Monitoring of respiratory function before and after cardiopulmonary bypass using side-stream spirometry.

Pulmonary impairment is more frequent after cardiac surgery than after other major surgical procedures. The present study investigates whether, by using standard respiratory monitoring, i.e. side-stream spirometry and blood gas analysis, it is possible to detect changes in pulmonary function secondary to cardiopulmonary bypass. We investigated 18 patients undergoing elective coronary bypass surgery or aortic valve replacement. Cardiopulmonary bypass resulted in a nonsignificant increase in alveolar-arterial oxygen difference from 33.0 +/- 10.6 kPa to 36.1 +/- 12.5 kPa and arterial to end-tidal CO2 tension difference from 0.67 +/- 0.39 kPa to 0.79 +/- 0.54 kPa. Respiratory system resistance was unaltered. In contrast, dynamic compliance decreased significantly after cardiopulmonary bypass from 78.6 +/- 22.9 to 65.4 +/- 22.4 mL cmH2O-1 with open chest and from 61.0 +/- 10.2 to 51.1 +/- 17.2 mL cmH2O-1 with closed chest, compared with corresponding values before cardiopulmonary bypass. In conclusion, pulmonary gas exchange was not compromised after cardiopulmonary bypass, but a diminished respiratory compliance was a consistent finding, even in uncomplicated cardiac surgery using routine respiratory monitoring.

In vivo morphology of woven, collagen-sealed Dacron prostheses in the thoracic aorta.

BACKGROUND: Long-term changes in knitted Dacron grafts inserted into the infrarenal aorta have been addressed by a number of studies indicating their potential for postoperative dilatation. In contrast, the behavior of woven, collagen-presealed, double-velour Dacron grafts used to replace the thoracic aorta is not known. METHODS: Forty-five patients were examined at a mean of 32.4 +/- 14.8 months after insertion of woven, collagen-coated, Dacron double-velour prostheses (Meadox woven with Hemashield, Meadox, Oakland, NJ) in the thoracic position under highly standardized conditions using spiral computed tomography. RESULTS: Compared with a manufactured diameter of 26 mm, all grafts showed an increase of 1 to 5 mm (mean, 3.0 +/- 1.2 mm [11.6% +/- 4.4%]; p < 0.0001) with greater enlargement of the ascending than of the descending aortic portions (p = not significant). A further statistically significant progressive dilatation failed to occur. Degenerative changes, including false aneurysm formation, could be excluded. CONCLUSIONS: Woven, collagen-coated Dacron prostheses are considered a safe replacement material for the thoracic aorta.

[Proximal radioulnar synostosis within the scope of fetal alcohol syndrome]. / Die proximale radioulnare Synostose im Rahmen des fetalen Alkoholsyndroms.

The extremely rare finding of a proximal radio-ulnar synostosis in a 5 years-old girl with a fetal alcohol syndrome is presented. Despite the elbow's being fixed at 30 degrees pronation, the patient exhibits good ipsilateral arm function. The difficulties in differential diagnosis and treatment modalities are discussed.

Multifunctional tryptophan-synthesizing enzyme. The molecular weight of the Euglena gracilis protein is unexpectedly low.

After developing a suitable procedure to produce large amounts of Euglena gracilis as well as a reliable protocol to purify the multifunctional tryptophan-synthesizing enzyme derived from it (Schwarz, T., Bartholmes, P., and Kaufmann, M. (1995) Biotechnol. Appl. Biochem. 22, 179-190), we here describe structural and catalytic properties of the multifunctional tryptophan-synthesizing enzyme. The kinetic parameters kcat of all five activities and Km for the main substrates were determined. The relative molecular weight under denaturing conditions as judged by SDS-polyacrylamide gel electrophoresis is 136,000. Cross-linking as well as gel filtration experiments revealed that the enzyme exists as a homodimer. Neither intersubunit disulfide linkages nor glycosylations were detected. On the other hand, the polypeptide chains are blocked N-terminally. Complete tryptic digestion of the protomer, high pressure liquid chromatography separation of the resulting peptides, and N-terminal sequence analysis of homogenous peaks as judged by matrix-assisted laser/desorption ionization time-of-flight mass spectrometry was performed. Depending on the sequenced peptides, alignments to all entries of the SwissProt data base resulted in both strong sequence homologies to known Trp sequences and no similarities at all. Proteolytic digestion under native conditions using endoproteinase Glu-C uncovered one major cleavage site yielding a semistable, N-terminally blocked fragment with a molecular weight of 119,000. In addition, an increase in beta-elimination accompanied by a decrease in beta-replacement activity of the beta-reaction during proteolysis was observed.

Previous open heart operation: a contribution to impaired outcome after cardiac transplantation?

BACKGROUND: There is still debate about whether previous cardiac operations are a risk factor for patient outcome after cardiac transplantation. As waiting lists for cardiac transplantation increase, adverse outcome criteria should be identified. METHODS: To assess this problem, we retrospectively analyzed 53 patients with previous cardiac operations before heart transplantation and compared them with 53 control patients matched for sex and age. Patient groups were analyzed regarding their preoperative, intraoperative, and postoperative variables and survival. RESULTS: Ischemic times were comparable in both groups, but the duration of the operation was significantly longer in the study group (206.5 +/- 62.5 minutes, versus 156.0 +/- 36.7 minutes in controls; p < 0.05). In addition, postoperative blood loss was greater for the patients with previous cardiac operations (1,360 +/- 260 mL, versus 730 +/- 310 mL for controls; p < 0.01). Postoperatively, the rate of rejection episodes and the incidence of graft atherosclerosis were comparable within the first 2 years. However, survival was significantly reduced in the study group (60.1%) after 4 years (versus 83.1% for controls; p < 0.05). CONCLUSIONS: Heart transplantation in patients with previous cardiac operations will lead to an impaired overall outcome. In addition, these patients have more postoperative complications.

Open heart operations after renal transplantation.

BACKGROUND: Because of the increasing number of renal transplantations performed, secondary cardiac operations in these patients are discussed concerning their impact on patient and graft survival. METHODS: We reviewed our experience in 45 patients (33 male and 12 female) who underwent open heart operations after previous renal transplantation. Thirty-one patients (group I) received coronary artery bypass grafting and 14 (group II) underwent valve replacement. Mean age at the time of operation was 55 +/- 9 years. The interval between renal transplantation and cardiac operation was 57 +/- 39 months (range, 5 days to 174 months). All patients had functioning renal allografts with preoperative serum creatinine levels ranging from 100 to 338 mol/mL (mean +/- standard deviation, 195 +/- 86). RESULTS: Overall early operative mortality (30 days) was 8.8% (group I, 1 patient; group II, 3 patients). Underlying causes of death were septic endocarditis (n = 2, group II), necrotizing enterocolitis (n = 1, group I), and myocardial infarction (n = 1, group II). One further patient in group II also died of septic endocarditis after 69 days (in-hospital death). The mean follow-up of the 40 surviving patients was 44 +/- 31 months. There was another late death (24 months postoperatively) caused by coagulopathy. Four patients had returned to hemodialysis at intervals of 27 to 83 months (mean, 51 months) because of renal transplant failure. In all patients, the function of the renal allograft was not impaired by open heart operation. CONCLUSIONS: Open heart operations in renal transplant recipients have acceptable mortality and morbidity rates. In almost all patients, function of the transplanted organ can be maintained at the preoperative level.

[Surgical therapy of primary malignant melanoma of the esophagus]. / Chirurgische Therapie des primären malignen Melanoms des Oesophagus.

The case of a 59-year-old man with the extremely rare finding of a primary malignant melanoma of the oesophagus is reported. Seven months after transthoracic oesophagectomy the patient is well without signs of recurrence. The difficulties in preoperative diagnosis and therapy are discussed.

Development, stability, and clinical correlations of allogeneic microchimerism after solid organ transplantation.

To assess the development, stability, and clinical relevance of donor-type microchimerism, skin and blood were analyzed in heart (n = 53) and liver (n = 18) transplant recipients by nested polymerase chain reaction. Microchimerism was detectable in 40 (75%) and 13 (72%) patients after heart and liver transplantation, respectively. In heart transplantation, chimerism-positive patients showed a lower frequency of acute rejection as compared with negative patients, although this was only of borderline statistical significance. Repeated intraindividual analyses demonstrated variable patterns of microchimerism over time, but changes did not correlate to the clinical state. In liver transplantation, chimeric state showed no clear correlation with the patients' immunological situation. Our results demonstrate that peripheral microchimerism frequently develops after different types of organ transplantation and represents a dynamic process but without diagnostic value to predict the immunological risk for individual patients.

Early clinical results with VDD pacing in patients with atrioventricular block.

In patients with intact sinus node function and atrioventricular block III(o) VDD pacing with a single pass lead may have advantages compared to conventional DDD systems. The purpose of this study was to evaluate the reliability of a new VDD pacemaker with regard to problems encountered with the implantation and the stability of the atrial sensing potential in the postoperative course. 24 patients (10 male, 14 female; age 61 +/- 17 years) underwent implantation of the Intermedics UNITY 292+07 VDD pacemaker. Patients were analyzed postoperatively with respect to stimulation parameters applied. The mean follow-up was 10+/- 3 months. While early on 23 of 24 patients were paced in a VDD mode, one patient was programmed to the vvi mode due to atrial flutter. One patient died early after aortic valve replacement, while another lost his atrial sensing one month postoperatively. Two patients were reprogrammed to the vvi mode because of atrial arrhythmias. The other 20 patients demonstrated stable atrial sensing potential aside from unchanged ventricular stimulation parameters. No infectious or unchanged ventricular stimulation parameters. No infectious or technical problems were observed. From these results it is concluded that VDD pacing may represent an excellent alternative in patients with intact sinus node function and AV block III(o). The atrial sensing was found to be reliable with the additional technical advantage that the single pass lead is less prone to dislocation than the atrial leads in DDD pacing.

Thalidomide as replacement for steroids in immunosuppression after lung transplantation.

Steroids have been implicated in postoperative complications after lung transplantation: infections, delayed wound healing, and poor bronchial anastomotic healing. Thalidomide (alpha-phthalimidoglutarimide), a sedative drug with known immunomodulatory properties, was used to replace corticosteroids after canine lung transplantation. Fifteen mongrel dogs underwent single-lung transplantation: group I (n = 5) received cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Group II (n = 5) received standard immunosuppression of cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and prednisone (2 mg/kg once a day), and group III (n = 5) received cyclosporin A (10 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Open lung biopsy and bronchoscopy were performed weekly until sacrifice on day 28. Serum thalidomide and cyclosporin A levels were followed up weekly. Group I showed essentially no rejection until week 2 and minimal rejection (grade 1) until day 28. Group II had moderate rejection (grade 2) of the graft at all time points. Group III animals had moderate to severe rejection (grades 3 to 4) after 21 days (p < 0.05 for group I versus groups II and III). The number of clinically evident episodes of pneumonia was also significantly lower in group I than in groups II and III (p < 0.05). We conclude that thalidomide appears to replace corticosteroids effectively in early postoperative immunosuppression after lung transplantation and is associated with a decreased incidence of pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet activating factor inhibition reduces lung injury after cardiopulmonary bypass.

Because cardiopulmonary bypass (CPB) produces a diffuse inflammatory reaction that may injure multiple organs and complicate cardiac surgical procedures, we examined the use of a competitive inhibitor of platelet activating factor (SDZ HUL-412) in a porcine model of CPB as a means to ameliorate pulmonary injury after CPB. Thirteen pigs (35 to 40 kg) underwent CPB at 28 degrees C for 2 hours, followed by 2 hours of observation. Group I (n = 6) received SDZ HUL-412 (a quinolinium compound) intravenously (3 mg/kg loading dose and 2 mg.kg-1.h-1 continuous infusion) starting before sternotomy. Group II (n = 7) received a saline vehicle. Peak airway pressure, pulmonary arterial pressure, left atrial pressure, and arterial blood gases were measured and flow cytometry evaluated surface expression of adhesion molecule subunit CD18 on circulating neutrophils. Pulmonary function was significantly improved in group I. Fifteen minutes after CPB, dynamic lung compliance in group I was 91% +/- 12% of baseline versus 49% +/- 5.2% in group II (p = 0.06 by analysis of variance). After CPB, the arterial oxygen pressure was also significantly better in group I than in group II (425 +/- 61 versus 234 +/- 76 mm Hg) (p < 0.05). The rise in pulmonary vascular resistance after CPB was less in group I (p < 0.05) (323 +/- 55 to 553 +/- 106 dynes.s.cm-5) than in group II (531 +/- 177 to 884 +/- 419 dynes.s.cm-5) at the end of the observation period. CD18 up-regulation increased similarly in the two groups during CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Preventive treatment of coronary vasculopathy in heart transplantation by inhibition of smooth muscle cell proliferation with angiopeptin.

BACKGROUND: The underlying mechanism of accelerated coronary vasculopathy in cardiac allografts still remains unclear. Our hypothesis was that inhibition of smooth muscle cell proliferation with the somatostatine analogue Angiopeptin may reduce vasculopathy. METHODS: Fifty-four patients received Angiopeptin injections (1500 micrograms x three times daily subcutaneously) for 21 days after the operation and three additional injections with every rejection treatment. Angiography was performed yearly, and data were compared with a matched historic control group. RESULTS: Actuarial survival was 85% at 1 year and 80% at 2 years, comparable with our results in general (80%/77%). Forty-six long-term survivors could be followed by coronary angiography. At 1 year, vasculopathy was assessed in nine patients (17%). Of the 18 patients investigated at 2 years thus far, an additional three patients were found to have vasculopathy. In the control group vasculopathy was comparable, being 13% after 1 year and 20% after 2 years. A significantly lower incidence of rejections and lower creatinine values were found in the study group within the entire observation period (p < 0.05). CONCLUSIONS: We conclude that Angiopeptin treatment appears to be safe without significant side effects; it may reduce the number of acute rejections, at least during the first year after heart transplantation. However, the results of the 2-year follow-up in the remaining patients would have to be included in assessing the effect of Angiopeptin. Long-term follow-up will be necessary to decide whether Angiopeptin will be helpful in reducing the incidence of transplant vasculopathy.

Neutrophil modulation results in improved pulmonary function after 12 and 24 hours of preservation.

Neutrophils are important mediators of reperfusion injury, and suppression of neutrophil function or numbers can reduce reperfusion injury and improve long-term organ preservation in transplantation. NPC 15669, a leumedin, is a novel compound that prevents recruitment of neutrophils at inflammatory foci by inhibiting CD11b/CD18 adhesion molecule expression. NPC 15669 was used to inhibit neutrophil adhesion during reperfusion of isolated rabbit lungs after 12 and 24 hours of cold storage. Lungs (New Zealand White male rabbits, 2 to 3 kg) were flushed with 4 degrees C Euro-Collins (EC) solution, harvested en bloc, stored under various study conditions, and reperfused for 3 hours with fresh whole blood at 37 degrees C in an isolated perfusion system at constant flow and an inspired oxygen fraction of 1. Four groups (n = 6 each) were studied. Group I underwent immediate whole blood reperfusion. Group II were stored for 12 hours in 4 degrees C EC solution before reperfusion. Group III were stored for 12 hours in 4 degrees C EC solution and reperfused with whole blood containing NPC 15669 (10 mg/kg whole body weight). Group IV were stored for 24 hours in 4 degrees C EC solution and reperfused with whole blood containing NPC 15669 (10 mg/kg). Pulmonary artery and peak airway pressures were significantly lower and compliance higher in groups III and IV lungs after 3 hours of reperfusion (p < 0.05) compared with group I. Group I and III lungs had significantly less edema than group II (p < 0.05). The arterial partial pressure of oxygen was similar in all stored groups (II to IV).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of platelet adhesion during cardiopulmonary bypass reduces postoperative bleeding.

BACKGROUND: Thrombocytopenia and impaired platelet function after cardiopulmonary bypass (CPB) contribute to postoperative bleeding and may increase blood transfusion requirements. We tested the hypothesis that reversible inhibition of glycoprotein IIb/IIIa integrin-mediated platelet adhesion would reduce postoperative bleeding after CPB. METHODS AND RESULTS: Twelve mongrel dogs (21 to 24 kg) underwent 2.5 hours of hypothermic CPB followed by 6 hours of observation. The study group (n = 6) received a 90-micrograms/kg IV bolus of the glycoprotein IIb/IIIa inhibitor Integrelin, followed by continuous infusion (2 micrograms/kg per minute) during CPB; the control group (n = 6) received only drug vehicle. Platelet number and aggregometry, PaO2, and chest tube output were assessed serially. Lung wet weight, histology, and myeloperoxidase activity were also measured. At 120 minutes after CPB, the control group had significantly lower platelet counts (expressed as percent of pre-CPB values) when compared with the Integrelin group (control, 35.2 +/- 4.6%; Integrelin, 68.2 +/- 4.9%; mean +/- SEM; P < .05). Three hundred sixty minutes after CPB, platelet function (expressed as percent of pre-CPB aggregation induced by 10 mumol/L ADP) was better preserved in the Integrelin group (Integrelin, 20.8 +/- 3.0%; control, 43.9 +/- 10.4%; P < .05). The Integrelin group also had less total postoperative blood loss (control, 447 +/- 97 mL; Integrelin, 248 +/- 30 mL; P < .05). PaO2, lung wet weight, histology, and myeloperoxidase activity did not differ significantly between groups. CONCLUSIONS: This study demonstrates that inhibition of platelet adhesion during CPB results in (1) less platelet consumption, (2) better preservation of platelet function, and (3) less postoperative bleeding. Reversible platelet inhibition may have clinical utility in minimizing postoperative bleeding and reducing blood transfusions.

Patterns of donor-type microchimerism after heart transplantation.

Allogeneic microchimerism of donor-type has been demonstrated in stable patients in the long-term after organ transplantation. We have analysed microchimerism in skin and blood of 47 heart-transplanted patients after transplantation with polymerase-chain-reaction amplification specific for donor HLA-DRB1. Microchimerism was detectable in 50% of the patients in the first 6 months, in 100% between 6 months and 2 years, and in 58% in the third postoperative year or later. The state of chimerism was not related to acute or chronic rejections. Patterns of microchimerism after heart transplantation may be dynamic, but any association with clinical and immunological variables remains to be elucidated.