Development of a new method of impedance cardiography, the “Multi-Site–Frequency- Electromechano-cardiography” (msf-ELMC)” for the measurement of stroke volume and ejection fraction. The method calculates an “electrically operative length” between the electrodes instead of measuring the commonly used but irrelevant “surface distance” between the electrodes and it also defines the body by electrical measurements at multiple sites at multiple frequencies . Most importantly it also eliminates body weight and body height from the formula since this introduced strong bias towards normal values in the past and therefore made it useless in heart failure where the method would be needed most. The msf-ELMC method also uses “black box models” such as neuronal nets for the calculation of stroke volume and ejection fraction instead of the necessarily incomplete and incorrect geometrical models.The method enables the quantification of heart function for the first time also in heart failure
Characterisation of the haemodynamic and autonomic consequences associated with B12 deficiency using the above equipment. Patients with B12 deficiency show a lack of rise of total peripheral resistance, a diminished rise of sympathicovagal balance and lack of modulation of baroreceptor reflex sensitivity on upright tilt.
This technique has also enabled the extensive analysis of substrates and hormones in the interstitial space.
This technique was used successfully to analyse continuously and on-line subcutaneous glucose concentration.
Development of a new technique for the analysis of interstitial fluid, the “open tissue perfusion with ionic reference technique”.
“The bone is the bank account and if it is low it is commonly the result of an imbalance of deposits and of disbursements, but not the result of a corrupt bank account manager”
(Skrabal et al. Yearbook: “What`s New in Medicine 2002")
Patients with primary osteoporosis in a high percentage show previously unconsidered subclinical disturbances for the development of osteoporosis. These include minor disturbances of gastrointestinal function causing an impaired calcium absorption (eg subclinical pancreatic insufficiency, often symptomless lactose malabsorption etc) and/or mild renal tubular disturbances (renal hypercalciuria, mild phosphate diabetes, incomplete renal tubular acidosis).Often these subclinical disturbances are combined and the more risk factors present the more severe the “primary osteoporosis”. This implies that type I and type II osteoporosis are very heterogenous diseases and in most instances not a bone disease but a disease of the gut and the kidney causing negative electrolyte (calcium, phosphate and alkali) balance.
Renal tubular acidosis in patients with primary osteoporosis is more common than in the community and may be an important factor in a subset of patients with “primary” osteoporosis (together with M. Weger, W. Weger first authors).
Carriers of the Gly16 variant of the beta-2 adrenoceptor show an impaired vasodilatory response to beta 2 agonists (together with first author G Gratze).
African Caribbians with essential hypertension exhibit a preponderance of the Gly16 allele as compared to the normotensive control population (together with P. Kotanko, first author)
Cultured skin fibroblasts of salt sensitive subjects show a reduced expression of beta-adrenoceptors but normal expression of alpha-2 receptors (together with P. Kotanko, First Author)
Salt resistant subjects may have arisen from a low salt environment since they show a stable extracellular volume and preserved fight and flight reaction also during a low salt intake whereas salt sensitive subjects show evidence for a markedly reduced extracellular volume and a reduced pressor response to stress under a low salt intake.
Healthy subjects after sodium restriction from 13g/d to 3g/d show a marked fall of central sympathetic drive as assessed by the 0.1 Hz band of systolic blood pressure.
Formulation of the “Salt Sensitivity Hypothesis for the Pathogenesis of Essential Hypertension”: Enhanced Upregulation of the Operative alpha2/beta2 adrenoceptor ratio by Salt in Salt Sensitive Subjects.
Salt sensitive subjects show an exaggerated upregulation of the “operative alpha2/beta2 adrenoceptor ratio” in response to salt.
A low salt intake in healthy subjects leads to upregulation of vasodilating beta-2 adrenoceptors and downregulation of vasoconstricting alpha-2 adrenoceptors.
Salt sensitive subjects are also noradrenaline sensitive showing an exaggerated pressor response to the infused NA regardless of the level of salt intake.
Salt resistant subjects have a very stable extracellular volume regardless of their level of salt intake as shown by a very constant uric acid/creatinine clearance ratio on low and high salt intake. In contrast salt sensitive subjects are volume expanded on a high salt intake and volume contracted on a low salt intake as shown by a high uric acid/creatinine clearance ratio (reduced proximal tubular uric acid reabsorption) on a high salt intake and by a low uric acid/creatinine clearance ratio (enhanced proximal tubular uric acid reabsorption) on a low salt intake.
Salt sensitive subjects have a reduced salivery sodium concentration implying altered transcellular sodium transpor.
Normotensive subjects with a positive family history of hypertension as a group are salt sensitive, showing a fall of blood pressure after salt restriction only detectable using the bMAPa: This implies that the parents of the salt sensitive subjects acquired the hypertension on the basis of salt sensitivity and that salt sensitivity may have a genetic basis.
Use of bMAPa enables to show that about 30 to 40 % of normotensive subjects show a fall of blood pressure after salt restriction from 200 mmol (13g/day) to 50 mmol/day (3g/day) which is reversible after re-exposure to the high salt diet.
Improvement of baroreceptor reflex sensitivity by a high potassium diet.
Introduction of the “basal blood pressure average (bMAPa)” for the accurate assessment of individual blood pressure level.
Lactose intolerance in patients with type I osteoporosis is more common than in the population and may through impaired calcium absorption be a major factor in “primary” osteoporosis (together with G. Finkenstedt, first author).
Description of a diurnal rhythm of transmucosal potential difference in healthy subjects not being related to the secretion of adrenal steroids.
The same level of renin in essential hypertension and renal hypertension results from different mechanisms, namely increased sympathetic tone in essential hypertension, being blockable by iv propranolol in essential but not in renal hypertension.
Increased half life of renin in malignant hypertension contributing to the inappropriately high levels of this enzyme and to the vicious cycle in this condition.
Nomogram to obtain normal values of plasma renin activity based on fasting urinary sodium and fasting urinary creatinine: A smaller normal range can be obtained as compared to the normal range obtained by 24 hour urinary sodium since not only sodium balance but also the state of hydration of the subject is considere.
Equations for the prediction of normal values of total body water, exchangeable sodium and potassiu.
Use of the above technique for the detection of a “sick cell syndrome” in secondary adrenocortical insufficiency encompassing intracellular sodium accumulation.
Introduction of 77Br into clinical medicine (1970) , Use for the isotope dilution technique together with 43K and 24Na to enable discrimination of the three isotopes without previous separation