[Artificial heart valves and intravascular hemolysis].
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Biomedical subjects
Publications and source records attributed to E Erdmann.
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The time course of the reversal of toxic and nontoxic effects of digoxin by digoxin-specific antibody fragments (Fab) was measured in isolated human ventricular myocardium. A concentration of 2 X 10(-6) mol/l digoxin was used to produce positive inotropy followed by mechanical signs of toxicity. After addition of a 1.5-fold higher molar concentration of digoxin-specific Fab, signs of toxicity disappeared within 30 min and digoxin-induced force of contraction decayed with a monoexponential time course with a half-life of 52 min. This rate of decay was almost identical to that observed for the dissociation of the digoxin-(Na+ + K+)-ATPase complex in human heart cell membranes. It is concluded that digoxin-specific Fab are capable of completely removing digoxin from its binding sites, the maximal rate of removal of digitalis glycosides from the (Na+ + K+)-ATPase is limited by the dissociation rate constant, and there is a close correlation between the degree of binding of digitalis glycosides to the (Na+ + K+)-ATPase and the increase in force of contraction.
Percutaneous transfemoral valvuloplasty was performed in 20 patients (aged 25-83 years; mean 62) with marked signs of aortic valve stenosis, some calcified, others noncalcified. The transvalvar systolic pressure gradient was reduced from a mean of 104 +/- 7 mm Hg to a mean of 46 +/- 4 mm Hg, the valvar opening area from 0.38 +/- 0.04 cm2 to 0.74 +/- 0.04 cm2. The result was judged to be unsatisfactory in four patients and required aortic valve replacement after initially good results from the balloon dilatation. Serious complications were reversible ventricular fibrillation and reversible cerebral ischemia with partial hemiparesis in one patient each. In three patients the femoral artery had to be repaired at the site of puncture, twice the balloon ruptured without sequelae, once reversible pericardial effusion occurred, and twice there were reactions to antibiotics given after the procedure. Invasive re-catheterizations were performed in four patients, at intervals of three months: no increase in pressure gradient was observed. The results indicate that reduction of the transvalvar pressure gradient by 40 mm Hg can produce rapid reversal of heart failure and a symptom-free state even in patients who were already decompensated.
Cardiac catheterisation and coronary angiography were performed in 100 patients preceding a planned renal transplantation. Coronary heart disease was revealed in 64 patients: stenoses of 50-70% in 28, 71-90% in 16, over 90% in 20 patients. For stenoses above 50% the sensitivity of clinical symptoms was 0.52, their specificity 0.64. For stenoses over 70% the specificity was 0.58; over 90% it was 0.70. Typical symptoms of angina were less common in dialysis patients with coronary heart disease than is usual in other patients with coronary heart disease. Total duration of dialysis as well as frequency and severity of coronary heart disease did not correlate. In 19 of the 100 patients valvar disease was also present, with a discrepancy between the severity of clinical and of hemodynamic findings. Incidence and severity of valvar disease increased with the duration of dialysis. Transplantation was postponed in 11 patients (bypass operation in 3, balloon dilatation in 2, valve replacement in 6). Transplantation was advised against in four (severe coronary heart disease in 2, cardiomyopathy in 2).
Positive inotropic responses to dobutamine have been examined using isolated myocardium from guinea pigs und humans. The potency (EC50) of dobutamine was 1.5 X 10(-6) mol/l on guinea pig papillary muscles, 1.8 X 10(-6) mol/l on guinea pig left atria and 2.5 X 10(-6) mol/l on human papillary muscle strips. In guinea pig cardiac muscles, Schild plots for the beta 1-selective antagonist, 1-practolol, using dobutamine as agonist, had slopes of less than unity. This suggested the involvement of other receptors in the inotropic response to dobutamine. The beta 2-selective antagonist, ICI 118,551, but not the alpha 1-selective antagonist, prazosin, attenuated the dobutamine response in guinea pig papillary muscles. Both ICI 118,551 and prazosin shifted the dobutamine concentration-response curve in guinea pig left atria. The positive inotropic response to dobutamine in human papillary muscles was antagonised by l-practolol and ICI 118,551 but not by prazosin. The maximal inotropic response to dobutamine was 90% that of calcium measured in the same guinea pig papillary muscles but only 37% that of calcium in human papillary muscle strips. This reduced maximal effect of dobutamine in human myocardium is probably a disease-induced change but species variations cannot be excluded.
The different causes of cardiogenic shock and circulatory failure have to be treated according to their aetiology and the state of the patient. Recent experience with percutaneous transfemoral valvuloplasty in 33 patients with aortic stenosis and angioplasty of occluded coronary arteries in acute postoperative myocardial infarction in 13 patients is in favour of active treatment of patients before and even after circulatory failure has occurred. Aortic valvuloplasty was performed successfully and with minor complications in 5 patients in cardiogenic shock.
Plasma levels of ANF were determined and chromatographically analysed in normotensive controls, cirrhotic patients with and without ascites, hypertensive patients, patients with congestive heart failure and heart transplant recipients. A comparison of baseline plasma levels allowed for the conclusion that cirrhotic patients do not differ in this regard from control subjects (9.0 +/- 1.3, n = 41 vs. 9.6 +/- 1,0 fmol/ml, n = 51). Cirrhotic patients with ascites do not have lower plasma levels than cirrhotic patients without ascites (8.8 +/- 1.4, n = 8 vs 8.6 +/- 1.5 fmol/ml, n = 10). Stimulation of the ANF-system by head-out water immersion, however, revealed an impaired increase in ANF release in cirrhotic patients with ascites (146 +/- 18% vs 204 +/- 16%). Patients with cardiovascular disease display tonically-elevated ANF plasma levels. Heart failure patients displayed the highest plasma concentration (81.5 +/- 32.7 fmol/ml, n = 17), whereas plasma levels in hypertensive patients ranged from normal to greatly elevated (61.7 +/- 13.2 fmol/ml, n = 36). Heart transplant recipients also had significantly elevated plasma levels as compared to control subjects (31.2 +/- 7.9 fmol/ml, n = 14) but levels were lower than in hypertensive patients in spite of a comparable arterial pressure. Short term ventricular pacing (f = 150/min for 5 min) revealed an impaired phasic activity of the ANF system in heart failure patients and heart transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
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Primary chylopericardium proved to be the (rare) cause of chronic, symptom-poor pericardial effusion in a 19-year-old man. Echocardiography and pericardiocentesis provided a firm diagnosis. Lymphography demonstrated extravasation into the mediastinum but no direct connection into the pericardial sac. Ligation of the thoracic duct at diaphragmatic level and pericardiostomy achieved a cure. Secondary chylopericardium requires treatment of the underlying disease, e.g. mediastinal tumor. Chylopericardium after thoracic or cardiac operation without signs of tamponade is preferably treated conservatively by pericardiocentesis and diet.
The effect of antihypertensive treatment with 6-12 mg of the loop diuretic piretanide over 12 weeks on Na+-Li+ countertransport, and on extra- and intracellular electrolyte composition was studied in 10 previously untreated patients with essential hypertension. These data were compared with 10 sex- and age-matched controls. Blood pressure fell from 180 +/- 18.3/110.5 +/- 9.8 to 154.7 +/- 9.7/92.5 +/- 10.9 mmHg during treatment. Na+-Li+ countertransport was significantly higher in hypertensives (0.36 +/- 0.13 mmol X l-1 rbc X h-1) compared with controls (0.25 +/- 0.05; P less than 0.05). Na+-Li+ countertransport and intracellular electrolyte composition remained unchanged whereas the extracellular potassium concentration fell from 4.28 +/- 0.51 to 3.98 +/- 0.36 mmol/l (P less than 0.05). No increase in the intracellular Na+ content as compared with normotensive controls was found. It is concluded that the intracellular Na+ concentration is not a marker for essential hypertension. The Na+-Li+ countertransport does not seem to be directly related to elevated blood pressure but seems to be a general marker for diseases associated with an increased risk for the development of hypertension.
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The assumption that the red blood cell can be used as a model for ouabain receptor regulation in heart muscle has been tested using isolated tissues from humans, guinea pigs, and chickens. The following results were obtained: The affinity of the ouabain receptor was similar in both human erythrocytes and right atrial appendage, but the density of binding sites was much lower on the erythrocytes. There was no correlation between the binding capacity in both tissues. Ouabain receptor occupation was closely correlated with inhibition of Na+/K+-transport in human erythrocytes and chick heart nonmuscle cells in culture. In contrast, in chick heart muscle cells, an occupation of 40% of the receptors decreased the Na+/K+-transport rate by only 10%. In hypokalemia, the ouabain binding capacity was increased in human and guinea pig erythrocytes but not in guinea pig heart muscle. Such increases were seen in chick heart nonmuscle cells in moderate hypokalemia but in heart muscle cells only after severe hypokalemia. Incubation of chick heart muscle cells in toxic but not in "therapeutic" ouabain concentrations increased the number of ouabain receptors. Increases in receptor number attenuated the positive inotropic and toxic actions of ouabain. These variations between ouabain receptor regulation in red blood cells and heart muscle of several species may be attributable to the lack of a "sodium pump reserve" in erythrocytes and heart nonmuscle cells. Such variations indicate that the human erythrocyte is not a suitable model for the ouabain receptor in the human heart.
The interactions of milrinone, ouabain and calcium on force of contraction in isolated, contracting human papillary muscle strips were measured. Milrinone (EC50, 8 X 10(-5)M) increased force of contraction maximally by 2.8 +/- 0.8 mN at 5 X 10(-4)M; significantly less than either ouabain (1 X 10(-7)M; 4.8 +/- 0.5 mN increase) or calcium (15 mM; 6.2 +/- 0.6 mN increase). A submaximal, but not a maximal, inotropic effect of ouabain could be increased by the addition of milrinone; in contrast, both ouabain and calcium increased the maximal inotropic effect of milrinone by 1.7 +/- 0.2 mN and 2.7 +/- 0.3 mN, respectively. The combined inotropic effect of milrinone with either ouabain of 4.2 +/- 0.3 mN or calcium of 5.6 +/- 0.4 mN was not different from that with calcium or ouabain alone. We conclude that further positive inotropic effects should be expected when digitalis is given to patients with congestive heart failure who are already optimally treated with milrinone.
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