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Biomedical subjects

R Hetzer

Publications and source records attributed to R Hetzer.

At least 19 recordsLinked to original sources

Level and diurnal variations of hormones of interest to the cardiovascular system in patients with heart transplants.

The lack of a nocturnal decrease in blood pressure in cyclosporine-treated cardiac transplant recipients may indicate abnormalities in the mechanism(s) responsible for circadian variability in other physiologic parameters such as in circulating hormones. This possibility was addressed through repeated determinations of circulating catecholamines, neuropeptide Y, pancreatic polypeptide, calcitonin gene-related peptide, plasma renin activity, aldosterone, atrial natriuretic factor and cortisol. The results from 10 patients with heart transplants were compared with those of 12 age-matched, healthy control subjects. Both groups were studied during 24-hour supine rest. There was no difference between patients and control subjects in mean levels of catecholamines, neuropeptide Y, pancreatic polypeptide and aldosterone. Patients had higher levels (+/- SD) of plasma renin activity (6.4 +/- 1.3 vs 2.6 +/- 0.4 ng/ml/hour, p less than 0.001), calcitonin gene-related peptide (47.7 +/- 9.9 vs 33.3 +/- 5.7 pmol/liter, p less than 0.01) and atrial natriuretic factor (93.0 +/- 56.7 vs 20.7 +/- 8.9 pg/ml, p less than 0.001) than control subjects, respectively. Cortisol was not detected in patients. Abnormal diurnal profiles in patients were found for calcitonin gene-related peptide, aldosterone and atrial natriuretic factor, and for pancreatic polypeptide, together with decreased levels, in patients with greater than 6 months follow-up. Except for hormones reflecting sympathetic nervous activity, all hormonal systems studied showed abnormalities in level or circadian rhythmicity, or both. The pancreatic polypeptide results suggest that parasympathetic neuropathy could develop in cyclosporine-treated heart transplant recipients.

Adrenal Cortex Hormones

Role of prostacyclin in normal and arteriosclerotic human coronary arteries during hypoxia.

Human coronary arteries were taken from heart transplant patients. Arteriosclerotic arteries were more depolarized and constricted over the whole PO2 range between 535 and 0 mm Hg. During oxygen deficiency, control preparations showed a maximal hyperpolarization of delta V = 10.9 mV and a maximal relaxation of delta T = 0.466 g. Arteriosclerotic arteries, however, became hyperpolarized by merely delta V = 7.1 mV and relaxed by delta T = 0.258 g. The isometric pretension was 2 g in all investigations. Two series of experiments, one with an application of indomethacin and another one with deendothelialized blood vessels, confirmed the hypothesis that the endothelium of arteriosclerotic coronary arteries arteries, indomethacin reduced the hypoxic hyperpolarization and dilatation at 30 mm Hg PO2 but about 51%. The reduction was 26% in arteriosclerotic vessels. The complete removal of the endothelium caused a 49% (74%) restriction of dilatory vascular reactivity. The relation was quite similar for a carbogen Krebs solution (resting, control conditions). The hyperpolarizing and dilatory contribution by prostacyclin was 32% in normal and 12% in arteriosclerotic coronaries. The rest can be attributed to the basal release of the endothelial dilator EDHR. Thus, it may be concluded that, in arteriosclerotic blood vessels, PGI2 synthesis and release are predominantly diminished or its effectivity is impaired. Finally we found the ratio PGI2/EDHF in the voltage and tension changes strongly shifted to the PGI2 side with a declining oxygen concentration. This is true for normal and arteriosclerotic vessels. In accordance with the activation curve for vascular smooth muscle, the hyperpolarization leads to relaxation via a closure of Ca2+ channels. 2.5 mV hyperpolarization reduces the tension developed by half.

Arteriosclerosis

Urodilatin: a new peptide with beneficial effects in the postoperative therapy of cardiac transplant recipients.

Renal failure after heart transplantation (HTx) still remains a serious problem, especially when cyclosporin A is used for immunosuppression in the early postoperative therapy. To preserve good renal function without reducing immunosuppressive cyclosporin A treatment, we administered urodilatin (CDD/ANP-95-126) in a long-term, low-dose infusion in addition to the usual medication after heart transplantation. From November 1990 to June 1991, 51 patients (46 male and 5 female; mean age 48 years) were treated with a 6-20 ng/kg bw.min infusion for 96 h after HTx. The renal function and hemodynamic parameters of these urodilatin-treated patients were compared in this sequential study with 40 patients (33 male and 7 female; mean age 49 years) who had undergone HTx previously from May to November, 1990, as controls. In this phase IIa study, both groups did not differ significantly with respect to age, sex, indication for HTx, and preoperative renal function. In comparison with controls patients treated with urodilatin had a significantly better renal function: a reduction in the peak plasma creatinine (PC values day 4: 1.5 +/- 0.11 vs. 2.19 +/- 0.19 mg/dl; P = 0.002), a lower peak serum urea (SU values day 4: 109 +/- 8 vs. 154.7 +/- 8.94 mg/dl; P = 0.0036), and a lower incidence of hemodialysis (6% vs. 10%) were observed. Adequate diuresis was maintained in spite of the reduction of furosemide by more than 60% (P = 0.005) on each day of urodilatin infusion in comparison with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury

Early diastolic left ventricular function as a marker of acute cardiac rejection: a prospective serial echocardiographic study.

Changes in left ventricular early diastolic time intervals are sensitive indicators of incipient left ventricular dysfunction. We tested the hypothesis that acute rejection in cardiac transplant recipients is associated with alteration of early diastolic myocardial function, as expressed by the time interval Te, a parameter derived from digitized M-mode echocardiograms. Te is defined as the time interval between maximal posterior wall contraction and the point of peak posterior wall endocardium retraction velocity, as determined by the nadir of the computed first derivative curve. In transplant patients without rejection (group A, n = 48), Te was prolonged compared to healthy individuals (group C, n = 35) (79.0 +/- 12.5 ms vs 64.0 +/- 7.9 ms; p < 0.0001). During acute rejection (group B, n = 18) transplant patients had significantly longer mean Te values compared to transplant patients without rejection (group A) (97.8 +/- 17.9 ms vs 79.0 +/- 12.5 ms; p < 0.0001). Longitudinal studies in individual patients (group D, n = 18) demonstrated that rejection is associated with prolongation of Te (94.5 +/- 16.0 ms during rejection vs 79.0 +/- 10.3 ms before rejection; p < 0.0002) and that Te returns to individual baseline values in response to treatment (79.2 +/- 9.4 ms after therapy vs 79.0 +/- 10.3 ms before rejection; NS). In a prospective study, Te changes in transplant patients (group E, n = 96) were correlated with myocardial biopsy results. Sixty-one biopsies showed acute rejection, and 115 biopsies were negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Recovery of end-organ failure during mechanical circulatory support.

To evaluate organ recovery during mechanical assistance, respiratory, hepatic and renal function parameters of 40 patients who underwent bridge-to-transplant procedures were reviewed retrospectively. Mechanical circulatory support was indicated if the hemodynamic and clinical status deteriorated despite pharmacotherapy with catecholamines, vasodilators, and intravenous use of the phosphodiesterase inhibitor enoximone. Sequelae of cardiogenic shock such as renal, hepatic and respiratory insufficiency were not considered a contraindication for mechanical support. The analysis of preimplant data such as serum creatinine, liver enzymes and pulmonary gas exchange did not identify any predictive indicator of irreversible organ damage. Functional recovery of preexisting respiratory, hepatic and renal dysfunction was found in 91%, 90%, and 85%, respectively. Subsequent transplantation, however, was affected by the number of failing organs prior to mechanical support. Of 17 patients with isolated organ failure prior to assist, 14 (82%) were transplanted. By contrast, 9 (75%) of 12 with combined failure of two organs, and only 6 (54%) of 11 patients with clinical patterns of three failing organ systems received transplants. In all patients who underwent successful transplantation, transplantability was associated with rapid organ recovery within 10 to 15 days after initiating mechanical assistance.

Adolescent

Enoximone in newborns with refractory postoperative low-output states (LOS).

Enoximone was administered to 16 newborns with postoperative, catecholamine-refractory cardiac low-output states in addition to high-dose catecholamine treatment. Haemodynamic changes were assessed at baseline and during treatment. Haemodynamic parameters were improved in 12 newborns ("responders"), 9 of these survived. Three responders died; one from cardiac low-output and 2 from uncorrectable congenital heart disease verified by autopsy. Four newborns did not respond to enoximone therapy ("non-responders") and died. The haemodynamic effects of enoximone were characterized by an increase in cardiac index (+160%, P less than 0.0008), and a fall in right (-26%, P less than 0.0004) and left (-34%, P less than 0.003) atrial pressures. It is concluded that enoximone can be an effective agent in the treatment of cardiac low-output states refractory to high-dose catecholamines in neonates up to 7 months old.

Cardiac Output, Low

First clinical experiences with a new angioscopic system for diagnosing peripheral vascular changes.

Conventional angiography allows a global view of regional vascular anatomy but precise information can only be deduced indirectly using contrast medium. The use of the three-dimensional picture of angioscopy, however, allows a direct evaluation of the vascular system. In order to extend our experiences with angioscopy, we employed a new micro-cardio-angioscopic system which consists of four components: a CCD color camera (360,000 pixels); a highly flexible optical probe which can be resterilised (1.4-0.6 mm diameter) incorporating 10,600-6,000 glass fibers, with a viewing angle of 140 degrees, 70 degrees, and 50 degrees and a focusing system that allows a distance from 2 mm to infinity; a high power light source and an insertion catheter with inflatable balloon. Using a known technique (intermittent blood-flow blockage and continual rinsing with NaCl solution), 36 cases involving 27 patients were examined before and after desobliteration of the femoral artery. In 88% of the cases it was possible to control the result of the intervention by angioscopy. Smaller intimal lips, the thrombotic wall, and intimal ruptures were clearly visible. Quantification of the stenoses was also successful in 88% of the cases, and in 8 patients the angioscopic findings deviated from the conventional angiogram. In 14% of the cases, angioscopic examination of the recanalisation result showed that thrombolytic therapy was necessary. Angioscopy offers the possibility of qualitative vascular diagnosis. It is a valuable addition to angiography.

Angioplasty, Laser

The use of dopexamine after cardiac surgery: acute and long-term effects in patients with impaired cardiac function.

The haemodynamic efficacy of dopexamine, a beta 2-adrenergic agonist with dopaminergic activity, was evaluated during dosetitration and longterm infusion in 20 cardiosurgical patients with low cardiac output following coronary artery bypass grafting and/or valve replacement or repair. After infusion of four doses (1, 2, 4, and 6 micrograms/kg/min), the dose producing the optimal response was administered for up to 36 h. Dopexamine infusion resulted in a dose-dependent significant increase in cardiac index (CI: 2.2-->3.3 L/min/m2) associated with a marked reduction of systemic vascular resistance (SVR: 1820-->1144 dyn.sec.cm-5). Heart rate increased significantly (HR: 89-->117 beats/min), while mean arterial blood pressure remained unchanged (MAP: 94-->89 mmHg). Unwanted effects (tachycardia and hypotension) were chiefly seen at higher doses (-->4 micrograms/kg/min). The beneficial haemodynamic effects were well maintained during the extended infusion period up to 36 hours at a mean dopexamine dose of 2.8 micrograms/kg/min. At these low doses, the positive chronotropic response to the drug remained within the limits of clinical acceptability. During long-term infusion up to 36 hours there was no indication of tolerance or an effect attenuation. It can be concluded that dopexamine acting as "inodilator" with dopaminergic properties is an useful adjunct to the pharmacological spectrum in the management of low-output states following cardiac surgery.

Adrenergic Agonists

[Patients with late-life vision damage in occupational rehabilitation. Preliminary ophthalmologic treatment, concomitant manifestations and an illustration provided by the growing number of patients with juvenile diabetes].

The rehabilitation centre in Veitshöchheim (near Würzburg) offers different kinds of training programs for the adult visually handicapped. This is usually preceded by a long time of unemployment. Diabetes mellitus was the third most common disease at the centre and 25% of the patients with diabetes mellitus were already legally blind. In a retrospective study we looked at the medical and ophthalmological treatment and the education the 76 patients with diabetes mellitus had received before coming to the rehabilitation center. All charts from February, 87, to September, 90, were included in the study. According to the classification of visual acuities by the WHO we formed four groups (less than or equal to 1/50; 1/35-0.1; 0.125-0.3; greater than 0.3) and compared them with each other. In the groups with the lowest visual acuity the medical management of the diabetes mellitus had been much poorer than in the better groups. Related to the bad visual acuity was the higher incidence of proliferative diabetic retinopathy and the significantly lower percentage of panretinal lasercoagulations. 47% of the patients with diabetes mellitus had been trained in jobs that would not have been recommended to a potential visually disabled by an ophthalmologist or the office for labour exchange. Only in 10% of the cases could a job be maintained by the help of technical devices (including low vision aids). To ensure best medical treatment and counselling concerning the choice of an appropriate job a close team work between practising ophthalmologist, general practitioner, and the office for labour exchange is needed. Thereby the cost and psychological impact of a retraining program could hopefully be lowered.

Adult

[Etiology and occupational rehabilitation of late vision disorders].

Advising patients about means of rehabilitation is an important task for the ophthalmologist. There is a lack of up-to-date studies on the outcome of job measures for various ophthalmic disorders. In a retrospective study the charts of 334 patients (October 86-November 89) at the rehabilitation centre for adults with late onset visual impairment (Veitshöchheim) were analyzed. Retinitis pigmentosa, optic atrophy, diabetic retinopathy and refractive anomalies were the most frequent diseases (13-19%). In comparison to the other disorders the incidence of diabetic retinopathy is increasing. Other ophthalmic diseases (mainly traumatic injuries), macular degeneration, retinal detachment and primary and secondary cataract made up 6-9% of all cases. About half of the patients were legally blind (visual acuity 1/50 or worse), 20% severely visually handicapped with a visual acuity of 0.02-0.05, 24% had a visual acuity of 0.05-0.3. Regarding the age distribution the group of patients between 30 and 39 years of age was the largest followed by the group of the 25-29-year-old and, last, the group of the 20-24-year-old patients. Due to the high proportion of blind and severely visually disabled a basic rehabilitation (including mobility training, learning the Braille letters) was necessary in 62% of cases. The most popular job measure was the field of massage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Haemodynamic effects of different doses of dopexamine hydrochloride in low cardiac output states following cardiac surgery.

We studied the haemodynamic effects of dopexamine hydrochloride, a beta 2-adrenergic agonist with dopaminergic (DA1) activity, in 20 patients with low cardiac output following surgery for coronary artery bypass grafting and/or valve replacement or repair. Following titration of four doses (1, 2, 4 and 6 micrograms.kg-1.min-1), the dose producing the optimal response was infused for up to 48 h (five patients). During the infusion, significant increases in cardiac index and stroke volume were accompanied by significant decreases in systemic vascular resistance. Heart rate increased significantly up to 6 h and thereafter returned to control levels. Mean blood pressure was reduced but did not fall below 60 mmHg. However, in five patients treated for 48 h mean blood pressure had returned to control levels. Unwanted effects (tachycardia and hypotension) were seen chiefly at higher doses, leading us to conclude that infusion rates of 4 micrograms.kg-1.min-1 or less will be useful in the treatment of low cardiac output following cardiac surgery.

Adrenergic Agonists

CD3+ CD57+ lymphocytes are not likely to be involved in antigen-specific rejection processes in long-term allograft recipients.

Cytofluorometric investigation of peripheral blood lymphocytes in 380 long-term (greater than 1 year posttransplantation) allograft recipients showed a significant increase in the proportion of CD3+57+ lymphocytes (greater than 20%) in 20% of patients with renal allografts, 66% of patients with cardiac allografts and 44% of patients with liver allografts. Most of these CD3+57+ cells expressed the CD8 antigen and a variable proportion the HLA-DR antigen. A retrospective analysis showed a poorer prognosis for the clinical outcome in those patients with elevated numbers of CD3+57+ cells in peripheral blood. However, CD57+ lymphocytes could rarely be detected in renal infiltrates by immunohistology. Using the Southern blot technique to analyse the T cell receptor rearrangement of separated CD57+ cells, no clonal or oligoclonal expansion of T cell clones could be detected. Nevertheless, there might be a bias towards the use of particular TCR-V beta gene families in at least some patients, as shown by analysis with monoclonal antibodies. In summary, CD57+ T cells are not likely to be directly involved in the rejection process. The data support the idea of a polyclonal and/or superantigen-driven expansion, but not of an antigen-driven expansion of these cells.

Antigens, CD

[Heart transplantation--indications and results].

Heart transplantation has become a standard procedure in the treatment for irreversible heart failure. Criteria for both recipients and donors have been extended. One year survival now reaches 81%. In the immediate postoperative course patients are endangered by infection. In the long-term course coronary artery disease of the transplanted heart becomes the most serious problem. Alteration of liver and kidney function due to chronic medication as well as malignancies and hypertension also occur. In case of chronic transplant failure retransplantation may be indicated. Acute cardiac failure before transplantation nowerdays can be treated by mechanical circulatory assist devices.

Follow-Up Studies

[Combined surgical-interventional procedure in congenital heart defects with postoperative, left ventricular dysfunction].

Creation of a communication between the left and right atrium to decompress the left ventricle can be life-saving after corrective surgery in some patients with congenital heart disease and small left ventricle. After adaptation of the left ventricle, surgical closure of this anastomosis becomes mandatory. We report four patients (2.9 to 8.2 kg) where non-surgical, transcatheter-closure was performed in the first year of life using the Rashkind-PDA-Occluder System (USCI). In a newborn with d-transposition of the great arteries (2.9 kg), in a patient with atrial septal defect (5.1 kg), and in a patient with tetralogy of Fallot with atrial septal defect (4.9 kg) atrial septal defects were not completely closed during correction because of left-ventricular dysfunction. Five to 12 days postoperatively transcatheter closure was performed utilizing the 8F-Rashkind-PDA-Occluder System in the first two patients (2.9 kg and 4.9 kg) and by use of the 11F-Rashkind-PDA-Occluder System in the third patient (4.9 kg). In the patient with supracardiac total anomalous pulmonary venous drainage via a vertical vein, the vertical vein was not closed during surgical correction at the age of 2 months. Transcatheter closure was performed 6 months later using the 11F-Rashkind-PDA-Occluder-System. It is concluded that small, defined atrial septal defects can be closed, even in newborns, using the Rashkind-PDA-Occluder System (USCI) and, furthermore, that large vessels, even without luminal narrowing can be occluded completely. Thus, this combined "surgical-interventional approach" is not limited by age and could reduce the risk of surgical correction in patients with congenital heart disease and small left ventricle.

Cardiac Catheterization

[Progress in heart transplantation].

Within the past 10 years, heart transplantation has become established as a standard procedure in heart surgery. Improvements in immunosuppressive therapy and diagnosis of graft rejection have been crucial. The criteria for transplantation have been broadened for recipients as well as for donors. Newborns, pediatric patients, diabetics, and patients with impaired renal function will no longer be excluded from transplantation due to improved postoperative therapy. Furthermore, progress has been made with assisted circulation. Patients with acute heart failure can now be bridged to transplantation.

Adult

[Coronary revascularization in end-stage coronary heart disease in relation to assessment of myocardial vitality].

From 4/1986-12/1990, 177 pts. with endstage coronary artery disease (CAD) and left ventricular ejection fraction 10-30% received coronary artery bypass grafting (CABG). Preoperatively myocardial infarction rate was 1.5 (mean). Presupposition for CABGs was myocardial ischaemia at present demonstrated in myocardial viability test. 66.1% of the pts. had signs of ischaemia at e.c.g. after work. Additionally 97.6% of the pts. had myocardial ischaemia defined as redistribution in myocardial scintigraphy. Angina pectoris was present in 93.8% of the pts. preoperatively. 1-5 (mean 2.9) CABG per pt. were performed. 35 pts. received an internal mammaria bypass to the left coronary artery also. Operative mortality was 11.3% (1986-1990) and in 1990 alone 7.3%. Actuarial survival rate was calculated after one year to 87.4% after two years to 86.1% and after three years to 84.8%. Postoperatively all pts. were free from angina pectoris. 5 months after the operation e.c.g. after work was performed. The physical stress bearing area was increased to 82.7 Watt (mean) compared to 51.7 Watt (mean) preoperatively (p less than 0.001 s.). In conclusion pts. with endstage CAD and left ventricular ejection fraction 10-30% appeared to be good candidates for CABG with good prognosis and significant symptomatic improvement when signs of myocardial ischaemia are present preoperatively.

Aged

[Therapeutic control of premedication with famotidine given on the evening before surgery for the prevention of pneumonitis in heart surgery patients].

Pulmonary damage after aspiration of acid gastric content is one of the major risks of general anaesthesia. Antisecretory therapy with different H2-antagonists can effectively decrease the risk of aspiration. The effective dosage and the method and timing of administration remain unclear. PATIENTS AND METHODS. A series of 38 patients scheduled for elective cardiac surgery (coronary artery bypass graft) were premedicated at random at 10:00 p.m. on the evening prior to surgery with famotidine 40 mg and flunitrazepam 0.5 mg p.o. or with flunitrazepam alone. Continuous intragastric pH monitoring (720 values/h) with a combined glass electrode was started immediately after induction and continued for at least 12 h after surgery, in most cases up to extubation. The time periods analyzed were the first 30 min after induction, time of surgery, 12 h after surgery, and time of extubation. For each period the number of pH values less than 2.5 and pH less than 4, mean and median, and significance of differences were calculated. STATISTICS. Test statistics were evaluated using the Wilcoxon test and the Mann-Whitney U-test. RESULTS. (see Table 1, Fig. 1). The mean time interval between oral premedication and induction of anaesthesia was 9.7 h. There were no differences between the groups concerning age and duration of surgery. The average age was 51 in the group of treated patients (n = 15) and 59 years in the control group (n = 23). The average duration of surgery was 3.36 h and 4.02 h. During induction and in the following 30 min, in the famotidine treatment group 28.7% of all pH values were pH less than 2.5, as against 45.4% in the control group (P = 0.08). Intraoperative values: 16.3% pH less than 2.5 against 24.7% (not significant); 12 h postoperative: 21.1% vs 17.8% and during extubation 40% vs 21% (not significant). During induction there were more pH values less than 2.5 in the control than in the treatment group (P = 0.08). Treated patients had nearly 30% pH values less than 2.5 and therefore, a persisting risk of acid aspiration. In both groups intragastric acidity decreased during surgery. Postoperatively there was no difference between the two groups, and during extubation more patients in the famotidine-treated group had values below pH 2.5. CONCLUSION. Prophylaxis of acid aspiration before, during and after cardiac surgery can be achieved by increasing the pH of the gastric content. The timing and the method of administration must be selected to a safe decrease in intragastric acidity before the induction of general anaesthesia. Famotidine 40 mg given orally at 10.00 p.m. on the evening before surgery is not a reliable means of decreasing intragastric acidity or, consequently, of preventing of acid aspiration syndrome.

Administration, Oral

Skin microcirculation and laser Doppler blood flow in patients supported by the Berlin heart biventricular assist device.

Microcirculatory forearm cutaneous blood flow was monitored continuously and non-invasively by laser-doppler-flowmetry (LDF) in 10 patients treated with the Berlin Heart biventricular assist device (BVAD) system for end-stage heart failure (BVAD-pts). Ten normal human subjects served as controls (C). The cutaneous blood flow was measured before, during, and after external brachial artery occlusion to evaluate the postocclusive reactive hyperemia (PORH) as a standardized response. To examine micro-vasculatory responses to macro-hemodynamic changes the cardiac output (CO) was decreased by reducing the BVAD-pump rate by 20%. No significant differences in base-line LDF measurements were ascertained in the two groups. After sudden cuff pressure release (1 min later) a statistically significant (p less than 0.004) three- to fourfold blood flow increase (PORH) occurred in both groups. The period of the PORH response was altered in all BVAD-pts. The time to peak PORH values were significantly diminished (p less than 0.05) A markedly delayed return to base-line level occurred in the BVAD-pts. The 20% reduction in the BVAD-pump rate significantly decreased CO (p 0.05) and increased systemic vascular resistance (SVR) (p less than 0.01), whereas LDF levels remained unchanged.

Adult