Adiponectin--its potential to predict and prevent coronary artery disease.

BACKGROUND: Recent evidence suggests that epicardial adipose tissue may contribute locally to the pathogenesis of coronary artery disease (CAD). We investigated how local and systemic adiponectin, an adipokine with anti-inflammatory and insulin sensitizing properties, is related to the presence of CAD and cardiovascular risk factors. METHODS: Serum and adipose tissue samples from subcutaneous and pericoronary depots were collected from sixty consecutive patients with CAD who required coronary artery bypass grafting or patients without CAD who underwent cardiac surgery for aortic valve replacement. Western blot, ELISA and PCR were used to detect and determine the adiponectin concentrations and expression in the samples. RESULTS: Adiponectin concentrations in the serum and pericoronary fat of patients without CAD were significantly higher than in patients with CAD ( P < 0.01). However, the expression of adiponectin mRNA did not differ in any instances. Male gender, BMI > 30 and type 2 diabetes were significantly correlated to decreased serum adiponectin ( P < 0.03). CONCLUSION: Pericoronary fat specifically secretes metabolically active adiponectin. Its local and systemic concentrations are inversely correlated to the presence of coronary artery disease, indicating its anti-atherogenic effects. As for patients with CAD, adiponectin might be a promising marker for intra-individual monitoring of cardiovascular risk factors and thus a course of secondary prevention. Further evaluation is necessary to elucidate whether a novel therapeutic option could be derived against the onset and progression of CAD.

Unchanged heat-shock protein 70 expression in myocardium of patients with permanent atrial fibrillation.

AIM: Cardiomyocytes respond to permanent atrial fibrillation (AF) with an increase in mitochondrial heat shock proteins (Hsp). The aim of our study was to test if there is a cytoplasmic response to stress by investigating the expression of Hsp70. METHODS: Right atrial samples from 18 patients undergoing elective cardiac surgery were excised and immediately frozen in liquid nitrogen. Eight patients had permanent AF (> 3 months) and 10 patients were in sinus rhythm (SR). Hsp70 was determined by SDS-PAGE, Western blot and quantified with optical densitometry. RESULTS: We found no increase in Hsp70 expression in myocardial samples from patients with permanent AF. CONCLUSION: The unchanged expression of Hsp70 may indicate that the cytoplasmic stress response in permanent AF is exhausted.

[Thoracic alterations after surgical closure of the ductus arteriosus botallo in preterm infants]. / Thoraxveränderungen nach operativem Ductus-arteriosus-Botallo-Verschluss bei Frühgeborenen.

BACKGROUND: Left-sided thoracotomy for ligation of patent ductus arteriosus (PDA) dissects the musculus latissimus dorsi and notches a small part of the musculus trapezius. After ductal closure the 4 (th) and 5 (th) rib are adapted. This follow-up study investigated if mid- or long-term consequences on the thorax occur after this procedure. PATIENTS AND METHODS: Status of the thoracic scar, functionality of the shoulder and presence of scapulata alata or scoliosis was evaluated at median age of 6 years (range: 2.9-11.9) in 57 pre-term infants (30 male; gestational age 26 weeks (24-32); birth weight 805 g (450-2140)). RESULTS: Scoliosis was diagnosed in 1 patient (=1.8%) with Rubinstein-Taybi syndrome. The length of the thoracic scar (13.8 cm; 9.4-25.5) correlated with the patient's age (r=0.61; p=0.001). The scar was relocatable except for one case. The distance of the ventral end of the scar to the nipple was 2 cm or less in 22% of the female patients. None of the patients showed impaired function of the shoulder. Scapula alata was found in 16 (28%) patients. CONCLUSION: Thoracotomy for PDA ligation was not associated with an increased risk for scoliosis or disturbed function of the shoulder. One quarter of all infants developed scapula alata which meant an aesthetic issue for some parents.

Chronic atrial fibrillation: decreased actin expression in patients with chronic atrial fibrillation.

AIM: Chronic atrial fibrillation (AF) is characterized by a severe contractile dysfunction and myolysis, which develops progressively. Myolysis and the remodelling of the cellular ultrastructure is associated with the replacement of sarcomeres by glycogen. The aim of our study was to determine if myolysis is characterized by a reduction in actin concentration. METHODS: Right atrial samples from 18 patients undergoing elective cardiac surgery were excised and immediately frozen in liquid nitrogen. Eight patients had chronic AF (>3 months) and 10 patients were in sinus rhythm (SR). Actin concentration was determined by sodium dodecyl sulfate-polycrylamide gel electrophoresis (SDS-PAGE), Western blot and quantified by optical densitometry. RESULTS: Immunoblot analysis demonstrated actin expression in all hearts. In myocardial samples from patients with chronic AF we found a 2.1 fold reduction in actin expression. (P<0.001) CONCLUSION: The decrease in actin concentration via myolysis, might decrease energy consumption and be an additional mechanism for contractile dysfunction in chronic AF.

Cardiac surgery in a patient with haemophilia A.

In this report we describe the successful cardiac surgery in a patient with haemophilia A. To undergo to triple on-pump coronary artery bypass grafting the level of factor VIII was estimated to be 100 %, during the operation and the first postoperative week. To reach this level, bolus therapy with B-domain deleted recombinant factor VIII was administered in a low substitution scheme. There was no bleeding complication. The patient discharged on the 14th postoperative day.

Development and prospective evaluation of a multimedia teaching course on aortic valve replacement.

BACKGROUND: Participation in heart surgery requires procedural and factual knowledge and intensive preparation. There is evidence in the literature that multimedia driven learning has advantages in medical fields where an understanding of complex temporal and spatial events plays an important role. This work describes the development and evaluation of a multimedia driven, online teaching course on aortic valve replacement for students and residents. METHODS: The instructional model followed a methodological approach with scalable information for different user groups. Various interactive multimedia development tools were employed. In a prospective study, 20 students and 10 residents were exposed to the program in a standardized environment. Both groups completed a 20-item multiple choice pre- and post-test. Psychometric evaluation with HILVE (Heidelberg inventory for the evaluation of teaching courses, 50 items) was performed. RESULTS: The multimedia course integrates more than 200 high quality surgical video and audio sequences, interactive 2 D and 3 D models, as well as illustrations and text. It is available at www.lamedica.de. Study time in the student group was 103 +/- 11 min and 70 +/- 10 min in the resident group. Mean number of correct responses to the knowledge pre-test was 6.23 +/- 2.71 in the student group and 12.2 +/- 2.66 in the resident group. Mean number of correct responses to the knowledge post-test was 15.24 +/- 2.06 in the student group ( p < 0.0001 vs. pre-test) and 17 +/- 2.98 in the resident group ( p = 0.004 vs. pre-test). The HILVE test showed positive results for teaching conditions, the program's instructional competence, student motivation and individual learning. CONCLUSION: Our data demonstrate that multimedia driven training can adapt to the individual needs of learners and improves procedural knowledge required for open heart surgery. Consequently, the whole course forms part of the training of residents and students.

Delayed repair of stanford type-A dissection following fulminant cerebral infarction.

We report an impressive case in which a complete infarction of the right hemisphere due to an acute occlusion of the right carotid artery had developed. After cerebral decompression and neurological rehabilitation, the persisting dissection of the ascending aorta and both carotid arteries was successfully repaired in one session.

Heat shock protein 60 expression in patients undergoing cardiac operations.

AIM: Cardiomyocytes respond to stress with the expression of different heat shock proteins (HSP). The mitochondrial HSP60 is known to be expressed by various stress factors, including ischemia and reperfusion. The aim of this study was to investigate if HSP60 is increased in human myocardium after cardiac surgery. METHODS: To determine if heat shock protein 60 accumulated in the myocardium of patients undergoing car-diac operations, right atrial samples before and after extracorporeal circulation were excised and immediately frozen in liquid nitrogen. PATIENTS: we obtained 10 sequential right atrial specimens from 5 male patients in sinus rhythm undergoing elective cardiac surgery. MEASURES: the HSP60 protein level was determined by SDS-PAGE, Western blot and quantified by optical densitometry according to the immunoreactive bands of actin. RESULTS: The HSP60 concentration was unchanged in hearts after a single episode of hypothermic ischemia and reperfusion. Immunoblot analysis demonstrated HSP60 expression in all hearts. There was no correlation with the endurance of cardiopulmonary bypass or reperfusion time. CONCLUSION: These findings indicate that myocardial HSP60 of patients undergoing cardiac operations is not increased after an obligatory period of ischemia, cardioplegic arrest and reperfusion. This might reflect an effective cardioprotection during ECC.

The CardioOP-Data Clas (CDC). Development and application of a thesaurus for content management and multi-user teleteaching in cardiac surgery.

OBJECTIVES: Self-directed and customized medical education programs are gaining importance in health care instruction. We prototypically implemented a repository-driven online computer system (CardioOP) for teleteaching in Heart Surgery. It supports authoring and multiple re-use of multimedia data for different user groups in different instructional applications and therefore requires a process of content management. METHODS: We defined objectives for a terminological system to support semantic, cross-media type annotation and retrieval of learning objects: domain completeness, German (natural) language processing, multi-user concepts, extensibility and maintenance, content based annotation and technical implementation. Existing terminologies (ICD10, READ V3, Snomed III, UMLS 1997, MESH) have been analysed according to these objectives. RESULTS: We found that the analysed terminologies did not meet our criteria sufficiently. Therefore, we developed a domain-specific thesaurus, the CardioOP-DataClas (CDC). The application of the CDC within a database-driven authoring process using specifically developed tools is reported. CONCLUSIONS: Metadata play an important role in the effective discovery and search, access, integration and management of educational multimedia data in medicine but so far, there is no terminology to support content management for instructional multimedia. We prototypically designed and applied a thesaurus for the CardioOP educational system. Additional work is needed to evaluate the system in terms of user-friend-liness, concept coverage and information retrieval performance.

Gender-related plasma levels of progesterone, interleukin-8 and interleukin-10 during and after cardiopulmonary bypass in infants and children.

BACKGROUND: It is known that proinflammatory and anti-inflammatory cytokines are released during and after cardiopulmonary bypass (CPB) in infants and children. Sex steroids are known to have immunomodulatory functions, and release of the anti-inflammatory cytokine IL-10 is stimulated by progesterone in vitro. The purpose of the present study was to investigate the plasma levels of progesterone, IL-8 (proinflammatory cytokine) and IL-10, and to relate them to sex and postoperative morbidity. METHOD: Eighteen infants and children (eight female) undergoing CPB were prospectively studied. Plasma levels of progesterone, IL-8 and IL-10 were determined before and 10 min after the start of CPB, and immediately after CPB; and 6 h, 24 h, 3 days and 7 days postoperatively. Organ dysfunction was identified on the basis of arbitrarily defined criteria. RESULTS: After CPB, all patients showed significant increases in plasma levels of progesterone, IL-8 and IL-10. Plasma levels of IL-10 were significantly higher in female patients, except for during the immediate postoperative period. According to the criteria used, six out of 10 male patients, but none of the female patients developed multiple organ dysfunction (MOD). CONCLUSION: The present study shows that CPB induces a significant and marked increase in plasma levels of progesterone in infants and children. Studies of administration of progesterone-blocking substances to male and female animals may help to elucidate the roles of sex and progesterone in the setting of CBP.

Accuracy of beat-to-beat cardiac output monitoring by pulse contour analysis in hemodynamical unstable patients.

BACKGROUND: Continuous determination of cardiac output (CO) by transpulmonary thermodilution calibrated pulse-contour analysis is gaining clinicical acceptance. However there is doubt, whether this method is reliable in hemodynamic instable patients. We compared pulse-contour analysis to thermodilution in patients with profound changes of CO. MATERIAL AND METHODS: 24 patients were investigated. CO was measured by thransthoracic thermodilution and pulse-contour analysis in intervals of 60 min during study periods of 8-44 h without recalibration of the pulse-contour computer. Results of 517 measurements were compared by regression, structural regression and Bland-Altman analyses. RESULTS: Mean change of CO was 40 +/- 27% (range 20-139%), range of systemic vascular resistance was 450 dyn x s/cm(-5) - 2360 dyn x s/cm(-5). Correlation of pulse-contour analysis CO to thermodilution CO was r=0.88 with p=0.0001, bias was 0.2 l/min with 1.2 l/min standard deviation. Mean CO by pulse-contour analysis did not differ significantly from CO by thermodilution during the study period. There were no influences of heart rate or arterial pressure on the difference between both methods. CONCLUSIONS: CO measurement by arterial pulse-contour analysis is reliable even in patients with profound changes of CO or during hemodynamic instability.

Changes of gut barrier function during anesthesia and cardiac surgery.

The aim of this clinical study was to investigate the time sequence between intraoperative and postoperative endotoxemia, changes in intramucosal pH(I), mediator release, and acute phase proteins and their relationship to postoperative infections. In 60 patients (median age 61 [33-72] years, male/female: 50/10) plasma levels of endotoxin, endotoxin neutralizing capacity (ENC), leukotriene-C4 (LTC4), 6-ketoprostaglandin-F-1alpha (PGF), thromboxane-B2 (TxB2), interleukin-6 (IL-6), and C-reactive protein (CRP) were measured before, during, and after cardiac surgery. The intraluminal pH(I) of the stomach was assessed as a marker of splanchnic blood circulation. Patients were divided in one group with postoperative infections (group A, n = 8) and another groups without infections (group B, n = 52). Among all measured parameters, endotoxin plasma levels showed the most rapid changes. A significant increase of endotoxin plasma levels and a decrease in ENC appeared after the induction of anesthesia, culminating in a peak after reperfusion. Endotoxin showed a significantly higher increase in group A (14fold) compared to group B (sixfold, p<0.001), whereas ENC decreased by eightfold in both groups. The parameters of the arachidonic cascade increased and pH(I) decreased, however, there were no significant differences between both groups. The latest increase was observed for the acute phase proteins IL-6 and CRP. IL-6 levels peaked 6 hours postoperatively with a 20fold (group B) and 30fold (group A) increase (p < 0.001 vs baseline; no differences between groups), whereas CRP rose at the first postoperative day with a 21 fold (group B) and 25fold (group A) increase at day 2 (p<0.001 vs baseline, no difference between groups). Differences between both groups appeared at the second postoperative day for IL-6 (median values group A/B: 421/219 pg/mL; p <0.05) and at the fifth postoperative day for CRP (median values group A/B: 321/81 mg/L; p < 0.05). In conclusion, endotoxin seems to be the earliest trigger of the mediator cascade in acute phase response and may indicate infections in the postoperative course.

Endocarditis after nipple piercing in a patient with a bicuspid aortic valve.

Piercing the skin for cosmetic reasons can be dangerous in young adults who have previously undergone surgery for congenital defects of the heart. We report the case of a 24-year-old man in whom coarctation of the aorta had been corrected 15 years earlier. Two months after piercing his left nipple without antibiotic prophylaxis, he developed a local mastitis, followed by bacterial endocarditits that required replacement of the aortic valve.

[Neoangiogenesis by local gene therapy: a new therapeutic concept in the treatment of coronary disease]. / Neoangiogenese durch lokale Gentherapie: Ein neues therapeutisches Konzept in der Behandlung der koronaren Herzkrankheit.

This article presents the results of our initial clinical experience with the human growth factor FGF-1 as applied to the ischemic human myocardium. After the completion of extensive preliminary animal experiments, the human angiogenetic growth factor FGF-1, obtained from a genetically transformed strain of E. coli was introduced into aortocoronary bypass surgery as an additional therapeutic agent. A double-blind study was carried out in a total of 40 patients with coronary heart disease. The patients were randomized into growth-factor and control groups, each containing 20 patients. All patients underwent aortocoronary bypass surgery because of their coronary multivessel disease, in each case with an IMA bypass for the LAD and single venous bypasses for the RCX and/or RCA. In order to bridge over additional stenosis of the LAD or one of its branches, the human growth factor FGF-1 was injected into the myocardium during the operation. In the control group heat-denatured growth factor was substituted for FGF-1. After three months as well as three years postoperatively, the IMA bypasses were selectively depicted by intraarterial DSA. These angiographies were then quantitatively evaluated. After the application of the growth factor, the formation of new vessels could be demonstrated after three months as well as three years postoperatively. A capillary network initiating from the coronary artery could be found and the computer-supported evaluation of the angiographs revealed a significant increase in the blood supply of the region of the myocardium injected. According to the angiographic findings there was also a clinical improvement of the patients with FGF-1 application compared to the patients of control group, concerning the NYHA classification as well as the need for antiangina drug therapy. In the meantime, the results of other research groups support the evidence that the induction of neoangiogenesis by human growth factor could become a therapeutic approach especially in patients with diffuse coronary artery disease. Nevertheless further studies have to be carried out in order to prove the long-term clinical profit of those patients after the growth factor treatment.

Endotoxemia and mediator release during cardiac surgery.

Endotoxemia in man is a controversial issue. However, endotoxin is a potent trigger of the inflammatory response. Therefore, endotoxin translocation and mediator release was investigated in patients undergoing cardiac surgery. In 40 patients (13 women and 27 men, ages ranging from 30 to 73 years with a median of 60 years), plasma concentrations of endotoxin, interleukin-6 (IL-6), and C-reactive protein (CRP) were determined during and after cardiovascular bypass. In a subgroup of 10 patients, myeloid-related proteins: MRP8, MRP14, and the soluble heterocomplex (MRP8/MRP14) levels were additionally studied. A significant increase (p < 0.01) of plasma endotoxin concentrations was found during surgery, culminating in a peak (median value of 0.82 EU/mL) during reperfusion. Plasma levels of endotoxin continued to be slightly raised until the 5th postoperative day, whereas those of interleukin-6 rose at the end of the operation and were at their highest level 6 hours postoperatively (median value of 218 pg/mL). CRP levels were increased 24 hours postoperatively with a median value of 114 mg/L and peaked on day 2 (191 mg/L). A statistically significant correlation between the intraoperative endotoxin plasma concentrations and IL-6 concentrations was established (p < 0.05). The MRP8/MRP14 heterocomplex increased until day 2 after surgery, except MRP14, which showed the highest level at day 1 (55 ng/mL). Cardiac surgery is associated with endotoxemia and a marked acute-phase response. Therefore, endotoxin must be regarded as a pathophysiologic mediator. The role of the gut as a source of endotoxemia following cardiac surgery deserves further attention.

CardioOp: an integrated approach to teleteaching in cardiac surgery.

INTRODUCTION/PURPOSE: The complexity of cardiac surgery requires continuous training, education and information addressing different individuals: physicians (cardiac surgeons, residents, anaesthesiologists, cardiologists), medical students, perfusionists and patients. Efficacy and efficiency of education and training will likely be improved by the use of multimedia information systems. Nevertheless, computer-based education is facing some serious disadvantages: 1) multimedia productions require tremendous financial and time resources; 2) the obtained multimedia data are only usable for one specific target user group in one specific instructional context; 3) computer based learning programs often show deficiencies in the support of individual learning styles and in providing individual information adjusted to the learner's individual needs. In this paper we describe a computer-system, providing multiple re-use of multimedia-data in different instructional sceneries and providing flexible composition of content to different target user groups. TOOLS AND METHODS: The ZYX document model has been developed, allowing the modelling and flexible on-the-fly composition of multimedia fragments. It has been implemented as a DataBlade module into the object-relational database system Informix Dynamic Server and allows for presentation-neutral storage of multimedia content from the application domain, delivery and presentation of multimedia material, content based retrieval, re-use and composition of multimedia material for different instructional settings. Multimedia data stored in the repository, that can be processed and authored in terms of our identified needs is created by using a next generation authoring environment called CardioOP-Wizard. High-quality intra-operative video is recorded using a video-robot. Difficult surgical procedures are visualized with generic and CT-based 3D-animations. RESULTS: An on-line architecture for multiple re-use and flexible composition of media data has been established. The system contains the following instructional applications (prototypically implemented): a multimedia textbook on operative techniques, an interactive module for problem based-training, a module for creation and presentation of lectures and a module for patient information. Principles of cognitive psychology and knowledge management have been employed in the program. These instructional applications provide information ranging from basic knowledge at the beginner's level, procedural knowledge for the advanced level to implicit knowledge for the professional level. For media-annotation with meta-data a metainformation system, the CardioOP-Clas has been developed. The prototype focuses on aortocoronary bypass grafting and heart transplantation. CONCLUSION: The demonstrated system reflects an integrated approach in terms of information technology and teaching by means of multiple re-use and composition of stored media-items to the individual user and the chosen educational setting on different instructional levels.

Leaflet escape in a TEKNA and an original duromedics bileaflet valve.

We report a case of leaflet escape in an Edwards-TEKNA bileaflet valve, in the mitral position. The examination findings of the explanted valve are compared with a similar case of leaflet escape in an original Edward-Duromedics prosthesis. Based on our findings alone, it is not certain whether the TEKNA valve continues to have a higher risk for fracture.

[Neoangiogenesis by local gene therapy: a new therapeutic approach in the treatment of coronary artery disease]. / Neoangiogenese durch lokale Gentherapie: Ein neues therapeutisches Konzept in der Behandlung der koronaren Herzkrankheit.

This article presents the results of our initial clinical experience with the human growth factor FGF-1 as applied to the ischemic human myocardium.After the completion of extensive preliminary animal experiments, the human angiogenetic growth factor FGF-1, obtained from a genetically transformed strain of E. coli was introduced into aortocoronary bypass surgery as an additional therapeutic agent. A double-blind study was carried out in a total of 40 patients with coronary heart disease. The patients were randomized into growth-factor and control groups, each containing 20 patients. All patients underwent aortocoronary bypass surgery because of their coronary multivessel disease, in each case with an IMA bypass for the LAD and single venous bypasses for the RCX and/or RCA. In order to bridge over additional stenosis of the LAD or one of its branches, the human growth factor FGF-1 was injected into the myocardium during the operation. In the control group heat-denatured growth factor was substituted for FGF-1. After three months as well as three years postoperatively, the IMA bypasses were selectively depicted by intraarterial DSA. These angiographies were then guantitatively evaluated. After the application of the growth factor, the formation of new vessels could be demonstrated after three months as well as three years postoperatively. A capillary network initiating from the coronary artery could be found and the computer-supported evaluation of the angiographs revealed a significant increase in the blood supply of the region of the myocardium injected. According to the angiographic findings there was also a clinical improvement of the patients with FGF-1 application compared to the patients of control group, concerning the NYHA classification as well as the need for antiangina drug therapy.In the meantime, the results of other research groups support the evidence that the induction of neoangiogenesis by human growth factor could become a therapeutic approach especially in patients with diffuse coronary artery disease. Nevertheless further studies have to be carried out in order to prove the long-term clinical profit of those patients after the growth factor treatment.

Influence of several solutions used in bypass surgery on the permeability of the endothelium of carotid arteries in New Zealand rabbits.

BACKGROUND: Alteration of endothelial permeability by perfusion solutions used may influence the outcome of bypass grafts. METHOD: Carotid arteries of New Zealand rabbits were locally perfused in situ for 20 or 60 min with various solutions used in bypass surgery. After restoring normal circulation, horseradish peroxidase was injected in the ear vein. Endothelial permeability was measured by electronmicroscopy as the peroxidase accumulation in the subendothelial space during 6min circulation. RESULTS: The density indices (mean standard deviation) as a parameter for permeability in comparison to the control vessels were significantly greater than 100% for all solutions: for physiological saline 254+/-22% and 358+/-15%, for Ringer's lactate 206+/-26% and 302+/-17%, for St. Thomas' Hospital solution 163+/-15 % and 252+/-29%, and for Bretschneider's HTK solution 130+/-15% (p=0.003) and 169+/-26%, after 20 and 60 min perfusion. Addition of heparin (50IU/ml) caused a significant increase in endothelial permeability (p<0.05). CONCLUSIONS: Bretschneider's is the most suitable of the solutions studied as a graft storage medium in bypass and cardiothoracic surgery, but a solution causing even less damage is desireable.

The urgent pulmonary embolectomy: mechanical resuscitation in the operating theatre determines the outcome.

BACKGROUND: The urgent pulmonary embolectomy as a surgical treatment of acute massive pulmonary embolism (PE) is still the subject of controversial discussion regarding indication, operative technique, and prognosis. METHODS: From 10/89 to 9/97 40 patients underwent urgent exploration of the pulmonary artery with the aid of extracorporeal circulation (ECC). RESULTS: The overall operative mortality was 35%. Univariate and multivariate logistic regression analysis showed preoperative hemodynamics and cardiopulmonary resuscitation (CPR) as the most important predictive factors for outcome: mortality rate was significantly higher after CPR (=63%) than without CPR (=10%) (p = 0.001). Other factors such as immobility, overweight, and concomitant cardiopulmonary disease also had an influence on the postoperative outcome. CONCLUSIONS: Pulmonary embolectomy (on the beating heart with ECC under total bypass) under stable hemodynamics, without CPR however, still constitutes an important form of treatment of acute massive PE with excellent long-term results.