Biomedical subjects
Publications and source records attributed to R Hetzer.
Two infants with anomolous origin of the left circumflex coronary artery from the pulmonary artery had to be operated on at ages 40 days and 30 days because of severe myocardial dysfunction. This illustrates that the clinical course of anomalous origin of the circumflex artery from the pulmonary artery may not always be as favorable as reported in the literature.
On the occasion of the hundredth anniversary of heart surgery, this article presents the remarkable work of the Russian scientist and surgeon Nikolai Terebinski. The medical world today remains largely unaware that he performed the first successful open valve operations. These experimental operations were conducted in Russia between 1926 and 1937 through the use of an extracorporeal circulation device known as the autojector. The experiments were reviewed based on Terebinski's original articles and experimental notes. Here we present the techniques and results of his landmark open valve operations on dogs. He performed more than 250 open valve operations, which were the first of their kind. In his attempt to create and then later correct tricuspid and mitral valve stenosis and insufficiency, Terebinski developed many principles of open heart surgery that are valid today. His work represents a milestone in the history of heart surgery.
BACKGROUND: Until a few years ago, the incidence of humoral rejection after heart transplantation was underestimated. These episodes were frequently very aggressive and often fatal, because the maintenance and emergency immunosuppression available at the time only inadequately covered the humoral branch of the immune response. In spite of individual case reports, the effects of blood purification procedures or cyclophosphamide in this situation can only be insufficiently estimated. METHODS: To evaluate this therapy concept, 20 dog-lymphocyte-antigen-matched dogs underwent heterotopic neck-heart transplantation. Fourteen dogs underwent transplantation after having been previously sensitized through multiple skin transplantations, 6 dogs were not sensitized (control). The animals received an induction with 3x 250 mg prednisolone, as well as triple immunosuppression (cyclosporine, azathioprine, and cortisone). Biopsy (light microscopy, immunofluorescence), intramyocardial voltage, electric myocardial impedance (>200 kHz, <10 kHz), and echocardiographic (left ventricular wall thickness, diastolic relaxation velocity) examinations were performed daily to monitor rejection. Rejection therapy was continued for 3 days according to the following regimen: apheresis, cortisone boluses (CB), and cyclophosphamide in group A1 (n = 4), apheresis and CB without cyclophosphamide in group A2 (n = 4), and CB only in group C (n = 6). The subsequent course under triple immunosuppression was then observed. RESULTS: In the sensitized animals the onset of severe humoral rejection on the fifth day deteriorated cardiac function down to 75% (70% to 80%) of the initial values. In groups A1 and A2, apheresis resulted in recovery to near-control values (89% to 94%) within two hours, and indeed to complete recovery (97% to 101%) after the second apheresis, that is, within 1 day. In group C recovery was delayed (2 days) and incomplete (84% to 91 %). After therapy was discontinued, rejection-related functional deterioration recurred immediately in group C, and from 2 to 3 days after apheresis, regardless of whether cyclophosphamide therapy was performed (group A1) or not (group A2). In the control group all animals showed a rejection-free posttransplantation course. CONCLUSIONS: By diluting inflammatory mediators, apheresis leads to a rapid improvement in cardiac function during severe humoral rejection after head transplantation. Neither apheresis nor cyclophosphamide therapy are able to have an immediate positive influence on the activation of the immune cascade and to prevent an ongoing rejection.
Seventeen patients were treated with endovascular stent grafts for AAA (seven Stentor, two Vanguard, three Talent and three EVT grafts). Intraoperative conversion to open procedure was necessary in three cases. One patient had open operation 24 h postoperatively for graft thrombosis. All patients had uneventful recovery. During follow-up (1-35 months) nine patients did not require reintervention. One patient had open repair for persistent endoleak: within 2 months postoperatively one midgraft endoleak, one graft limb thrombosis and one groin infection were treated. We did not observe any late complications.
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BACKGROUND: Following left ventricular assist device (LVAD) implantation in end-stage heart failure, the management of right ventricular dysfunction presents a therapeutic problem unresolved by conventional drug therapy (catecholamines, nitrates, and prostacyclin). This study was performed to investigate the effects of supplemental inhalation of nitric oxide (NO), a selective pulmonary vasodilator, postoperatively and prospectively. METHODS AND RESULTS: Intraindividual dose titration of NO was performed (0 to 40 ppm) according to a standardized protocol. Thereafter treatment was continued with the individually most effective dose of NO (25 to 40 ppm). In 8 consecutive male patients presenting with right ventricular dysfunction postoperatively, a significant dose-dependent improvement in hemodynamic function was observed: pulmonary vascular resistance decreased from 336+/-110 to 210+/-59 dynes x s x cm(-5) (P<.0001), cardiac index rose from 2.0+/-0.4 to 2.7+/-0.4 L x min(-1) x m(-2) (P<.003) at 40 ppm; doses of >20 ppm were effective in increasing cardiac index (P<.05). With continuous NO inhalation up to 48 hours, pulmonary vascular resistance decreased further to 155+/-33 dynes x s x cm(-5) (P<.0001) as the cardiac index increased to 3.3+/-0.6 L x min(-1) x m(-2) (P<.003). Pulmonary artery pressure decreased (P<.0001) as did systemic vascular resistance with hemodynamic improvement (P<.01). Central venous pressure and mean arterial pressure remained unchanged. Right ventricular ejection fraction at transesophageal echocardiography increased from 24+/-7% to 44+/-7% (P<.01) at the end of the study, and right ventricular end-diastolic volume decreased (P<.05). Weaning from NO therapy was successful at 2 to 8 days, and all patients were extubated. Right ventricular function remained stable thereafter. CONCLUSIONS: In the treatment of right ventricular dysfunction following LVAD implantation, inhalation of NO markedly decreased right ventricular afterload by its selective vasodilating effects on the pulmonary circulation without producing systemic hypotension; this merits further evaluation.
Measurement of right ventricular (RV) function is essential for complete assessment of the effects of inhaled nitric oxide in the postoperative cardiac patient; nitric oxide therapy can result in a decrease in pulmonary vascular resistance and improved echocardiographic RV ejection fraction without necessarily inducing a significant change in pulmonary artery pressure.
BACKGROUND: Implantation of mechanical cardiac support systems (MCSS) in patients with idiopathic dilated cardiomyopathy (IDC) may improve cardiac function and allow explantation of the device. We report of long-term effects of ventricular unloading on cardiac function, humoral anti-beta1-adrenoceptor autoantibodies (A-beta1-AABs), and myocardial fibrosis. METHODS AND RESULTS: Seventeen patients in New York Heart Association functional class IV with nonischemic IDC received MCSS. All had a cardiac index of < 1.6 L x min(-1) x m(-2) of body surface area, a left ventricular ejection fraction (LVEF) of <16%, and a left ventricular internal diameter in diastole (LVIDd) of >68 mm and tested positive for A-beta1-AABs. Echocardiographic evaluation, serum tests for A-beta1-AABs, and histological assessment of myocardial fibrosis were performed before and after MCSS implantation. The mean support duration was 230+/-201 days. Six patients died, four were transplanted, and two are still on MCSS. Five patients with significant cardiac recovery (mean LVIDd, 54+/-2.3 mm; LVEF, 47+/-3.7%) were weaned after 160 to 794 days and are now device free for 51 to 592 days. A-beta1-AABs disappeared gradually during MCSS without increase after weaning; cardiac function and volume density of fibrosis remained normal. Nine patients' cardiac function hardly improved during ventricular unloading. CONCLUSIONS: Cardiac function can be normalized in selected patients with end-stage IDC by MCSS. The degree of preoperative myocardial fibrosis may be an indicator for outcome; A-beta1-AABs can be used to monitor myocyte recovery. Weaning from MCSS offers an alternative to cardiac transplantation in certain patients.
BACKGROUND: Implantation of a mechanical cardiac support system (MCSS) in patients with idiopathic dilated cardiomyopathy (IDC) may improve cardiac function and allow explantation of the device. Our experience now includes 13 patients who have been "weaned" from MCSS and we report about the overall results of this treatment as well as the effects of ventricular unloading on cardiac function, anti-beta 1-adrenoceptor-autoantibody (A-beta 1-AAB) level and the degree of myocardial fibrosis. METHODS: 13 patients with non-ischemic IDC who had been admitted here in cardiogenic shock (CI < 1.61.min-1.m2, left ventricular ejection fraction [LVEF] < 16% and left ventricular internal diameter in diastole [LVIDd] > 68 mm) and who all tested positive for A-beta 1-AABs were implanted with an uni-(12 patients) or a biventricular (1 patient) mechanical assist device. Echocardiographic evaluation and A-beta 1-AAB-level-monitoring was routinely performed after implantation and explantation of the MCSS and the degree of myocardial fibrosis was assessed at the time of implantation and after explantation. RESULTS: During a mean duration of mechanical support of 236 +/- 201 days (range: 30 to 794 days), LV-EF improved to a mean of 46% and LVIDd decreased to a mean value of 56 mm in these 13 patients. A-beta 1-AABs decreased and disappeared 11.7 weeks after implantation of the device and did not reincrease thereafter. The highly pathologic degree of fibrosis at the time of implantation diminished to normal values about 1 year after explantation. One patient died of anesthesiologic complications and another patient shortly presented with a new episode of cardiac insufficiency 6 months after explantation. He was implanted again with an univentricular assist device was successfully transplanted 3 weeks later. Mean observation period of the remaining 11 patients now amounts to 12.6 +/- 9.77 (range: 3 to 26) months after explantation of the device--as of May, 31, 1997--with a cumulative observation period of 139 patient months. CONCLUSION: Temporary implantation of a MCSS may normalize cardiac function in selected patients with IDC. The striking degree of myocardial fibrosis can reduce to normal values after explantation of the device. A-beta 1-AABs disappear during ventricular unloading and do not increase thereafter. "Weaning" from mechanical device may constitute an alternative treatment to cardiac transplantation in selected patients.
From 11/1994 to 4/1997 we enrolled 140 patients with diffuse CAD refractory to maximum antianginal therapy who are not candidates for PTCA or CABG for transmyocardial laser revascularisation (TMLR). Of these patients aged 63.5 +/- 15 years, 98 had coronary 3-vessel disease, and the average left ventricular ejection fraction was 44%. Eleven out of these 140 patients died from different reasons (pneumonia, myocardial infarction, septicemia). Seven patients who died between the 1st and 20th postoperative day underwent a postmortem examination with histological analysis of the areas treated by TMLR. On the seven investigated ventricles a total of 220 channels were created. The predominant finding in specimens within five days after TMLR was recently closed channels. Furthermore, a zone of necrosis with an average extension of 500 microns on each side of the channel was evident. Many changes were noticeable in specimens from patients who died two or three weeks after TMLR. Freshly clotted material had been replaced by a granular tissue of variable density. High macrophage and monocyte activity was evident. The extent of this cellular activity could be depicted by staining with a special proliferation marker, such as MiB. On the one hand numerous dividing macrophages were observed, on the other, active fibroblasts indicative for the transformation into scar-like tissue. After staining for type-4-collagen, typical for the basal membrane of capillaries, a large number of stained structures was noticeable in the closed channel lumen. Numerous garlandlike structures became visible under higher magnification. By CD 31 incubation, these structures, were found to be lined with endothelium. Further research will be required to indicate whether the laser channels later are partially or completely open, from where the capillaries are supplied, and whether they even connect to the ventricle lumen. But in conclusion, it seems unlikely, that TMLR follows the mechanism of the amphibian heart.
In recent years, as the importance of humoral-mediated rejection has increasingly become recognized, the fact that endomyocardial biopsies (BX) evaluated according to the criteria of the International Society for Heart and Lung Transplantation often produce false-negative results has become a matter of concern. To evaluate the reliability of measuring intramyocardial ECG amplitude (IMEG) and immunofluorescence evaluation (FITC-labeled anti-IgG/ IgM staining) of endomyocardial biopsies (IFM), heterotopic neck-heart transplantation (HTX) was performed on eight beagles previously sensitized through skin transplantations. After HTX, IMEG, echo, and donor-specific antibodies in serum (IgG, IgM) were determined daily and myocardial biopsies (IFM, BX) were performed once every 2 days. Accelerated (humoral) rejection occurred on the 5th (4th-5th) postoperative day and sensitivity of IMEG, IFM, and BX was 100%, 75%, and 12.5%, respectively. In each case rejection was recognized so early that it was possible to initiate therapy with "restitutio ad integrum". Our results show that, as opposed to endomyocardial biopsy (IFM, BX), IMEG diagnosis detected humoral-mediated rejection early and with high reliability.
BACKGROUND: Inhaled nitric oxide (NO) has been shown to selectively lower pulmonary vascular resistance and is applied in patients with pulmonary hypertension (PHT). However, application and monitoring is complex and not always successful ("non-responders"). We evaluated the effect of aerolized prostacyclin (aePGI2) as a therapeutic alternate to NO. PATIENTS AND METHODS: aePGI2 and NO were applied to patients with different causes of pulmonary hypertension (Group 1a: preoperative patients with intracardiac shunting defects and Eisenmenger's disease, n = 30; Group 1b: patients with primary or postoperative PHT, n = 13; Group 2: PHT immediately following surgery for congenital heart disease, n = 6). RESULTS: Pulmonary vascular resistance could be lowered significantly (Group 1a: from 91% of systemic vascular resistance to 58% with NO and 53% with aePGI2; Group 1b: from 20.2 Wood Units*m2 to 13.4 and 11.3; Group 2: from 24.9 Wood Units*m2 to 9.5 and 10.5); cardiac index increased (Group 1b: from 2.96 to 3.55 and 3.96 l/min*m2, Group 2: from 1.57 to 1.89 and 2.00 l/min*m2). CONCLUSIONS: The short-term application of aePGI2 shows a selective pulmonary vasodilation similar to NO. Given adequate monitoring, aePGI2 appears to be useful for the acute treatment of PHT.
We report on a 28 year old woman with congenital ventricle-septum defect and Eisenmenger-reaction who developed acute GvHD on 10th postoperative day after successful heart-lung transplantation. The patient died on the 34th postoperative day of dissociated brain death after intracerebral bleeding.
BACKGROUND: Left ventricular function is the most important predictor of survival in patients with coronary artery disease. It is also an important indicator for hospital and late mortality after operation for endstage coronary artery disease. METHODS: Between April 1986 and December 1994, 514 patients with end-stage coronary artery disease and left ventricular ejection fraction between 0.10 and 0.30 underwent coronary artery bypass grafting at the German Heart Institute Berlin. Two hundred twenty-five of these patients had been referred as possible candidates for heart transplantation. The prime criterion for bypass grafting was ischemia diagnosed by myocardial scintigraphy and echocardiography ("hibernating myocardium"). RESULTS: Operative mortality for the group was 7.1%. The actuarial survival rate was 90.8% after 2 years, 87.6% after 4, and 78.9% after 6. Left heart catheterizations performed 1 year after the operation showed that left ventricular ejection fraction had increased from a mean of 0.24 +/- 0.03 preoperatively to 0.39 +/- 0.06 postoperatively (p < 0.0001). Preoperatively 91.6% of the patients were in New York Heart Association (NYHA) class III or IV; 6 months postoperatively 90.2% of the surviving patients were in NYHA class I or II. Two hundred thirty-one patients with end-stage coronary artery disease and predominant heart failure underwent heart transplantation. Their actuarial survival rate was 74.9% after 2 years, 73.2% after 4, and 68.9% after 6. All of the patients could be recategorized into NYHA class I or II after the operation. CONCLUSIONS: We conclude that coronary artery bypass grafting and heart transplantation can be used successfully to improve the life expectancy of patients with end-stage coronary artery disease. Coronary artery bypass grafting leads to an excellent prognosis for these high-risk patients when the myocardium is preoperatively identified as being viable.
BACKGROUND: Heart transplantation has a dramatic impact on both life expectancy and quality of life in patients with terminal heart failure. The aim of the study was to evaluate psychologic, social, occupational, and somatic status of patients living long-term, 9 to 13 years after orthotopic heart transplantation. PATIENTS AND METHODS: Seventy-seven of 182 patients who received transplants between July 1983 and January 1988 in Hannover (1983-1985; n = 69 patients) and Berlin (1986-1988; n = 113 patients) have survived up to now, 9 to 13 years after transplantation (mean, 10 years 4 months). The patients and their medical records (eg, cardiac catheter studies, echocardiography) were examined to assess their somatic status. Psychologic, social, and occupational status and quality of life data were assessed by combination of self-rating questionnaires (the Short Form Health Survey Questionnaire, Giessener Beschwerdebogen [the Giessen Subjective Complaints List], the Sickness Impact Profile, and the Hospital Anxiety and Depression Scale) and semistructured interviews. RESULTS: Ninety-one percent of the patients were in New York Heart Association functional class I (70%) or II (21%). The results of the psychologic investigation revealed a definite impact of the side effects of chronic immunosuppression; however, overall, the quality of life rating was within the normal range. Sixty-seven (86%) patients were married, 51 (66%) patients were retired, 17 (22%) worked full-time or part-time, and 9 (12%) were housewife or houseman. Four male patients have fathered five healthy children 1 to 10 years after the transplantation. More than 75% of the patients had normal systolic ventricular function (mean left ventricular ejection fraction, 0.63). Coronary angiograms were normal or with minor wall irregularities in 86% (n = 66 patients), and revealed severe obstructions in 14% (n = 11). Normal function of all valves was found in one-third of the patients, tricuspid valve incompetence was not found or was insignificant in 87% (n = 67 patients) and severe in 8% (n = 10). Six patients had undergone tricuspid valve replacement, invariably for structural valve defects attributable to biopsy injuries. Fifty-eight patients (75%) exhibited various degrees of compensated renal insufficiency, 7 of them were on chronic hemodialysis, and 2 patients have undergone kidney transplantation. Hepatic function was normal in 68% (n = 52) of the patients, and 1 patient has developed liver cirrhosis. Osteoporosis was diagnosed of the discrete form in 7 (9%) and of a significant degree in 24 patients (31%); 38.5% (n = 30) complained of symptoms of polyneuropathy. CONCLUSIONS: The patients surviving 9 to 13 years after orthotopic heart transplantation are mostly in good physical status, the quality of life is comparable to the general population, and only a few of them have significantly limited in their life style. They do show the substantial chronic side effects of long-term immunosuppression, remaining treatment-dependent for a lifetime.
A massive pulmonary embolism, demonstrated by echocardiography developed in a 3-week-old preterm infant. An etiologic explanation could not be obtained from either history or clinical and laboratory findings. Pulmonary embolectomy was performed as an emergency procedure because of severe hemodynamic impairment despite intensive medical therapy. In children who have massive pulmonary embolism who remain in a compromised hemodynamic state despite intensive medical therapy, pulmonary embolectomy may be considered the alternative emergency treatment.
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