Checklist identification of candidates for systemic therapy in adult patients with atopic dermatitis in Germany: A multicentre study.

BACKGROUND: The German S2k guideline is the first to include a checklist that captures atopic dermatitis (AD) signs and symptoms as well as the lack of treatment response to identify patients eligible for systemic therapy. OBJECTIVES: Identifying candidates for a start/switch of systemic therapy in adult AD patients in Germany by applying the S2k guideline's checklist. METHODS: In this German multicentre, cross-sectional, non-interventional study (German Clinical Trials Register number: DRKS00023296), adult patients with mild to severe AD were enrolled at dermatological outpatient clinics and offices between April and October 2021. Demographics, clinical characteristics and quality of life were collected using questionnaires during one single visit. Eligibility for a start/switch of systemic AD therapy was evaluated according to the criteria of the German S2k guideline's checklist. RESULTS: Atopic dermatitis patients (575) were included in the analysis. One hundred and sixty-four patients (28.5%) received systemic (SYS) AD therapy and 411 patients (71.5%) did not (TOP). Of the TOP therapy patients, 38.7% were eligible to start systemic AD therapy, and about half of those (49.1%), were scheduled to start systemic AD therapy. The most frequent reason deciding against a systemic therapy was the patient's wish. Although 29.3% of SYS patients were eligible for a switch according to the criteria of the German S2k guideline's checklist, the majority (81.3%) did not switch AD therapy. CONCLUSIONS: This is the first study on the implementation of the German S2k guideline's checklist in everyday care of AD patients in Germany. More than one-third of the TOP patients were identified as eligible for systemic treatment. By applying the guideline's checklist criteria, another one-third of SYS patients may have benefited from a change of current systemic therapy. The use of the German S2k guideline's checklist in routine care represents an important tool to ensure effective patient care and identify inadequately treated patients.

Neuroprotection by bilobalide in ischemia: improvement of mitochondrial function.

Bilobalide, an active constituent of Ginkgo biloba, is known to have neuroprotective properties, but its mode of action remains unclear. In this study, bilobalide significantly reduced brain damage in mice (indicated by TTC staining) when given before transient middle cerebral artery occlusion (tMCAO). As measured by microdialysis in the ischemic striatum, local perfusion with bilobalide (10 microM) reduced ischemia-induced glutamate release by 70% while glucose levels were not affected. Mitochondria isolated from ischemic brain showed a decrease of respiration compared to non-ischemic controls. Treatment with bilobalide (10 mg/kg) before tMCAO improved respiratory capacity of complex I significantly when measured ex vivo. In addition, mitochondrial swelling induced ex vivo by calcium was used to estimate opening of the mitochondrial permeability transition pore. In this assay, the changes induced by tMCAO were completely reversed when mice had received pretreatment with bilobalide. We conclude that neuroprotection by bilobalide involves a mechanism in which the drug reverses ischemia-induced changes in mitochondria, leading to a reduction of glutamate release.

Differentiated expression patterns of growth factors in routine formalin-fixed endomyocardial biopsies in the early postoperative phase after heart transplantation.

BACKGROUND: Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) seem to play a key role in immunological reactions shortly after heart transplantation (HTx). The aim of this study was to analyze the time course of the expression of PDGF A and B, PDGF-receptor alpha (PDGF-Ralpha) and beta, aFGF, and bFGF on formalin-fixed routine endomyocardial biopsies. PATIENTS AND METHODS: Right ventricular endomyocardial biopsies were obtained from 36 heart transplant recipients up to 2 weeks after HTx. According to the clinical course in the first postoperative year, 3 groups were formed: (1) clinically uneventful course (n = 12); (2) cardiac/systemic infections (n = 12); (3) acute rejection (n = 12). The growth factor expression was examined immunohistochemically. RESULTS: In the early phase after HTx, PDGF A, PDGF B, PDGF-Ralpha, and PDGF-Rbeta were predominantly expressed in endothelial cells. The main expression of PDGF-Ralpha and bFGF was found in cardiomyocytes, endothelial cells, and smooth muscle cells. During the first 2 postoperative weeks, PDGF A, PDGF B, and PDGF-Rbeta showed a similar time course of expression: A significantly elevated expression in the first week was followed by a decrease in the second week. In the rejection group, PDGF A was significantly elevated after the first week. CONCLUSIONS: The increased expression of PDGF in the first postoperative week can be interpreted as an unspecific reaction to peritransplant injury. The prolonged expression of PDGF A, PDGF B, and PDGF-Rbeta showed that there were ongoing immunological reactions in the transplant during week 2. The persistence of elevated PDGF A expression might be of prognostic value in terms of a risk factor for either infection or rejection.

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.

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.

Three-dimensional color Doppler: a clinical study in patients with mitral regurgitation.

OBJECTIVES: The purpose of this study was to assess the clinical feasibility of three-dimensional (3D) reconstruction of color Doppler signals in patients with mitral regurgitation. BACKGROUND: Two-dimensional (2D) color Doppler has limited value in visualizing and quantifying asymmetric mitral regurgitation. Clinical studies on 3D reconstruction of Doppler signals in original color coding have not yet been performed in patients. We have developed a new procedure for 3D reconstruction of color Doppler. METHODS: We studied 58 patients by transesophageal 3D echocardiography. The jet area was assessed by planimetry and the jet volumes by 3D Doppler. The regurgitant fractions, the volumes, and the angiographic degree of mitral regurgitation were assessed in 28 patients with central jets and compared with those of 30 patients with eccentric jets. RESULTS: In all patients, jet areas and jet volumes significantly correlated with the angiographic grading (r = 0.73 and r = 0.90), the regurgitant fraction (r = 0.68 and r = 0.80) and the regurgitant volume (r = 0.66 and r = 0.90). In patients with central jets, significant correlations were found between jet area and angiography (r = 0.86), regurgitant fraction (r = 0.64) and regurgitant volume (r = 0.78). No significant correlations were found between jet area and angiography (r = 0.53), regurgitant fraction (r = 0.52) and regurgitant volume (r = 0.53) in the group of patients with eccentric jets. In contrast, jet volumes significantly correlated with angiography (r = 0.90), regurgitant fraction (r = 0.75) and regurgitant volume (r = 0.88) in the group of patients with eccentric jets. CONCLUSIONS: Three-dimensional Doppler revealed new images of the complex jet geometry. In addition, jet volumes, assessed by an automated voxel count, independent of manual planimetry or subjective estimation, showed that 3D Doppler is also capable of quantifying asymmetric jets.

Decreased concentration of myofibrils and myofiber hypertrophy are structural determinants of impaired left ventricular function in patients with chronic heart diseases: a multiple logistic regression analysis.

OBJECTIVES: The aim of this study was to perform a multiple logistic regression analysis to identify independent structural determinants of impaired left ventricular function. BACKGROUND: The association between contractile failure and structural alterations of the myocardium has been demonstrated in several studies, and multiple interactions between myocardial structure and cardiac performance are likely. METHODS: Morphometric data assessed from 130 left ventricular biopsy specimens were analyzed. The endomyocardial specimens were obtained from 57 patients with normal coronary arteries (17 with normal left ventricular ejection fraction and 40 with impaired left ventricular function [dilated cardiomyopathy]), 15 patients with hypertrophic cardiomyopathy and 32 patients with aortic valve disease. Transmural biopsy specimens were assessed in 6 donor hearts before heart transplantation and in 20 patients with left anterior descending coronary artery disease whose specimens were obtained from the left ventricular anterior wall during aortocoronary bypass surgery. Global or regional left ventricular function was evaluated from left cineventriculograms. The volume fraction of cardiac fibrous tissue, intracellular volume fraction of myofibrils, volume fraction of myofibrils related to myocardial tissue (including fibrosis) and myofiber diameters were determined from semithin sections of the biopsy specimens with the use of light microscopic morphometry. RESULTS: Multiple logistic regression analysis revealed decreased volume fraction of myofibrils (p < 0.005) and increased fiber diameter (p < 0.002) as independent determinants of impaired left ventricular function. CONCLUSIONS: These data indicate that, independent of the underlying heart disease, both decreased concentration of contractile proteins and myocyte hypertrophy are independently associated with impaired left ventricular function.

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.

Endothelin-A and -B antagonists protect myocardial and endothelial function after ischemia/reperfusion in a rat heart transplantation model.

OBJECTIVE: Previous studies suggested that endothelin-1 (ET-1) may play a pathophysiological role in myocardial ischemia/reperfusion injury. This study was designed to investigate the effects of the selective ET-A receptor antagonist BQ123 and the selective ET-B receptor antagonist BQ788 on myocardial and endothelial function after reversible deep hypothermic ischemia in a heterotopic rat heart transplantation model. METHODS: Isogenic intraabdominal heterotopic transplantation was performed in Lewis rats. After 1 h of cold ischemic preservation reperfusion was started either after application of placebo (control), BQ123 (3 mumol/kg/min). BQ788 (3 mumol/kg/min), ET-1 (8 pmol/kg/min) or simultaneous infusion of BQ123 or BQ788 and ET-1, respectively (n = 12 each). An implanted balloon was used to obtain pressure-volume relations of the transplanted heart. Myocardial blood flow (MBF) was assessed by the hydrogen-clearance method. Measurements were taken after 1 and 24 h of reperfusion. Endothelium-dependent vasodilation to acetylcholine (ACH) and endothelium-independent vasodilation to sodium nitroprusside were also determined. RESULTS: Both BQ123 and BQ788 significantly improved myocardial and endothelial functional recovery during early reperfusion, whereas ET-1 significantly impaired myocardial and endothelial function. Simultaneous infusion of ET-1 diminished the effects of BQ123 and BQ788. Although myocardial function and baseline MBF were similar in all groups after 24 h of reperfusion, endothelium dependent vasodilation to ACH was still significantly higher in the BQ123 and BQ788 groups and lower in the ET-1 groups (p < 0.05). CONCLUSIONS: These results suggest that endogenous ET release is involved in the pathogenesis of reperfusion injury after heart transplantation. ET-A and ET-B receptor antagonists may be useful to reduce ischemia/reperfusion injury.

Adjustable tricuspid valve annuloplasty assisted by intraoperative transesophageal color Doppler echocardiography.

Intraoperative transesophageal echocardiography (TEE) can play a major role in active guidance of cardiac surgery. This study describes a new application of TEE for assisting tricuspid suture annuloplasty. Twenty-five patients (aged 52 +/- 11 years) who underwent mitral valve replacement and tricuspid valve annuloplasty were studied intraoperatively by TEE. After cardiopulmonary bypass, the suture annuloplasty was adjusted on the beating heart until palpable regurgitation was eliminated. Further adjustment of the suture was performed under echocardiographic guidance until color Doppler flow imaging showed the most adequate correction of tricuspid regurgitation (TR). A significant decrease in the semiquantitative grade of TR, of regurgitant jet area and of the ratio jet area/right atrial area was obtained when the suture was adjusted under echocardiographic guidance. The peak inflow velocity and the gradient across the tricuspid valve did not show significant changes throughout the procedures. The results showed that the tricuspid suture annuloplasty guided by TEE enables a substantial reduction in residual TR without creating valve stenosis.

Three-dimensional color Doppler reconstruction of intracardiac blood flow in patients with different heart valve diseases.

An improved perception of the magnitude and dynamics of intracardiac flow disturbances has been made possible by the advent of 3-dimensional (3-D) color Doppler, a new diagnostic procedure developed at our institution. This study describes the new insights derived from 3-D reconstruction of color Doppler flow patterns in patients with different heart valve diseases. The color Doppler flow data from 153 multiplanar transesophageal or transthoracic echocardiographic examinations has been obtained from 133 patients with heart valve disease; 73 patients had mitral regurgitation, 15 had mitral stenosis, 18 had aortic regurgitation, 26 had aortic stenosis, and 21 patients had tricuspid regurgitation. Four patients had pulmonary regurgitation associated with mitral valve disease. The 3-D reconstructions of color Doppler flow signals were accomplished by means of the "Heidelberg Raytracing model," developed at our institution. The 3-D color Doppler reconstructions were obtained in all patients. The 3-D images revealed for the first time the complex spatial distribution of the blood flow abnormalities in the heart chambers caused by different heart valve diseases. New patterns of intracardiac blood flow disturbances were observed and classified. Three-dimensional color Doppler provides a unique noninvasive method that can be easily applied for studying intracardiac blood flow disturbances in clinical practice.

The influence of extracorporeal circulation and hemoseparation on red cell deformability and membrane proteins in coronary artery disease.

Extracorporeal circulation and hemoseparation may lead to coupled mechanical and chemical blood trauma and thus influence red cell deformability. Ten patients with coronary artery disease underwent coronary bypass. Patients' blood samples were drawn preoperatively, after extracorporeal circulation, and after hemoseparation. Ten healthy adults served as control subjects. Red blood cell deformability was determined by direct microscopic observation of red blood cells subjected to shear stresses of 1.2 to 13.3 Pa with a counter-rotating rheoscope. Red cell membrane proteins were separated by one-dimensional polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. At 1.2 Pa, preoperative red cell deformability was significantly greater in patients with coronary artery disease than in control subjects. Neither extracorporeal circulation nor hemoseparation changed red cell deformability significantly. Electrophoretic separation of membrane proteins failed to show any quantitative or qualitative differences between patients and control subjects. Moreover RBC membrane proteins of red blood cells in the patients were not altered as a result of extracorporeal circulation or hemoseparation. The preoperatively increased red cell deformability in the patients may be drug-induced. Our data suggest that the extracorporeal circulation and hemoseparation techniques used in this study do not lead to red blood cell damage.

The effect of triiodothyronine on myocardial contractile performance after epinephrine exposure: implications for donor heart management.

BACKGROUND: This study analyzes in the experimental model of isolated human atrial myocardium whether the myocardial contractile depression occurring after high-dose/long-term catecholamine exposure (as typically occurring in brain-dead organ donors) can be reversed by thyroid hormone administration. METHODS: Isolated trabeculae were prepared from atrial myocardium from patients undergoing coronary artery bypass (n = 15). Initial measurements of isometric force were carried out (measurement conditions of 37 degrees C, Krebs Henseleit solution, supramaximal electrical stimulation, 1 Hz, at optimal length). Then the trabeculae were incubated for 6 hours at 26 degrees C in a Krebs Henseleit solution containing epinephrine 10(-7) mol/L and the fluorescent dye FURA-2/AM for calcium measurements. At the end of the incubation period, isometric force, isotonic shortening, and intracellular calcium transient (FURA-2 "ratio method") were measured. After 30 minutes administration of triiodothyronine (5 x 10(-9) mol/L), the measurements were repeated. Control groups included 6 hours incubation in 4 degrees C Krebs Henseleit solution (n = 5); 6 hours incubation in 26 degrees C FURA-2/AM (n = 5); and 6 hours incubation in epinephrine 10(-7) mol/L (n = 5). RESULTS: After 6 hours catecholamine exposure isometric force declined significantly to 56.8% (p < .0001) and isotonic shortening to 54% of its initial value (p < .01). Administration of triiodothyronine was associated with a significant recovery of the isotonic shortening amplitude (p < .005), of isometric force development (p < .01), an increased velocity of force development (p < .0001), and of diastolic force decay (p < .005). At the same time the shape of the intracellular calcium transient became smaller as a result of an accelerated diastolic decay. The amplitude of the calcium transient remained unaltered, whereas the calcium time integral was reduced (p < .05). CONCLUSION: In the model of isolated human myocardium, experimental depression of the contractile performance resulting from long-term catecholamine exposure could be reversed by a 30-minute triiodothyronine incubation. The experimental data showing increased force amplitudes at unaltered amplitudes of the intracellular calcium transient and an even-reduced calcium time integral provide strong evidence for a sensitization of the contractile apparatus for calcium by triiodothyronine. The data provide additional knowledge to explain the successful administration of triiodothyronine in donor heart management.

Role of neural and humoral factors in hyperdynamic reaction and cardiac dysfunction following brain death.

BACKGROUND: Although hemodynamic instability and cardiac dysfunction after brain death are reported in the potential organ donor, the underlying mechanisms, for example, neurohumoral changes, myocardial injury, and altered loading conditions, have not been differentiated in clinical and experimental settings. In the present study, we performed a load-independent analysis of cardiac function, focusing on the influence of brain death-associated neural and humoral factors. METHODS: In a canine in situ cross-circulated heart model, brain death was induced by inflation of a subdural balloon catheter. Preload, afterload, and coronary perfusion pressure were kept identical in all hearts throughout the experiment. In Group H (humoral factors), the hearts of healthy dogs were perfused with blood from brain-dead support dogs (n = 6). In Group N (neural factors), the hearts of brain-dead dogs were perfused with blood from healthy support dogs (n = 6). In Group H + N (humoral and neural factors), the hearts of brain-dead dogs were perfused parabiotically in situ with the animals' own blood (n = 6). Systolic and diastolic pressure-volume relationships and coronary blood flow were measured. RESULTS: Induction of brain death led to a significant hyperdynamic response in all groups, with a maximal reaction in Group H + N followed by Group H and Group N. After the initial hyperdynamic phase, cardiac function returned to baseline within 15 minutes and remained stable in all groups for the 2-hour observation period. CONCLUSIONS: (1) Both neural and humoral factors contribute to the initial hyperdynamic reaction after brain death, and only in combination do they cause a maximal hemodynamic effect. (2) If loading conditions and perfusion pressure are kept constant, no cardiac dysfunction occurs after brain death. This indicates that poor cardiac function in the potential donor may reflect altered loading conditions and impaired coronary perfusion rather than neurohumorally mediated direct myocardial injury.

Effects of brain death on myocardial function and ischemic tolerance of potential donor hearts.

BACKGROUND: An increasing number of experimental and clinical studies reports hemodynamic instability in the donor organism after brain death. However, the relative importance of brain death-related cardiac dysfunction on posttransplantation cardiac function and the reversibility of the observed changes remain controversial. In this study a load-independent analysis of cardiac function after brain death was performed. Special interest was focused on a possible interactive influence of brain death and cardiac preservation on postischemic cardiac function. METHODS: In 12 anesthetized dogs, brain death was induced by inflation of a subdural balloon; 12 sham-operated animals served as control subjects. After a 2-hour observation in situ, the hearts were explanted and perfused parabiotically either immediately or after hypothermic ischemic preservation (4 hours, 4 degrees C). Heart rate, cardiac output, left ventricular pressure, the maximum of left ventricular pressure development and aortic pressure were measured in situ. In addition, the slope of the end-systolic pressure-volume relationship, coronary blood flow, and myocardial oxygen consumption were estimated in the cross-circulated hearts. RESULTS: In spite of a brain death-associated hemodynamic deterioration in situ (expressed as low mean aortic pressure and significant decrease of maximal dP/dt), myocardial function was similar to control after explantation, if assessed ex vivo. Furthermore, after hypothermic ischemic preservation and reperfusion, complete functional recovery of control and brain-dead hearts could be observed. CONCLUSIONS: These data indicate that hemodynamic instability after brain death may rather reflect altered loading conditions than irreversible myocardial damage or primary cardiac dysfunction. Furthermore, there is no evidence for a brain death-related impairment of ischemic tolerance.

Transferral of extrathoracic donor neoplasm by the cardiac allograft.

The transference of neoplasm from the donor to the recipient is a rare but recognized complication of organ transplantation. It has been reported after kidney transplantation from cadaver donors. We report a case in which an extrathoracic tumor was transmitted by the donor heart. The donor heart was harvested from a 46-year-old local donor and immediately transplanted to a 62-year-old female recipient. While implantation was performed, a hypernephroma was detected in the multiorgan donor. The ongoing heart transplantation could not be stopped. Four weeks after operation, the patient was discharged from the hospital. During the first year after transplantation, the clinical course was uneventful. One year after operation, the patient was admitted to the hospital with symptoms of weakness and fever. A right facial hemiparesis occurred, and a soft tumor was palpable subcutaneously in the right supraorbital region. Histologic examination revealed a malignant tumor with characteristics identical to the donor hypernephroma. In spite of chemotherapy and radiation therapy, dramatic tumor progression occurred with multiorgan metastases, which led to the death of the patient 2 months after admission.

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.

Rescue therapy with C1-esterase inhibitor concentrate after emergency coronary surgery for failed PTCA.

Administration of C1-esterase inhibitor (C1-INH) attenuates myocardial necrosis and sustains normal cardiac performance after myocardial ischemia and reperfusion in animal experiments. We report on our first experience of C1-INH application as rescue therapy in patients undergoing emergency surgical revascularization after failed percutaneous transluminal coronary angioplasty. Three patients were treated, because post-operative hemodynamic stabilization could not be achieved despite prolonged reperfusion periods, high-dose inotropic support, inodilators and aortic counterpulsation. As there was no surgical or medical option remaining, C1-INH was administered starting with a 2000 unit bolus, followed by 1000 U 12 and 24 h after surgery. C1-INH therapy resulted in rapid hemodynamic stabilization of all patients; weaning from aortic counterpulsation and epinephrine support was possible within 1 day. All patients survived and were discharged from hospital. In this group of patients suffering from severe reperfusion injury after coronary surgery, C1-INH seemed to be an effective adjuvant therapy to restore myocardial function by blocking the complement cascade. These results should encourage the performance of controlled studies on the effects of prophylactic C1-INH substitution therapy in patients undergoing coronary surgery at high risk conditions.

Temporary atrial electrode for the treatment of supraventricular tachycardia after cardiac operations.

BACKGROUND: Supraventricular tachycardia is a common postoperative complication early after cardiac operations. A temporary atrial patch electrode for low-energy atrial defibrillation was developed in 1992 and subsequently tested. METHODS: The electrode first was tested and removed intraoperatively during open heart operations in 10 patients (phase I). After the intraoperative testing, the temporary atrial patch electrode was implanted in 20 patients for postoperative termination of spontaneous episodes of supraventricular tachycardia (phase II). When supraventricular tachycardia occurred, biphasic shocks (1.2 to 5 J) were applied and the atrial defibrillation thresholds were measured. RESULTS: In phase I, the mean intraoperative atrial defibrillation threshold was 1.6 +/- 1.4 J, with a mean shock impedance of 64 +/- 7.3 omega. In phase II, 6 of 20 patients (30%) had 7 episodes of atrial fibrillation (n = 6) and atrial flutter (n = 1) after operation. In 5 patients, the supraventricular tachycardia could be converted to a sinus (n = 5) or normofrequent atrioventricular rhythm (n = 1). The mean postoperative defibrillation threshold was 2.7 +/- 2.1 J, with a mean shock impedance of 50.2 +/- 6.8 omega. CONCLUSIONS: The temporary atrial patch electrode allows low-energy defibrillation of episodes of atrial fibrillation. It may serve as an alternative therapeutic option for the treatment of supraventricular tachycardia.

Acute effects of aortocoronary bypass surgery on left ventricular function and regional myocardial mechanics: a clinical study.

The acute effects of myocardial revascularization on overall left ventricular performance and on myocardial segmental wall motion were assessed intraoperatively in 22 patients who had unstable (11 patients) or stable angina pectoris (11 patients). Segmental contraction patterns were evaluated using an ultrasonic transit-time method. In 9 patients with unstable angina pectoris, notable improvement in segmental wall motion was observed as the short-term response to coronary bypass grafting. Hypokinetic patterns were rendered normal after revascularization. Despite marked changes in segmental myocardial function, overall left ventricular performance was not altered notably. In contrast, reperfusion did not lead to acute effects on either segmental wall motion or total left ventricular function in patients with stable angina pectoris. The results indicate that aortocoronary bypass grafting may improve segmental wall motion in patients with unstable angina.