In situ preservation of cadaver kidneys for transplantation: laboratory observations and clinical application.

Many kidneys obtained from cadaver donors undergoing sudden cardiac arrest cannot be transplanted due to the long periods of warm ischemia from the moment of arrest to nephrectomy. A double-ballon-triple-lumen catheter for the rapid in situ preservation of cadaver kidneys has been designed. Used in combination with equipment routinely found in any hospital, it can cool human kidneys in situ to 10-15 C and maintain this temperature until nephrectomy can be performed. Kidenys preserved with this catheter have functioned after transplantation into suitable recipients. This report describes the design and laboratory evaluation of this new device, its clinical effectiveness and technique of insertion.     

Interaction between isolated human myocardial mast cells and cultured fibroblasts

INTRODUCTION: Previously, we reported an increase in interstitial collagen and total mast-cell numbers in heart failure versus normal myocardium. A secondary increase, primarily in chymase-negative mast cells, occurred following LVAD support compared to matched pre-LVAD tissue samples and was associated with a decrease in interstitial collagen and bFGF. To further elucidate the changes in interstitial collagen, we investigated the direct interaction between mast cells, isolated from failing myocardium with or without previous LVAD support, and human fibroblasts in a coculture model. Additionally, the expression of HSP-47, the pro-collagen-specific chaperone protein, was determined in the particular myocardium. MATERIALS AND METHODS: Myocardial tissue was obtained from 10 patients with end-stage dilated cardiomyopathy (DCM) at the time of transplantation. Five patients were transplanted following LVAD support, five patients without previous LVAD support. Mast cells were isolated according to a standard protocol, including collagenase digestion and cell separation. The isolated mast cells were co-cultured with human fibroblasts for 12 h, with or without stimulation of degranulation, and protein synthesis was measured by [(3)H]-proline incorporation. HSP-47 immunostaining was performed in the different myocardial samples and the positive cells were quantified. RESULTS: Stimulated mast cells isolated from DCM tissue (without previous LVAD support) caused a 92% increase in [(3)H]-proline incorporation and consequently in protein production in fibroblasts compared to mast-cell free culture (P < 0.01), while conversely stimulated mast cells isolated from LVAD supported myocardium decreased the [(3)H]-proline incorporation by 63% (P < 0.01) below baseline. Nonstimulated mast cells did not significantly alter the protein production over baseline. There was also a significant increase in the number of HSP-47-positive cells in DCM myocardium compared to normal (P < 0.01) and there was a shift toward normal after LVAD support (P < 0.01). CONCLUSION: We demonstrate that fibroblast protein production in vitro is significantly altered by mast cells and that the direction of change is dependent on whether myocardium was supported by LVAD. We suggest that under long-term LVAD support there is a phenotypic alteration in myocardial mast cells, which leads to a change in concentration and/or composition of mediators, capable of re-remodeling the myocardial matrix.     

What price support? Ventricular assist device induced systemic response

Use of ventricular support systems has been associated with myriad systemic complications. Engendered by the blood-biomaterial interface of a unique host/device relationship, these complications include diverse humoral dyscrasias that frequently culminate in episodes of bleeding, hemolysis and thrombogenicity, heightened susceptibility to inflammation and infection, and transient immunal compromise. Recent endeavor in biocompatibility research has served to illustrate the critical role played by cellular, humoral, and neurohormonal components in regulating cytokine expression and has provided insight into the complexities involved in such biomechanical juxtapositions. The following is intended as a review of current literature attempting to address the many aspects of this host/device interaction and their consequences for the supported patient.     

Correlation between plasma neurohormone levels and left ventricular functional and morphological improvement in LVAD patients

Objective: Certain neurohormones (e.g., brain natriuretic peptide (BNP), endothelin-1 (ET-1)) have demonstrated reliability as clinical markers of left ventricular (LV) function. The aim of this study was to examine the relationship between plasma levels of these neurohormones, LV function and histological evidence of morphological improvement in left ventricular assist device (LVAD) recipients to determine whether serial hormonal expression may be used to assess cardiac status in the LVAD setting. Methods: Plasma levels of BNP and ET-1 were measured in 19 end-stage congestive heart failure patients directly before and up to 18 weeks after implantation with various devices (DeBakeyVAD, Novacor, TCI HeartMate). Echocardiographic indices corresponding to the time-points of serial hormonal measurement were evaluated. Immunohistochemical collagen staining of LV tissue samples derived from LVAD patients at the time of device insertion and removal were then contrasted. Patients were grouped according to device employed and etiology (ischemic/dilated cardiomyopathy, ICMP/DCMP). Results: LVAD therapy significantly enhanced LV ejection fraction (EF%: 21% ± 3.8% to 37% ± 11.39%) and cardiac output (CO: 3.49 ± 1.3 to 7.3 ± 0.2 l/m) in all patients; other parameters were not appreciably altered. Absolute BNP and ET-1 plasma levels remained significantly lower in all patients after LVAD implantation (both: p < 0.001). The NOV group exhibited the most BNP reduction and EF% increase (p < 0.0004 and p < 0.038, respectively), whereas ET-1 was lower in the DVAD group (p < 0.06). In all categories, the ICMP group experienced more significant change when compared to those in the DCMP grouping. Collagen levels were sharply reduced in all patients (p < 0.0005); however, while those in the DVAD demonstrated the most evident change (p < 0.0036), there was little difference between the DCMP/ICMP groups (p < 0.012 vs p < 0.022). Both BNP and ET-1 manifested bi-phasic tendencies and an inverse proportionality to EF% measurements. Conclusions: Plasma BNP and ET-1 levels appear to correlate both with device-related LV functional and myocardial morphological improvement and may be of potential use as therapeutic indicators.     

Surgical outcome in 85 patients with primary cardiac tumors

BACKGROUND: We present a large, single institution experience with adult cardiac tumors and address factors affecting outcome. METHODS: A retrospective review was made of all patients who underwent surgery for primary cardiac tumors from April 1975 through August 2002. RESULTS: Eighty-five patients (33 male and 52 female) with a mean age of 54 years were identified with follow-up available for 80 (94%) patients. There were 68 (80%) benign tumors and 17 (20%) malignant tumors. Three tumors recurred and were resected giving a total of 88 surgeries. All benign tumors were grossly resected and the extent of resection for malignant disease ranged from 14 (78%) gross resections and 3 (17%) debulkings to 1 (5%) biopsy. There were 4 (5%) early hospital deaths. Median survival was 9.6 months and 322 months for patients with malignant and benign diseases, respectively. Significant predictors of long-term mortality were malignant disease (P <0.0001) and New York Heart Association class (P <0.03). CONCLUSIONS: Surgical resection provides excellent outcome in patients with benign cardiac tumors. Malignant tumors continue to pose a challenge with good local tumor control but limited survival owing to metastatic disease.