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.     

Understanding the impact of variation in the delivery of healthcare services

In the past several years, healthcare providers have coped with the financial aspects of managed care and the resultant constraints on revenue. In fact, working with decreasing margins of return has become routine for many providers. Beyond straightforward cost cutting, providers must also consider a variety of other operational factors to achieve success. To this end, higher patient satisfaction and improved utilization and efficiency of resources are natural objectives. Ironically, fundamental to the pursuit of better operations management is the fact that the delivery of healthcare services can vary between and among patients, providers, and organizations for many reasons. Unfortunately, such variation may be overlooked or trivialized if the phenomenon is not well understood by healthcare managers. Knowing how variation affects the delivery of services creates opportunities for focused improvement.     

Increased post-operative haemorrhage seen in adult coblation tonsillectomy

Coblation is a new soft tissue surgical technique that is being used for tonsillectomy. Published results show a significant decrease in the amount of post-operative pain experienced by patients undergoing coblation tonsillectomy. There has been no published work to date on the incidence of post-operative haemorrhage. From August 2001 to November 2002 one surgeon performed 36 coblation tonsillectomies on adults. On another list he performed 29 by his standard method of dissection and bipolar coagulation. Retrospective analysis found a significant increase in the secondary haemorrhage rate in adult patients undergoing coblation tonsillectomy (22.2 vs. 3.4 per cent). At our department coblation tonsillectomy has been abandoned until further work into its safety has been published.     

老年胃癌患者围手术期并发症及其处理

目的 研究老年胃癌患者的临床特点,总结老年胃癌患者的年龄、术前各种合并症等对术后并发症发生的影响.方法 总结自2005年1月至2007年1月接受手术的181例胃癌患者的临床资料,其中老年患者(年龄大于65岁者)65例,回顾性分析老年胃癌患者的年龄、术前各种合并症与术后并发症发生的关系.结果 老年胃癌组术前合并症总发生率为83%,非老年胃癌组为59%;老年胃癌组中有52%存在2种或2种以上合并症,发生率最高的合并症为高血压,达40%;老年胃癌患者的根治率为86%,非老年胃癌组的根治率为93%;老年胃癌组术后并发症的发生率为37%,术前合并高血压、糖尿病、肺部疾病、低蛋白血症、贫血者术后并发症发生率较高.结论 老年胃癌患者手术治疗后的总并发症发生率和病死率与非老年胃癌患者相比无差异.     

Rapid suppression of complex ventricular arrhythmias with high-dose oral amiodarone

Although amiodarone is effective for the suppression of complex ventricular arrhythmias, a major problem with its use is the long delay between the initiation of therapy and the onset of effective suppression of arrhythmia. To test the hypothesis that rapid loading with oral amiodarone to a target serum concentration can overcome much of this delay, eight patients with refractory, sustained, hemodynamically compromising ventricular arrhythmias and 10 patients with potentially life-threatening ventricular arrhythmias were treated with a flexible, very high dose, oral loading protocol (800 to 2000 mg two to three times a day). Dosage was adjusted on the basis of amiodarone serum concentrations to maintain the trough serum concentrations between 2.0 and 3.0 micrograms/ml. Comparison of 24 hr Holter electrocardiograms obtained before and during therapy revealed statistically significant reductions in premature ventricular complexes (PVCs) and paired PVCs beginning the first day of therapy and a reduction in ventricular tachycardia (VT) beginning the second day. By day 2, four of eight patients with sustained VT and six of 10 patients with nonsustained VT showed no VT. Pulmonary arterial catheterization during the first 24 hr (mean amiodarone dose 3933 mg) revealed no significant hemodynamic alterations. Minor side effects were common (10 patients) but major side effects were rare (one patient). High-dose oral loading with amiodarone utilizing serum concentration guidelines is a safe and effective method of rapidly controlling life-threatening arrhythmias in selected patients.     

Use of pre-operatively obtained platelets and plasma in patients undergoing cardiopulmonary bypass

Thirty-seven patients requiring cardiopulmonary bypass were prospectively studied and assigned to plateletpheresis or control groups in a non-randomized, non-blinded fashion according to apheresis exclusion criteria and our ability to perform apheresis within 24 hours of surgery. Patients were grouped by potential for hemostatic abnormalities following a risk point factor assignment established for this study. The study indicated improvement of hemostasis with autologous platelets and plasma as demonstrated by clinical and laboratory parameters and by overall blood component utilization. We conclude that pre-operative plateletpheresis in this patient population is feasible, safe, and effective.