Bruno J. Messmer

Fibrin gel – advantages of a new scaffold in cardiovascular tissue engineering

OBJECTIVE The field of tissue engineering deals with the creation of tissue structures based on patient cells. The scaffold plays a central role in the creation of 3-D structures in cardiovascular tissue engineering like small vessels or heart valve prosthesis. An ideal scaffold should have tissue-like mechanical properties and a complete immunologic integrity. As an alternative scaffold the use of fibrin gel was investigated. METHODS Preliminary, the degradation of the fibrin gel was controlled by the supplementation of aprotinin to the culture medium. To prevent tissue from shrinking a mechanical fixation of the gel with 3-D microstructure culture plates and a chemical fixation with poly-L-lysine in different fixation techniques were studied. The thickness of the gel layer was changed from 1 to 3 mm. The tissue development was analysed by light, transmission and scanning electron microscopy. Collagen production was detected by the measurement of hydroxyproline. Injection molding techniques were designed for the formation of complex 3-D tissue structures. RESULTS The best tissue development was observed at an aprotinin concentration of 20 microg per cc culture medium. The chemical border fixation of the gel by poly-L-lysine showed the best tissue development. Up to a thickness of 3 mm no nutrition problems were observed in the light and transmission electron microscopy. The molding of a simplified valve conduit was possible by the newly developed molding technique. CONCLUSION Fibrin gel combines a number of important properties of an ideal scaffold. It can be produced as a complete autologous scaffold. It is moldable and degradation is controllable by the use of aprotinin.

Percutaneous transluminal coronary angioplasty immediately after intracoronary streptolysis of transmural myocardial infarction.

Percutaneous transluminal coronary angioplasty (PTCA) was performed in 21 patients with acute myocardial infarction (AMI) treated by intracoronary infusion of streptokinase within 8 hours after the onset of symptoms. Streptolysis therapy began a mean of 3.6 1.2 hours (±± SD) after the onset of symptoms. The vessel was occluded in 14 patients and highly stenosed in seven. After the infusion of 67,300 ± 63,200 IU of streptokinase over 26.1 21.5 minutes, patency of the occluded vessels was reached. PTCA as performed 20-60 minutes after the end of streptokinase treatment in 19 patients and 24 and 31 hours after treatment in two patients. The dilation was successful in 17 patients (81%). The degree of vessel obstruction was reduced from 90.2 ± 7.3% to 58.6 19.5% (area method) and from 71.4 ± 12.4% to 39.2± 19.7% (diameter method). The improvement was 31.5 18.4% and 32.2 ± 19.3%, respectively. No reocclusion was induced by PTCA. Twenty patients were discharged. One died during hospitalization; at autopsy, the treated vessel was still patent. During the follow-up period, two reinfarctions and one asymptomatic reocclusion occurred. The clinical findings during the hospital course and the follow-up period were compared with those of a control group of 18 patients with AMI and comparable coronary stenoses who were treated only with streptokinase infusion. Four of these patients had a reinfarction during the hospital course, and three died during the follow-up period. PTCA can be performed safely and successfully immediately after intracoronary infusion of streptokinase in patients with AMI. By reducing the subtotal stenosis, this treatment contributes to the reperfusion of the ischemic myocardium, diminishes the risk of a reocclusion and seems to improve the prognosis.

Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations.

We studied the inflammatory reaction related to cardiopulmonary bypass in 24 neonates (median age 6 days) undergoing the arterial switch operation for simple transposition of the great arteries, with respect to the development of postoperative capillary leak syndrome. Complement proteins, leukocyte count, tumor necrosis factor-alpha, and histamine levels were determined before, during, and after cardiopulmonary bypass. Additionally, protein movement from the intravascular into the extravascular space during cardiopulmonary bypass was assessed by the measurement of plasma concentrations of proteins with molecular weights ranging from 21,200 to 718,000. Capillary leak syndrome developed in 13 of the 24 neonates. Patients with capillary leak syndrome, as compared with those without, had preoperatively higher C5a levels (C5a, 3.0 +/- 0.6 microgram/L vs 0.9 +/- 0.2 microgram/L) (mean +/- standard error of the mean) (p < 0.05) and higher leukocyte counts (leukocytes, 17.9 +/- 2.1 X 10(3) cells/ml versus 11.7 +/- 0.8 X 10(3) cells/ml) (p < 0.05), suggesting in these neonates a preoperative inflammatory state. Preoperative clinical and operative data were identical in both patient groups. Before cardiopulmonary bypass, serum protein concentrations were similar in all patients. Ten minutes after institution of cardiopulmonary bypass, protein concentrations fell to significantly lower values in patients with capillary leak syndrome than in those without: albumin (19% +/- 1.5% vs 30% +/- 6% of the prebypass value, p < 0.05), immunoglobulin G (17% +/- 1.5% vs 29% +/- 5.5%, p < 0.001), and alpha 2-macroglobulin (15% +/- 1.2% vs 25% +/- 4%, p < 0.02). During cardiopulmonary bypass, albumin concentrations remained significantly lower in patients with capillary leak syndrome than in those without, whereas hematocrit values were similar in both groups. During cardiopulmonary bypass, patients with capillary leak syndrome also had lower concentrations of complement proteins C3 and C4 but not C1 inhibitor. C3d/C3 ratio and C5a levels were similar in both patient groups. In contrast, histamine liberation during cardiopulmonary bypass was significantly more pronounced in patients with capillary leak syndrome than in those without (725.2 +/- 396.7 pg/ml vs -54.1 +/- 58.4 pg/ml, p < 0.05). Tumor necrosis factor-alpha levels after protamine administration were also significantly higher in patients with capillary leak syndrome (38.1 +/- 10.0 pg/ml vs 15.3 +/- 3.4 pg/ml, p < 0.05). Leukocyte count during and after cardiopulmonary bypass was similar in both patient groups. This study demonstrates increased protein leakage as early as 10 minutes after initiation of.

Long-term Clinical and Echocardiographic Follow-up After Surgical Correction of Hypertrophic Obstructive Cardiomyopathy With Extended Myectomy and Reconstruction of the Subvalvular Mitral Apparatus

BACKGROUND The standard surgical approach to hypertrophic obstructive cardiomyopathy (HOCM) was modified in the present series with a combination of extended myectomy with partial excision and mobilization of the papillary muscles. METHODS AND RESULTS Between 1979 and 1992, 58 patients (38 men and 20 women; mean age, 49 +/- 24 years) with HOCM were operated on with the use of this different technique. Their intraventricular gradients were 79 +/- 33 (+/- SD) mm Hg at rest and increased to 147 +/- 48 mm Hg with provocative maneuvers. Mild-to-moderate mitral regurgitation was present in 60% of the patients, and severe regurgitation was present in 5%. Ten patients required additional aortocoronary bypass graft surgery. Follow-up (mean, 84 months) was complete (100%). Hemodynamic improvement was documented by a significant (P < .01) decrease in left ventricular end-diastolic pressure from 19 +/- 9 to 14 +/- 6 mm Hg and reduction of basal outflow tract gradients to 5 +/- 7 mm Hg at rest and 16 +/- 24 mm Hg after provocation. Late mortality was 1.4% per patient-year, and no sudden cardiac deaths occurred during follow-up. Functional status was excellent for 84% of the patients; 8 patients were in New York Heart Association functional class III, and none were in class IV. Echocardiography revealed no outflow tract obstruction. CONCLUSIONS Extended myectomy and reconstruction of the subvalvular mitral apparatus in HOCM result in excellent functional improvement with relief of outflow tract obstruction. The technique can be performed safely despite its more aggressive surgical nature and allows an individualized strategy depending on the patients extent and distribution of left ventricular hypertrophy.

Twenty years experience with pediatric pacing: epicardial and transvenous stimulation

OBJECTIVE Permanent cardiac pacing in children and adolescents is rare and often occurs by means of epicardial pacing. Based on two decades of experience, operative and postoperative data of patients with epicardial and transvenous pacing were analyzed retrospectively. METHODS Between October 1979 and December 1998, 71 patients (mean age, 5.3+/-4.2, range, 1 day-16.2 years; mean body weight, 18+/-12; range, 8-56 kg) underwent permanent pacemaker implantation. Indications were sinus node dysfunction and atrio-ventricular block following surgery for congenital heart disease (69%), or congenital atrioventricular block (31%). Pacing was purely atrial (1.4%), purely ventricular (73%), ventricular with atrial synchronization (5. 6%), or atrioventricular synchronized (20%). Epicardial pacing was established in 49 (69%), transvenous in 22 (31%) patients. Follow-up was 3.4+/-3.8 years (epicardial) and 3.0+/-4.0 years (transvenous). RESULTS Epicardial leads were implanted in younger patients (mean age: 4.5 vs. 7.0 years, P<0.05) and preferably after surgery induced atrioventricular block (78 vs. 46%, P<0.05). The youngest patient with transvenous pacing was 1.3 years old (weight, 8.5 kg). At implantation epicardial ventricular stimulation threshold at 1.0 ms was 1.07+/-0.46 vs. 0.53+/-0.31 V (transvenous) (P<0.05). The age-adjusted rate of lead-related reoperations was significantly higher in patients with epicardial leads (P<0.05), mainly due to increasing chronic stimulation thresholds resulting in early battery depletion. In three patients who received steroid-eluting epicardial leads initial low thresholds persisted after five month to one years. In two patients with recurrent epicardial threshold increase, steroid-eluting epicardial leads led to good acute and chronic thresholds after nine to 15 month. Two post-operative death (2.8%) were probably due to a dysfunction of the (epicardial) pacing system. CONCLUSIONS Transvenous pacing in the pediatric population is associated with a lower acute stimulation threshold and a lower rate of lead-related complications. If epicardial pacing is necessary (e. g. small body weight, special intracardiac anatomy (e.g. Fontan), impossible access to superior caval vein), steroid-eluting leads may be considered.

Potential benefit of biventricular pacing in patients with congestive heart failure and ventricular tachyarrhythmia.

Treatment of congestive heart failure (CHF) aims for symptomatic relief and reduction of mortality both from sudden death and pump failure. The implantable cardioverter defibrillator (ICD) is highly effective in the prevention of sudden death, but no mortality benefit in advanced CHF has yet been shown. Biventricular pacing may lead to functional improvement in selected patients with CHF. Thus, a biventricular pacemaker with defibrillation capabilities may be ideal for patients with advanced CHF. We retrospectively analyzed the data from 384 patients (age 59 +/- 12 years, 322 male and 62 female) with regard to New York Heart Association (NYHA) CHF class, mean QRS duration, mean PR interval, presence of a QRS > 120 msec and incidence of atrial fibrillation at the time of ICD implantation. Based on eligibility criteria from studies in biventricular pacing, we analyzed how many patients may benefit from biventricular pacing. Patients with CHF were older (NYHA class III: 60.9 +/- 9.7, class II: 61.3 +/- 10 versus class I: 50.8 +/- 13.6 years, p < 0.001 each) and mean QRS duration was longer with advanced CHF (NYHA class III 127.8 +/- 30 msec; class II 119.4 +/- 27.7 msec; class 0-1: 103.9 +/- 17.7 msec, p < 0.001, analysis of variance) as was the mean PR interval (NYHA class III 189.9 +/- 33.5 msec; class II 176.1 +/- 29.3 msec; class 0-1 162.7 +/- 45.9 msec, p < 0.001, analysis of variance). The incidence of atrial fibrillation was higher in class III (25.5%) compared with class 0-1 (16.9%) and class II patients (14.1%, p = 0.043, chi-square test). A total of 28 patients (7.3%) fulfilled eligibility criteria for biventricular pacing if NYHA class III patients were considered candidates and 48 (12.5%) if patients with NYHA II CHF and ejection fraction < or = 30% were included. Thus, biventricular pacing may offer a promising therapeutic approach for a significant proportion of patients with CHF at risk for ventricular tachyarrhythmia.

Cantrell's syndrome : a challenge to the surgeon

We present a case of partial Cantrells syndrome with ventricular septal defect, left ventricular diverticulum, dextrorotation of the heart, an anterior diaphragmatic defect, and a midline supraumbilical abdominal wall defect with omphalocele. At the age of 20 months, the patient underwent a successful cardiac surgical procedure. To detect risk factors and to define therapeutic strategies, we analyzed the spectrum and the frequency of malformations described in 153 patients with Cantrells syndrome. Despite modern surgical standards, Cantrells syndrome represents a challenge to the surgeon because of the wide spectrum of anomalies, the severity of the abdominal and cardiac malformations, and the high mortality.

Anatomical risk factors for mortality and cardiac morbidity after arterial switch operation

BACKGROUND The arterial switch operation (ASO) is the treatment of choice for transposition of the great arteries. METHODS Anatomical risk factors on mortality and morbidity were analyzed retrospectively in 312 patients who underwent ASO between 1982 and 1997. RESULTS Survival was 95%, 92%, and 92% after 30 days, 5, and 10 years, respectively. Operative survival improved after 1990 to 97% (p < 0.001). Risk factors for operative mortality were complex anatomy (p = 0.018), coronary anomalies (p = 0.008), and prolonged bypass time (p < 0.001). Determinants of late mortality were coronary distribution (p = 0.03), position of the great arteries (p = 0.0095), bypass time (p = 0.047), and aortic coarctation (p = 0.046). After a follow-up of 3.6 +/- 2.7 years (0.1 to 14.9 years), 98% had good left ventricle function, 94% were in sinus rhythm, 2.4% had moderate to severe pulmonary stenosis, 0.3% had significant aortic regurgitation, and 1% had coronary stenosis. Freedom from reoperation was 100%, 96%, and 94% after 1, 5, and 10 years, respectively. No preoperative anatomic parameter correlated with long-term morbidity. CONCLUSIONS ASO can be performed with low operative mortality (< 5%) and long-term morbidity. Malformations associated with complex transposition of the great arteries influence early and late mortality.

Thromboembolic complications after Fontan procedures: comparison of different therapeutic approaches.

BACKGROUND Although patients after Fontan procedure have a high incidence of thromboembolic complications, anticoagulant therapy is not handled uniformly. We analyzed the frequency and clinical relevance of thromboembolism after Fontan procedure and compared different therapeutic approaches. METHODS From 1986 to 1998, 101 patients (mean age, 7.3 +/- 8.1 years) underwent Fontan type procedure (modified Fontan, n = 40; total cavopulmonary connection, n = 61). In 85 of 87 survivors, transthoracic echocardiography was performed; and in 31 transesophageal echocardiography and/or angiography was performed. Mean follow-up was 5.7 +/- 3.5 years. Three groups with different anticoagulant regimen were compared: group I without medication (n = 45), group II with acetylsalicylic acid therapy (n = 14) and group III with Coumadin (n = 26). RESULTS Thromboembolic events occurred in 13 of 85 patients (15.3%; 3.3 events/100 patient-years). Type of operation as well as other known risk factors had no influence on the rate of thromboembolism. Within the first postoperative year, seven of 13 events occurred. A second peak developed beyond 10 years of follow-up. Patients benefit significantly from Coumadin compared with those who did not receive any medication, with similar results in the entire population and the subgroup of patients with total cavopulmonary connection (log-rank, p = 0.031 and p = 0.033, respectively). With 4.2 events/100 patient-years, the cumulative event rate was substantially higher in group I than with 1.6 in group II and with 1.1 in group III. No relevant bleeding complications occurred. CONCLUSIONS Thromboembolism is frequent after Fontan procedure with a peak during the first postoperative year and another peak beyond 10 years of follow-up. Coumadin is the most effective prophylactic therapy in preventing thromboembolism. Therefore, we suggest initial oral anticoagulation therapy in patients with Fontan type operation.

Intraoperative amiodarone as prophylaxis against atrial fibrillation after coronary operations.

BACKGROUND New onset of atrial fibrillation is a frequent complication after coronary artery bypass grafting and is a major cause of postoperative morbidity. Preoperative oral treatment with amiodarone hydrochloride has been shown to be efficacious as prophylaxis. The present study investigated whether intraoperative use of intravenous amiodarone has a preventive effect on the incidence of atrial fibrillation after coronary revascularization. METHODS In a prospective study, 150 consecutive patients (mean age, 63 +/- 8 years; 132 men and 18 women) undergoing coronary artery bypass grafting were randomly assigned to one of three groups. Two groups received different doses of intravenous amiodarone (group I, 300-mg bolus and 20 mg x kg(-1) x day(-1) for 3 days; group II, 150-mg bolus and 10 mg x kg(-1) x day(-1) for 3 days) after aortic cross-clamping and one group, placebo (group III). Continuous electrocardiographic online monitoring was performed for 10 days. Arrhythmias were analyzed with respect to type, frequency, duration, and clinical relevance. RESULTS New onset of atrial fibrillation occurred in 24% of patients in group I, 28% in group II, and 34% in group III (p = not significant). Atrial fibrillation with a rapid ventricular response (>120 beats per minute) was significantly more frequent in the control group (group I, 14%; group II, 24%; group III, 32%; p < 0.05, group I versus group III) and appeared significantly earlier (group I, day 4.3 +/- 2.5; group II, day 4.8 +/- 2.9; group III, day 2.6 +/- 1.3; p < 0.05, group III versus groups I and II). Temporary atrial pacing because of bradycardia (<60 beats per minute) was necessary significantly more often in group I (group I, 48%; group II, 40%; group III, 28%; p < 0.05, group I versus group III). Early mortality rate (group I, 4%; group II, 2%; group III, 4%), rate of perioperative complications (group I, 14%; group II, 20%; group III, 14%), and duration of hospital stay (group I, 14.0 days; group II, 14.4 days; group III, 14.7 days) were not different between groups. CONCLUSIONS Intraoperative prophylactic use of amiodarone does not prevent new onset of atrial fibrillation in patients undergoing coronary artery bypass grafting and had no effect on outcome. Therefore, intraoperative prophylactic treatment with amiodarone at the tested doses does not appear to be justified.