Search PubMed⌕ Search

Biomedical subjects

S Ljungman

Publications and source records attributed to S Ljungman.

At least 37 records · Page 2Linked to original sources

Renal function in severe congestive heart failure during treatment with enalapril (the Cooperative North Scandinavian Enalapril Survival Study [CONSENSUS] Trial).

The effect on renal function of long-term treatment with either enalapril (n = 123) or placebo (n = 120) in addition to conventional therapy was studied in a randomized trial in patients with severe congestive heart failure (New York Heart Association functional class IV; the Cooperative North Scandinavian Enalapril Survival Study). Enalapril was administered in a dose of 2.5 to 40 mg/day. The analysis was restricted to the first 6 months of treatment. There was an average initial increase of 10 to 15% (10 to 20 mumol/liter) irrespective of baseline serum creatinine within the first 3 weeks of enalapril treatment, whereafter mean serum creatinine remained on a similar level during the first 6 months. Enalapril was well-tolerated by most patients, and serum creatinine was reduced in 24%. Serum creatinine increased by greater than 100% in 13 patients (11%) in the enalapril group (mainly as a consequence of intercurrent disease or severe hypotension, and usually transiently) and in 4 (3%) in the placebo group. The maximal increase in serum creatinine in the enalapril group was inversely correlated to the diastolic blood pressure (p = 0.008) at baseline and to the mean diastolic and systolic blood pressures measured at the time of the maximal increase in serum creatinine (p = 0.0001). According to multivariate regression analysis, the maximal increase in serum creatinine was also slightly influenced by the dose of furosemide taken. The development of hypotension emerged as the strongest factor explaining an abnormal increase in serum creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

A comparative study of lisinopril and atenolol on low degree urinary albumin excretion, renal function and haemodynamics in uncomplicated, primary hypertension.

The presence of slightly increased urinary albumin excretion (UAE), even at levels well below levels detectable by an ordinary dipstick, has been suggested as a predictor of cardiovascular morbidity and as a reflection of the degree of overall vascular permeability. The aim of the present investigation was to study the effects of two different antihypertensive drug regimens, an ACE inhibitor and a beta-adrenoceptor antagonist, on the low UAE rate observed in subjects with uncomplicated, mild to moderate primary hypertension. After a 4-week placebo run-in period, 49 patients (mean age 54 y) were randomly assigned in a double blind manner either to further 4 weeks on placebo (P, n = 15), 8 weeks on lisinopril (L, n = 17; 20 mg/40 mg o.d.) or 8 weeks on atenolol (A, n = 17; 50 mg/100 mg o.d.). The 24-h UAE was measured every second week. At entry and after 4 weeks the glomerular filtration rate and the renal plasma flow were measured. Both drugs lowered blood pressure (BP) to a similar extent after 4 and 8 weeks of treatment; the blood pressures were 160/106 (P), 159/104 (L) and 154/103 (A) at entry, and 133/83 (L) and 134/87 (A) at the end of the study after 8 weeks. On entry the 24-h UAE in all patients ranged from 4 to 49 mg (mean 14.1 mg), and it did not differ significantly between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Withdrawal of antihypertensive drug treatment: time-course for redevelopment of hypertension and effects upon left ventricular mass.

OBJECTIVES: To examine: (1) in how many treated hypertensive patients it was possible to discontinue drug treatment; (2) the time-course for redevelopment of hypertension after discontinuation of therapy; and (3) whether drug withdrawal was associated with an increase in left ventricular mass (LVM). DESIGN: Fifty-four men with primary hypertension treated for a mean period of 6 years (primarily beta 1-selective beta-blockade) were evaluated for withdrawal of treatment. Exclusion criteria were signs of organ damage, severe hypertension, other serious disease and unwillingness. Treatment was reinstituted if blood pressure increased above a safety level or if symptoms occurred. Echocardiographic estimations of LVM were obtained before withdrawal and 1, 4 and 8 weeks after withdrawal or before return to treatment. SETTING: Outpatient clinic in a city hospital. PATIENTS: A random sample of 56-year-old hypertensive men. INTERVENTION: Gradual discontinuation of treatment with close follow-up of blood pressure. MAIN OUTCOME MEASURES: Number of patients who could withdraw from treatment and who had to return to pharmacological therapy; time-courses for development of hypertension; absolute changes in LVM. RESULTS: Thirty-two patients withdrew from treatment for 1-1000 days. Therapy was reinstituted in all owing to hypertension or symptoms. Serial echocardiograms were obtained in 22 patients. During the drug-free period, relative wall thickness increased, but LVM did not. Patients with rapid redevelopment of hypertension had larger prewithdrawal LVM than patients whose blood pressure increased more slowly. CONCLUSION: It was possible to withdraw treatment and obtain readable echocardiograms in a minority of the patients. After drug-withdrawal, relative wall thickness increased, but not LVM. We suggest that previously treated patients should be avoided in studies examining reversal of left ventricular hypertrophy.

Antihypertensive Agents↗

Microalbuminuria in essential hypertension.

Clinically apparent proteinuria in essential hypertension is associated with increased cardiovascular and total mortality and is an independent risk factor for cardiovascular and cerebrovascular disease. Subclinical elevation of urinary albumin excretion is seen more frequently than clinical proteinuria in essential hypertension and the levels of microalbuminuria (excretions of 30 to 300 mg/24 h) correlate with blood pressure. The increased urinary albumin excretion in hypertension may be explained by several factors such as renal hemodynamic changes, permselectivity changes of the glomerular filter, and structural arteriolar and glomerular changes due to nephrosclerosis. It has been clearly demonstrated that microalbuminuria is a risk factor for the development of clinical proteinuria, renal failure and increased cardiovascular mortality in insulin-dependent diabetes mellitus. It is still not known whether microalbuminuria also predicts development of proteinuria and decline in renal function in hypertension but there is some evidence indicating that microalbuminuria may be a marker of increased cardiovascular risk in hypertensives.

Albuminuria↗

Role of the kidney in congestive heart failure. Relationship of cardiac index to kidney function.

Because of inappropriate signals from the volume-regulation system and a reduction in renal blood flow, the kidney is not able to prevent sodium and water retention in chronic congestive heart failure (CHF). A brief summary of normal renal function and renal involvement in CHF is given and a study of renal function in patients with moderate or severe chronic CHF is presented. To evaluate the impact of cardiac output reduction on the regulation of the glomerular filtration rate (GFR) in heart failure, GFR (inulin clearance), renal plasma flow [p-aminohippurate (PAH) clearance], invasive haemodynamics, blood volume, plasma renin and plasma catecholamines were measured in 34 patients with chronic CHF. The patients were divided into 3 groups according to their cardiac index (CI): CI greater than 2.0 L/min/m2 (group A), CI 1.5 to 2.0 L/min/m2 (group B), and CI less than 1.5 L/min/m2 (group C). Differences in the relationship between GFR, renal plasma flow and filtration fraction for the 3 groups emerged. Despite an intergroup reduction in the renal fraction of cardiac output and renal blood flow, GFR was similar in groups A and B (62 and 67 ml/min/1.73 m2, respectively), and was accompanied by a compensatory increase in filtration fraction, from 24% in group A to 35% in group B. Group C had a much lower GFR (38 ml/min/1.73 m2), however, the filtration fraction (28%) was intermediate in value between those of groups A and B. The differences in GFR were reflected by blood urea nitrogen levels but not by serum creatinine levels. The occurrence of a non-compensatory filtration fraction response in the patients with the greatest impairment of CI and renal blood flow suggests that GFR becomes dependent on afferent arteriolar flow in the most severe heart failure, despite stimulation of haemodynamic and hormonal pathways, which would normally increase efferent arteriolar tone. It is thus suggested that GFR becomes flow dependent in patients in the most severe stage of chronic CHF.

Adult↗

Atrial natriuretic peptide (ANP) in relation to blood pressure: a study in middle-aged men with normal and elevated blood pressure.

In order to investigate the potential role of atrial natriuretic peptide (ANP) in mild to moderate essential hypertension, a study was conducted in groups of normotensive and hypertensive middle-aged men born in 1926 and 1927. Venous plasma concentrations of immunoreactive ANP (irANP) were studied in relation to measurements of cardiac structure and function, urinary electrolytes as well as some cardiovascular hormones. Plasma irANP did not differ between normotensive controls (31 +/- 14 pmol l-1) and borderline or untreated hypertensive patients. However, irANP concentrations were slightly but significantly (P less than 0.05) lower in the borderline (26 +/- 8 pmol l-1) compared to the untreated established hypertensives (35 +/- 14 pmol l-1). No relationships were found between irANP and blood pressure, indices of left ventricular structure and function or hormone parameters in subgroups or the whole study group. Our data do not support the view that plasma irANP is increased in uncomplicated essential hypertension, since our groups of borderline or established hypertensive middle-aged men without major cardiac involvement did not differ in irANP concentrations compared to normotensive controls. Thus, during the development or in the early stages of essential hypertension, ANP secretion does not seem to be abnormal.

Antihypertensive Agents↗

Cardiovascular and renal effects of long-term antihypertensive treatment.

To study whether restoration of a normal circulatory system could be achieved with antihypertensive treatment, 13 hypertensive men with structural cardiovascular changes and 37 normotensive control subjects were investigated by echocardiography, apexcardiography, plethysmography, inulin and p-amino-hippurate clearance, and determination of 24-hour urinary excretion of albumin, first at age 49 years and again seven years later. All men were untreated at the first investigation. Immediately thereafter, therapy with the cardioselective beta-adrenoceptor blocker metoprolol tartrate was initiated in the hypertensive men. Seven years of antihypertensive treatment resulted in (1) normalization of central and peripheral hemodynamic variables, (2) reversal of left ventricular hypertrophy in proportion to achieved blood pressure control, (3) normalization of systolic wall stress and a well-preserved systolic left ventricular function, (4) normalization of diastolic left ventricular function, and (5) normalization of increased microalbuminuria and a decrease in renal vascular resistance, with no change in glomerular filtration rate compared with control subjects. In conclusion, the findings strongly indicate that regression of cardiovascular structural changes can be achieved with long-term antihypertensive treatment.

Drug Therapy, Combination↗

Regulation of glomerular filtration rate in chronic congestive heart failure patients.

The purpose of this study was to identify the factor(s) that characterize impaired glomerular filtration rate (GFR) in congestive heart failure (CHF) patients. We studied 34 patients, measuring systemic hemodynamics, vasoactive hormones, and sodium and volume status. Renal plasma flow (para-aminohippurate) and GFR (inulin) were assessed by steady-state clearance techniques. Both linear and multiple regression analyses were performed. Impaired GFR was characterized by reduction of renal blood flow and renal fraction of cardiac output, and by an increase of renal vascular resistance. The correlation between GFR and filtration fraction (r = 0.492, P less than 0.003) indicated that individuals with greatest impairment of GFR had the lowest filtration fraction and increased overall renal vascular resistance, indicating dependence of GFR on afferent, rather than efferent vasoconstriction, under conditions of low renal perfusion. Mean vasoactive hormones and blood volume were increased, but without clear cut correlation with GFR. The greatest impairment of GFR was observed in elderly CHF patients, as renal blood flow and function demonstrated an age-dependent decline, in addition to the adverse effects of CHF. In a multiple regression model, renal blood flow and filtration fraction accounted for 69% and 25%, respectively, of the variability of GFR, with a co-linear influence of age. Thus, we have identified age-related, abnormal renal hemodynamic patterns in CHF, and the fragile nature of GFR in the elderly CHF population.

Adult↗

A longitudinal study of urinary creatinine and creatinine clearance in normal subjects. Race, sex, and age differences.

The purpose of this study was to examine the variability of 24-hour urinary and serum creatinine levels and creatinine clearance in normal subjects and to develop nomograms for assessing the adequacy of 24-hour urine collections. The data were from a longitudinal research program examining biochemical, hormonal, and hemodynamic parameters in normal subjects. Bloods and 24-hour urine specimens were collected at yearly intervals from 144 people over 9 years, and from an additional 110 over 4 years. The subjects were originally distributed equally by sex, race (black, white), blood pressure (three groups within the normal range), and age (three groups). Men had 33% higher urine creatinines per weight than females (P less than 0.001). Because they only had 8% higher creatinine clearance per weight they also exhibited 21% higher serum creatinine. Blacks had 5% higher urine creatinine per weight than whites, perhaps reflecting greater muscle mass, but their serum creatinines were not different from those of whites, reflecting a 5% higher creatinine clearance by weight than whites (P less than 0.01). Interestingly, older black men (age greater than 60 years) had 12% lower urine creatinine/weight than younger black men (P less than 0.001). They also had 13% lower creatinine clearance by weight, resulting in no net difference in serum creatinine. The intraindividual variability in urine creatinine excretion averaged 15% and did not differ between blacks and whites and men and women. The within individual variability in serum creatinine and creatinine clearance averaged 14 and 20%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Different patterns of cellular sodium turnover in essential hypertension.

Erythrocyte sodium turnover was studied in 22 men aged 56 years who had been treated for hypertension for 7 years. Investigations were performed during treatment, and 1 and 4 weeks after withdrawal of therapy, and when hypertension had returned (blood pressure greater than or equal to 170/105 mmHg). Hypertension returned early in 11 patients (group A) and late in 11 patients (group B). There was no difference in blood pressure, therapy, body weight or peripheral resistance between the groups, but group A had a greater left ventricular mass. Intra-erythrocyte sodium was determined by flame photometry. Sodium influx and the rate constant of sodium efflux were calculated from uptake values of 22Na. In group B the return of hypertension was accompanied by a tendency for an increase in intra-erythrocyte sodium and a decrease in sodium efflux. In group A opposing changes were seen, so that significant differences occurred in sodium efflux and intra-erythrocyte sodium between the groups occurred at the reappearance of hypertension. The results are compatible with the appearance of a membrane abnormality in patients with a slow return of hypertension, whereas other mechanisms, e.g. increased sympathetic activity, may be associated with the more rapid rise in blood pressure in the other group.

Antihypertensive Agents↗

Renal function before and after withdrawal of long term antihypertensive treatment in primary hypertension.

Glomerular filtration rate (GFR) and renal plasma flow (inulin and para-aminohippurate clearance) were measured in a random sample of 17 normotensive and 20 untreated patients with primary hypertension. At the 7-year follow-up, 19 patients were on metoprolol (as the sole drug or in combination with either hydrochlorothiazide or hydralazine) and 1 patient was on hydrochlorothiazide. They were re-examined after withdrawal of treatment and return of hypertension. At the 7-year follow-up GFR was more reduced in the hypertensive (-17%) than in the normotensive group (-9%). The percentage decrease in renal blood flow was the same in both groups. No significant renal function changes appeared after withdrawal of treatment. In conclusion, there was a slightly greater deterioration in GFR in the hypertensive patients after long term treatment with metoprolol than can be explained by normal ageing.

Antihypertensive Agents↗

Pharmacokinetics and pharmacodynamics of ramipril in renal failure.

The pharmacokinetics and pharmacodynamics of the novel angiotensin converting enzyme (ACE) inhibitor ramipril were studied in 6 patients with a glomerular filtration rate of less than 20 ml/min/1.73 m2 of body surface area. A single oral dose of 5 mg was given and serum concentrations of the compound and its diacid, the active metabolite (ramiprilat), as well as ACE activity, blood pressure and pulse rate were monitored for 28 days. The original compound reached peak serum concentrations of 42.8 +/- 26.5 ng/ml about 1 hour after dosing and was completely eliminated from the serum after 24 hours. Ramiprilat reached peak values of 14.4 +/- 11.6 ng/ml after about 6 hours. In contrast with the parent compound, low concentrations of ramiprilat were still detected in the serum after 28 days. ACE activity decreased to approximately 5% of baseline values, remained low for the next 48 hours, then increased slowly thereafter but reached only 84.5% of initial values after 28 days. Blood pressure decreased significantly and remained low for 24 hours after dosing. The drug was well tolerated in all patients. It is concluded that a single 5 mg dose of ramipril was effective in inhibiting plasma ACE activity and lowering blood pressure in patients with renal failure. There was a slower decline in ramiprilat concentrations compared with subjects with normal renal function.

Adult↗

The relationship between obesity-related metabolic factors and vascular changes in early hypertension.

The relationships of obesity, glucose metabolism and hormonal variables to mean arterial pressure (MAP) regional vascular resistance and signs of structural vascular changes, were determined in 70 men aged 49 years with normal to mildly elevated MAP randomly selected from a population sample. Regional vascular resistances and signs of structural vascular changes were measured in the calf by plethysmography at rest and during maximal dilatation, and in the kidneys by renal blood flow determination during graded subpressor doses of angiotensin II. MAP was positively correlated to body fat, waist circumference, fat cell size, and to blood glucose 60 minutes after an oral load. This supports an association between central obesity, impairment of glucose tolerance and hypertension. MAP was, however, unrelated to sodium intake, blood volume and indices of sympathetic nervous activity and the renin-angiotensin system. Resting vascular resistance in the calf was unrelated to MAP, while renal vascular resistance rose significantly with increasing MAP. Signs of structural change were significantly correlated to MAP in both these vascular areas. These signs were also associated with central obesity of the hypertrophic type and with impairment of glucose tolerance, even when the association to MAP was accounted for. These factors may be involved in the pathogenesis of the structural adaptation of resistance vessels as hypertension develops.

Blood Glucose↗

Cardiovascular response to exercise and regional haemodynamics during treatment with prizidilol hydrochloride (SK & F 92 657) in moderately severe essential hypertension.

Fourteen men with moderately severe essential hypertension were treated with prizidilol hydrochloride 400-700 mg once daily (mean +/- S.D. 612 +/- 56 mg/day). The study was open and ambulatory, with an initial placebo period followed by dose titration of prizidilol. Prior to treatment and during optimal control of blood pressure cardiovascular adaptation was examined in a submaximal exercise test. Plethysomographic assessment of vascular flow, resistance and tone in the calf musculature during supine rest and during maximal vasodilatation was also performed. A highly significant reduction in systolic (from 164 +/- 4.5 to 141 +/- 2.7 mmHg; p less than 0.001) and diastolic blood pressure (from 105 +/- 1.6 to 87 +/- 1.3 mmHg; p less than 0.001) at supine rest was noted during therapy with prizidilol. There was no significant change in heart rate. Systolic pressure in the standing position was reduced (from 159 +/- 4.2 to 139 +/- 2.9 mmHg; p less than 0.001) and so was the diastolic pressure (from 111 +/- 2.5 to 95 +/- 1.9 mmHg; p less than 0.001). The heart rate in the standing position was significantly increased compared to supine rest in the placebo period and during optimal treatment with prizidilol. The beta-adrenoceptor blocking properties of prizidilol were apparent as a reduction in the exercise-induced heart rate response at even the lowest work load. During prizidilol therapy an increase in resting calf muscle blood flow was found from 3.1 +/- 1.5 ml/min X 100 ml to 4.3 +/- 2.1 ml/min X 100 ml (p less than 0.025). Vascular resistance and vascular tone were significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The relation between cardiac hypertrophy and hypertension.

Left ventricular mass determined echocardiographically was related to blood pressure in a stratified random sample (n = 120) of 49-year-old men selected from a blood pressure screening and covering a wide range of blood pressures. Only subjects not on antihypertensive treatment were studied. Left ventricular mass was also related to sympathetic activity, the renin-angiotensin-aldosterone system and glucose metabolism. A poor correlation between left ventricular mass and blood pressure was found in the entire study group. In the upper blood pressure range only blood pressure during isometric exercise was significantly correlated with left ventricular mass. In this range there were significant correlations between left ventricular mass and 24 hour urinary noradrenaline excretion and plasma aldosterone. In the intermediate blood pressure range there was an association between left ventricular mass and blood glucose and plasma insulin. It is concluded that in mild to moderate hypertension other factors probably modify the hypertrophic response to rising arterial pressure.

Aldosterone↗

Left ventricular mass in middle-aged men. Relationship to blood pressure, sympathetic nervous activity, hormonal and metabolic factors.

Left ventricular (LV) mass was studied echocardiographically in 120 middle-aged men representing a wide range of blood pressures (BP) and its relation to the following factors was analysed: BP measured in different resting situations and during isometric exercise, 24 hour urinary noradrenaline excretion and plasma noradrenaline, plasma renin activity, plasma angiotensin II, plasma aldosterone, blood glucose and plasma insulin. Each BP measurement showed weak but significant correlation with LV mass in the entire study group. In the upper BP range only BP measured during isometric exercise was correlated with LV mass. In the upper BP range there were also significant correlations between both the 24 hour urinary noradrenaline excretion and plasma aldosterone and LV mass, while blood glucose and plasma insulin were significantly correlated with LV mass in the intermediate BP range. Thus there was a surprisingly low correlation between LV mass and arterial BP. The findings regarding sympathetic nervous activity, hormonal and metabolic factors might indicate that these factors are involved in the pathogenesis of an increased LV mass in some individuals with essential hypertension.

Angiotensin II↗