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Biomedical subjects

I Tikkanen

Publications and source records attributed to I Tikkanen.

At least 19 recordsLinked to original sources
PubMed1992

Alpha-human-ANP response to preanesthetic volume expansion and subsequent renal transplantation in diabetic and nondiabetic uremic patients.

alpha-Human atrial natriuretic peptide (ANP) concentrations were measured in 11 diabetic patients with uremia and in 16 nondiabetic uremic controls undergoing renal transplantation after preanesthetic volume expansion with 1000 ml saline solution within 10 min. Two diabetic and seven nondiabetic patients received grafts from living donors and the rest from cadaveric donors. Volume expansion induced a significant increase in the cardiac filling pressures (P less than 0.001), which were kept at that level especially at declamping, which was preceded by mannitol infusion. The baseline mixed venous ANP levels were significantly higher in the diabetic (252 +/- 6 pg/ml) than in the nondiabetic group (103 +/- 14 pg/ml; P less than 0.05). In the nondiabetic group, ANP increased to 177 +/- 40 pg/ml as a response to volume loading (P less than 0.05); it was not clearly changed in the diabetic group. Arterial ANP increased from 267 +/- 55 to 343 +/- 75 pg/ml in the diabetic group (P less than 0.05 and from 102 +/- 17 to 147 +/- 31 pg/ml in the nondiabetic group (P less than 0.05). During transplantation, mixed venous ANP decreased to 125 +/- 55 pg/ml in the diabetic and to 80 +/- 10 pg/ml in the nondiabetic group (P less than 0.001). About 30% of circulating ANP was taken up by the transplant irrespective of postoperative graft function. Two patients in each group showed delayed diuresis requiring postoperative dialysis therapy (22% of all cadaveric transplantations). ANP levels at declamping had no correlation to the outcome of kidney function.

Adult↗
PubMed1992

Normal renal sensitivity to atrial natriuretic peptide in Gordon's syndrome.

To test the hypothesis that renal sensitivity to atrial natriuretic peptide (ANP) is impaired in Gordon's syndrome (hypertension and hyperkalaemia with normal glomerular filtration rate) we infused alpha-hANP into two patients with this syndrome (a sister and a brother, 19 and 18 years of age). For comparison, 11 healthy volunteers were also examined. The infusion of alpha-hANP increased urinary volume and excretion of sodium similarly in the patients and controls. The excretion of potassium did not change in either the patients or the controls. The infusion of alpha-hANP had no effect on the serum potassium levels or the plasma CO2 content in the patients. The present results do not confirm the hypothesis of lack of sensitivity to ANP as a pathophysiological concept in Gordon's syndrome.

Adolescent↗
PubMed1992

Pharmacokinetics and effects of atrial natriuretic factor during hypothermic cardiopulmonary bypass.

The pharmacokinetics of a bolus dose of synthetic atrial natriuretic factor (ANF) 50 micrograms and its effects on urine output, blood pressure and plasma renin activity have been studied in 5 patients undergoing hypothermic cardiopulmonary bypass for cardiac surgery. The half-lives of the fast and slow components were 2.4 min and 14.2 min, respectively. The volume of the central compartment was 16.7 l and the volume of distribution at steady-state was 38.9 l. The total plasma clearance was 3.8 l.min-1. ANF significantly increased urine output and decreased blood pressure, but it did not affect plasma renin activity.

Atrial Natriuretic Factor↗
PubMed1992

Responses of atrial natriuretic factor to long-term sodium restriction in mild to moderate hypertension.

The effects of long-term sodium restriction on plasma atrial natriuretic factor (ANF) concentrations, and the role of baseline plasma ANF concentration as an indicator of changes in haemodynamics and left ventricular hypertrophy during this treatment were studied in 40 middle-aged previously untreated mildly to moderately hypertensive men and women in a 6-month controlled randomized study. The main emphasis of the treatment programme was to reduce daily sodium intake to less than 70 mmol. Mean sodium excretion decreased from 148 +/- 74 mmol 24 h-1 to 79 +/- 71 mmol 24 h-1 in the treatment group, but remained unchanged in the control group (173 +/- 68 mmol 24 h-1 vs. 186 +/- 62 mmol 24 h-1; P less than 0.01 for the difference in changes between the groups). Mean plasma ANF concentrations in the treatment group were 52.4 +/- 20.7 (median 50) pg ml-1 at baseline and 38.7 +/- 26.3 (median 42) pg ml-1 at 6 months, and the corresponding values in the control group were 55.5 +/- 20.5 (median 50) pg ml-1 and 46.1 +/- 32.4 (median 50) pg ml-1, respectively (P = NS for the difference in changes). The ANF concentration decreased from 70 +/- 14 pg ml-1 to 32 +/- 26 pg ml-1 in treated subjects with a high baseline plasma ANF concentration (greater than 50 pg ml-1), but increased from 37 +/- 11 pg ml-1 to 45 +/- 27 pg ml-1 in subjects with a low baseline plasma ANF concentration (less than or equal to 50 pg ml-1) (difference in changes P less than 0.001). Compared with treated subjects with low baseline plasma ANF levels and with controls, treated subjects with high baseline plasma ANF levels showed a decrease (P less than 0.05) in interventricular septal and left posterior wall thicknesses, in relative wall thickness, and in peripheral resistance. These results suggest that in mildly to moderately hypertensive subjects long-term sodium restriction decreases high plasma ANF concentrations concomitantly with regression of concentric left ventricular hypertrophy, probably as a result of changes in haemodynamics.

Adult↗
PubMed1992

Renal transplantations from the same kidney donor: outcome of diabetic and non-diabetic patients.

Diabetic (DM) nephropathy is an indication of renal transplantation in 30% of all cases in our hospital. We assessed retrospectively the outcome of these diabetics (DM) in comparison with their non-diabetic (NDM) controls. Each diabetic (n = 24) had a control (n = 24) receiving a kidney from the same donor. There was no difference in the stage of uraemia preoperatively. Anaesthesia and fluid therapy were standardized. Peroperative hypotension occurred more often in diabetics (NS). All operating parameters including cold ischaemia were comparable. Kidney function started immediately in 14/24 in the DM group and 13/24 in the NDM group and was delayed in 10/24 and 11/24, respectively. One diabetic patient rejected the transplant as did two non-diabetic patients. Postoperatively diuretics could be discontinued more often in the DM than in the NDM group (p < 0.05). Antihypertensives had to be started in the NDM more often (NS) than in the DM group. In conclusion, the outcome of diabetic patients after renal transplantation was comparable to their NDM controls.

Adult↗
PubMed1992

Plasma atrial natriuretic factor during ethanol ingestion in volume-loaded subjects.

The present study was designed to test whether ethanol ingestion affects plasma atrial natriuretic factor (ANF) concentration in healthy volunteers. On the basis of previous studies showing that ethanol induces a diuretic response and a decrease in atrial size (atrial distension), it was hypothesized that ethanol intake might be associated with a decrease in plasma ANF level. To somewhat increase plasma ANF level, the subjects were slightly loaded with water before the trial. As compared with juice, ethanol, 1 g/kg within 1 hr, increased urine output [405 +/- 37 (mean +/- SEM) ml/hr vs. 197 +/- 20 ml/hr, P less than 0.001]. Left atrial size decreased similarly (P less than 0.001) with both drinks. Plasma ANF concentration did not change with either ethanol or juice during the 3-hr study period. No changes were observed in plasma arginine vasopressin concentration and plasma renin activity. Our results are in conflict with previous reports in fasted subjects showing significant changes in plasma concentrations of the same hormones. Thus, the basal fluid balance seems to be crucial to the hormonal response to ethanol. The plasma concentrations of the hormones measured in this study do not directly explain the diuretic response to ethanol observed in slightly volume-loaded subjects.

Adult↗
PubMed1991

Prolonged neutral endopeptidase inhibition in heart failure.

We studied the hormonal, renal and hemodynamic effects of prolonged treatment with SCH 39370, a new neutral endopeptidase (NEP) inhibitor, in experimental congestive heart failure (CHF). Coronary-ligated CHF rats and sham-operated controls received vehicle or SCH 39370 30 mg/kg s.c. twice daily for six days. In rats with heart failure, SCH 39370 elevated the high plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) levels 2-fold both initially and at the end of the experiment. Initially, water balance was more negative in SCH 39370-treated CHF rats than in those treated with vehicle. In all SCH 39370-treated rats, ANP, cGMP and electrolyte excretion and diuresis were pronounced for 6 h after injection but attenuated thereafter. Blood pressure and pulse remained unchanged. On reverse phase high performance liquid chromatography (HPLC), ANP-(99-126) appeared to be the only circulating form of ANP in rats with heart failure. Three forms have been discovered in patients with heart failure. HPLC revealed only intact ANP in plasma of rats with heart failure during SCH 39370 treatment. NEP inhibitors may provide a new tool for treating chronic heart failure.

Animals↗
PubMed1991

Neuroendocrine activity in untreated heart failure.

Neuroendocrine activity was studied in 60 consecutive untreated patients with dyspnoea and a clinical suspicion of heart failure. On the basis of the so-called Boston clinical criteria the diagnosis of heart failure was regarded as unlikely in 26 patients, possible in 15 patients, and definite in 19 patients. These groups were studied before any drug treatment was started and were compared with a control group of 69 healthy individuals. Plasma atrial natriuretic peptide concentration was clearly raised in patients with definite heart failure and slightly raised in patients with possible heart failure. Plasma adrenaline concentration was somewhat raised in patients with definite or possible heart failure, whereas plasma noradrenaline concentration was raised only in patients with definite heart failure. Plasma renin activity was not increased in any of the patient groups and plasma aldosterone concentration was slightly increased only in patients with definite heart failure. In the total patient series there were significant correlations between plasma atrial natriuretic peptide concentration and markers of the severity of left ventricular dysfunction. There was some evidence of neuroendocrine activation in untreated heart failure: plasma concentrations of atrial natriuretic peptide and catecholamines were increased but the renin-angiotensin-aldosterone system showed little or no activation.

Aged↗
PubMed1991

Renal and vascular effects of atrial natriuretic factor during cardiopulmonary bypass.

STUDY OBJECTIVE: To evaluate renal and vasodilator effects of synthetic atrial natriuretic factor (ANF) in patients undergoing cardiopulmonary bypass (CPB) with special reference to the applicability of ANF as a diuretic and natriuretic. DESIGN: The study consisted of two parts. The first 15 consecutive patients in a university hospital received a pharmacologically effective bolus dose of 100 micrograms ANF, as demonstrated previously in other studies, or placebo. After analysis of the bolus data (see "Results" section below), the 12 subsequent patients were administered ANF 50 micrograms as a constant 30-min infusion at a rate of 1.67 micrograms/min or placebo. PATIENTS: The patients were scheduled for elective coronary artery bypass grafting operation. There was no evidence of congestive heart failure in any patient, and no one had an endocrine or renal disorder. INTERVENTIONS: After achievement of hypothermia (29 to 30 degrees C of rectal temperature) during CPB, a bolus dose of ANF 100 micrograms was given or an infusion of ANF 1.67 micrograms/min for 30 min, ie, a total dose of 50 micrograms was started. The control patients received placebo correspondingly. Intravenous fluids were administered according to a predetermined scheme. MEASUREMENTS AND MAIN RESULTS: For the pharmacologic effects of ANF urine volume, urinary sodium excretion and mean arterial pressure (MAP) were measured. Only three of the eight patients receiving the bolus dose of ANF had a diuretic and natriuretic response to the drug, and the responses were significantly related (r = 0.91, p less than 0.05 and r = 0.98, p less than 0.001, respectively) to the prevailing MAP at the time of the bolus administration. The bolus dose of ANF decreased MAP significantly (p less than 0.001 vs placebo) from 65 +/- 6 (mean +/- SEM) to 55 +/- 6 mm Hg within 5 min. The infusion of ANF did not affect MAP, but it increased urine output (16.1 +/- 5.0 ml/min, when the data obtained during the 30-min infusion and a 30-min period after the infusion were combined) and urinary sodium excretion (1,651 +/- 514 microEq/min) significantly (p less than 0.05 and p less than 0.01, respectively) as compared with the corresponding values of 3.3 +/- 1.1 ml/min and 386 +/- 141 microEq/min after placebo. CONCLUSIONS: Prevailing arterial pressure is an important determinant of the diuretic and natriuretic activity of synthetic ANF in patients undergoing CPB. A low-dose infusion of ANF (50 micrograms within 30 min) provides diuresis and natriuresis without significant changes in MAP in these patients.

Atrial Natriuretic Factor↗
PubMed1991

Effect of enalapril on plasma atrial natriuretic peptide in late recovery phase of acute myocardial infarction.

A 12 week randomised, double blind, placebo controlled study on the effect of enalapril (5-20 mg daily) on the concentration of plasma atrial natriuretic peptide level and activity of the sympathetic nervous system and renin angiotensin system was done on 27 patients who had suffered an uncomplicated acute myocardial infarction two to six months earlier. None of our patients needed drug treatment for heart failure, but their exercise capacity was markedly limited. Plasma neurohormone concentrations at baseline and after 12 weeks of treatment were also compared with those of healthy controls. Concentrations of plasma atrial natriuretic peptide concentrations remained high throughout the study in those patients on beta-blockers. Enalapril treatment had no definite effect on the concentrations of plasma atrial natriuretic peptide or other neurohormone.

Aldosterone↗
PubMed1990

Raised plasma endothelin-I concentration following cold pressor test.

Plasma concentration of immunoreactive endothelin-1 was measured by radioimmunoassay in 6 healthy subjects before and following cold pressor test by immersion of one fore-arm into ice-water. Mean (SEM) plasma endothelin-1 concentration rose from 1.2 (0.7) to peak value 8.4 (2.3) pg/ml in venous plasma from the immersed hand, and, reaching peak 2 minutes later, from 1.4 (0.5) to 4.6 (2.3) pg/ml in venous plasma from the contralateral hand. In 66 healthy control subjects, venous plasma concentration of endothelin-1 was 2.9 +/- 1.2 pg/ml (mean +/- SD). Exposure to cold is associated with raised blood levels of endothelin-1, which points to a relation between endothelin-1 and vasoconstriction associated with low temperature.

Cold Temperature↗
PubMed1990

Atrial pressure and hormonal and renal responses to acute cardiac tamponade.

The effect of acute cardiac tamponade on atrial pressures, plasma atrial natriuretic factor concentration and renin activity, and renal water and electrolyte excretion was studied in pigs loaded intravenously with hydroxyethyl starch and maintained on a continuous intravenous infusion of isotonic saline solution. Saline solution was infused into the pericardial space in 6 anesthetized pigs until a predetermined decrease of 20% in mean arterial pressure was achieved. Another 6 sham-treated pigs served as controls. Tamponade increased atrial intracavitary pressures but decreased atrial transmural (distending) pressures. These changes in atrial pressures were reversed after release of tamponade. Changes in plasma atrial natriuretic factor concentration correlated positively with changes in atrial transmural pressures. Tamponade increased plasma renin activity and decreased urine flow and renal sodium and potassium excretion, and release of tamponade reversed these changes. Thus, the tamponade-induced reduction in atrial distention is associated with hormonal changes, which may contribute to the reductions in diuresis and natriuresis observed in this connection.

Acute Disease↗
PubMed1990

Correlation of patent ductus arteriosus shunting with plasma atrial natriuretic factor concentration in preterm infants with respiratory distress syndrome.

The concentration of plasma atrial natriuretic factor (ANF) and the mechanism for its secretion were investigated in 17 preterm infants with respiratory distress. Their mean gestational age was 29 wk and wt 1250 g. The infants were followed during the first week of life by sequential Doppler ultrasound studies. Ductal openness versus closure and amount of ductal flow were correlated with plasma ANF concentrations. In a subset of 10 infants, sequential Doppler color flow mapping was used to quantify the ductal flow. During the first 72 h, plasma ANF was high, 361 pg/mL; it decreased to 96 pg/mL by the end of the 1st wk. The ANF level was significantly higher when the ductus was open than closed (393 versus 123 pg/mL, p less than 0.05). In patients with open ductus and bidirectional foramen ovale shunting (n = 3) ANF was 567 pg/mL and in those with left-to-right shunt 355 pg/mL (n 15, NS). The left atrial size, i.e. the left atrial to aortic root ratio, correlated with the amount of ductal shunting (r = 0.63, p less than 0.01) and with ANF concentration (r = 0.46, p less than 0.02). The correlation of ANF values and the magnitude of left-to-right ductal shunting assessed by color flow mapping was highly significant (r = 0.66, p less than 0.001). In these patients, the elevation of ANF is reflective of ductal flow.

Age Factors↗
PubMed1990

Elevation of plasma atrial natriuretic peptide in rats with chronic heart failure by SCH 39370, a neutral metalloendopeptidase inhibitor.

Hormonal, renal and blood pressure effects of SCH 39370, a selective inhibitor of neutral metalloendopeptidase (endopeptidase 24.11, NEP), were studied in a chronic, congestive heart failure (CHF) model produced by coronary artery ligation in the rat. Sham-operated control rats and rats with CHF were treated either with vehicle or SCH 39370, 30 mg/kg s.c. b.i.d. for 2.5 days. Plasma levels of atrial natriuretic peptide (ANP) and urinary excretion of cyclic GMP (cGMP) were clearly raised in rats with CHF as compared with controls during vehicle treatment. SCH 39370 caused a further increase in plasma ANP in CHF rats but not in control rats. Urinary excretion of immunoreactive ANP and cGMP increased during SCH 39370 treatment both in CHF rats and in controls. SCH 39370 treatment resulted in an initial increase in urine volume in rats with CHF whereas urine sodium excretion did not change significantly. No changes in renal function due to SCH 39370 treatment were seen in control rats. Systolic blood pressure, plasma renin activity and urine excretion of catecholamine metabolites (4-hydroxy-3-methoxyphenyl acetic acid and metanephrines) did not change during SCH 39370 treatment either in controls or in CHF rats. We conclude that the NEP-inhibitory compound SCH 39370 is capable of increasing plasma ANP concentration and urinary excretion of cGMP in rats with chronic CHF. In this severe heart failure model, the possible beneficial effects of additional ANP increments may be blunted, however. NEP inhibitors offer a novel approach to study the significance of ANP elevation in chronic CHF.

Animals↗
PubMed1990

Plasma level of atrial natriuretic peptide as an indicator of increased cardiac load in uremic patients.

Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay in 43 non-dialyzed uremic patients at rest and during maximal exercise to assess the possible relationship between plasma ANP levels and cardiac function, as judged by M-mode echocardiography and exercise tolerance. Patients with poor exercise capacity (exercise time less than 6 min) on dynamic exercise test had decreased left ventricular ejection fraction, increased left atrial diameter, and increased left ventricular mass index (LVMI), compared with patients with better exercise capacity (exercise time greater than 6 min). Plasma ANP was significantly higher in patients with poor exercise capacity and impaired cardiac function (202 pg/ml [95% confidence interval 119 to 284] at rest and 227 pg/ml [149 to 304] during exercise), compared with patients with better exercise capacity (75 pg/ml [50 to 102], p less than 0.005, and 123 pg/ml [80 to 167], p less than 0.05, respectively). Plasma ANP increased significantly (p less than 0.005) during exercise only in patients with better cardiac function. The best correlation among the variables studied was found between LVMI and plasma ANP concentration at rest (r = 0.56, p less than 0.001) and during exercise (r = 0.51, p less than 0.005), whereas neither blood pressure nor renal function showed any significant correlation with ANP levels. We conclude that plasma ANP levels are elevated in uremic patients with impaired cardiac function, correlating with increased LVMI. Plasma ANP determinations are useful in identifying increased cardiac load and consequent cardiac hypertrophy and dysfunction with known associations with increased cardiovascular mortality in patients with chronic renal failure.

Adult↗