1.25), p0.01). Renal extraction of ir-ET was the same on the affected side (15.1% (-3.7-33.2)) and on the unaffected side (11.2% (0.5-46.4)). In the aorta, ir-ET was significantly lower than in peripheral venous plasma (p0.05). The renal handling of ir-ET did not change in response to captopril in either the affected or unaffected kidney. It is concluded that circulating levels of ir-ET are normal in renovascular hypertension associated with unilateral renal artery stenosis and in essential hypertension. There is significant renal extraction of ir-ET which is unaffected by renal artery stenosis and captopril.

mus levels (ng/mL) were generally lower for the C-1H v. controls: month 1-6 (8.6 v. 11.4, p 0.00001), month 7-12 (9.9 v.10.9, p 0.0008), month 13-18 (9.8 v. 10.4, p 0.09), month 19-24 (8.8 v. 10.1, p 0.0009) month 25-30 (8.9 v. 10.0, p 0.006), months 31-36 (9.2 v. 9.3, p 0.86). Survival at 3 years was not different between C-1H and controls, 81% v. 77% p 0.35. At 3 years overall freedom from rejection (ISHLT 3A/2R) was superior in the C-1H group: 79% v. 62%, p 0.0005.

Purpose The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant recipients. Nevertheless, switch to everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst thoracic transplant recipients with advanced renal failure. Methods and Materials In this 12-month multicenter Scandinavian study 282 maintenance thoracic transplant recipients were randomized to everolimus with calcineurin inhibitor (CNI) reduction (56% reduction in CNI exposure achieved) or standard CNI therapy. GFR was measured at baseline and 1-year using Cr-EDTA clearance. Results In patients with baseline GFR 60 ml/min the effect was more modest. Time since transplant was a mediating factor as GFR improvement was limited to patients with time since transplant Conclusions Conversion to everolimus and reduced CNI significantly improves renal function amongst maintenance thoracic transplant patients with pre-existing advanced renal failure. This beneficial effect is limited to patients undergoing conversion less than 5 years after transplant indicating a "window of opportunity" that is appropriate for pharmacological intervention with everolimus.

Purpose We recently presented preliminary data on the preventive effects of everolimus (EVE) on biopsy-proven microvasculopathy (MVP) after heart transplantation (HTx). Here we show the final analysis from re-evaluation of the European cohort of the RAD B253 Trial (EVE 3 mg or 1.5 mg vs. azathioprine [AZA] in primary HTx pts). Methods and Materials We studied 135 pts, mean age 56 yrs, and 567 biopsies harvested 1 wk (n=125), 4 wks (n=131), 3 months (n=128), 1 yr (n=101) and 2 yrs (n=82) after HTx. Acute cellular rejection (ACR; ISHLT) and both endothelial disease (endothelial cell layer at least as thick as its cell cores) and MVP (ratio of luminal radius to media thickness Conclusions Everolimus suppresses MVP in biopsy early after HTx and seems to have preventive effects on endothelial disease, also. Its effects beyond the first post-transplant yr deserve further study.

The effects of a 2-h intravenous infusion of glucagon 5 ng kg-1 min-1 or placebo on glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium handling as judged by the lithium clearance method, and plasma concentrations of angiotensin II (AngII), aldosterone (Aldo), and atrial natriuretic factor (ANF) were investigated in two groups of healthy human volunteers, glucagon group (n = 10), and placebo group (n = 10). Glucagon infusion resulted in a maximal increase in plasma concentrations of glucagon of 400%. GFR increased 5.9% (range 1.3-12.4, p0.001) through the whole infusion period, whereas RPF only increased transiently during the first hour of infusion 6.5% (range 2.6-15.3, p0.05). Whereas filtered load of sodium increased significantly in response to glucagon infusion (p0.001), urinary sodium excretion was unchanged. Neither of these variables were affected by placebo. As judged from assessments of tubular sodium handling derived from the renal clearance of lithium, the increased filtered load of sodium resulted in an increase in the output of sodium from the proximal tubules of a similar magnitude, and an increase in absolute reabsorption of sodium in the distal tubules totally counterbalancing this increased input to the distal tubules. These alterations in tubular sodium handling did not involve Ang II, Aldo, or ANF. We conclude that an increase in plasma concentration of glucagon within the physiological range is capable of inducing a small and sustained increase in GFR, whereas RPF increases only transiently.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-nine patients with unilateral renal artery stenosis or occlusion were investigated. The veno-arterial gradient (VA-gradient) of erythropoietin (EPO), haemoglobin oxygen saturation and plasma renin activity (PRA) was determined separately in each kidney before and 1 h after angiotensin converting enzyme inhibition (ACE-inhibition). The VA-gradient of EPO and of hemoglobin oxygen saturation were the same in the affected and unaffected kidney during basal conditions. During ACE-inhibition the VA-gradient of EPO disappeared on the affected side but not on the unaffected side. A fall in s-EPO after ACE inhibition was demonstrated in the renal vein on the affected side (-1.4 U l-1, p0.01), in the contralateral vein (-0.8 U l-1, p0.01) and in the aorta (-0.6 U l-1, p0.01). The O2-gradients were reduced on both sides after captopril, from 10.8-7.5% (p0.04) on the affected side and from 10.8-9.0% (p0.04) on the contralateral. It is suggested that the stimulated renin-angiotensin system may be important for EPO production in the affected kidney in unilateral renal disease.

Atrial natriuretic peptide (ANP) was given as an intravenous bolus injection (2.0 micrograms kg-1) to 12 essential hypertensive patients (EH) and 13 normotensive control subjects (C) in order to study the effect of ANP on renal glomerular and tubular function using the lithium clearance technique. Urinary sodium excretion (EH, + 370% vs. C, + 120%; P less than 0.001) and urine volume (EH, + 137% vs. C, + 62%; P less than 0.01) increased significantly more in EH than in controls after ANP injection. Glomerular filtration rate, renal plasma flow, and plasma concentrations of angiotensin II, aldosterone and arginine vasopressin remained almost unchanged after ANP injection, whereas the filtration fraction increased to the same extent in both groups. Both proximal (EH, - 15% vs. C, - 5%; P less than 0.01) and distal fractional reabsorption (EH, - 12% vs. C, - 5%; P less than 0.01) of sodium decreased more markedly after ANP in EH than in controls. The increase in plasma cGMP and urinary excretion of cGMP was the same in the two groups. Mean blood pressure decreased and heart rate increased to the same extent in both groups. It is concluded that the increase in urinary sodium excretion and urine volume induced by ANP bolus injection is exaggerated in EH due to a more pronounced reduction in the reabsorption of sodium and water in both the proximal and the distal tubule.

Renal plasma flow (RPF), glomerular filtration rate (GFR), renal proximal tubular delivery of sodium and water evaluated by lithium clearance, and hormonal parameters were measured in 12 patients with congestive heart failure NYHA class II-IV before and after captopril treatment for 4 wk and in 13 healthy control subjects. RPF and GFR were significantly decreased in heart failure, whereas the filtration fraction (FF) was increased. Treatment with captopril increased RPF and decreased FF, whereas GFR was unchanged. Total and fractional urinary excretion of sodium were reduced in the patients compared with the controls, but increased after captopril. Fractional excretion of lithium was normal in heart failure and was increased by captopril. Atrial natriuretic peptide, guanosine 3',5'-cyclic monophosphate, and aldosterone in plasma were significantly elevated in heart failure and were reduced by treatment with captopril. Plasma renin activity was increased in patients, correlated inversely with RPF, and increased further after captopril treatment. It is concluded that the reduced sodium excretion in heart failure was caused by a combination of diminished glomerular filtration and enhanced tubular reabsorption beyond the proximal tubule and that treatment with captopril increased urinary sodium excretion partly due to an attenuated sodium reabsorption in the proximal tubule. The present data in patients with congestive heart failure are consistent with an increased intrarenal angiotensin II generation and an elevated plasma level of aldosterone being involved in the pathogenesis of the glomerular hemodynamic changes and the enhanced distal tubular reabsorption, respectively.

The effect of an analogue of atrial natriuretic peptide (P-ANP) on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary flow rate, urinary sodium excretion, tubular function estimated by the lithium clearance technique, and plasma levels of sodium and water homeostatic hormones, has been studied in 40 healthy males. Placebo or P-ANP 0.3, 1.5, or 3.0 micrograms.kg-1 bwt were given as an intravenous bolus injection to different groups. P-ANP did not cause any immediate change in GFR or RPF, but significant dose-dependent increases in filtration fraction, urinary flow rate and urinary excretion rate of sodium were detected during the first 30 min after administration. Proximal absolute and fractional tubular reabsorption and distal absolute tubular reabsorption of sodium did not change after injection of P-ANP, while the distal fractional reabsorption of sodium was reduced in a dose dependent manner during the first 30 min. Plasma angiotensin II and aldosterone were significantly increased 30 and 150 min after dosage, whereas plasma atrial natriuretic peptide, plasma arginine vasopressin, and urinary excretion of prostaglandin E2 were unchanged. Cyclic guanosine monophosphate both in plasma and urine were increased in a dose-dependent manner. P-ANP cause a significant reduction in diastolic blood pressure and an increase in pulse rate. Two subjects had vasovagal syncope 30-60 min after injection of P-ANP. It is concluded that P-ANP has natriuretic, diuretic and hypotensive properties in healthy man.

The effect of a continuous infusion of human brain natriuretic peptide, 2 ;pmol·min-1·kg-1, during 60 ;min was studied in nine patients with congestive heart failure and in 10 healthy control subjects. Brain natriuretic peptide increased from 1.6 to 101 ;pmol/l in control subjects and from 25 to 173 ;pmol/l in congestive heart failure during infusion. Urinary sodium excretion increased significantly in both congestive heart failure (60%) and control subjects (71%), but the absolute increase was significantly lower in congestive heart failure (27 ;μmol/min) than in control subjects (190 ;μmol/min). Urinary flow rate did not change. The lithium clearance technique was used to evaluate the segmental tubular function; the distal fractional reabsorption of sodium decreased significantly less in congestive heart failure (DFRNa: -0.8%) than in control subjects (DFRNa: -3.7%). Baseline values for glomerular filtration rate and renal plasma flow were reduced in congestive heart failure, but brain natriuretic peptide induced no significant changes between congestive heart failure and control subjects. Brain natriuretic peptide induced the same absolute increase in secondary messenger cGMP in plasma and urine in both patients and healthy subjects. It is concluded that the natriuretic response to brain natriuretic peptide infusion was impaired in patients with congestive heart failure compared with healthy subjects, and it is likely that the impaired natriuretic response was caused by a reduced responsiveness in the distal part of the nephron.

Objective To study the influence of blood pressure reduction with sodium nitroprusside on the renal glomerular and tubular actions of atrial natriuretic peptide. Design Forty-nine healthy subjects were examined in four different groups receiving placebo, sodium nitroprusside alone, atrial natriuretic peptide alone (10 ng/kg per min), or sodium nitroprusside and atrial natriuretic peptide in combination. The infusion rate of sodium nitroprusside was gradually increased until a 10 mmHg decrease in diastolic blood pressure was obtained. Methods Lithium clearance was used to evaluate segmental tubular reabsorption. Results In the placebo group neither renal nor hormonal parameters were changed. Except for a fall in urinary flow, sodium nitroprusside alone had no effect on renal parameters. Urinary excretion of cyclic GMP (cGMP) was slightly increased, whereas the plasma cGMP level was not changed in response to sodium nitroprusside. The plasma aldosterone level was elevated during sodium nitroprusside infusion, although neither the plasma angiotensin II level nor the plasma atrial natriuretic peptide level were changed. Atrial natriuretic peptide alone caused an increase in filtration fraction and a decrease in renal plasma flow. Urinary sodium excretion, fractional sodium excretion, and urinary flow were increased, and distal fractional tubular sodium absorption decreased, whereas lithium clearance and proximal fractional tubular re-absorption were not changed by atrial natriuretic peptide. Atrial natriuretic peptide alone caused a decrease in plasma aldosterone and an increase in plasma and urinary cGMP levels. During blood pressure reduction with sodium nitroprusside, atrial natriuretic peptide caused no changes in the renal parameters except for an increase in filtration fraction. Thus, the increase in urinary sodium excretion (-8 versus +37 micromol/min) and the decrease in distal fractional sodium excretion (0.0 versus -2.4%) caused by atrial natriuretic peptide were attenuated. The atrial natriuretic peptide-induced changes in proximal fractional tubular reabsorption (-0.5 versus +0.6%) and cGMP were not changed by blood pressure reduction. Conclusions Blood pressure reduction causes an attenuation of the natriuretic action of atrial natriuretic peptide in normotensive humans that is at least partly caused by attenuation of the distal tubular action of atrial natriuretic peptide. The results support the hypothesis that the action of atrial natriuretic peptide on distal tubular sodium reabsorption is pressure-dependent in humans.

OBJECTIVE The aim was to study the physiological effects of angiotensin II upon the glomerular and tubular handling of sodium. DESIGN Healthy volunteers were examined before and during infusion with either low-dose angiotensin II (n = 11) or placebo (n = 13). METHODS Lithium clearance was used to estimate the segmental tubular reabsorption of sodium. RESULTS During infusion with angiotensin II a sustained and marked fall in renal plasma flow was observed. The glomerular filtration rate (GFR) decreased to a minor extent so that the filtration fraction increased during angiotensin II infusion. Angiotensin II caused an extensive and instantaneous fall in both urinary flow and urinary sodium excretion. Proximal absolute reabsorption of sodium was unchanged despite the fall in GFR, showing that proximal fractional reabsorption was enhanced by angiotensin II. Distal absolute reabsorption was decreased during the entire period of angiotensin II infusion. However, when the distal reabsorption was related to the delivery of sodium from the proximal tubules, distal fractional reabsorption in fact increased after 30 min angiotensin II infusion. None of the measured parameters changed during infusion with placebo. A significant increase in plasma aldosterone was observed 30 min after the start of the angiotensin II infusion. Plasma atrial natriuretic peptide did not change during infusion with either angiotensin II or placebo. CONCLUSIONS We conclude that physiological increments in angiotensin II affect glomerular haemodynamics and cause a marked antinatriuresis in man. The antinatriuretic effect of angiotensin II is caused initially by a combination of a decrease in the GFR and an increase in proximal fractional sodium reabsorption, and later by the enhanced distal fractional reabsorption of sodium.

Eiskjaer H, Christensen T, Pedersen EB (Department of Medicine C and Department of Radiology R, Aarhus Kommunehospital and Aarhus University, Aarhus, Denmark). Abnormal structure and increased stiffness of the femoral arterial wall in young patients with sustained essential hypertension. Thickness, elastic modulus, and stiffness of the common femoral arterial wall were estimated in 11 patients with essential hypertension and in 11 age-matched normotensive control subjects by use of an in vivo, non-invasive, ultrasound time-motion display technique (M-mode). Hypertensive patients had significantly higher levels than normotensive subjects with regard to arterial wall thickness (0.23 cm vs. 0.18 cm, medians: P < 0.01). elastic modulus (10.6 × 107 Pa vs. 6.18 × 107 Pa, medians; P < 0.05) and arterial wall stiffness (3.80 × 107 Pa vs. 2.07 ± 107 Pa, medians: P < 0.01). It is concluded that structural changes in the wall of the large arteries contribute to the increase in arterial wall stiffness in young patients with sustained essential hypertension.

In 14 patients with arterial hypertension secondary to chronic renal parenchymal disease and impaired renal function, 24-h ambulatory blood pressure, casual blood pressure, plasma concentrations of angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide, serum creatinine, plasma lipids and lipoproteins, and body weight were determined at the end of two consecutive 3-week periods; placebo was administered in the first period and verapamil sustained-release 240 mg was given in the second period. Verapamil reduced mean 24-h ambulatory blood pressure from 152/104 mm Hg (means) to 142/97 mm Hg. Blood pressure was reduced significantly during the daytime, in the evening, and in the early morning, but not at night. Casual blood pressure was also significantly reduced from 176/106 mm Hg to 154/96 mm Hg. No significant changes were determined in the hormones, serum creatinine, plasma lipids and lipoproteins, heart rate, or body weight. Atrial natriuretic peptide was correlated significantly with serum creatinine (p = 0.733, n = 14, p less than 0.01). We conclude that verapamil sustained-release 240 mg in one daily dose has a moderate blood-pressure-lowering effect in patients with chronic renal disease and hypertension without inducing tachycardia, activation of the renin-angiotensin-aldosterone system, or increase in body weight, and without altering renal function and plasma lipids and lipoproteins. The positive correlation between atrial natriuretic peptide and serum creatinine may support the hypothesis that extracellular volume increases during progression of renal disease.

Glomerular filtration rate (GFR) and tubular function were measured by means of the lithium clearance technique in 14 patients with renovascular hypertension (RVH) and eight patients with essential hypertension (EH) before and after oral administration of captopril 25 mg. In RVH captopril reduced 51-Cr-EDTA clearance (67.3 (median) to 47.5 ml min-1, P less than 0.01), proximal absolute reabsorption of fluid (53.9 to 41.5 ml min-1, P less than 0.01) and distal absolute reabsorption of sodium (2195 to 1402 mumol min-1, P less than 0.01), whereas proximal fractional reabsorption increased slightly (77.5 to 80.2%, P less than 0.02). In EH, however, these parameters were practically unaffected by captopril. In both RVH and EH plasma concentrations of angiotensin II and aldosterone were reduced after captopril, but atrial natriuretic peptide in plasma and urinary excretion rate of prostaglandin E2 were unchanged. Blood pressure decreased after captopril in both groups, but the maximum fall in systolic BP was more pronounced in RVH (22%) than EH (13%). It is concluded that angiotensin converting enzyme inhibition markedly reduced absolute reabsorption in both the proximal and distal tubules in RVH, in contrast to EH, predominantly due to fall in the GFR, and that the slight increase in proximal fractional reabsorption may be attributed to a reduction in the hydrostatic pressure in the peritubular vessels.

The urinary excretion rate of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) was determined in patients with the nephrotic syndrome both before and after an oral water load in 21 patients and 17 control subjects, and before and after remission of the syndrome in 8 of the patients. In the nephrotic syndrome PGE2 excretion rate varied considerably during basal conditions, remission was accompanied by an increase in the PGE2 excretion, and both basal PGF2 alpha excretion rate and the normal response in PGF2 alpha water loading were reduced. A significant, positive correlation was found between urine flow rate and excretion rate of PGE2 in the periods with the largest urine flow rate in both patients and control subjects. It is suggested that a relatively suppressed renal prostaglandin production may be a pathogenetic factor for sodium and water retention in the nephrotic syndrome, although it cannot be excluded that the abnormal prostaglandin excretion pattern is secondary, at least partially, to the reduction of urine flow rate.

PurposeThe purpose was to assess outcomes with durable continuous-flow left ventricular assist device (LVAD) in Scandinavia.MethodsSince 1993, 497 durable LVADs have been implanted among 9 centers in Scandinavia. Of those, 273 were 2nd and 3rd generation LVAD, 80% as bridge to transplant. We performed a retrospective analysis of 252 patients with complete data. Postoperative complications and survival, with censorship at transplantation, were compared between groups and Cox proportion hazard regression analysis was used to identify factors associated with reduced long-term survival.ResultsThe actuarial survival rate was 71%, 64% and 62% at 1 year, 3 years and 5 years respectively and similar for 2nd and 3rd generation LVADs (Figure). The most common complication were drive line infection (24%), right heart failure (24%), gastrointestinal bleeding (11%), pump thrombosis (9%) and thromboembolic events (8%) (Table), again similar for 2nd and 3rd generations LVADs. Univariable predictors of mortality were higher age, creatinine, bilirubin and lower platelet count and pulmonary vascular resistance.ConclusionPrognosis after continuous flow LVAD in Scandinavia is modest. Careful selection considering markers of renal insufficiency and liver congestion as well as previously reported risk markers may improve the risk / benefit ratio.

The morphological and functional characteristics of isolated subcutaneous resistance vessels (about 230 microns internal diameter) from 13 patients treated for essential hypertension for a median period of 14 months and from 15 matched normotensive controls were examined. The blood pressure of the patients and the controls were not significantly different at the time of examination. However, although compared with the controls, the lumen diameter of the vessels from the patients was not significantly different, the media thickness to lumen diameter ratio was 19% greater. Furthermore, although there was no difference in the active pressure response of the vessels from the two groups, the vessels from the patients had a lower sensitivity to calcium, relaxed faster after a contraction and the sensitivity to exogenous noradrenaline shifted more to the left with cocaine. Since the abnormalities found here have previously also been found in vessels from patients with untreated essential hypertension, the study suggests that despite antihypertensive treatment to normotensive levels for about 1 year, some morphological as well as functional characteristics of the resistance arteries are not fully normalized. This could have consequences for the prognosis of essential hypertension.