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Biomedical subjects

K Kochsiek

Publications and source records attributed to K Kochsiek.

At least 109 records · Page 6Linked to original sources
PubMed1985

Muzolimine therapy in patients with congestive heart failure in comparison with furosemide pretreatment. Effect on digoxin plasma concentration.

Eight patients suffering from congestive heart failure (NYHA III-IV) and pretreated with digoxin received muzolimine over 14 days in an open clinical study. The muzolimine dose was adjusted to 3/4 of the daily furosemide dose necessary to keep the body weight constant at least three days prior to the onset of muzolimine treatment. Plasma concentrations of epinephrine, norepinephrine, aldosterone, renin and digoxin were determined on the last day of the furosemide treatment period and on the last day of the muzolimine period. No significant changes were observed in plasma concentrations of epinephrine, aldosterone, renin, creatinine, and potassium. After muzolimine treatment, however, body weight and sonographically determined liver size decreased further and plasma norepinephrine concentrations were significantly lower. The digoxin concentrations did not change after muzolimine treatment. The results demonstrate the beneficial effect of muzolimine in heart failure patients. Since plasma concentration of digoxin does not change despite marked diuretic effects of muzolimine no relevant interaction between both substances has to be expected.

Adult↗
PubMed1984

[Effect of nifedipine and nitroglycerin on epicardial vessels in coronary heart disease].

The effect of nifedipine and nitroglycerin on the diameter of epicardial coronary arteries, the stenosis diameter, as well as arterial blood pressure and heart rate were recorded in 20 patients with coronary-heart disease. Nifedipine (20 mg sublingually) caused a significant fall in arterial pressure and a significant rise in heart rate. Additional administration of nitroglycerin (0.8 mg sublingually) caused a further fall in arterial pressure while heart rate remained constant. A definite relaxation (vasodilatation) of the epicardial vessels was demonstrated after nifedipine and a further increase after nitroglycerin. While nifedipine on average led to a significant increase in the diameter at the site of stenosis, response of individual stenoses was highly variable. In one patient with subtotal stenosis of the anterior interventricular branch a complete, transitory occlusion at the site of the stenosis occurred during nifedipine medication. This paradoxical reaction was not noted after nitroglycerin. Relaxation of the epicardial coronary arteries by nifedipine with suppression of phasic tone thus seems to be the major part of its anti-anginal effect. This effect is potentiated by nitroglycerin so that the combination of nitrate and calcium-antagonist appears to be therapeutically reasonable. In individual patients, however, there may be a paradoxical reaction to nifedipine.

Adult↗
PubMed1984

Role of the renin-angiotensin system in the development of congestive heart failure in the dog as assessed by chronic converting-enzyme blockade.

Hormonal factors may be important in the regulation of peripheral vascular resistance (PVR) in congestive heart failure (CHF). The role of the renin-angiotensin system in the development of CHF was studied in 16 unanesthetized dogs. CHF was induced by rapid right ventricular pacing, with and without chronic converting-enzyme inhibition (CEI) by captopril. The hemodynamic changes and the activity of renin, aldosterone, norepinephrine and vasopressin were studied. The control dogs showed a greater decrease in cardiac output and a greater increase of mean pulmonary artery pressure than the captopril-treated group. In the group with CEI, only a small, transient increase in PVR was observed during the development of CHF; in the control group, there was an increase of 94% of basal values. The control group showed a continual increase of renin, aldosterone and norepinephrine. Four control dogs showed an inappropriately high secretion of arginine vasopressin. The increase of sympathetic nervous activity was only insignificantly attenuated by angiotensin II inhibition and was without a considerable influence on PVR except for an early transient increase in vascular tone. In our animal model, the renin-angiotensin system plays an important role in the regulation of PVR in CHF. In this kind of CHF the sympathetic nervous system appears to be of minor importance for the long-term regulation of PVR. Plasma arginine vasopressin levels were increased in control dogs; this increase may contribute to the increased vascular tone.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Different effects of interventions suppressing free fatty acid metabolism on myocardial ischemia.

We studied the effects of different metabolic interventions, which stimulate oxidative myocardial carbohydrate metabolism, on ischemic stress during repeated coronary occlusions of three minutes in open-chest dog hearts. Increase of glucose concentration in plasma and decrease of peripheral lipolysis by glucose-insulin-potassium (n = 6) had no substantial beneficial effects on myocardial damage indicated by hemodynamic, electrocardiographic, and metabolic parameters. Infusion of lactate and pyruvate (10 mM, n = 6) was detrimental. Only activation of pyruvate dehydrogenase by dichloroacetate (n = 6) without influence on plasma osmolality reduced epicardial ST-segment elevations (-42%) and myocardial release of potassium (-36%), phosphate (-58%), and lactate (-39%). Elevations of plasma osmolalities by 10 and 20 mOsm with the metabolically inert mannitol increased ECG changes, functional loss and release of potassium, phosphate, and lactate during ischemia in our model. It is suggested, that the oxygen-saving potency of metabolic interventions can exert univocal beneficial effects in experimental and in clinical conditions only when systemic hyperosmolality and hypervolemia are avoided.

Animals↗
PubMed1984

Demonstration of organ specific antibodies against heart mitochondria (anti-M7) in sera from patients with some forms of heart diseases.

Using submitochondrial particles (SMP) from beef heart, pig kidney and rat liver in the ELISA, we detected partial organ specific anti-mitochondrial antibodies (AMA) against heart and kidney SMP in sera from patients with different forms of cardiomyopathies. Serum samples from 50 of 159 patients with congestive or hypertrophic cardiomyopathy (31%) and from two of 15 patients with acute myocarditis (13%) were AMA positive. These AMA could be clearly differentiated from other known AMA (anti-M1-M6) and were therefore named anti-M7. Thirteen of the 52 sera (25%) reacted only with heart SMP (type a) and 39 showed a cross-reaction with kidney, lung and pancreas mitochondria (type b). However, using liver SMP, no positive reaction was found. The anti-M7 type a and b activity was abolished completely by absorption with heart SMP. The anti-M7 antibodies were directed against an antigen which co-purified with the inner mitochondrial membrane and had a molecular weight of 67,000-72,000. They seem to be confined to some forms of cardiomyopathies and myocarditis of unknown aetiology and were not detected in sera from patients with other diseases.

Animals↗
PubMed1984

Comparative haemodynamic studies on the acute cardiac effects of alcohol in the rat and guinea pig.

Left ventricular pressure-volume relations, indices of contractility and the resting tension curve were recorded in wistar rats and guinea pigs prior and during acute intoxication with ethyl alcohol. Indices were recorded at blood alcohol concentrations between 2% (200 mg per 100 ml) and 6% in rats and 1.6% and 2.8% in guinea pigs. Due to the higher heart weight and body weight, end-diastolic volume in guinea pigs was increased for any end-diastolic pressure as compared with rats. On the other hand maximal isovolumetric pressure in the rats was twice as high as in the guinea pigs. At a blood alcohol level of 2.8% left ventricular isovolumetric pressure was reduced by 13%, and maximal rate of pressure rise by 25% in rats and guinea pigs. Though the experimental method was identical in rats and guinea pigs, a blood alcohol concentration of 1.6% in the guinea pigs was associated with a mortality of 55% and a blood alcohol concentration of 2.8% with a mortality of 75% whereas the mortality rate in rats was 0% at these blood alcohol concentrations. The reason for this difference could not be entirely clarified. In conclusion, acute alcohol intoxication results in a comparable dose-dependent cardiac depression in rats and guinea pigs despite marked differences in basic haemodynamics of the two species.

Alcoholic Intoxication↗
PubMed1984

[Acute hemodynamic effects of alifedrine in patients with heart failure].

The newly synthesized cardiotonic agent alifedrine (1-cyclohexyl-3-[(1S, 2R)-2-hydroxy-methyl-2-phenylethylamino]-propan-1-one) was shown to have vasodilating and positive inotropic effects in experimental animals. The effectiveness was tested in 8 patients with congestive heart failure already receiving digitalis and diuretics. After the intravenous administration of 40 mg alifedrine, cardiac output and stroke volume index increased and systemic vascular resistance and left ventricular filling pressure decreased. Left ventricular ejection fraction improved and there were no significant changes in heart rate and mean aortic pressure. Alifedrine, therefore, improves left ventricular performance in patients with congestive heart failure treated with digitalis and diuretic agents.

Adult↗
PubMed1983

Quantification of antimyosin antibodies in experimental myocarditis by a new solid phase fluorometric assay.

A solid phase fluorometric assay of high sensitivity and specificity for detection of antimyosin antibodies is described. The method consists of 4 basic steps: (1) coating the carrier stiQ with myosin; (2) incubation of the stiQ in the test serum; (3) labeling of the bound antibodies by FITC-anti-immunoglobulin antibodies; and, (4) quantitation of the bound antibodies in a fluorometer (FIAXTM). Using a purified myosin preparation as antigen, the assay was tested in experimental myocarditis of rabbits injected with cardiac proteins. Reproducibility was excellent, standard deviation of intra-assay variance being 7.86%, and inter-assay variance 9.45%. When compared with immunodiffusion, a complement fixation test with myosin and indirect immunofluorescence, the assay described proved superior since it allows simple monitoring of serum concentrations of antimyosin antibodies.

Animals↗
PubMed1983

Diagnostic relevance of humoral and cytotoxic immune reactions in primary and secondary dilated cardiomyopathy.

Circulating muscle-specific antimyolemmal antibodies (AMLAs) were found in 18 of 61 patients with secondary dilated cardiomyopathy (DC). All 18 patients had clinical or histologic evidence of previous perimyocarditis. AMLAs were found both in patients' serum samples and bound to the sarcolemmal sheath of the autologous myocardial biopsy specimen. Only AMLAs in postmyocardiac DC induced cytolysis of vital cardiocytes in the presence of complement, whereas hepatocytes remained unaffected. Titers of AMLAs correlated with the degree of cardiocytolysis. In contrast, antiinterfibrillary antibodies were found in 49% patients with primary DC (n = 79) and in 61% of patients (n = 30) with alcoholic DC. The incidence of antifibrillary antibodies of the antimyosin type was 23 and 24%, respectively. Incidence of both antibodies increased according to the severity assessed by New York Heart Association functional classes. Circulating immune complexes assayed by a new Clq-solid phase fluorometric assay were present in 30% of patients with postmyocarditic DC only. Lymphocyte-mediated cytotoxicity against heterologous cardiac target cells (K-cell activity) was measured in 33% of patients each with primary and secondary alcoholic DC but not postmyocarditic DC. There were no blocking factors in primary but were some in alcoholic heart disease.

Antibodies↗
PubMed1983

Alpha-receptor restriction of coronary blood flow during atrial fibrillation.

The effects of atrial fibrillation (AF) on coronary circulation before and after alpha-receptor blockade were studied in 14 anesthetized, open-chest dogs. AF was induced by electrical stimulation of the left atrial appendage; identical rhythmic heart rates were adjusted by left atrial pacing. During atrial pacing, coronary vascular resistance (CVR) was 0.97 +/- 0.10 mm Hg X min X 100 g/ml (resistance units [RU]), coronary blood flow (CBF) 125 +/- 14 ml/min X 100 g, and oxygen saturation 30 +/- 2%; plasma epinephrine was 193 +/- 42 pg/ml and norepinephrine 584 +/- 111 pg/ml. During AF, CVR was higher (1.16 +/- 0.11 RU, p less than 0.0005), whereas CBF (92 +/- 9 ml/min X 100 g, p less than 0.001) and coronary sinus oxygen saturation (24 +/- 2%, p less than 0.0025) were lower than during atrial pacing. When AF was induced, epinephrine increased to 333 +/- 98 pg/ml (p less than 0.05) and norepinephrine to 1,005 +/- 214 pg/ml (p less than 0.005). The large increase in plasma catecholamines suggested an activation of the sympathoadrenal system during AF. In addition, the alpha-receptor blocker phenoxybenzamine (10 mg/kg, intravenously) abolished the differences in CVR, CBF and oxygen saturation between AF and atrial pacing. The data suggest that the decrease in CBF and increase in CVR during experimentally induced AF are caused by coronary vasoconstriction, mediated by sympathetic activation of alpha receptors in the coronary vascular bed.

Animals↗
PubMed1983

Effect of intravenous and intracoronary nifedipine on coronary blood flow and myocardial oxygen consumption.

The effect of intravenous and intracoronary nifedipine on coronary sinus blood flow, coronary vascular resistance, and myocardial oxygen consumption was studied in 20 patients with coronary artery disease. An intravenous infusion of 1.0 mg nifedipine resulted in a decrease in mean aortic pressure, an increase in heart rate and coronary blood flow, and no significant change in myocardial, oxygen consumption. In contrast, the intracoronary injection of 0.1 mg nifedipine led to a moderate reduction in mean aortic pressure, no change in heart rate, an increase in coronary blood flow, and a significant reduction in myocardial oxygen consumption. During rapid atrial pacing before and approximately 6 minutes after the intracoronary nifedipine injection, coronary blood flow and myocardial oxygen consumption reached identical levels. Thus, only intracoronary injection of nifedipine increases coronary flow in the presence of reduced myocardial oxygen consumption. After intravenous administration, reflex tachycardia counteracts the direct myocardial effect of nifedipine and the potential oxygen-saving effect of afterload reduction. There is no evidence of a prolonged oxygen-sparing effect after cessation of the immediate effects.

Adult↗
PubMed1983

Immune reactions in infective endocarditis. I. Clinical data and diagnostic relevance of antimyocardial antibodies.

Clinical data from 72 patients with infective endocarditis (41 with defined pathogen, 31 with no pathogen isolated) were analyzed with respect to the diagnostic relevance of immunologic parameters. In our patients from a rural area, no significant changes in the epidemiology and pathogenesis of infective endocarditis were observed. Antiendocardial and antisarcolemmal (ASA) antibodies were demonstrated in 60% to 100% of cases. Their frequency depended on the endocarditic pathogen and on the clinical course: in subacute or chronic endocarditis these antibodies were found regularly, in acute lethal cases their occurrence was diminished. Whereas antiendocardial antibodies are diagnostic markers of endocarditis, ASA and antimyolemmal antibodies in particular most likely indicate myocardial involvement in endocarditis. Only complement fixing antimyolemmal antibodies induced cytolysis of vital, adult, heterologous cardiac cells. Our data suggest that antibody-mediated cytolysis in vitro may also play a pathogenetic role in vivo.

Adult↗
PubMed1983

Immune reactions in infective endocarditis. II. Relevance of circulating immune complexes, serum inhibition factors, lymphocytotoxic reactions, and antibody-dependent cellular cytotoxicity against cardiac target cells.

Circulating immune complexes (IC) were detected in 35 out of 41 patients (85%) with infective endocarditis of known bacterial origin in contrast to only 9 out of 20 patients (45%) with endocarditis but negative blood cultures (p less than 0.05). Peak IC levels of 33.25 +/- 24.33 micrograms/ml in the early period fell significantly to 8.38 +/- 13.37 micrograms/ml after antibiotic treatment (p less than 0.001). High levels of IC coincided with relative hypocomplementemia. Erythrocyturia was observed in 51 of 58 IC-positive patients demonstrating peripheral sequelae of circulating IC. Incidence and concentrations of IC correlated neither with the mere presence of the rheumatoid factor nor with the titers of antimyolemmal antibodies, nor with antibody mediated cytolysis in the presence of complement. Serum inhibition factors (SIF) and E-rosette inhibitory factors (RIF) were not demonstrated, indicating that IC in endocarditis do not suppress phytohemagglutinin-induced lymphocyte proliferation or the E-rosetting of T cells. Significant lymphocytotoxicity against heterologous cardiac target cells without serum (LC) could be demonstrated in 11 out of 23 patients (48%) with endocarditis as compared to its absence in controls (n = 33, p less than 0.01). In assays of antibody-dependent cellular cytotoxicity (ADCC), either enhancement or blocking of lymphocytotoxicity by autologous serum or both was observed. The modulation of lymphocytotoxicity was most likely due to antimyolemmal antibodies, to IC, or to both, although effects of other serum factors cannot be ruled out completely.

Antibody-Dependent Cell Cytotoxicity↗