[CorBene: a new model for collaborative care of patients with congestive heart failure]. / CorBene: Ein neues, kooperatives Versorgungsmodell für Patienten mit Herzinsuffizienz.

Congestive heart failure (CHF) is one of the most common medical disorders. The prognosis tends to be unfavorable and the quality of care needs further improvement. The aim of the CorBene project is to improve the health-related quality of life and the prognosis in patients in all stages of CHF and to reduce the hospitalization rate. For this purpose a modern collaborative treatment program involving all relevant health care professionals was developed. The key feature is the close collaboration between family physicians, practicing cardiologists, hospitals and rehabilitation facilities. The CorBene model was launched in Cologne and then spread to North-Rhine/Westphalia and to Saarland. Currently, there is the possibility to offer it in all German states. Preliminary analyses confirm an optimal, guideline-based therapy of CHF.

Influence of hospitalization and placebo therapy on blood pressure and sympathetic function in essential hypertension.

The decline in blood pressure (BP) in essential hypertensives following hospitalization may result from: 1) regression toward the mean; 2) reduction of anxiety as patients habituate to a new environment; 3) the placebo effect of medication; and 4) an independent effect of hospitalization itself. A randomized crossover study of 12 essential hypertensives demonstrated a fall in supine blood pressure from 165.0/97.9 +/- 2.3/1.1 mm Hg to 154.3/89.6 +/- 2.7/1.1 mm Hg (p less than 0.005) due to hospitalization. A similar reduction in BP from 164.9/99.5 +/- 8.4/4.1 mm Hg to 151.9/93.4 +/- 4.5/1.9 mm Hg (p less than 0.005) resulted from regression toward the mean and habituation during the study period. Urinary catecholamines fell from 68.7 +/- 5.0 to 55.1 +/- 4.3 micrograms/g creatinine/24 hours (p less than 0.05) due to hospitalization and from 56.1 +/- 5.4 to 49.7 +/- 4.3 micrograms/g creatinine/24 hours (p less than 0.05) with time. Although placebo therapy tended to reduce BP, it failed to do so significantly. When expressed as a percentage of the individual's overall mean, urinary catecholamine excretion fell from 110.5% +/- 3.7% to 89.5% +/- 3.7% (p less than 0.001) during hospitalization and from 105.8% +/- 3.9% to 94.2% +/- 3.9% (p less than 0.05) during the outpatient period. Blood pressure and sympathetic activity rapidly returned to prehospitalization values on discharge. These factors may confound the analysis of drug effects on BP and sympathetic activity in essential hypertensives following admission to hospital.

Norepinephrine release in essential hypertension.

Supine basal plasma norepinephrine was higher in a group of newly diagnosed patients with mild essential hypertension than in age- and sex-matched "laboratory-naive" volunteers. Sympathetic activation by exercise and change of posture increased plasma norepinephrine in both groups, with a tendency toward higher values in the hypertensive patients, but norepinephrine clearance was slower and half-life longer in these patients. Thus the estimate of neuronal norepinephrine release obtained by correction of plasma norepinephrine for individual values of clearance was in the same range in both groups. Plasma norepinephrine was lower in younger "laboratory-adapted" subjects than in the "laboratory-naive" normotensive subjects, but clearance was in the same range in both. Thus, variations in kinetics may contribute to differences in plasma norepinephrine between patients with essential hypertension and matched controls. In contrast, the lower plasma concentration of norepinephrine in "laboratory-adapted" than in "laboratory-naive" controls appears to reflect a lower level of sympathetic activity in the former.

Sedative and cardiovascular effects of clonidine and nitrazepam.

Five healthy male subjects, aged 26 to 35 yr, received single oral doses of clonidine 0.3 mg, nitrazepam 20 mg, or placebo double-blind with an interval of at least 1 wk between each treatment. Clonodine induced a maximal fall in systo9lic blood pressure from 104.2 +/- 1.6 to 84.7 +/- 1.4 mm Hg (mean +/- SEM) after 3.5 hr and nitrazepam from 102.9 +/- 1.9 to 90.3 +/- 2.6 mm Hg after 1.0 hr while after placebo blood pressure rose steadily from 102.5 +/- 2.9 to 109.6 +/- 3.5 mm Hg at the end of the 8-hr study. Total sleep time increased from 90.3 +/- 2.5. min after placebo to 256.2 +/0 21.0 min after clonidine (p < 0.001) and 281.0 +/- 40.3 min after nitrazepam (p < 0.001). Stage I sleep increased from 49.7 +/- 11.2 to 76.9 +/- 10.2 min after clonidine and to 76.3 +/- 25.2 min after nitrazepam (p < 0.0), while the greatest increase was observed in stage II: 230.7 +/- 25.6 min after clonidine and 236.6 +/- 35.4 min after nitrazepam compared with only 48.5 +/- 15.8 min after placebo (p < 0.001). Plasma norepinephrine did not change after placebo but fell after nitrazepam from 0.28 +/- 0.04 to 0.14 +/- 0.02 ng/ml after 3 hr (p < 0.05) and after clonidine from 0.23 +/- 0.07 to 0.07 +/- 0.02 ng/ml after 2 hr (p < 0.01). Clonidine and nitrazepam both induced similar hypnotic and hypotensive effects with some evidence that this might be due to a reduction in sympathetic tone.

Interindividual variation in kinetics of infused epinephrine.

1-Norepinephrine was infused continuously for 10 hr into 5 normotensive, male laboratory subjects (mean age, 32.4 +/- 1.9 yr) at a mean rate of 0.06 microgram/kg/min. Mean plasma norepinephrine (NE) rose from the preinfusion level of 0.19 +/- 0.02 microgram/l to a steady state level of 1.22 +/- 0.29 microgram/l. The mean increase in blood pressure was 21.8 +/- 0.9 mm Hg systolic and 14.1 +/- 1.0 mm Hg diastolic. The mean depression in heart rate was 12.7 +/- 1.7 beats/min. The clearance of norepinephrine ranged from 27.9 to 100.0 ml/kg/min (mean. 58.0 +/- 13.8) and was little influenced by acute hemodynamic changes. The volume of distribution ranged widely (0.09 to 0.40 l/kg), the mean value being 13.51 1. The mean norepinephrine half-life was brief, ranging from 1.45 to 2.9 min (mean, 2.09 +/- 0.34 min). There was no evidence of a slowly accumulating high-capacity low-affinity pool of norepinephrine. These results support the use of plasma norepinephrine as an index of sympathetic activity within an individual but not its validity in interindividual comparisons.

Controlled trial of ancrod in ischemic stroke.

In a randomized, single-blind study, 30 patients with acute ischemic stroke were treated with either low-molecular weight dextran and mannitol alone (group A, mean age, 63.3 +/- 11.8 years, n = 15) or in combination with the viper venom enzyme ancrod (group B, mean age, 67.9 +/- 7.6 years, n = 15). Lowering of plasma fibrinogen levels to 100-130 mg/dL with ancrod resulted in a significant reduction of the apparent blood viscosity, ie, of 37% at a shear rate of 0.03 s-1, compared with only 7% in group A. Fibrin degradation products increased considerably from 3.1 +/- 0.4 to 154.3 +/- 31.6 mg/L on day 3, while plasminogen decreased from 98.2% +/- 2.0% to 79.8% +/- 2.9% in group B. Global coagulation and platelet function tests were not influenced by either treatment. Neurological score improved by 1.1 arbitrary units (AU) in group A and by 2.6 AU in group B. Five patients in group A and two in group B died during the first two weeks. This preliminary study indicated a slightly better outcome in the ancrod treated patients. The beneficial effect may be due to the anticoagulative and fibrinolytic activity of ancrod rather than its effect on blood viscosity.

Microsphere analysis of local cerebral and extracerebral blood flow after complete ischemia of the cat brain for one hour.

In normothermic anesthetized cats complete cerebral circulatory arrest for one h was produced and followed by blood recirculation of the brain for 30 min to 4 h. Total and local blood flow of the brain, kidney, heart and liver were measured before and after ischemia using radioactive labelled microspheres. Before ischemia blood flow of the brain was 39.1 +/- 2.3 ml/100 g/min, of the kidney 307.2 +/- 28.3 ml/100 g/min, of the heart 241.1 +/- 32.5 ml/100 g/mmin and of the liver 87.8 +/- 25.6 ml/100 g/min (means +/- SEM). Regional flow rates within the brain varied between 35 and 51 ml/100 g/min. Reactive hyperemia was present in the brain 30 min after the beginning of recirculation following ischemia for 1 h. Local cerebral flow rates increased three to five times above the control flow, depending on the respective region. Mean cerebral blood flow returned to or slightly below normal, 2 to 4 h after ischemia, but there was considerable redistribution of flow rates within the brain. The filter capacity of the brain for microspheres of 15 mu and 50 mu diameter did not change after ischemia indicating that postischemic blood recirculation was not accompanied by an opening of arteriovenous shunts.

Effect of intravascular platelet aggregation on blood recirculation following prolonged ischemia of the cat brain.

Reversible complete cerebro-circulatory arrest was produced in normothermic, anesthetized cats for 1 h by clamping the innominate and subclavian arteries, followed by blood recirculation of the brain for 30 min to 4 h. Blood volume of tissue samples was measured by intravenous injection of 125I-albumin and the platelet number by labelling of autologous platelets with 51Cr. The number of platelets trapped in the tissue was determined by subtracting from the total platelet count of the tissue sample those contained in the streaming blood, calculated from the blood volume by 125I-albumin. In sham-operated animals, after recirculation of autologous 51Cr labelled platelets for 60 min, no platelets were entrapped in the brain vasculature and total platelet number and fibrinogen concentration in the venous blood did not change. In animals submitted to complete cerebral ischemia for 1 h the number of trapped platelets increased significantly in the whole brain after 30 min of recirculation, i.e. the period of maximal postischemic vasodilatation and hyperemia, and highest concentrations were found in the border zone with 270 +/- 60 x 10(4) platelets/g tissue and in the brainstem with 240 +/- 70 x 10(4) platelets/g tissue. Blood platelets and fibrinogen concentration in the venous blood decreased significantly from 288 +/- 37 x 10(6)/ml and 299 +/- 50 mg% to 186 +/- 25 x 10(6)/ml platelets and 112 +/- 22 mg+ of fibrinogen, respectively. Platelets were nearly completely washed out of the brain after 4 h of recirculation. The highest increase of platelets was found in the kidney, lung and liver after 30 min of recirculation, indicating that intravascular coagulation following prolonged cerebral ischemia affects the extracerebral organs more than the brain itself.

High-resolution real-time ultrasound of the carotid bifurcation in patients with hyperactive carotid sinus syndrome.

The carotid bifurcations and the common carotid arteries of 36 patients with the diagnosis hyperactive carotid sinus syndrome (HCSS) were investigated by continuous wave (CW) Doppler ultrasonography and high-resolution real-time B-scan. Using these non-invasive tests, the functional impact of luminal stenosis and the morphological changes resulting from arteriosclerotic deformities could be established. Significant differences were found in comparison with a reference group of 199 patients with a high risk of arteriosclerosis. In the HCSS group, 5 patients had a stenosis of more than 50% at the origin of the internal carotid artery on both sides, or on one side in combination with large plaques or a complete occlusion on the contralateral side. Seventy-five per cent of patients in the HCSS group, as compared to only 23.5% of the control group, had effective arteriosclerotic changes in the carotid bifurcation on both sides; 4 patients had such changes only unilaterally. Marked additional bilateral arteriosclerotic depositions were detected in the common carotid arteries of 17 patients (47.2%). In 5 patients no arteriosclerotic lesions were detectable in the carotid bifurcations, but marked changes were found in both common carotid arteries. These data indicate that bilateral arteriosclerotic changes in the carotid bifurcations and/or the common carotid arteries represent an important pathophysiological factor for the development of an HCSS.

Haemorheology in adolescent hypertensives.

Fifty-three untreated borderline hypertensives and 73 normotensives were randomly selected from 1342 adolescents (age range 23-27 years) who were examined in 1975, 1976 and 1980 in an epidemiological study. Blood pressure was 127.2 +/- 1.0/79.0 +/- 0.8 mmHg in normotensives and 147.2 +/- 1.6/93.7 +/- 1.1 mmHg in hypertensives (P < 0.001). Erythrocyte deformability was measured with a positive pressure filter system (pore diameter 5 microns) at 37 degrees C. Erythrocyte deformability was significantly increased in hypertensives with a value of 1.77 +/- 0.05, compared with 1.64 +/- 0.04 in normotensives (P < 0.05). No difference in apparent whole blood viscosity, haematocrit and plasma fibrinogen was measurable between the groups. Although plasma noradrenaline and adrenaline concentration at rest and after 3 min standing were not different, excretion of urinary catecholamines was significantly elevated in hypertensives with 155.0 +/- 3.3 micrograms/24 h (normotensives: 100.7 +/- 5.3 micrograms/24 h; P < 0.001).

Sodium transport and red cell deformability.

Inhibition of the Na-K pump by a circulating factor is thought to be of importance in the pathophysiology of essential hypertension. We tested the correlation between an inhibition of the Na-K pump by digoxin and the deformability of red blood cells (RBC) both in vitro and in vivo. Erythrocytes were incubated with digoxin (0-1.3 mumol/l) for 1 h at 37 degrees C. Highest concentration of digoxin (0.13 and 1.3 mumol/l) significantly diminished Na-K pump activity, measured by uptake of 86rubidium (Rb). There was a parallel decrease in red cell filtrability. In nine healthy volunteers, intake of digoxin (0.2 mg b.i.d.) over a 5-day period did not alter red cell deformability and uptake of 86Rb. Taken together, inhibition of the Na-K pump in vitro correlates with a reduced red cell deformability. However, this occurs at a toxic dosis of digoxin.

Antiplatelet effects of intravenous iloprost in patients with peripheral arterial obliterative disease. A placebo-controlled dose-response study.

The dose-dependent inhibition of platelet aggregation by the chemically stable, prostacyclin-mimetic, iloprost, was studied in patients suffering from stage II-III peripheral arterial obliterative disease (PAOD). The study was designed as a randomized placebo-controlled cross-over trial. Iloprost was administered i.v. to six patients at doses of 0.5, 1.0, 2.0 or 3.0 ng/kg X min for 4 h, with an interval of 2-3 days between the infusions. During iloprost infusion, systolic and diastolic arterial blood pressure, heart rate and blood flow in the affected limb remained unchanged. In contrast, there was a considerable, dose-dependent inhibition of ADP- and thrombin-induced platelet aggregation and secretion ex vivo at doses of 0.5-2.0 ng/kg X min iloprost, indicating that iloprost reduced platelet stimulation by 50%-70%. The antiplatelet action of iloprost remained unchanged during infusion but ceased with 2 h after administration had ended. The agent was tolerated by the patients without unacceptable side-effects at doses up to 2 ng/kg X min. It is concluded that iloprost administered i.v. at doses of 1-2 ng/kg X min in patients with stage II-III PAOD does not involve haemodynamic side-effects and might be considered an effective antiplatelet agent.

Coagulopathy following experimental cerebral ischemia.

In adult normothermic cats cerebral blood flow was interrupted for 1 hour by clamping the innominate and subclavian arteries. Following ischemia the brains were recirculated with blood, and the coagulation system was investigated by measuring coagulation times and blood content of fibrinogen and platelets. Ischemia induced progressive consumption coagulopathy with an increase in coagulation times and a decrease of platelets and fibrinogen by more than 40%. Coagulopathy was accompanied by a respiratory distress syndrome with a significant increase in the alveolar-arterial carbon dioxide gradient from --3.3 to --13.5 mm Hg. A correlation was found between plasma fibrinogen concentration, cerebral blood flow and electrophysiological function, indicating that a relationship exists between the severity of postischemic coagulopathy and functional recovery following prolonged cerebral ischemia.

[Depression of sinus nodal automaticity during permanent atrial pacing for the determination of the sinoatrial conduction time (author's transl)]. / Anderung der Sinusknotenautomatie unter der Bestimmung der sinuatrialen Leitungszeit mittels permanenter Vorhofstimulation.

In 36 patients sinoatrial conduction time (SACT) was calculated by the continuous-atrial-pacing technique, first described by Narula et al. (9). Using three different stimulation frequencies, it could be shown that the return cycles A2A3 and the postreturn cycles A3A4 both were linearly correlated with rising stimulation frequency. Thus, if the formula given by Narula et al. was used [SACT = (A2A3 - A1A1) : 2] the calculated SACT-values linearly rose, too, which was caused by a stimulation frequency dependent progressive depression of the sinus nodal automaticity. This interfering influence of sinus nodal depression could be corrected by applying a modified formula for calculation of the SACT, i.e. SACTM = (A2A3 - A3A4) : 2. Thus calculation of sinuatrial conduction time by the modified continuous-atrial-pacing technique represents a method widely applicable in routine electrophysiological testing.

[Atropine in intraoperative isorhythmic AV dissociation]. / Atropin bei intraoperativ auftretender isorhythmischer AV-Dissoziation.

40 patients of the ASA groups I and II in whom intra-operatively an isorhythmic AV dissociation occurred under inhalation narcosis with halothane or enflurane, were examined in a randomized study. Within an observation period of 15 minutes the spontaneous rate of return to the sinus rhythm was 20 per cent (group A, n = 20). Intravenous administration of 0.01 mg/kg atropine sulphate produced a significantly higher rate of return of 80% within the same period. On the whole, no influence on arterial blood pressure was noted. Atropine increases the heart rate by 32%, and this is considered to be an important drawback. The possibility of influencing the AV dissociation via atropine points to the pathogenetic importance of the vagus in so far as it acts as a depressant on the sinus node.

Vasopressor and vasodepressor hormone-systems in adolescent hypertension.

We investigated the activity of the renin-angiotensin-aldosterone-system, the secretion of catecholamines and the kallikrein-kinin-system in 126 adolescents randomly selected from a large study of 1342 young people examined in an epidemiological survey conducted in Cologne in 1975, 1976 and 1980. 73 of them with arterial blood pressures below 145/90 mm Hg were called "normotensives" (systolic blood pressure 127.2 +/- 1.0 mm Hg, diastolic bp 79.7 +/- 0.8 mm Hg). They were compared with 53 "hypertensives" (systolic blood pressure 147.2 +/- 1.6 mm Hg, diastolic bp 93.7 +/- 1.1 mm Hg). Urinary catecholamines were significantly higher in the hypertensives (155.0 +/- 13.3 micrograms/d) compared to the normotensives (100.7 +/- 5.3 micrograms/d) (p less than 0.001) whereas plasma levels of adrenaline and noradrenaline were similar. Serum aldosterone levels and plasma-renin-concentrations were not different between the two groups. Angiotensin-converting-enzyme-activity was slightly higher in the hypertensive group (107.1 +/- 3.5 U/l versus 98.0 +/- 2.6 U/l, p less than 0.001). Urinary kallikrein excretion was found to be modestly lower in hypertensives compared to normotensives (0.40 +/- 0.05 versus 0.55 +/- 0.06 mU/mg creatinine). Urinary excretion of sodium and potassium, blood levels of glucose, uric acid, cholesterol and triglycerides were similar in both groups. The results of the present study suggest an increased sympathetic activity in the early stage of hypertension in adolescents.

Antithrombin III deficiency in ischaemic stroke.

AT III activity and concentration were measured in 36 patients (mean age 65.5 yrs, range 43-77 yrs) with ischaemic stroke within maximally 48 h of the acute event. In 12 patients (= 33%) AT III activity was reduced below 18.4 IU/ml: 50% of these patients showed normal and 50% reduced AT III concentration of less than 22 mg/dl. In 15 patients AT III activity and concentration were measured in the acute phase on admission to hospital and 12 months later. In the acute phase, AT III activity was reduced when compared with AT III concentration (y = 0.19 chi + 15.5) and did not correlate with the latter. 12 months later, however, AT III activity and concentration correlated significantly (r = 0.92; p less than 0.001) and the regression line was steeper (y = 0.8 chi). During the acute phase of ischaemic stroke, intravascular coagulation is evidently increased and inactive AT III-thrombin complexes are formed, whereby the concentration of active AT III decreases. A patient with progressive stroke and reduced AT III activity of 14.2 IU/ml was therefore substituted with AT III concentrate. The further neurological course was favourable.