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Biomedical subjects

K Theisen

Publications and source records attributed to K Theisen.

At least 19 recordsLinked to original sources
PubMed1992

Photoaffinity labeling of plasma membrane receptors for aldosterone from human mononuclear leukocytes.

Non-genomic effects of aldosterone on the sodium-proton-antiport have been shown in human mononuclear leukocytes which could be related to a new aldosterone membrane receptor. In the present paper plasma membranes from human mononuclear leukocytes were covalently photolabeled with a [125I]-aldosterone derivative. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed significant aldosterone binding at a molecular weight of approximately 50000 Dalton which was absent with 1 microM cold aldosterone, but not cortisol in the binding media. The presence of the sulfhydryl agent dithiothreitol did not affect results suggesting the absence of disulfide bridges in the steroid binding domain of the receptor. These data are the first to define the molecular weight of the membrane receptor for aldosterone.

Affinity Labels↗
PubMed1992

[Myocardial contrast echocardiography for the follow-up after percutaneous transluminal coronary angioplasty].

Myocardial contrast echocardiography was performed, before and after successful elective percutaneous transluminal angioplasty (PTCA) of a main coronary artery, in 35 patients (31 men, 4 women; mean age 56 +/- 6 years). After intracoronary injection of microbubbles-containing 2 ml iopromide, contrast half-life (t/2) and maximal echo-intensity (Imax) in the myocardial region supplied by the target vessel were measured. While t/2 decreased from 8.3 +/- 5.4 s to 5.7 +/- 3.3 s (P less than 0.0002), mean Imax remained unchanged (27.4 +/- 10.7 vs 26.1 +/- 10.1 grey value units). Repeat cardiac catheterization with contrast echocardiography was performed a mean of 37 weeks (7-53) later in 13 of 35 patients with optimal echo image quality. Re-stenosis of at least 75% was demonstrated in six patients, while in seven vessel diameter had decreased by less than 30%. In all patients with re-stenosis t/2 had increased by about 20 to 100% of the initial value. It was always over 5 s (mean 6.2 +/- 1.6 s before, 4.7 +/- 1.7 after PTCA, and 6.2 +/- 1.2 s at the end of the follow-up). In one patient a prolonged t/2 persisted due to vessel dissection. Mean t/2 remained unchanged in patients without re-stenosis (5.6 +/- 2.1 s before, 3.5 +/- 1.15 s immediately after PTCA, and 3.6 +/- 1.25 s at the follow-up examination). These data suggest that contrast half-life is suitable for demonstrating changes in myocardial perfusion after PTCA.

Angina Pectoris↗
PubMed1992

Conversion of atrial fibrillation to sinus rhythm: a possible side effect of transesophageal echocardiography.

Transesophageal echocardiography (TEE) is accepted as the procedure of choice for the diagnosis of intracardiac sources of systemic embolism. A case report is presented on a 74-year-old patient with atrial fibrillation referred for TEE evaluation after an acute embolic event. During TEE, atrial fibrillation converted to sinus rhythm. Although TEE is a very safe method, which is performed in increasing numbers of patients, this is the first reported case of conversion of atrial fibrillation to sinus rhythm during the procedure. We suggest that no restriction should be imposed on the use of TEE in patients with atrial fibrillation, as the small risk associated with conversion of atrial fibrillation is outweighed by the potential diagnostic benefits.

Aged↗
PubMed1992

Effects of graded exercise on blood pressure, heart rate, and plasma hormones in cardiac transplant recipients before and during antihypertensive therapy.

The effects of graded supine ergometry on blood pressure, heart rate, and plasma hormones were studied in 14 hypertensive heart transplant recipients before and after 2 weeks and 6 months of enalapril (20 mg/day) plus furosemide (20-80 mg/day) alone or combined with verapamil (120-360 mg/day). Each time, measurements were obtained at rest and at 25 and 50 W exercise. Antihypertensive therapy normalized blood pressure, while heart rate and the blood pressure response to exercise remained unaltered. Pretreatment resting plasma renin activity and catecholamine levels were normal, while atrial natriuretic factor and cyclic guanosine monophosphate concentrations were elevated. All hormones increased significantly with exercise. During treatment, plasma renin activity increased and atrial natriuretic factor and cyclic guanosine monophosphate levels decreased significantly, with a blunted exercise response; concentration of catecholamines increased significantly, with augmented exercise response. Thus, the chosen regimen allowed effective, lasting BP control in hypertensive transplant patients but was associated with significant changes in plasma hormones. Whereas the rise in plasma renin activity may be attributed to converting enzyme inhibition, the decreases in atrial natriuretic factor and cyclic guanosine monophosphate and increases in catecholamine levels seem to indicate marked changes in resting and particularly exercise hemodynamics during antihypertensive therapy.

Adult↗
PubMed1992

Serial Doppler echocardiographic assessment of left and right ventricular filling for non-invasive diagnosis of mild acute cardiac allograft rejection.

Detection of acute cardiac allograft rejection (AR) remains an important clinical challenge. The role of Doppler echocardiography for the non-invasive diagnosis of AR is controversial, in particular with regard to milder forms of rejection. This study was designed to evaluate the potential of Doppler echocardiography for the non-invasive diagnosis of mild AR. Serial measurements of left and right ventricular filling parameters were performed in 31 heart transplant recipients and compared with simultaneously obtained endomyocardial biopsies. To account for biological and technical variability, consecutive rejection-free studies were used to calculate 95% confidence limits for mitral and tricuspid maximum early flow velocity and pressure half time. Measurements obtained during mild AR were then compared to these data. The study demonstrated that all parameters varied considerably between consecutive rejection-free examinations. Changes in left and right ventricular filling parameters during mild AR rarely exceeded the calculated 95% confidence limits. Thus Doppler echocardiography appears of little value for the non-invasive diagnosis of mild acute cardiac rejection.

Adult↗
PubMed1992

The early mineralocorticoid effector mechanism, the sodium-proton exchanger, is sensitized in lymphocytes from patients with Cushing's syndrome.

OBJECTIVE: In-vitro binding of aldosterone to mineralocorticoid receptors on human mononuclear leucocytes and its effects on the intracellular sodium and potassium concentrations, the sodium-proton exchanger and cell volume of human mononuclear leucocytes have been described for normals. In the present paper this easily accessible human cell model was studied in Cushing's syndrome to detect abnormalities of the mineralocorticoid effector mechanism. DESIGN: The rate of cell swelling in isotonic sodium propionate reflecting the activity of the sodium-proton exchanger and the stimulatory activity of 1.4 nM aldosterone were determined in a Coulter Channelyzer. PATIENTS: Nine female patients with pituitary-dependent (7) and adrenal hypercortisolism (2) were included in the study. MEASUREMENTS: Compared with controls from matched normals, the cell volume of human mononuclear leucocytes in a physiological buffer was significantly increased in the patients. The increment of cell size in isotonic sodium propionate was elevated in the presence of 1.4 nM aldosterone only. RESULTS: These findings are equivalent to an excess stimulation of the sodium-proton exchanger by aldosterone in these patients. Plasma cortisol was inversely correlated with the cell swelling in propionate. CONCLUSIONS: These data indicate that the early mineralocorticoid effector mechanism in human mononuclear leucocytes from patients with Cushing's syndrome has an increased sensitivity to aldosterone compared with that from normals. This could reflect an adaptation of the cellular electrolyte metabolism to the decreased mineralocorticoid activity balancing the increased glucocorticoid activity. If representative of other cell systems, e.g. renal tubular cells, these findings would identify accompanying electrolyte disorders in these patients not as a side-effect of glucocorticoids, but as a result of an increased sensitivity to endogenous mineralocorticoids.

Adolescent↗
PubMed1992

Membrane receptors for aldosterone: a novel pathway for mineralocorticoid action.

Rapid nongenomic in vitro effects of aldosterone on intracellular electrolytes, cell volume, and Na(+)-H+ antiport have been found in human mononuclear leukocytes (HML). Binding of 125I-labeled aldosterone to plasma membranes of HML shares important features with these functional data. This includes a very low apparent dissociation constant (Kd) of 0.1 nM for both aldosterone and the effect on the Na(+)-H(+)-antiport, a high turnover rate, and the almost exclusive binding selectivity for aldosterone. Dexamethasone, RU 26988, corticosterone, ouabain, amiloride, and 18-hydroxyprogesterone were inactive as ligands. Deoxycorticosterone acetate had an intermediate activity with an apparent Kd of 100 nM. These findings are the first to demonstrate membrane binding of aldosterone being compatible with major aspects of its nongenomic effects.

Aldosterone↗
PubMed1992

Quality of life in long-term survivors of orthotopic heart transplantation.

This study was designed to evaluate quality of life and life changes after heart transplantation in long-term survivors, to compare the patients' results with those obtained from healthy subjects of similar age, and to correlate quality of life with psychological and clinical variables. Questionnaires were mailed to all 43 adult German-speaking transplant patients operated between 1982 and 1986. Forty-one (95%) of this patient population completed the questionnaires; 52 controls answered those questions not addressing transplant-specific issues. 83% of the transplant patients versus 88% of the controls rated global quality of life as "good" or "excellent". Psychological affect and well-being were comparable in both groups. 70% of the transplant patients versus only 30% of the controls stated "to be bothered by symptoms". Despite that response, heart transplant recipients perceived postoperative life changes mostly as positive, although sexual function and professional situation had worsened in 34% and 41%, respectively. Global quality of life correlated best with job satisfaction (r = 0.65, p less than 0.01), satisfaction about health (r = 0.64, p less than 0.01), well being (r = 0.53, p less than 0.01), and everyday life function (r = 0.53, p less than 0.01), and correlated negatively with depression (r = -0.40) and physical symptoms (r = -0.36). The study shows that the subjective quality of life of long-term survivors after heart transplantation is similar to that of healthy individuals of the same age group. Thus, survival is certainly not the only indicator of success; aspects of quality of life must also be included in cost effectiveness and/or cost benefit considerations in transplantation policies.

Activities of Daily Living↗
PubMed1992

[ST-segment depressions and spontaneous changes in blood pressure and heart rate in simultaneous 24-hour recording in hypertensive patients].

In 15 patients with essential hypertension (but without coronary heart disease) simultaneous 24-h monitoring of the ST-segment and blood pressure was performed. Twenty-six periods with significant ST-segment depressions were recorded. In 10/26 periods with ST-segment depressions blood pressure was elevated, heart rate was increased in 20/26 ST-segment depressions. During nine periods with ST-segment depressions angina pectoris was reported, and 27 anginal attacks without ST-segment depressions were observed. These data show ischemic episodes in hypertensive patients without coronary heart disease being associated with spontaneous increases of blood pressure and/or heart rate.

Angina Pectoris↗
PubMed1991

High affinity aldosterone binding to plasma membrane rich fractions from mononuclear leukocytes: is there a membrane receptor for mineralocorticoids?

In vitro effects of aldosterone on the intracellular concentrations of sodium, potassium and calcium, cell volume and the sodium-proton-antiport have been described in intact human mononuclear leukocytes (HML). In the present paper, the binding of a [125I]-labeled aldosterone derivative to plasma membrane rich fractions of HML was studied. High affinity binding of the radioligand with an apparent Kd of approximately 0.1 nM was found. Aldosterone displaced the tracer at a similar Kd. Both canrenone and cortisol were inactive as ligands up to concentrations of 0.1 microM. The findings are the first to demonstrate membrane binding sites with a high affinity for aldosterone, but not for cortisol. These data are perfectly compatible with major properties of steroidal effects on the sodium-proton-antiport in HML and thus very likely represent membrane receptors for aldosterone.

Aldosterone↗
PubMed1991

Short-term effects of oral enoximone on hemodynamics, exercise capacity, anaerobic threshold, and arrhythmias in congestive heart failure.

Enoximone, a phosphodiesterase-inhibitor, is a potent inotropic vasodilator agent that causes a marked improvement in hemodynamics in patients with congestive heart failure. The acute effects of oral enoximone on rest and exercise hemodynamics, ejection fraction, aerobic metabolism, exercise capacity, and arrhythmias were studied in 11 patients with moderate to moderately severe dilative cardiomyopathy after 8 days of enoximone (100 mg tid) in addition to baseline therapy (diuretics and digitalis). The cardiac index increased from 2.44 +/- 0.45 to 2.72 +/- 0.50 l/min/m2 (p less than 0.01) at rest and from 4.00 +/- 0.96 to 4.75 +/- 0.95 l/min/m2 (p less than 0.005) during exercise. Pulmonary wedge pressure decreased from 16.8 +/- 7.3 to 12.5 +/- 6.5 mmHg (p less than 0.005) at rest and from 28.2 +/- 8.0 to 24.5 +/- 10.3 mmHg (p less than 0.05) during exercise. Systemic vascular resistance decreased from 1608 +/- 243 to 1495 +/- 300 dynes*sec*cm-5 (p less than 0.05) at rest and from 1152 +/- 155 to 1027 +/- 236 dynes*sec*cm-5 (ns) during exercise. The anaerobic threshold, which was recorded simultaneously, increased from 13.2 +/- 2.7 to 15.5 +/- 2.5 ml/kg/min VO2 (p less than 0.02). The radionuclide ventriculography ejection fraction improved from 21.7 +/- 5.0 to 28.1 +/- 9.1% (p less than 0.01) during exercise; the changes at rest were not significant (20.8 +/- 6.2 vs 25.8 +/- 8.4%). Exercise tolerance showed an increase of 16% (492 +/- 133 to 573 +/- 135 sec, p less than 0.005). The resting heart rate remained unchanged (81.8 +/- 13.4 vs 81.8 +/- 11.9). Interestingly, 24-h Holter monitoring revealed more or new repetitive arrhythmias in 9/11 patients.

Adult↗
PubMed1991

The Na(+)-H+ exchanger is stimulated and cell volume increased in lymphocytes from patients with essential hypertension.

A stimulation of the Na(+)-H+ exchanger has been shown in platelets of hypertensive man and lymphocytes of spontaneously hypertensive rats. In the present paper, human mononuclear leukocytes (HML) were investigated in 12 patients with essential hypertension with regard to the activity of the Na(+)-H+ exchanger and HML volume. The swelling of HML in isotonic sodium propionate was determined using a Coulter Channelyzer. Compared with matched normotensives, the cell volume of HML in a physiological buffer was significantly increased in essential hypertension (P less than 0.05). The amiloride-inhibitable rate of cell swelling in isotonic sodium propionate was also increased in HML from hypertensives. Amiloride (400 mumol/l) abolished the difference in cell volume within 1 min. These data show a functional swelling of HML in essential hypertension, probably due to an activation of the Na(+)-H+ exchanger. If also representative of smooth muscle cells, these findings could explain hypertensive vessel wall hypertrophy, in part, as functional cell swelling.

Amiloride↗
PubMed1991

Rapid effects of mineralocorticoids on sodium-proton exchanger: genomic or nongenomic pathway?

High-affinity aldosterone binding sites have been described in human mononuclear leukocytes (HML), and in vitro effects of aldosterone on intracellular sodium, potassium, and calcium concentrations and cell volume have been shown in HML. In the present paper, the response of the sodium-proton exchanger of the cell membrane to agonists and antagonists was studied by determining the kinetics of HML swelling in isotonic sodium propionate. Within 1-2 min of incubation, aldosterone significantly stimulated propionate-induced swelling by an additional 30-50% at concentrations as low as 0.07 nM. This effect was not blocked by the classical aldosterone antagonists potassium canrenoate or canrenone at concentrations of 140 or 700 nM. Hydrocortisone and dexamethasone were effective agonists only at much higher concentrations (4,000 nM). These data are not well explained by a mechanism of steroid action involving the interaction of a steroid receptor complex with nuclear DNA, since the effect on the sodium-proton exchanger is too fast. The findings could indicate distinct membrane receptors with a high affinity for aldosterone, but not hydrocortisone, and rapid direct membrane effects of aldosterone. These putative novel receptors may in turn bind novel aldosterone antagonists with possible diuretic and vasodilator effects distinct from those of spironolactones.

Aldosterone↗
PubMed1991

Regression of left ventricular hypertrophy in hypertensive heart transplant recipients treated with enalapril, furosemide, and verapamil.

BACKGROUND: This prospective study was designed to examine whether left ventricular (LV) hypertrophy of the denervated transplanted heart may be reversed by medical therapy and, if so, to investigate the time course of this process and its effect on exercise capacity, myocardial function, and cardiac hemodynamics. METHODS AND RESULTS: Ten hypertensive heart transplant recipients with LV hypertrophy were evaluated before therapy with enalapril plus furosemide alone or combined with verapamil, at initial blood pressure (BP) control and after 3, 6, 9, and 12 months, using 24-hour noninvasive ambulatory BP monitoring, M-mode and two-dimensional echocardiography, and supine bicycle ergometry. Average 24-hour systolic and diastolic BP declined from 158 +/- 10 and 104 +/- 7 mm Hg to 129 +/- 9 and 84 +/- 10 mm Hg at initial BP control (p less than 0.005 and p less than 0.025, respectively) and total peripheral resistance from 1,687 +/- 177 to 1,376 +/- 122 dyne.sec.cm-5 (p less than 0.025), remaining normal thereafter. Exercise capacity remained unchanged during the study. LV mass, mass-to-volume ratio, and end-diastolic septal plus posterior wall thickness decreased progressively from 211 +/- 30 g, 2.49 +/- 0.62 g/ml, and 25.7 +/- 2.6 mm to 184 +/- 26 g, 2.22 +/- 0.46 g/ml, and 22.5 +/- 1.9 mm after 3 months (all p less than 0.025) and to 174 +/- 25 g, 2.07 +/- 0.38 g/ml, and 21.5 +/- 1.5 mm after 6 months (all p less than 0.005), remaining unaltered at 9 and 12 months. A correlation was found between the decrease in average 24-hour mean BP and LV mass after 3 months of antihypertensive therapy (r = 0.71, p less than 0.05). Systolic meridional wall stress, LV end-diastolic and stroke volume, ejection fraction, and cardiac output remained unchanged throughout the observation period. CONCLUSIONS: The results indicate that regression of LV hypertrophy is induced by effective antihypertensive therapy in the denervated transplanted heart. The extent of decrease in average 24-hour BP appears to be the main determinant for the extent of reduction in LV mass. LV afterload as characterized by systolic meridional wall stress, LV size and pump function, and physical exercise capacity of the transplant patients are not influenced by the therapeutic regimen chosen in this study.

Adult↗