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Biomedical subjects

B Reichart

Publications and source records attributed to B Reichart.

At least 181 records · Page 10Linked to original sources

Thirty-year results of Starr-Edwards prostheses in the aortic and mitral position.

BACKGROUND: Between 1963 and 1977 a total of 415 patients admitted to the University Hospital Munich underwent an isolated valve replacement with a Starr-Edwards prosthesis in the aortic or mitral position. METHODS: A retrospective follow-up of 87.1% of the patients representing 4,254 patient-years was completed. Surviving patients were examined by means of echocardiography. RESULTS: Survival rates after 10, 20, and 30 years were 62.3%, 39.4%, and 19.9% after aortic valve replacement and 75%, 36.5%, and 22.6% after mitral valve replacement (operative mortality excluded). Freedom from all valve-related complications, reoperations, and valve-related death was 66.4%, 43.3%, and 23.8% after aortic valve replacement and 73.4%, 35.4%, and 14.3% after mitral valve replacement. Of the surviving patients, 82% and 76% who received aortic or mitral valves, respectively, are in New York Heart Association class I or II. The pressure gradients of the aortic valves were between 20 and 73 mm Hg; those of the mitral valves were between 9 and 30 mm Hg. Fifty-two percent of aortic and 68% of mitral valves show no echocardiographic peculiarities. The left ventricular function in both groups is normal in 64%. CONCLUSIONS: The long-term results together with the echocardiographic results show that after 30 years the Starr-Edwards valve represents a standard that still needs to be achieved by newer prostheses.

Adult↗

Thirty years survival after double valve replacement with Starr-Edwards prostheses in aortic and mitral position.

We report about a patient who underwent double valve replacement with two Starr-Edwards prostheses in aortic and mitral position 30 years ago. Under anticoagulation medication he survived 28 years without any valve-related events. In the 29th year he sustained a cerebral infarction from which he recovered, having only a residual left arm paresis. His NYHA functional class today is II-III. Chest X-ray shows a mildly enlarged configuration of the heart, echocardiography reveals no irregularities of the implanted prostheses. We conclude, that the Starr-Edwards valve presents an outstanding standard concerning durability in mechanical valve replacement.

Adult↗

Endothelialized biological heart valve prostheses in the non-human primate model.

OBJECTIVE: The main disadvantage of implanted cardiac valve bioprostheses remains primarily tissue failure due to calcification. Coating of bioprostheses with viable autologous endothelial cells may delay or even eliminate tissue calcification and subsequent cardiac dysfunction. METHODS: Glutaraldehyde-preserved Hancock bioprostheses (n = 5), pretreated with glutamic acid (8%) and cryopreserved allografts (n = 5) were lined, using endothelial cells harvested from the external jugular vein. Coated specimens were cultivated for 9 days in Medium 199 supplemented with 20% fetal calf serum and basic fibroblast growth factor. Endothelialized grafts were anastomosed into the descending thoracal aorta of adult Chacma baboons. Untreated valve bioprostheses (n = 4) served as controls. Forty days after implantation the prostheses were examined morphologically and immunohistochemically. RESULTS: After implantation endothelialized prostheses showed a positive Factor VIII related antigen reaction by immunohistochemistry on all valve surfaces. Scanning electron microscopy showed confluently lined leaflets with transplanted endothelial cells and displayed cobblestone morphology on all coated allografts. In contrast, the surface of pretreated xenograft valves revealed uncoated areas with platelet and leucocyte aggregates. No endothelium was observed on the leaflets of untreated controls 40 days after implantation. CONCLUSION: In vitro endothelialization of cardiac valve bioprostheses with autologous endothelial cells is possible. The newly created endothelium is shear stress resistant and the antithrombotic as well as the antiaggregatory capacity of the transplanted cells were retained. Lining with autologous endothelial cells could improve the durability and clinical outcome of biological valve prostheses.

Animals↗

Surgery of the thoracic aorta using deep hypothermic total circulatory arrest. Are there neurological consequences other than frank cerebral defects?

OBJECTIVE: Deep hypothermic total circulatory arrest has reduced primary morbidity and mortality in thoracic aortic surgery. Although frank neurological deficits have been proven to be a rare complication of this technique, the rate of subtle but irreversible neuropsychological disorders remains unknown. METHODS: A total of 23 patients (15 male, 8 female) who had undergone surgery for dissection or aneurysm of the thoracic aorta using deep hypothermic total circulatory arrest (mean 25.5 min, range 10-75 min) were studied retrospectively. The mean follow-up was 17 months. The following psychometric tests were conducted: a computer-based test battery to assess tonic alertness and sustained attention, the trail making test (TMT part A and B), the Münchner Gedächtnistest and a verbal learning test. In addition, a cerebral dopamine D2 receptor scintigraphy (using the SPECT technique) was performed. For comparison, 10 healthy subjects were studied. RESULTS: With regard to tonic alertness, 69.6 and 30.4% were below the 50th and 10th centiles, respectively, according to age- and education-corrected standard values. The impairment in sustained attention correlated significantly with the duration of the circulatory arrest. On the tests assessing short-term memory, the patients scored 30% below their age- and education-corrected peers. In terms of long-term memory, 60.9 and 39.1% of the patients were below one and two standard deviations, respectively. Concerning speed of information processing whilst 78.3% of the patients were below the 50th and 21.7% below the 10th centile. Indicative of some persistent and functional brain alteration, the dopamine D2 receptor binding was significantly reduced when compared with healthy subjects. CONCLUSIONS: These data prove a substantial and chronic reduction of higher cognitive function in some of the patients who underwent cardiac surgery using deep hypothermic total circulatory arrest; this was accompanied by a depression of the cerebral dopamine D2 receptor binding.

Adult↗

Improvement of heart-, lung-, and liver-performance during mechanical circulatory support by the Novacor-system.

OBJECTIVE: Since its clinical introduction, the Novacor left ventricular assist system (LVAS) has proved to be a reliable and safe method for bridging to cardiac transplantation. To find out whether univentricular assistance is sufficient in patients with severe global heart failure, multi organ monitoring using the COLD system was performed. METHODS: In seven patients (mean age 38.8 years), the wearable Novacor system N100 was implanted. Preoperatively, during the first 72 h thereafter and before heart transplantation right and left ventricular cardiac output, right ventricular ejection fraction, pulmonary-, intrathoracic-and total blood volume, extravascular lung water and excretory liver function were monitored by means of double indicator dilution technique with the COLD system. Conventional hemodynamic parameters have also been documented. RESULTS: During left ventricular assistance, both pulmonary and systemic arterial cardiac outputs increased significantly (Student's t-test, P < 0.05). Right ventricular ejection fraction rose from 17 to 26%, preoperatively elevated pulmonary and intrathoracic blood volumes and extravascular lung water fell significantly to normal ranges. Total blood volume remained constant, excretory liver function improved markedly. CONCLUSIONS: Pulmonary cardiac output improves due to the reduced right ventricular afterload by unloading the impaired left ventricle with the Novacor pump. The drop in pulmonary blood volume, intrathoracic blood volume and extravascular lung water also indicates a decrease of pulmonary congestion. Since total blood volume remains unchanged, a volume shift to the systemic circulation is suggested, resulting in an improved splanchnic perfusion as demonstrated by a better excretory liver function. In the absence of primary pulmonary hypertension, treatment of global heart failure with a left ventricular assist device is possible. The COLD system is a useful tool for managing this patient group during the postoperative period.

Adult↗

Resection of hypernephromas with vena caval or right atrial tumor extension using extracorporeal circulation and deep hypothermic circulatory arrest: a multidisciplinary approach.

OBJECTIVE: Among retroperitoneal tumors, renal cell carcinoma most often invades the retrohepatic inferior vena cava or the right atrium. Even in these cases, radical nephrectomy may be performed with curative intention. The aim of this retrospective study was to elucidate the impact of cardiopulmonary bypass and hypothermic circulatory arrest on surgical complications, primary mortality, and long-term survival. PATIENTS AND METHODS: From Jan. 1981 till Aug. 1996, 44 patients were operated upon for renal cell carcinoma with advanced vena caval extension. The patients were divided into two groups. In 19 cases (Cardiopulmonary Bypass Group), extracorporeal circulation and deep hypothermic circulatory arrest was used. The Conventional Technique Group comprised 25 patients who had radical nephrectomy, paraaortic lymphadenectomy and extirpation of the intracaval tumor thrombus applying common principles in vascular surgery. The median age was 59 years with a range from 42 to 78 years in the Cardiopulmonary Bypass Group, and 60 years, ranging from 22 to 72 years, in the Conventional Technique Group. In addition, both groups did not differ in gender, UICC TNMG staging classification, and perioperative risk factors. A review of the patient charts was done and surveys were sent to survivors or nearest of kin. Wilcoxon test and log-rank test were used as appropriate. RESULTS: A lower intraoperative complication rate was found in patients who had surgery using cardiopulmonary bypass. This was especially true with embolization of the tumor thrombus into the pulmonary arteries: 0.0% in Cardiopulmonary Bypass Group and 16.0% in Conventional Technique Group (P < 0.05). Severe hemorrhage occurred in 10.5% (Cardiopulmonary Bypass Group) and 16.0% (Conventional Technique Group). This translated into a significantly lower perioperative mortality in the Cardiopulmonary Bypass Group when compared to the Conventional Technique Group (5.6 and 16.0%, respectively). In spite of these results, differences in long-term survival did not reach statistical significance. But, a trend to superior long-term survival was apparent. The mean survival was 1289 +/- 278 days in the Cardiopulmonary Bypass Group and 746 +/- 166 days in the Conventional Technique Group. CONCLUSIONS: Due to acceptable long-term results, the resection of hypernephromas showing extensive vena caval invasion seems to be justified. The use of cardiopulmonary bypass and hypothermic circulatory arrest is able to decrease primary morbidity and mortality. However, the influence on long-term survival remains to be proven.

Adult↗

Platelet morphology in patients with mechanical circulatory support.

OBJECTIVE: Mechanical circulatory support is a therapy for patients with end stage cardiac insufficiency. The thromboembolic events are feared complications during support, due to the surface thrombogenicity of the implanted device. Activated blood platelets play a major role in this context. Consequently the platelet morphology of patients was investigated. METHODS: Platelets of eight patients were observed by means of scanning electron microscopy during the period of support with the Novacor left ventricular assist system N100. Blood was collected preoperatively and daily during the first week as well as weekly during the first 3 months. Samples were fixed with cacodylic-acid buffered glutaraldehyde. Platelet alterations were classified as non-activated, activated and aggregated, based on the so-called 'shape change' morphology. In addition, blood coagulation parameters were evaluated (e.g. activated partial thromboplastin time, prothrombin time, antithrombin III). RESULTS: Preoperatively, 15.0 +/- 4.6% (overall mean values) of activated platelets were found. Within the first postoperative week, the mean level of activated platelets increased to 32.8 +/- 8.0% (P < 0.05). Comparing short- (< 30 days; n = 4) vs. long-period (> 30 days; n = 4) support, a significant difference of activated platelets was evaluated (24.3 +/- 3.3% vs. 34.8 +/- 3.4%, P = 0.004). A correlation was found between the values of activated clotting time and activated platelets. Specific platelet deformations and damages appeared during support, which could not be found preoperatively. CONCLUSIONS: The platelet morphology showed alterations in all patients probably most strongly induced by the surface activation of the implanted device. These observations should be taken into consideration in management of postoperative anticoagulation therapy.

Adult↗

Signs of vagal reinnervation 4 years after heart transplantation in spectra of heart rate variability.

Several investigators have shown signs of possible sympathetic but not parasympathetic reinnervation in heart transplanted patients. Spectral analysis of heart rate and blood pressure variability is a noninvasive tool appropriate to detect a functional autonomous reinnervation to the heart. In a follow-up study, 13 patients after heart transplantation (HTx) were investigated, mean age 50.6+/-8.5 years, 18 healthy volunteers were selected as control group. For each patient two recordings were performed which took part 14+/-5 months respectively 42+/-8 months after HTx. ECG and systolic blood pressure (SBP) have been recorded simultaneously for 5 min in supine position during controlled respiratory rate of 12 or 15 cycles/min. No graft rejection has been detected in the endomyocardial biopsy performed right after the recordings. Power spectral densities (PSD) were calculated for the beat-to-beat time series of RR-intervals (distance of two following QRS complexes) and SBPs. The area of PSD in the range of 0.05-0.17 Hz was defined as low frequency (LF) and that of 0.18-0.35 Hz as high frequency (HF). LF and HF are indicative of efferent sympathetic respectively parasympathetic activity at the sinus node. A significant increase of LF (226%) and HF (213%) during a mean period of 28 months could be found. No differences were to be shown for systolic blood pressure variability. Previous findings confirm that LF band increases 4 years after transplantation, suggesting a possible sympathetic reinnervation of the heart. On the other hand an increase of the HF band also suggests a parasympathetic reinnervation.

Adolescent↗

Long-term results of total repair of tetralogy of Fallot in adulthood: 35 years follow-up in 104 patients corrected at the age of 18 or older.

Long-term survival after surgical repair of tetralogy of Fallot (TOF) is reported to be excellent if the patients are corrected in childhood. However, age at operation has been demonstrated as an important risk-factor. The aim of our study was to investigate whether adult patients also benefit from surgery. From December 1958 to May 1977, 739 patients underwent a correction of their TOF with pulmonary stenosis at our institution. Foreigners (n = 52) and those who moved to a foreign country (n = 13) were excluded from further analysis. Sixteen patients were lost during follow-up (98% complete). Of the remaining patient population (n = 658; mean age: 12.2 +/- 8.6 years; range 2-67 years), 104 patients were 18 years or older at the time of correction. Operative (n = 25) and one-year (n = 8) deaths were excluded for long-term calculations, resulting in a study group of 71 patients. Actuarial 10, 20, 30, and 35-year survival rates were 94%, 93%, 83%, and 72% respectively, and not different from normal life expectancy. The most common cause of death was congestive heart failure (n = 3), followed by myocardial infarction (n = 2) and sudden death (n = 2). Parameters influencing longterm survival could not be detected. At follow-up (mean 27.7 years), more than 80% (n = 48) of the 58 survivors reported themselves to be in NYHA functional class I or II and 95% (n = 55) were in a better condition than before the operation. Repair of tetralogy of Fallot in adulthood shows excellent results with normal life expectancy for the patients.

Adult↗

Surgical treatment of the Bland-White-Garland syndrome in early infancy: subclavian to coronary artery anastomosis via left anterolateral thoracotomy extended by a transverse sternotomy.

The case of a 6-week-old girl with left coronary artery originating from the pulmonary artery (Bland-White-Garland syndrome) is reported. Therapy consisted of a subclavian-coronary artery anastomosis via left anterolateral thoracotomy extended by transverse sternotomy. This approach allowed both the easy dissection of the left subclavian artery and the use of extracorporeal circulation while doing the anastomosis. Operation and postoperative course were uneventful. Angiography after one year revealed a patent anastomosis and a totally recovered left-ventricular function.

Coronary Artery Bypass↗

[On-site laboratory monitoring on the intensive care unit. Blood gas, electrolyte, glucose, hemoglobin and lactate determination with the CIBA Corning 865 Analysis System].

INTRODUCTION: For decision-making in the ICU, rapid and accurate analysis of vital laboratory parameters is essential. The industry provides devices which analyse these parameters on a decentralised setting and which are designed for use by non-laboratory personnel. We investigated whether accuracy and handling of a new analyser (Ciba-Corning 865, Chiron Diagnostics, Medfield, USA) are good enough for basing clinical decisions on the measured parameters. MATERIALS AND METHODS: The Ciba-Corning 865 allows measurement of blood gases, electrolytes, haemoglobin, glucose and lactate by use of photometric, ion-selective, enzymatic and electrochemical sensors in less than 18 microliters of whole blood. In a cardiac surgical intensive-care unit the accuracy of the device was tested by comparison to 61 measurements of quality control reagents, 48 tonometered blood samples and 536 parallel measurements in the clinical laboratory. Besides a 10-minute instruction, the participating personnel had no formal training with the device. RESULTS: The differences between measurements in quality control reagents and tonometered blood and the expected value were lower than 5%. The comparison with clinical laboratory measurements showed correlation coefficients from 0.94 (sodium) to 0.99 (glucose, lactate). The biases in Bland-Altman analyses were below 5%, the limits of agreement were found to be in a clinically acceptable range for all parameters. During the test period no technical problems occurred with the analyser and good acceptance by the personnel was found. CONCLUSIONS: The measured parameters were accurate enough to be used for therapeutic decisions in acute care medicine. Although it should not be a complete alternative to the clinical laboratory, because of rapid analyses, small sample volumes and easy handling the use of the Ciba-Corning 865 is advantageous for patients and users.

Blood Chemical Analysis↗

Influence of anodal electrode position on transvenous defibrillation efficacy in humans: a prospective randomized comparison.

Nonthoracotomy lead systems for implantable cardioverter defibrillators (ICDs) have reduced operative mortality and morbidity as compared to epicardial lead systems but are usually associated with higher defibrillation thresholds (DFTs). The purpose of this prospective randomized trial was to investigate if the second defibrillation electrode in the left subclavian vein can increase defibrillation efficacy and decrease DFT as compared to the superior vena cava (SVC) position in nonthoracotomy lead systems for ICDs. Seventeen patients (mean age: 49.9 +/- 11.3 years, mean ejection fraction: 46.1% +/- 15.8%) were implanted with an investigational unipolar electrode (Medtronic 13001) used as the defibrillation anode. DFT testing was started in the SVC (n = 10, group A) or the left subclavian vein (n = 7, group B), and repeated in the alternative position starting at the DFT of the initial position. Fifteen patients were eligible for analysis (group A: n = 9, group B: n = 6). With the electrode in the SVC, ventricular fibrillation could be successfully terminated in 9 out of 15 patients (60%). In the left subclavian vein the success rate was 100% (P < 0.01). Mean DFT in the SVC was 13.0 +/- 5.2 J and in the left subclavian vein 10.2 +/- 4.9 J. DFTs in the left subclavian vein were either lower (group A: n = 5/9, group B: n = 5/6) or equal to the results in the SVC position (P < 0.001). Thus, the left subclavian vein appears to be a superior alternative for positioning of the defibrillation anode as compared to the SVC for nonthoracotomy lead systems using two separate leads.

Defibrillators, Implantable↗

[A comparison of ultrafast computed tomography, magnetic resonance angiography and selective angiography for the detection of coronary bypass patency].

PURPOSE: Validation of ultrafast-CT and MR-angiography (MRA) in comparison with angiography for detection of early postsurgical arterial and venous coronary artery bypass graft (CABG) patency. METHODS: 21 patients with a total of 55 CABG (34 venous and 21 arterial) were studied with angiography, ultrafast-CT (EBT), and MRA. RESULTS: With EBT, patency of 43/45 angiographically patent CABG could be correctly assessed (sensitivity: 96%). With MRA 26 CABG (17 venous and 9 arterial) were identified as patent (sensitivity: 67%). It was not possible to quantify proximal stenosis of three grafts (> 40%) and to evaluate the distal bypass anastomosis with both EBT and MRA. CONCLUSIONS: Ultrafast-CT is a promising minimal invasive screening method for the evaluation of venous and arterial CABG patency. The diagnostic significance of MRA is remarkably reduced.

Aged↗

Transgenic human decay accelerating factor makes normal pigs function as a concordant species.

BACKGROUND: Increasing interest has focused on xenotransplantation as a potential solution to the organ shortage. To overcome hyperacute rejection, pigs have been produced that are transgenic for human decay accelerating factor (DAF). For the evaluation of the effects of human DAF, an ex vivo working heart model was used. METHODS: We compared hemodynamic performance of four transgenic pig hearts (group A) with that of four Landrace pig hearts (group B) and eight rhesus monkey hearts (group C). For perfusion fresh blood had been taken from healthy volunteers. From the coronary sinus effluent, samples were taken for the determination of 6-keto prostaglandin F1 alpha, prostaglandin E2, creatine phosphokinase, and lactate dehydrogenase, respectively. Hemodynamic parameters were measured continuously for 150 minutes after the start. After 15 minutes of reperfusion, the Langendorff-mode was switched to the working heart model. After hearts failed to pump against the afterload column, experiments were terminated, and tissue sections were taken for electron microscopy. RESULTS: Groups A and C showed superior cardiac performance as measured by stroke work index (SWI) that exceeded group B by 2.5 to 3 times (p < 0.05). In all three groups the SWI slowly decreased during perfusion. In group B, SWI decreased to a minimum as early as 90 minutes after the start. In all groups, 6-keto prostaglandin F1 alpha and prostaglandin E2 as indicators of endothelial cell activation increased. In group B, however, the levels exceeded those of groups A and C by six and nine times, respectively (p < 0.05). As markers of myocardial damage, creatine phosphokinase and lactate dehydrogenase increased in all groups. But again levels in group B exceeded those of groups A and C by four to five times (p < 0.05). Electron microscopy revealed single cell necrosis in group B, whereas groups A and C showed interstitial edema only. CONCLUSIONS: Our experiments indicate a crucial role of DAF in preventing rejection in discordant species combinations. Transgenic human DAF seems to inhibit successfully complement-mediated damage to the endothelial cell, thus preventing endothelial activation and consequently myocardial damage. Transgenic human DAF makes a discordant species (pig) function as a concordant species, that is, hyperacute rejection does not occur.

6-Ketoprostaglandin F1 alpha↗

Surgical therapy for coronary artery disease in patients with a left ventricular ejection fraction of 25% or less.

BACKGROUND: In patients with advanced coronary artery disease (CAD) and markedly decreased left ventricular ejection fraction (EF) symptoms of myocardial ischemia and insufficiency may be complicated by ventricular arrhythmias. Appropriate surgical therapy must be tailored to the individual symptoms. The aim of this study was to compare the different current methods. METHODS: From 9/1990 to 9/1994 138 patients with coronary artery disease and a left ventricular EF of < or = 25% were operated. Patients with dominating Angina pectoris and vital myocardium were revascularized (ACB; n = 17); two of these patients were 12 and 37 months p.o. transplanted. Because of dominating dyspnea, diffuse CAD and missing AP heart transplantation seemed indicated (HTX; n = 102). In two of these patients ventricular assist devices were implanted as a bridge to transplantation; both patients survived. Patients with malign tachycardias received either an implantable cardio-defibrillator (ICD; n = 16) or had arrhythmia surgery (ARS; n = 3). Patients of the HTX-Group were younger (54 vs 60 years; p < 0.05), had more often previous surgery (28% vs 20%) and were in worse conditions (NYHA 3.5 vs 3.0; p < 0.05). RESULTS: The main cause of death after transplantation was multi-organ failure (MOF; 14/102; 13.8%). The best long-term survival (87% after 3.2 years, p < 0.01 vs HTX)-with low average functional classes (NYHA 2.9)-had the patients after ICD implantation. The best quality of live (NYHA 1.1; p < 0.01 vs ICD)-associated with a high mortality due to preoperatively impaired organ-systems (62% operative survival, 57% 4-years survival)-was achieved by transplantation. In patients with a history of ventricular arrhythmias, who are waiting for a transplantation, the implantation of an ICD should be considered. Bypass surgery as well as arrhythmia surgery showed good survival (1-year survival 82% and 66% respectively) and functional results (NYHA 1.7 and 1.5 respectively).

Arrhythmias, Cardiac↗

Tacrolimus: a superior agent to OKT3 for treating cases of persistent rejection after intrathoracic transplantation.

Acute myocardial rejection refractory to treatment still contributes significantly to patient death after intrathoracic transplantation. A historical series of 25 patients who received OKT3 (5 mg/day for 10 days) was compared with our current experience with 14 patients treated with tacrolimus (0.1 mg/kg/day targeting whole blood concentrations of 13 to 18 ng/ml): all 39 patients having persistent rejection unresponsive to treatment at the time of conversion. Mean periods of follow-up were 842.9 days and 342.6 days, respectively. Actuarial 1-year patient survival rates were 64.0% and 76.2% for the OKT3 and tacrolimus treatment groups, with most of the deaths in the OKT3 group occurring early (p = 0.064). Causes of death for patients receiving OKT3 included acute rejection (n = 5), infection (n = 3), carcinoma (n = 2), multiorgan failure (n = 1) and graft vessel disease (n = 1). The two deaths in the tacrolimus treatment group were the result of infections. Eighty percent of patients treated with OKT3 subsequently experienced further rejection episodes, in many cases necessitating methotrexate therapy. In contrast, only one patient (7.1%) from the tacrolimus group was diagnosed with rejection after conversion (p < 0.001). In conclusion, when compared with OKT3 therapy, a switch in baseline immunosuppression from cyclosporine to tacrolimus seems to be markedly more effective, as well as being safe for the treatment of persistent acute rejection.

Actuarial Analysis↗

S-methylisothiourea inhibits inducible nitric oxide synthase and improves left ventricular performance after acute myocardial infarction.

The contribution of increased inducible nitric oxide synthase (iNOS) activity to the development of left ventricular dysfunction after acute myocardial infarction (MI) was investigated New Zealand rabbits (n = 24) were randomly treated with either saline, S-methylisothiourea sulfate (SMT; selective iNOS inhibitor) or N-omega-nitro-L-arginine (NOLA; non-isoform selective NOS inhibitor). Left ventricular hemodynamics and myocardial blood flow were measured before coronary occlusion and on postoperative day 3 (POD 3). MI resulted in left ventricular dysfunction and increased myocardial iNOS activity. SMT and NOLA significantly inhibited iNOS activity; SMT, but not NOLA, significantly improved left ventricular maximum +dP/dt and decreased LVEDP; myocardial blood flow in the remote myocardium significantly increased after SMT. Induction of myocardial iNOS after MI on POD 3 contributes to the development of left ventricular dysfunction; modulation of iNOS activity by SMT improves left ventricular performance and may be beneficial after acute MI.

Animals↗

Prevention of hyperacute rejection by human decay accelerating factor in xenogeneic perfused working hearts.

As a potential source of organs for xenotransplantation, pigs that are transgenic for human decay accelerating factor (DAF) have been bred in order to overcome hyperacute rejection. We investigated the protective effect of human DAF in a porcine working heart model perfused by human blood. Hearts of normal landrace pits served as controls. The following parameters were measured: stroke work index, coronary flow and arteriovenous oxygen consumption, 6-keto prostaglandin F1alpha and prostaglandin E2 as markers of endothelial cell activation; creatine phosphokinase and lactate dehydrogenase for evaluation of the extent of myocardial damage; TNFalpha and IL-6 as markers of mononuclear cell activation. Histological and ultrastructural investigations from myocardial tissue sections were done at the end of perfusion. Human (h) DAF appeared to inhibit complement-mediated endothelial cell activation of transgenic pig hearts successfully. This was in contrast to landrace pig hearts, which had a sixfold increase of prostaglandin levels during perfusion with human blood. The cardiac weight increase during perfusion time due to interstitial edema tended to be less in the hDAF group. Myocardial damage was minimal in transgenic hearts, whereas normal pig hearts produced a threefold increase of creatine phosphokinase and lactate dehydrogenase levels. In these hearts, electron microscopy revealed single cell necrosis of myocytes and vacuolization of mitochondria with cristae rupture. According to the results obtained in the working heart model, the breeding of pigs that are transgenic for hDAF represents a promising step to making heart xenotransplantation a clinical reality in the future.

Acute Disease↗