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Biomedical subjects

S Hagl

Publications and source records attributed to S Hagl.

At least 19 recordsLinked to original sources

Intravital microscopy of pulmonary microcirculation after single lung transplantation in pigs.

BACKGROUND: Pulmonary reperfusion injury is a significant risk factor following lung transplantation (LTx). Unfortunately, in vivo observations and quantitative analyses of the pulmonary microcirculation following LTx are technically demanding. METHODS: Pigs, weighing 18 to 22 kg, served as the laboratory animals. The left lung was harvested and preserved using donor aortic vessel segments, the pulmonary artery, and the cuff of the lung veins were extended. After 4 hours of ischemia, the lungs were transplanted by direct connection of the conduits to the left atrial appendage and the left pulmonary artery of the recipient. The lungs were placed extrathoracically and ventilated. The recipient left lung was excluded. With this procedure, mechanical trauma to the lung and moving artefacts were avoided. Intravital microscopic observation became feasible. RESULTS: Following reperfusion, oxygenation of pulmonary venous blood was excellent. However, blood flow distribution was significantly reduced to the transplanted lung compared with the native right recipient lung. Pulmonary vascular resistance was significantly increased, dropping from 3500 to 1000 dynes x s x cm(-5) during reperfusion compared to a value of 500 for the native right lung. The pulmonary microcirculation showed a significant number of no-reflow areas with extremely reduced red blood cell velocities. Greater than 90% of microvessels (<30 microm) showed velocities below 0.1 mm/sec. In conclusion, microvascular injury seems to be a major pathogenic factor for the development reperfusion failure. Quantification of alterations within the microvasculature may shed light on various treatment modalities that reduce perfusion failure.

Animals↗

Coronary reconstructive surgery versus coronary artery bypass grafting--a documentation gap.

OBJECTIVE: Over the last years, there has been a clear trend that an increasing number of patients are admitted for CABG with advanced disease, complex pathomorphological alterations and impaired left ventricular function. The necessity of performing extensive reconstructive coronary surgery rather than coronary bypass grafting, in its original sense, is not appropriately documented by the current version of the German Documentation System for Cardiac Surgery, nor in other national and international documentation systems. PATIENTS AND METHODS: 5821 consecutive, unselected patients underwent isolated CABG from 7/1995 through 12/2003 at a single institution. A closing date follow-up procedure up to 8 years postoperatively was performed with a completeness of 98.8%. RESULTS: The need for reconstructive surgery in terms of extended anastomoses with or without coronary endarterectomy has doubled in our patients since 1995 and is steadily increasing with 15.7 % (n=102) of these patients requiring such surgery in 2003. Current documentation does not allow any prediction of complex coronary morphology. The Kaplan-Meier survival curve reveals no substantial difference between patients with and without coronary reconstructive surgery up to 8 years after CABG. CONCLUSION: The increase of complexity in CABG procedures currently remains undetected, since preoperative imaging methods often fail to predict complex coronary morphology. Survival after coronary reconstructive surgery is comparable to that of "classical" CABG. Therefore, a standardized documentation is required to evaluate surgical results and to contribute to the improvement of medical decision-making which presupposes valid data.

Aged↗

Bridge to operation with the GPIIb/IIIa inhibitor abciximab in high-risk coronary patients.

BACKGROUND: Glycoprotein-IIb/IIIa inhibitors are now frequently used in the cardiological treatment of high-risk coronary patients even if the patient is considered suitable for surgical intervention. However, there is no consensus whether GPIIb/IIIa inhibitors should be stopped before operation because of an increased risk of bleeding or if surgery should even be delayed until the anticoagulating effect subsides. METHODS: From June 2002 to August 2003 140 patients who had to undergo primary aorto-coronary bypass for ongoing myocardial ischemia were enrolled in the present study. The patients received either clopidogrel, aspirin and heparin or additionally abciximab until operation. RESULTS: Although the intraoperative need for blood products was higher in the abciximab group, there was no significant difference in postoperative blood loss. The hemodynamic situation of the abciximab patients after the operation was better compared to the other groups. 30-day mortality was not increased when compared to the elective control group (6.7 % vs. 6.1 %). CONCLUSION: The GPIIb/IIIa inhibitor abciximab can be safely used as a bridge to operation and results in a better hemodynamic outcome in high-risk coronary patients while reducing the incidence of major ischemic events.

Abciximab↗

The Eurotransplant High-Urgency Heart Transplantation Program: an option for patients in acute heart failure?

OBJECTIVE: The Eurotransplant High-Urgency (HU) Heart Transplantation Program allows urgent heart transplants to be carried out in rapidly deteriorating patients with acute-to-chronic heart failure on the elective waiting list. But do the results of HU heart transplantation justify performing primary heart transplantation in these critically ill patients and offer an acceptable outcome? METHODS: Between 2000 and 2004, 64 heart transplantations (HTx) (32 elective and 32 HU-HTx) were performed in our department. After having been accepted in an auditing process based on HU criteria, intensive care patients in NYHA functional class IV (cardiac index 1.7 l/min/qm BS), in end-organ failure (creatinine 1.5 mg/dl), and with catecholamine dependence (dobutamine 8 microg/kg/min), are given priority with respect to organ allocation, and their data were compared to data from elective patients from the same period. RESULTS: HU requests were accepted in 97 % of cases. Two requests were not accepted, and both patients with contraindications for assist device implantation died within one week. The HU patients were 100 % in NYHA class IV, 93 % of the elective patients were in NYHA class III. Waiting time on the HU list was 13 days, and 7 of these patients died before HTx. Following heart transplantation, survival rates at 30 days and at one year of the HU group were 88 % and 85 % versus 94 % and 93 % in the elective group. CONCLUSIONS: This study shows that end-stage heart failure patients in the HU program can be transplanted primarily with good results if an organ is available in time. We are still in the position where the HU program only manages the organ shortage; there are still too many patients on the waiting list who die before receiving a donor organ.

Acute Disease↗

Three-dimensional assessment of left ventricular geometry and annular dilatation provides new mechanistic insights into the surgical correction of ischemic mitral regurgitation.

BACKGROUND: The aim of this study was to investigate the relationship between LV geometry, annular shape and the amount of regurgitation in patients with ischemic mitral regurgitation (group 1, n = 30) compared to patients with primary mitral valve lesions (group 2, n = 30). METHODS: LV geometry was assessed by the sphericity index, i.e., LV volume divided by the volume of a sphere with a diameter equal to the longest axis. Annular geometry was evaluated by diameters, areas and their percentual shortening. The degree of mitral regurgitation was assessed as jet volumes by 3D-echocardiography. RESULTS: Group 1 showed significantly larger longitudinal (54.3 +/- 3.1 vs. 40.9 +/- 2.6 mm) and antero-posterior (32.2 +/- 3.3 vs. 27.1 +/- 2.9 mm) annulus diameters and areas (993.3 +/- 66.6 vs. 702.1 +/- 47.9 mm (2)) than group 2. No asymmetric annular enlargement was found in either group. Annular enlargement correlated to the degree of mitral regurgitation in group 1 but not in group 2. Annular area shortening was significantly impaired in group 2 and the sphericity index was larger in group 1 than in group 2. In group 1, the sphericity index was significantly correlated to the degree of mitral regurgitation (r = 0.87; P < 0.001). CONCLUSIONS: These findings suggest that ischemic mitral regurgitation was mostly associated with a global left ventricular enlargement, in which annulus dilatation and its reduced contraction play a significant role.

Echocardiography, Three-Dimensional↗

Right ventricular expression of extracellular matrix proteins, matrix-metalloproteinases, and their inhibitors over a period of 3 years after heart transplantation.

Fibrillar collagens I and III, nonfibrillar collagen IV, and the glycoproteins fibronectin and laminin, are elements of the myocardial extracellular matrix (ECM). Alterations in the normal concentrations and ratios of these elements may reflect remodeling in response to physiologic stress. In the case of patients' post-heart transplantation (HTx), specific patterns of alteration may herald myocardial dysfunction. Right ventricular biopsies were taken from the same 28 HTx patients before implantation and 1 week, 2 weeks, and 1, 2, and 3 years after HTx. The above-noted five ECM proteins, six matrix metalloproteinases (MMPs) and two of their tissue inhibitors (TIMPs) were detected by immunohistochemistry and scored as cells per square millimeter or semiquantitatively. The total connective tissue fibers were detected by connective tissue stain and morphometry. Variations in these ECM components were followed in the same patient cohort over 3 years. In summary, during the first 2 weeks after HTx, a predominant increase in connective tissue occurred. Increases in MMP-8 and MMP-9 were found. By 3 years after transplantation, there was a decrease of connective tissue fibers and a significant reduction of all ECM components and an increase in MMPs and TIMPs. These findings may reflect a pattern of remodeling specific to the transplanted heart.

Adolescent↗

Extracellular matrix proteins and matrix metalloproteinases differ between various right and left ventricular sites in end-stage cardiomyopathies.

This study was undertaken to investigate whether there might be differences in the distribution of extracellular matrix (ECM) proteins and matrix metalloproteinases (MMPs), depending on their specific sites within the heart. We investigated 33 explanted human hearts, 15 with dilated cardiomyopathy (DCM) and 18 with ischemic cardiomyopathy (ICM). Transmural samples from the right ventricle, the interventricular septum and the left ventricle, either from near the apex or from near the base were taken from every heart. Frozen sections were processed for connective tissue staining and immunohistochemistry for collagens type I, III, IV, laminin and fibronectin, as well as MMP-1, -2 and -9. Volume densities of laminin in ICM as well as of fibronectin and collagen types I and IV in DCM showed significant differences between right and left ventricular sites. The volume densities of matrix proteins usually did not reveal significant differences among the three left ventricular sites tested in both DCM and ICM. MMPs partly showed differences between the right and the left ventricular myocardium. These results suggest that the distributions of ECM proteins and MMPs differ between the two ventricles in both end-stage DCM and ICM. This gives rise to the hypothesis that a specific pattern of ECM degradation exists in the right and left ventricular myocardium.

Cardiomyopathy, Dilated↗

Expression and activity of matrix metalloproteinase-2 in calcific aortic stenosis.

Calcific aortic stenosis is the main heart valve disease in the elderly, leading to massive focal calcification and thickening of the valve cusps. Matrix metalloproteinases (MMPs) are thought to contribute to this process. Therefore, the study assessed the expression of the gelatinases MMP-2 and MMP-9 and the endogenous tissue inhibitor of metalloproteinase (TIMP)-2 as well as the gelatinolytic activity in normal and stenotic valves. Human tricuspid aortic valves with and without calcific aortic stenosis were studied by immunohistochemistry for MMP-2, MMP-9 and TIMP-2. The gelatinolytic activity in native valve sections was assessed by gelatin in situ zymography with or without addition of the MMP activator p-aminophenymercuric acetate (APMA). Staining intensities for MMP-2 and TIMP-2 were elevated in stenotic valves as compared to controls. Minor staining of MMP-9 was present exclusively in stenotic valves. The morphologic distribution of gelatinolytic activity was comparable to the staining pattern of MMP-2, and since MMP-9 immunostaining demonstrated only a low number of positive cells, the observed gelatinolytic activity is likely due to MMP-2. Gelatinolytic activity was low in normal valves but significantly increased by the MMP activator APMA. In contrast, stenotic valves showed a strong basal gelatinolytic activity that could not be significantly enhanced by APMA suggesting that MMP-2 is present as a latent pro-enzyme in normal valves and activated in stenotic valves. Thus, MMP-2 might be involved in the matrix remodeling during calcific aortic stenosis.

Aortic Valve↗

Poly-ADP-ribose polymerase inhibition reduces mesenteric injury after cardiopulmonary bypass.

BACKGROUND: We investigated the effects of PARS inhibition on intestinal injury in a canine model of cardiopulmonary bypass (CPB). METHODS: Twelve dogs underwent 90 minutes of hypothermic CPB. 6 dogs received 5 mg/kg PJ34, a selective PARP inhibitor during CPB, 6 vehicle-treated animals served as controls. Mesenteric blood flow (MBF) and mesenteric vascular resistance (MVR) were measured before and 60 minutes after weaning from CPB. Endothelium-dependent vasorelaxation to acetylcholine (ACH) and endothelium-independent vasorelaxation to sodium-nitroprusside (SNP) were expressed as percent change of MVR. In addition, mesenteric creatine kinase (CK) and lactate release were determined. RESULTS: Baseline hemodynamics, MBF, response to ACH (- 41 +/- 3 vs. - 55 +/- 6 %) and SNP (- 60 +/- 2 vs. - 56 +/- 4 %) did not differ significantly between the groups. The response to ACH decreased significantly in the control group while it remained unchanged in the PJ34 group (- 29 +/- 5 vs. - 46 +/- 9 %, p < 0.05). The response to SNP did not change. Mesenteric CK release (325 +/- 99 vs. 16 +/- 10 U/l, p < 0.05) and lactate production (0.96 +/- 0.17 vs. 0.4 +/- 0.2 mmol/l, p < 0.05) were significantly lower in the PJ34 group. CONCLUSION: PARP inhibition prevents CPB-induced mesenteric endothelial dysfunction and tissue damage.

Acetylcholine↗

Accuracy of diagnostic laparoscopy for early diagnosis of abdominal complications after cardiac surgery.

BACKGROUND: In the early postoperative period after major cardiac surgery using extracorporal circulation, abdominal complications can have serious consequences with a mortality rate of up to 70%. Early diagnosis and the timely institution of therapy are the most important factors to improve the outcome; however, clinical evaluation of the abdomen is difficult in these patients. Diagnostic laparoscopy is a minimally invasive procedure with low procedure-associated morbidity, even in critically ill patients. The aims of our study were to investigate the safety of laparoscopy in critically ill patients suspected to have intraabdominal pathology following cardiac surgery and to evaluate the accuracy of diagnostic laparoscopy compared to laparotomy in this setting. METHODS: A total of 17 patients were included (13 male, four female, age 52-80 years) in the early (3-30 days) postoperative period after cardiac surgery using extracorporal circulation (10 ACVB, four valve replacement, one aorto-coronary-venous-bypass (ACVB)+ valve replacement, two cardiac transplantation). Clinical and laboratory findings included distended abdomen (17 of 17), elevated white blood cells (12 of 17), elevated C-reactive protein (CRP) (13 of 17), and elevated lactate levels (11 of 17). The decision to perform laparotomy was taken in all patients on the basis of their clinical condition. Diagnostic laparoscopy was always performed immediately before laparotomy. The laparoscopic findings were then compared to the laparotomy findings. RESULTS: In one patient, laparoscopy showed no abnormal findings, this was confirmed on laparotomy. Five patients were found to have massive distension of the large bowel without ischemia on both laparoscopy and laparotomy. Colonic ischemia of the right hemicolon was found laparoscopically in six patients, which was confirmed in all cases by open resection and histological workup. Three patients suffered from acute cholecystitis, which was correctly diagnosed by laparoscopy in all cases. In one patient, laparoscopy revealed fibrinous peritonitis without other findings. Open exploration failed to identify the cause of the peritonitis in this patient. Laparoscopy showed no pathological findings in one patient, but laparotomy then revealed necrotizing pancreatitis confined to the lesser sac. There was one laparoscopy-associated intraoperative complication (6%) in this series. CONCLUSIONS: Diagnostic laparoscopy is a minimally invasive procedure that can be performed at low intraoperative risk in critically ill patients and has a high sensitivity (94%) for the correct diagnosis of intraabdominal complications after major cardiac surgery. These results suggest that bedside laparoscopy should be considered for all patients with equivocal abdominal symptoms in this setting.

Aged↗

Pathological changes of the myocardium in patients after atrial repair for transposition of the great arteries: a possible explanation for left ventricular dysfunction after secondary arterial switch.

BACKGROUND: Patients with transposition of the great arteries who underwent an atrial repair in infancy are likely to develop right ventricular dysfunction later in life. For these patients a two-stage arterial switch operation has been advocated by some groups but mortality even from the initial pulmonary banding procedure for retraining the left ventricle has been reported to be considerable. We asked whether pathological alterations of the left ventricular myocardium could explain for the failure of the left ventricle observed in patients after two-stage arterial switch operations. METHODS: Twelve patients aged 16.9 [8-25.4] years (median [range]) with transposition of the great arteries after atrial repair in infancy were enrolled. Median follow-up interval was 15.8 [7.8-22.1] years. Measurements of right and left ventricular systolic function were performed by echocardiography. In addition all patients underwent cardiac catheterization. Endomyocardial biopsies were taken from the right and left ventricle and examined histopathologically. RESULTS: Two out of twelve patients showed mildly reduced systolic right ventricular function. Systolic function of the left ventricle was normal in all patients on echocardiography but six out of twelve patients showed clusters of fibrous and fatty degeneration on biopsy specimens obtained from the left ventricle. CONCLUSION: We conclude that degenerative left ventricular myocardial changes could serve as an explanation for left ventricular failing when retraining the left ventricle during two-stage arterial switch operations.

Adolescent↗

Long-term results after repair of truncus arteriosus communis in neonates and infants.

BACKGROUND: We reviewed our experience of truncus arteriosus communis (TAC) repair. METHODS: Between 05/90 and 10/01, 16 patients underwent complete repair of TAC (primary repair: group I, 12 patients, secondary repair: group II, 4 patients). Age was 2.4 months [5 days-8.8 months] (median [range]) in group I, and 8.3 [5.6-13.5] years in group II. Continuity from the right ventricle to the pulmonary artery was achieved using a valved conduit. All patients had regular follow-up examinations. RESULTS: There was one early death in each group (12.5%). Follow-up was 9 [1.2-12.7] years. Valved conduit failure occurred in 8 patients (67 %) in group I (group II, 1 patient, 33 %) requiring replacement at 2.5 [0.3-4.3] years (group II, 5.8 years). Severe neo-aortic valve regurgitation after truncal valve repair was observed in one patient, requiring valve replacement at 8.5 years in association with repeat homograft replacement (group I). Actual echocardiographic examination revealed normal ventricular function. Moderate conduit dysfunction was noted in 2 patients (group I). CONCLUSIONS: Complete repair of truncus arteriosus communis can be performed with excellent long-term results.

Cardiac Surgical Procedures↗

The index of pulmonary vascular disease in children with congenital heart disease: relationship to clinical and haemodynamic findings.

OBJECTIVE: We asked whether a scoring system [index of pulmonary vascular disease (IPVD)] that quantifies the individual pulmonary vascular pathology would relate to postoperative survival in patients with congenital heart disease and pulmonary hypertension (PH). METHODS: Lung biopsy specimens from 28 patients at a median age of 6 months (1 month to 21 years) were analysed qualitatively and morphometrically. The IPVD and other morphometric parameters were related to haemodynamic findings and survival. RESULTS: Mean pulmonary artery pressure (PAP) was 44 mmHg (15-72 mmHg), and the resistance to pulmonary perfusion was 5 U x m(2) (0.9-14 U x m(2)). There were three early (in-hospital) and three late deaths during the follow-up period of 2.5 years (6 months to 7 years). Incipient plexiform lesions were observed in one infant with trisomy 21 and complete atrioventricular septal defect (cAVSD). An IPVD score above the upper critical limit (>2.2) was not observed during the first year of life. On discriminant analysis, morphometric parameters could not predict mortality ( P=0.08). CONCLUSIONS: The IPVD is not helpful to predict surgical mortality during the first year of life. Patients with trisomy 21 and cAVSD may show advanced pulmonary vascular disease in infancy.

Child↗

Effects of trifluoperazine on the contraction kinetics of the isolated intact tracheal and pulmonary artery smooth muscle.

BACKGROUND: We studied the effect of the calmodulin antagonist trifluoperazine (TFP) on isolated intact rat tracheal and pulmonary artery smooth muscle contractile behaviour. METHODS: Experimental series: 1) TFP-dose-response curves for TFP's effect on force generation were constructed using rat tracheal smooth muscles and rat pulmonary artery preparations (n = 8). A concentration of 1 micromol/l TFP was chosen for the subsequent experimental series. 2) Tracheas and pulmonary arteries (n = 14) were dissected in three segments. One of them was used immediately for experiments ("native"), the other two were treated for 12 h in 4 degrees C Tyrode solution without ("12 h cold storage") or with 1 micromol/l TFP ("12 h cold storage + TFP"). These preparations contracted after supramaximal effective electrical field stimulation. The force-clamping technique was used to analyse kinetic and mechanical parameters of smooth-muscle contraction in both types of preparation (measurement conditions: resting tension 2 mN, 37 degrees C, modified Krebs-Henseleit solution). RESULTS: 1) TFP decreased developed force dose-dependently in pulmonary artery and tracheal smooth muscle. 2) During sustained tonic activation, the contraction kinetics become slower both with and without TFP treatment (p < 0.0001). 3) TFP caused a dramatic retardation of the velocity of force generation in both types of preparation for any given time interval during the course of a tonic activation (p < 0.0005). 4) The dramatic effects of TFP on the contraction kinetics were not associated with effects on the extent of force generation. CONCLUSIONS: These results support the assumption that tracheal and pulmonary artery smooth muscle cross-bridge rates are controlled by a calcium-calmodulin-dependent myosin light chain kinase. This finding suggests the involvement of a calmodulin-independent regulator process responsible for the changes observed in the cross-bridge cycling rates during sustained tonic activation. A direct intervention on the contractile apparatus level is a measure for reduction of smooth-muscle tone without negative inotropic side effects.

Animals↗