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Biomedical subjects

R Dietz

Publications and source records attributed to R Dietz.

At least 181 records · Page 10Linked to original sources
PubMed1993

[Induction of the atrial and ventricular ANF synthesis in experimental heart failure after aortocaval shunt].

Using the aortocaval shunt as a model of chronic volume overload in the rat, changes of the ANF system were analyzed. A constant shunt volume of 57% increased the heart weight after 14 days by 28% (from 917 +/- 16 to 1177 +/- 28 mg, p < 0.001). The ANF plasma concentration increased from 30.4 +/- 15.1 to 108.2 +/- 30.6 pg/ml (p < 0.05), which corresponds to levels which are reached in early stages of heart failure. ANF tissue concentrations, however, were decreased in both atria while no significant change could be observed in the ventricles. The analysis of the ANF-mRNA expression as an indicator for the ANF-synthesis showed significant increase in the ANF-mRNA/Actin-mRNA ratio in the right atrium by 56% and in the left atrium by 63%. In ventricular tissue the relative ANF-mRNA increased by 58% (right) and 83% (left ventricle). Increased ANF plasma levels during chronic volume overload are due to increased atrial and ventricular ANF-synthesis. The induced ventricular mRNA indicates the participation of the ventricles in the humoral response to volume overload.

Animals↗
PubMed1993

[Interaction between the renin system and parasympathetic nervous system in heart failure].

UNLABELLED: The increase of sympathetic activity in heart failure is accompanied by a reduced parasympathetic tone. The renin-angiotensin system has not only multiple interactions with the sympathetic nervous system, but may also influence vagal tone directly by angiotensin II. Animal studies show a reduction of parasympathetic tone by a direct action of angiotensin II in the area postrema where the blood brain barrier is absent. It is possible that, in addition to the sympathetic and renin-angiotensin system, the parasympathetic nervous system may also influence prognosis in heart failure. Therefore, baroreflex sensitivity as (CBS) an index of vagal tone was examined in 35 patients with moderate to severe heart failure (NYHA II-III). Independent of the severity of heart failure BS was the lower the higher plasma-renin-activity was. Fifty-six months after the initial examination a comparison of the surviving patients (Group 1, n = 20) with the patients who died or underwent heart transplantation (Group 2, n = 15) did not reveal significant differences in the initial hemodynamic data. However, group 2 patients showed a tendency to higher initial plasma-renin-activity and significantly lower BS 1.3 +/- 0.2 vs. 2.2 +/- 0.3 ms/mm Hg; p < 0.05). CONCLUSION: In patients with heart failure a relation between the renin-angiotensin system and the parasympathetic nervous system is likely as there is a significant negative relationship between BS and plasma-renin-activity. Among patients with a similar degree of heart failure a low vagal tone identifies patients with a poor prognosis.

Adult↗
PubMed1993

Improvement of cardiac function by angiotensin converting enzyme inhibition. Sites of action.

BACKGROUND: The discovery of new properties of angiotensin converting enzyme (ACE) inhibitors in addition to their well-known ability to lower blood-pressure, such as antiproliferative actions and antiadrenergic and vagal-stimulating effects, has contributed to the usefulness of this class of agents in the prevention and treatment of cardiovascular diseases. METHODS AND RESULTS: The contribution of an activated endocrine and/or cardiac paracrine renin-angiotensin system to the progression of cardiovascular diseases with the exception of renovascular hypertension is not fully understood. In particular, the following questions were addressed: 1) Is the facilitation of noradrenaline release in the genesis of arrhythmias a target for ACE inhibition? 2) Is an impaired nutritional cardiac blood flow in heart failure a target for ACE inhibition? 3) Is the intimal hyperplasia that results from coronary angioplasty a target for ACE inhibition? 4) Is the diastolic dysfunction associated with left ventricular hypertrophy in essential hypertension a target for ACE inhibition? In an isolated rat heart preparation with ischemia-induced arrhythmias, none of the ACE inhibitors nor an angiotensin II antagonist was able to significantly suppress the incidence or severity of arrhythmias. In 12 patients with New York Heart Association functional class II-IV heart failure, a fall in cardiac filing pressures after ACE inhibition was associated with an immediate rise in cardiac output and an increase in coronary blood flow of almost 30%. In 24 patients with angina at rest, a preceding percutaneous transluminal coronary angioplasty, and a second angioplasty, control angiograms at 6 months revealed a high degree of restenosis in both ACE inhibitor-treated and placebo patients. Luminal narrowing amounted to 72% in the placebo group and 61% in the ACE inhibitor group. The differences between placebo and enalapril were statistically not significant. In 12 patients with essential hypertension treated with 5 mg cilazapril, left ventricular mass was reduced by 30%, which was closely related to the change in mean arterial blood pressure. The concomitant normalization of the diastolic filling pattern by ACE inhibition, however, was not related to the respective changes in blood pressure. CONCLUSIONS: Promising experimental data regarding the antiproliferative effects of ACE inhibitors in preventing restenosis could not be transferred into clinical benefits for patients who underwent repeat coronary angioplasty. Possible antiarrhythmic effects of ACE inhibitors are not likely to be caused by their suppression of noradrenaline release during myocardial ischemia. ACE inhibition was effective in reducing coronary resistance in patients with severe heart failure, thereby augmenting nutritional cardiac blood flow. ACE inhibition also effectively induced a regression of left ventricular hypertrophy in essential hypertension. The associated normalization of diastolic filling pattern may represent an important goal in the treatment of hypertension.

Angioplasty, Balloon, Coronary↗
PubMed1993

[Clinical findings with inhibitors of the renin-angiotensin system].

Cardiovascular diseases are often associated with increased activity of the systemic and/or local renin-angiotensin systems. Hence, with respect to the coronary vessels, it has been demonstrated that in patients with severe heart failure inhibition of the renin-angiotensin system with an angiotensin converting enzyme (ACE) inhibitor clearly reduces resistance in the systemic, renal and cardiovascular systems. This reduction in resistance improves the blood supply to the failing heart while, at the same time, diminishing the external workload. It is most likely this effect that contributes towards the improved progression of the underlying disease observed after ACE inhibitor administration. The clinical efficacy of ACE inhibitors in patients who had been subjected to repeated coronary angioplasty has, however, been disappointing. Although these agents exerted a clear inhibitory effect on neo-intima proliferation after balloon dilatation performed on animals, it was not observed in patients with coronary artery disease and did not prevent restenosis. In patients suffering from heart failure there is an increase in sympathetic tone and a decrease in parasympathetic tone. An increase in activity of the renin-angiotensin system produces an increase in sympathetic activity at the level of the peripheral sympathetic synapses and vagus blockage via its effect on the vagal centres in the postremal area. Both effects can be clearly diminished by administering ACE inhibitors. Although high sympathetic tone and low parasympathetic activity are indicators of low life expectancy in heart failure, a clear correlation between the incidence of sudden cardiac death and the changes in autonomic nervous system activity has not yet been established.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Angiotensin-converting enzyme inhibitors and renal function in heart failure.

Patients with severe heart failure often exhibit signs of an impaired renal function. As judged from serum urea and creatinine concentrations, renal function may deteriorate further after the addition of angiotensin-converting enzyme (ACE) inhibitors to therapy. The beneficial effect of unloading the failing heart by reducing the systemic outflow resistance is opposed by a potentially harmful effect of unloading the kidney by preferentially reducing the outflow resistance of the glomerulus. However, development of functional renal insufficiency is unlikely and is a rare cause for withdrawing ACE inhibitors when certain precautions are considered: (1) The initial dose of the ACE inhibitor has to be reduced with increasing severity of heart failure (the titration period thereafter should be monitored carefully); (2) an increase in serum creatinine not exceeding 30% of the basal value may be taken as evidence for a beneficial action of the drug, which in addition to altering cardiac function alters kidney function (when the increase in serum creatinine is considered to be of clinical significance, it seems wise to reduce the dose of diuretics first--thereby neuroendocrine stimulation can be attenuated and the dependency of renal filtration from angiotensin II-induced efferent vasoconstriction can be reduced); and (3) the coadministration of inhibitors of prostaglandin synthesis (e.g., acetylsalicylic acid) appears to be associated with a higher risk of impairing renal function: the decrease in glomerular filtration rate is more marked and the compensatory increase in renal plasma flow following ACE inhibition is no longer observed.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Baroreceptor-mediated release of vasopressin in patients with chronic congestive heart failure and defective sympathetic responsiveness.

In patients with congestive heart failure (CHF), overactivity of the sympathetic nervous system may be accompanied by an impairment of the baroreflex control mechanism. To evaluate the reflex responses of the sympathetic nervous system, the renin-angiotensin system and vasopressin release to baroreceptor unloading, 38 patients with left ventricular dysfunction were studied. Hemodynamic data, and plasma norepinephrine, renin activity and vasopressin concentrations were measured before and 60 minutes after administration of high-dose hydralazine (0.4 mg/kg intravenously). On the basis of blood pressure response to vasodilator administration, patients were divided arbitrarily into those with a decrease in mean arterial blood pressure greater than or equal to 15 mm Hg (group A; n = 12) and those with a decrease less than 15 mm Hg (group B; n = 26) compared with control values. In response to hydralazine, heart rate decreased in group A from 100 to 92 beats/min (p less than 0.001) and increased in group B from 90 to 96 beats/min (p less than 0.05). In group A, hemodynamic changes induced by hydralazine were accompanied by a decrease in plasma norepinephrine from 822 to 518 pg/ml (p less than 0.01) and an increase in plasma vasopressin from 8.4 to 45.2 pg/ml (p less than 0.001). In group B, plasma norepinephrine and vasopressin did not change significantly (407 vs 447, and 8.4 vs 8.3 pg/ml, respectively). Plasma renin activity remained unchanged in group A and increased in group B (p less than 0.001). The data show that baroreceptor-mediated release of vasopressin is not impaired in patients with CHF and a defective sympathetic reflex control mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Prostaglandin endoperoxide synthase substituted with manganese protoporphyrin IX. Formation of a higher oxidation state and its relation to cyclooxygenase reaction.

The heme in prostaglandin endoperoxide synthase (PGH synthase) was substituted with Mn(III)-protoporphyrin IX. The resulting enzyme, Mn-PGH synthase, showed full cyclooxygenase activity but only 0.9% of the peroxidase activity of the native iron enzyme. During the reaction with exogenous or endogenously produced hydroperoxides, a spectral intermediate of Mn-PGH synthase was observed. The electronic absorption bands of the resting enzyme at 376, 472, and 561 nm decreased, and the intermediate's bands at 417, around 513, and 625 nm appeared. The rate constant of the formation of the intermediate was about 10(4) M-1.s-1 at 22 degrees C, three orders of magnitude lower than with the iron enzyme. Spectral properties, conditions of formation, and the suppressed formation in the presence of electron donors provide evidence for a higher oxidation state of Mn-PGH synthase, tentatively a Mn(IV) species. This species was assigned to an intermediate in the peroxidase reaction of Mn-PGH synthase, the low activity of which was explained by the rate-limiting slow reaction of Mn-PGH synthase with hydroperoxides. The findings and interpretation are consistent with the published properties of other manganese-substituted peroxidases. Although the cyclooxygenase activity was similar to that of Fe-PGH synthase, the cyclooxygenase reaction of Mn-PGH synthase showed distinct differences in comparison with Fe-PGH synthase. A longer activation phase was observed which resembled the time course of the formation of the higher oxidation state. Glutathione peroxidase with glutathione, a hydroperoxide-scavenging system, inhibited the cyclooxygenase of Mn-PGH synthase at concentrations where the activity of Fe-PGH synthase was not affected. It is demonstrated that Mn-PGH synthase requires higher concentrations of hydroperoxides for the activation of the cyclooxygenase. These findings suggest that the substitution of iron with manganese in PGH synthase does not change the mechanism of the enzyme. The main difference is the much lower rate of the reaction with hydroperoxides which affects both the peroxidase activity and the hydroperoxide-dependent activation of the cyclooxygenase. A reaction scheme for Mn-PGH synthase is proposed analogous to that suggested for Fe-PGH synthase (Karthein, R., Dietz, R., Nastainczyk, W., and Ruf, H. H. (1988) Eur. J. Biochem. 171, 313-320).

Animals↗
PubMed1992

Target size analysis of prostaglandin endoperoxide synthase. Radiation inactivation of both cyclooxygenase and peroxidase correlated with the monomer of 72 kDa.

To determine the size of the functional catalytic unit of prostaglandin endoperoxide (prostaglandin H) synthase, radiation inactivation experiments were performed. Both microsomes from ovine seminal vesicles and purified enzyme were irradiated with 10 MeV electrons. The enzymic activities of prostaglandin H synthase, cyclooxygenase and peroxidase, showed mono-exponential inactivation curves dependent on radiation dose, indicating molecular masses of approximately 72 kDa. The enzyme in microsomes, in its native environment, as well as in its purified state after solubilisation with nonionic detergent showed identical molecular masses. The results clearly demonstrate that the monomer of the enzyme with an apparent molecular mass of 72 kDa (SDS/PAGE) is the functional unit for catalysis of both activities. Hence the two active sites of cyclooxygenase and peroxidase reside on the same polypeptide chain.

Animals↗
PubMed1992

Comparison of captopril with enalapril in the treatment of heart failure: influence on hemodynamics and measures of renal function.

Twenty-nine patients with severe heart failure (NYHA III) were randomly assigned to receive therapy with an angiotensin converting enzyme inhibitor (ACE inhibitor), either captopril or enalapril. The mean daily dosage of captopril was 56 +/- 5 mg and of enalapril 9.5 +/- 0.4 mg. After a mean of 8 +/- 1 days, the influence of both ACE inhibitors on hemodynamics and renal function was compared. The mean arterial pressure in the group treated with captopril (Group A) fell by 9 +/- 3 mmHg (p less than 0.01), and in the group treated with enalapril (Group B) it fell by 12 +/- 3 mmHg (p less than 0.001). The difference between the groups was not significant. Heart rate decreased in both groups; however, the change was significant (p less than 0.05) only in patients treated with enalapril (-11 +/- 3 bpm in Group B vs. -7 +/- 4 bpm in Group A). Stroke volume index increased by 6 +/- 3 ml/m2 in Group A (p less than 0.05) vs. 10 +/- 2 ml/m2 in Group B (p less than 0.01). The increase in stroke volume index was not significantly different between the two groups. Mean decreases in pulmonary artery and right atrial pressure were also comparable in both groups. Thus, hemodynamic improvements were similar during therapy with either captopril or enalapril. Serum sodium and potassium before therapy were 137 +/- 1 mmol/l and 4.1 +/- 0.1 mmol/l, respectively, in group A and 139 +/- 1 mmol/l and 4.0 +/- 0.1 mmol/l, respectively, in group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril↗
PubMed1992

[The importance of CT for the diagnosis of adrenal gland tumors: myelolipoma].

Myelolipoma is a rare benign tumour of the adrenal cortex. 20% of the patients have intratumoral, mostly tiny foci of calcifications. In most cases CT, as the gold standard for imaging the adrenal gland, is able to diagnose the myelolipoma. MR yields no additional information. Even large tumours with or without calcifications can remain without surgical intervention if there is a regular follow-up. The indications for surgical management are reduced by the characteristic appearance of this tumour on CT scan.

Adrenal Gland Neoplasms↗
PubMed1992

[Reparative effects of ACE inhibitors on the heart].

Diastolic dysfunction is often present in patients with arterial hypertension. It is not only the consequence of an increased left ventricular muscle mass but also due to a progressive fibrosis of the cardiac interstitium. Experimental studies have shown a close relationship between the degree of interstitial cardiac fibrosis and the activity of the renin-angiotensin system (RAS). Reversal of collagen deposition can be induced by inhibition of the RAS. The purpose of this study was to evaluate the therapeutic potential of ACE inhibitors not only in lowering blood pressure in patients with essential hypertension, but also in normalizing an impaired diastolic filling pattern in the left ventricle. Monotherapy with a single dose of 2.5-5 mg Cilazapril for a period of 6 months was effective in reducing mean arterial blood pressure by about 10 mmHg over the entire 24-h interval. The main reduction occurred throughout the day, but lower blood pressure values during the night were hardly affected at all. The pre- and post-treatment values of the 24-h blood pressure were subjected to a modified Fourier analysis, which did not reveal any disturbances in the circadian blood pressure rhythm by the ACE inhibitor. Left ventricular mass, as calculated from echocardiographic measurements, was reduced by 30% after 6 months of treatment. The degree of regression of LV hypertrophy was closely related to the drug-induced fall in mean arterial pressure. The abnormal left ventricular filling pattern before treatment with a predominance of the late diastolic filling period was corrected by 6 months of ACE inhibitor treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Comparative research on cellular immunostimulation by whole-body irradiation].

The effect of the cellular immune response by total body irradiation was investigated. The transplant survival (skin grafts) was determined as immune parameter. Donors were colony-bred Wistar rats and recipients were colony-bred Sprague-Dawley rats. The investigations were carried out with irradiated rats and with rats irradiated after thymectomy and/or adrenalectomy as well as with animals without irradiation. A single total-body irradiation (1 and 2 Gy) was administered. The skin graft survival in irradiated rats was significant shorter (radiogenic immunostimulation) than in unirradiated rats; there were no significant differences between the operated (thymectomy and/or adrenalectomy) and not operated animals. Including precedent examinations this radiogenic immunostimulation is caused by a relatively selective inactivation of T-suppressor cells.

Adrenalectomy↗
PubMed1991

Hemodynamic and neuroendocrine response to acute administration of the phosphodiesterase inhibitor BM14.478 in patients with congestive heart failure.

The benzimidazol analogue BM14.478 is a phosphodiesterase inhibitor with both vasodilator and positive inotropic properties. Hemodynamic parameters and plasma hormone levels of 8 patients (1 female, 7 male) with chronic congestive heart failure NYHA Classes II-IV (1 patient with coronary artery disease, 7 patients with primary dilated cardiomyopathy) were assessed before and until 6 h after the intravenous application of 1.0 mg BM14.478. There was a significant decrease of mean pulmonary artery pressure (28 +/- 11 vs. 23 +/- 11 mmHg; p less than 0.05), mean right atrial pressure (8.6 +/- 5.2 vs. 5.0 +/- 4.7 mmHg; p less than 0.02), and systemic vascular resistance (1651 +/- 484 vs. 1206 +/- 252 dynes.s.cm-5; p less than 0.05) as early as 10 min after injection of BM14.478. Pulmonary vascular resistance also was reduced (128 +/- 86 vs. 61 +/- 39 dynes.s.cm-5, 30 min after injection; p less than 0.02). Simultaneously there was a significant increase of cardiac index (2.3 +/- 0.7 vs. 3.1 +/- 0.8 l.min-1.m-2, 10 min after injection; p less than 0.02), and stroke volume index (28.8 +/- 11.7 vs. 33.9 +/- 8.5 ml.min-1.m-2; 30 min after injection; p less than 0.05). Although mean heart rate did not change significantly, some patients reacted with a transient increase. There was also a slight but insignificant increase of the double product. No serious side effects were observed. The hemodynamic improvement was followed by a delayed reduction of plasma levels of epinephrine (51 +/- 20 vs. 41 +/- 21 pg/ml; p less than 0.02; 30 min after injection) and atrial natriuretic peptide (229 +/- 283 vs. 121 +/- 168 pg/ml; p less than 0.05; 1 h after injection). Mean levels of plasma norepinephrine, however, did not change significantly and individual responses showed large variations, which could not be predicted by the behavior of the hemodynamic parameters. Three of eight patients (2 of these with elevated baseline filling pressures) even showed a marked increase of plasma norepinephrine levels after BM14.478. Response of plasma renin activity and plasma vasopressin levels to BM14.478 also was heterogeneous. According to the results of this study, acute administration of the phosphodiesterase inhibitor BM14.478 has an immediate beneficial hemodynamic effect in patients with severe congestive heart failure by reducing both preload and afterload, and by increasing cardiac index and stroke volume. However, this improvement of hemodynamic parameters is not necessarily accompanied by a favorable short-term response of plasma hormones, and therefore does not allow any conclusions on survival of these patients.

Adult↗
PubMed1991

Transcription, storage and release of atrial natriuretic factor in the failing human heart.

1. In this study the relationship between the synthesis of atrial natriuretic factor at the level of atrial natriuretic factor mRNA and the atrial storage and circulating plasma levels of atrial natriuretic factor were investigated in 15 patients with heart failure. The patients underwent right and left heart catheterization before cardiac surgery for valve replacement or coronary artery bypass grafting. 2. Plasma concentrations of atrial natriuretic factor were correlated to atrial levels of atrial natriuretic factor mRNA. Atrial levels of atrial natriuretic factor mRNA and plasma concentrations of atrial natriuretic factor exhibited a close correlation to both pulmonary artery pressure and left atrial pressure. No relationship, however, could be found between the right atrial content of atrial natriuretic factor and both the expression of atrial natriuretic factor mRNA in the atria and the plasma levels of atrial natriuretic factor. 3. From these data it may be concluded that increased plasma levels of atrial natriuretic factor in the pressure- and/or volume-overloaded heart are associated with an elevated level of atrial natriuretic factor mRNA. We suggest that not only plasma levels of atrial natriuretic factor but also the expression of atrial natriuretic factor in the atrial are related to left ventricular filling pressures in the failing human heart.

Atrial Natriuretic Factor↗