Extracorporeal cardiopulmonary resuscitation after out-of-hospital cardiac arrest in a Danish health region.

BACKGROUND: Extracorporeal Cardiopulmonary Resuscitation (ECPR) has emerged as a feasible rescue therapy for refractory, normothermic out-of-hospital cardiac arrest (OHCA). Reported survival rates vary and comparison between studies is hampered by heterogeneous study populations, differences in bystander intervention and in pre-hospital emergency service organisation. We aimed to describe the first experiences, treatment details, complications and outcome with ECPR for OHCA in a Danish health region. METHODS: Retrospective study of adult patients admitted at Aarhus University Hospital, Denmark between 1 January 2011 and 1 July 2015 with witnessed, refractory, normothermic OHCA treated with ECPR. OHCA was managed with pre-hospital advanced airway management and mechanical chest compression during transport. Relevant pre-hospital and in-hospital data were collected with special focus on low-flow time and ECPR duration. Survival to hospital discharge with Cerebral Performance Category (CPC) of 1 and 2 at hospital discharge was the primary endpoint. RESULTS: Twenty-one patients were included. Median pre-hospital low-flow time was 54 min [range 5-100] and median total low-flow time was 121 min [range 55-192]. Seven patients survived (33%). Survivors had a CPC score of 1 or 2 at hospital discharge. Five survivors had a shockable initial rhythm. In all survivors coronary occlusion was the presumed cause of cardiac arrest. CONCLUSION: Extracorporeal cardiopulmonary resuscitation is feasible as a rescue therapy in normothermic refractory OHCA in highly selected patients. Low-flow time was longer than previously reported. Survival with favourable neurological outcome is possible despite prolonged low-flow duration.

Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study.

In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6 ng/mL) with reduced-exposure calcineurin inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10 ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4 mL/min (standard deviation [SD] 20.2 mL/min) versus 59.2 mL/min (SD 17.4 mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3 mL/min (95% CI 11.1-25.6 mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade ≥2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p = 0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage.

The Effect of Everolimus Initiation and Calcineurin Inhibitor Elimination on Cardiac Allograft Vasculopathy in De Novo Recipients: One-Year Results of a Scandinavian Randomized Trial.

Early initiation of everolimus with calcineurin inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of calcineurin inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete calcineurin inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (± SD) recipient age was 49.9 ± 13.1 years. The everolimus group (n = 47) demonstrated significantly reduced CAV progression as compared to the calcineurin inhibitor group (n = 48) (ΔMaximal Intimal Thickness 0.03 ± 0.06 and 0.08 ± 0.12 mm, ΔPercent Atheroma Volume 1.3 ± 2.3 and 4.2 ± 5.0%, ΔTotal Atheroma Volume 1.1 ± 19.2 mm(3) and 13.8 ± 28.0 mm(3) [all p-values ≤ 0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the calcineurin inhibitor group (p = 0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.

Everolimus initiation and early calcineurin inhibitor withdrawal in heart transplant recipients: a randomized trial.

In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (3­6 ng/mL) with reduced-exposure cyclosporine (n = 56), or standard-exposure cyclosporine (n = 59), with both mycophenolate mofetil and corticosteroids. In the everolimus group, cyclosporine was withdrawn after 7­11 weeks and everolimus exposure increased (6­10 ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean ± SD: 79.8 ± 17.7 mL/min/1.73 m2 vs. 61.5 ± 19.6 mL/min/1.73 m2; p < 0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03 mm [95% CI 0.01, 0.05 mm] vs. 0.08 mm [95% CI 0.05, 0.12 mm], p = 0.03), and the incidence of cardiac allograft vasculopathy (CAV) was lower (50.0% vs. 64.6%, p = 0.003), with everolimus versus cyclosporine at month 12. Biopsy-proven acute rejection after weeks 7­11 was more frequent with everolimus (p = 0.03). Left ventricular function was not inferior with everolimus versus cyclosporine. Cytomegalovirus infection was less common with everolimus (5.4% vs. 30.5%, p < 0.001); the incidence of bacterial infection was similar. In conclusion, everolimus-based immunosuppression with early elimination of cyclosporine markedly improved renal function after heart transplantation. Since postoperative safety was not jeopardized and development of CAV was attenuated, this strategy may benefit long-term outcome.

Virtual histology assessment of cardiac allograft vasculopathy following introduction of everolimus--results of a multicenter trial.

In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continued standard CNI-therapy underwent matched virtual histology (VH) examination to evaluate morphological progression of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 ± 3.8% and 1.6 ± 3.9%, respectively; p = 0.65). However, VH analysis revealed a significant increase in calcified (2.4 ± 4.0 vs. 0.3 ± 3.1%; p = 0.02) and necrotic component (6.5 ± 8.5 vs. 1.1 ± 8.6%; p = 0.01) among everolimus patients compared to controls. The increase in necrotic and calcified components was most prominent in everolimus patients with time since HTx >5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal components and is more prominent in patients with a longer time since HTx. A significant increase in vWF and VCAM accompanied these qualitative changes and the prognostic implication of these findings requires further investigation.

Superiority of sandwich ELISA over competitive RIA for the estimation of ANP-270, an analogue of human atrial natriuretic factor.

ANP-270 is a 26 amino acid analogue of naturally occurring atrial natriuretic factor (ANF) which it was anticipated would be of value for the treatment of congestive heart failure and acute renal failure. Two sensitive assays--a radioimmunoassay (RIA) and a sandwich enzyme linked immunosorbent assay (ELISA)--were developed and validated for use in clinical investigations. The RIA utilized a single C terminal monoclonal antibody whereas two monoclonal antibodies directed against different epitopes were used for the ELISA. The two assays were comparable with respect to sensitivity and precision, but assay results obtained on samples from normal volunteers dosed intravenously with ANP-270 differed widely. Thus, in one volunteer the elimination half-life was estimated to be 123 min using RIA results but 6 min using the ELISA results. By reversed phase liquid chromatographic fractionation of plasma extracts followed by RIA and ELISA, these discrepancies were shown to be due to fragments of ANP-270 cross-reacting in the RIA but not in the ELISA. Consequently, the sandwich ELISA was the method of choice for estimating this compound in plasma.

Pressure-dependent distal tubular action of atrial natriuretic peptide in healthy humans.

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.

Glomerular and tubular antinatriuretic actions of low-dose angiotensin II infusion in man.

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.

Abnormal structure and function of isolated subcutaneous resistance vessels from essential hypertensive patients despite antihypertensive treatment.

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.

Differentiation between renovascular and essential hypertension by means of changes in single kidney 99mTc-DTPA clearance induced by angiotensin-converting enzyme inhibition.

Blood pressure (BP), plasma renin concentration (PRC), and 99mTc-labeled diethylenetriaminepenta acetate (DTPA) renography with determination of single kidney 99mTc-DTPA clearance and parenchymal mean transit time (MTT) were measured in exactly the same way on two consecutive days in 14 patients with renovascular hypertension (RVH), unilateral renal artery stenosis in nine and bilateral stenosis in five, and ten patients with essential hypertension (EH). The examination on day 1 served as a control for day 2 during which captopril (25 mg) was given orally one hour before measurements of PRC and DTPA clearance. Blood pressure was reduced by captopril in both groups, but the maximum decrease in systolic BP was slightly more pronounced (P less than .01) in RVH (22%, median) than EH (13%). Plasma renin concentration increased to a much greater extent (P less than .01) after captopril in RVH (366%) than in EH (46%), Single kidney 99mTc-DTPA clearance was significantly (P less than .01) reduced (-39.5%) and MTT considerably prolonged (170%) on the affected/most affected side in RVH, but both parameters were only slightly changed or unchanged on the unaffected/least affected side (-6.5%, -2% respectively) and were not significantly changed in any of the sides in EH. The degree of renal artery stenosis was significantly correlated to the increase in PRC (rho = -0.786, n = 14 patients, P less than .01), to the reduction in single kidney 99mTc-DTPA clearance (rho = 0.729, n = 19 kidneys, P less than .01) and to the prolongation in MTT (rho = -0.785, n = 16 kidneys, P less than .01). By analysis of the captopril-induced changes in 99mTc-DTPA clearance and MTT, it was possible to predict the existence of a moderate to several renal artery stenosis in arterial hypertension with a very high degree of probability, and the use of changes in 99mTc-DTPA clearance and MTT after angiotensin-converting enzyme (ACE) inhibition may become a valuable tool in differentiation between RVH and EH.

Interaction between cyclosporine and felodipine in renal transplant recipients.

The nephrotoxic adverse effect of cyclosporine in renal transplantation may be counteracted by calcium antagonists. The effect of a single oral dose of 10 mg of the calcium antagonist felodipine or placebo was studied in ten cyclosporine-treated renal transplant recipients before, during, and after an acute intravenous infusion of cyclosporine in a randomized, single-blind crossover study. Glomerular filtration rate, and renal plasma flow, and tubular function evaluated by the lithium clearance technique were determined. Both glomerular filtration rate, renal plasma flow, urinary sodium excretion, fractional excretion of sodium, and lithium clearance increased after felodipine, whereas proximal and distal fractional reabsorption and blood pressure were reduced. Intravenous infusion of cyclosporine per se did not influence any of the parameters. It is concluded that a single dose of felodipine in cyclosporine-treated renal transplant recipients has beneficial effects on renal hemodynamics, tubular function and blood pressure. It is suggested that these effects result from a direct vasodilatation and an effect on tubular function, and that felodipine given intravenously seems to antagonize at least some of the nephrotoxic effects of cyclosporine.

Attenuated renal excretory response to atrial natriuretic peptide in congestive heart failure in man.

The renal and hormonal effects of atrial natriuretic peptide given as a bolus injection (2.0 micrograms/kg) were studied in 12 patients with congestive heart failure before and after treatment with captopril for 4 weeks and in 13 healthy control subjects. Atrial natriuretic peptide caused a rise in urinary excretion of sodium and urinary flow in the controls, whereas no increases were observed in the patients. Both proximal and distal fractional reabsorption of sodium, as evaluated by the lithium clearance technique, decreased less in the patients than in the controls. Basal plasma concentrations of atrial natriuretic peptide and cyclic guanosine monophosphate (cGMP), and the basal urinary excretion of cGMP, were elevated in the patients. The increases in both plasma and urinary cGMP after administration of atrial natriuretic peptide were blunted in heart failure. Basal glomerular filtration rate and renal plasma flow were reduced, and filtration fraction increased, in the patients. A positive correlation (r = 0.958, P less than 0.01) was found between renal plasma flow and the relative increase in urinary excretion of sodium in the patients with heart failure. Treatment with captopril did not improve the natriuretic and diuretic effect of exogenous atrial natriuretic peptide, but resulted in an increase in filtration fraction after administration of atrial natriuretic peptide not present before captopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-response study of atrial natriuretic peptide bolus injection in healthy man.

The effects of human atrial natriuretic peptide (ANP) on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary flow rate, urinary sodium excretion, tubular function estimated by lithium clearance, and plasma levels of sodium and water homeostatic hormones were studied in a dose-response study with 50 healthy subjects. Placebo or ANP 0.5, 1.0, 1.5, or 2.0 micrograms kg-1 bwt was given as an intravenous bolus injection to five different groups. GFR rose after ANP, whereas no immediate change in RPF was observed. Significant increases with no distinct additional effect of ANP doses higher than 1.0 microgram kg-1 were detected in filtration fraction, urinary flow rate and urinary excretion rate of sodium. Both proximal and distal fractional reabsorption of sodium was reduced and the effect seemed to flatten out at doses higher than 1.0 microgram kg-1. Dose-dependent increases in cyclic guanosine monophosphate in urine and plasma were found after ANP bolus injection, and the rise in both was correlated with the increase in urinary sodium excretion. ANP caused a dose-dependent decrease in blood pressure and an increase in pulse rate. Plasma concentrations of angiotensin II and arginine vasopressin did not change after ANP. In summary, we found that ANP bolus injection caused a natriuresis and diuresis in healthy man with a threshold at a dose of 1.0 microgram kg-1. No distinct further renal effects were observed with higher doses despite dose-dependent increases in urinary cGMP excretion and plasma cGMP. Inhibition of both proximal and distal tubular fractional sodium reabsorption by ANP contributed to the natriuretic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between casual and ambulatory blood pressure in essential hypertension: the influence of work, duration of hypertension and antihypertensive treatment.

Casual blood pressure (BP) and ambulatory BP (mean 24-h BP) were determined in 23 untreated patients with essential hypertension and in 11 normotensive healthy control subjects. Mean 24-h BP was significantly lower than casual BP in patients with essential hypertension, but not in control subjects. This was demonstrated in the patients who did not work during the ambulatory BP monitoring and in the patients with newly recognized hypertension, whereas no differences were revealed either in the patients who went to work or had a known duration of hypertension longer than 6 months. The size of the difference between casual BP and mean 24-h BP was unaffected by antihypertensive therapy with metoprolol and also individually reproducible. An accordance between casual and ambulatory BP measurements in evaluation of the efficacy of antihypertensive treatment was found in 75% of the patients. Casual BP and mean 24-h BP were weakly correlated both before and during antihypertensive treatment. It is concluded that the higher casual BP than ambulatory BP in essential hypertension may be a specific characteristic of the disease. Both work and known duration of hypertension longer than 6 months eliminate the difference between casual ambulatory BP in essential hypertension. Ambulatory BP monitoring seems to be superior to casual BP measurements in the evaluation of antihypertensive treatment.

Effect of atrial natriuretic peptide on blood pressure, guanosine 3':5'-cyclic monophosphate release and blood volume in uraemic patients.

1. Eleven patients on chronic maintenance dialysis were investigated before and after intravenous bolus injection of atrial natriuretic peptide (2 micrograms/kg body weight). 2. Mean blood pressure was reduced to the same extent in the uraemic patients as in 11 healthy subjects, with a nadir 3 min after the atrial natriuretic peptide injection at which time mean blood pressure was reduced by 13% (median) in the uraemic patients and 11% in the healthy subjects. 3. Basal plasma atrial natriuretic peptide and guanosine 3':5'-cyclic monophosphate levels were higher in the uraemic patients than in the healthy subjects, but guanosine 3':5'-cyclic monophosphate increased markedly in both groups after atrial natriuretic peptide injection. 4. Using changes in gamma-emission from blood after previous labelling of erythrocytes with 51Cr, and changes in packed cell volume, haemoglobin and erythrocyte count, a reversible shift of fluid from the intravascular phase was demonstrated in the uraemic subjects. The blood volume was maximally reduced by 6% (median) of initial blood volume at 30 min after atrial natriuretic peptide injection. 5. Correlation analyses gave no evidence of a causal relationship between the changes in mean blood pressure and changes in blood volume, angiotensin II, aldosterone or arginine vasopressin after atrial natriuretic peptide injection. 6. It is concluded that a pharmacological dose of atrial natriuretic peptide reduces blood pressure in uraemic patients on maintenance dialysis to the same extent as in healthy subjects. The blood-pressure-reducing effect of atrial natriuretic peptide does not seem to be mediated by its diuretic effect or ability to displace fluid from plasma to the interstitial fluid compartment.

Enhanced renal production of cyclic GMP and reduced free water clearance during sodium nitroprusside infusion in healthy man.

A 90-min intravenous infusion of the direct vasodilator sodium nitroprusside (SNP) was compared with a placebo infusion in 32 healthy control subjects in order to study the acute effects of SNP on renal haemodynamics, tubular function evaluated by the lithium clearance technique, the plasma levels of atrial natriuretic peptide (ANP), angiotensin II (Ang II), aldosterone (Aldo) and arginine vasopressin (AVP) and the tubular transport of cGMP (TcGMP). SNP infusion induced a significant reduction in mean arterial blood pressure (from 89.5 to 81.5 mmHg), urinary output (from 7.7 to 4.5 ml min-1), free water clearance (from 4.0 to 1.3 ml min-1) and ANP (from 3.3 to 2.5 pmol l-1) and a significant increase in heart rate (from 57 to 64 beats min-1), Ang II (from 11 to 18 pmol l-1), Aldo (from 189 to 308 pmol L-1) and in the tubular secretion of cGMP (TcGMP from 28.8 to 214.4 pmol min-1), (all values are medians and changes from baseline to 90 min after infusion start). Glomerular filtration rate, renal plasma flow, urinary sodium excretion, lithium clearance and plasma level of AVP were not significantly changed. It is concluded that SNP infusion in healthy subjects decreases urinary output and free water clearance without any change in sodium excretion, indicating a dissociation between the salt and water retaining effects of SNP in the early phase of treatment, probably due to an enhanced distal tubular water reabsorption of water.(ABSTRACT TRUNCATED AT 250 WORDS)

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 less than 0.01), elastic modulus (10.6 x 10(7) Pa vs. 6.18 x 10(7) Pa, medians; P less than 0.05) and arterial wall stiffness (3.80 x 10(7) Pa vs. 2.07 +/- 10(7) Pa, medians; P less than 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.

Pressure-dependent, enhanced natriuretic response to low-dose, atrial natriuretic peptide infusion in essential hypertension.

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 (CLi) increased and FELi 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 < 0.05). The relative changes in GFR, CLi, and FELi during ANP infusion were not affected by the preceding BP reduction with NP. Mean arterial pressure was reduced from 122 to 101 mmHg during NP infusion. The relative increase in sodium excretion in EH was significantly correlated to mean arterial pressure. CONCLUSIONS: Low-dose ANP infusion causes an exaggerated natriuresis in untreated essential hypertensives due to a more pronounced reduction in tubular reabsorption. After BP reduction, the natriuresis induced by ANP in essential hypertensives is decreased, probably due to a less pronounced reduction in tubular reabsorption beyond the proximal tubules. We suggest that the enhanced natriuretic response to ANP in EH in secondary in some degree to the elevated systemic pressure.