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Bartley P Griffith

Publications and source records attributed to Bartley P Griffith.

At least 37 records · Page 2Linked to original sources
PubMed2005

Hypercoagulability affecting early vein graft patency does not exist after off-pump coronary artery bypass.

OBJECTIVE: Hypercoagulability may compromise the patency of bypass grafts. The authors hypothesized that perioperative in vitro platelet responses to varying agonists (eg, thrombin, platelet activating factor, collagen, adenosine diphosphate) correlate with early graft thrombosis after off-pump coronary artery bypass grafting (OPCAB). DESIGN AND PARTICIPANTS: Prospective study of 78 OPCAB patients with 151 venous bypass grafts treated with perioperative aspirin and intraoperative heparin (250 U/kg). SETTING: Tertiary, academic medical center. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hypercoagulability, defined by TEG (maximum amplitude [MA]>70 mm), whole-blood aggregometry (>15 ohms after 5 mcl/mL collagen) or hemoSTATUS (Ch5CR>0.5), was serially assessed around OPCAB. An immediate decline in platelet function after surgery and on postoperative day 1 returned to normal by postoperative day 3 in most patients. Graft blood flow was analyzed intraoperatively, and vein biopsies were analyzed for endothelial disruption. Graft patency was assessed by multichannel computed tomography coronary angiography on postoperative day 5. No differences in any of the platelet function assays were noted for the 8 patients with graft thrombosis (n=8 grafts) versus the 68 patients with all patent grafts (n=129 grafts). Ten patients developed a rise in platelet function postoperatively >1 SD above baseline; only 1 developed graft thrombosis (p=not significant v patients with normal platelet function). CONCLUSIONS: OPCAB is not associated with a significant activation in postoperative platelet function. This study suggests that if hypercoagulability exists after OPCAB, it is not involved in the pathogenesis of arterial thrombotic events such as early bypass graft failure.

Aged↗
PubMed2005

Imaging of left ventricular assist devices.

Left ventricular assist devices are used as a bridge to recovery, a bridge to transplant, or a permanent alternative to cardiac transplant. This exhibit demonstrates the imaging appearance of commonly used left ventricular assist devices and their complications.

Brain↗
PubMed2005

HLA-specific antibodies are risk factors for lymphocytic bronchiolitis and chronic lung allograft dysfunction.

Bronchiolitis obliterans syndrome (BOS) represents a major limitation in lung transplantation. While acute rejection is widely considered the most important risk factor for BOS, the impact of HLA-specific antibodies is less understood. Of 51 lung recipients who were prospectively tested during a 4.2 +/- 1.6-year period, 14 patients developed HLA-specific antibodies. A multi-factorial analysis was performed to correlate the prevalence of BOS with HLA antibodies, persistent-recurrent acute rejection (ACR-PR), lymphocytic bronchiolitis, and HLA-A, -B, and -DR mismatches. HLA-specific antibodies were associated with ACR-PR (10/14 vs. 11/37 with no antibodies, p < 0.05), lymphocytic bronchiolitis (8/14 vs. 10/37, p < 0.05), and BOS (10/14, vs. 9/37, p < 0.005). Other risk factors for BOS were: lymphocytic bronchiolitis (13/18 vs. 6/33 with no lymphocytic bronchiolitis, p < 0.0001), ACR-PR (12/21 vs. 7/30 with no ACR-PR, p < 0.05), and the number of HLA-DR mismatches (1.7 +/- 0.48 in BOS vs. 1.2 +/- 0.63 without BOS, p < 0.05). The presence of antibodies exhibited a cumulative effect on BOS when it was associated with either lymphocytic bronchiolitis or ACR-PR. The complex relationship between the development of HLA antibodies and acute and chronic lung allograft rejection determines the importance of post-transplant screening for HLA-specific antibodies as a prognostic element for lung allograft outcome.

Biopsy↗
PubMed2004

P-glycoprotein activity is decreased in CD4+ but not CD8+ lung allograft-infiltrating T cells during acute cellular rejection.

BACKGROUND: Modulation of P-glycoprotein (P-gp) activity in graft-infiltrating T cells may alter their susceptibility to immunosuppression. METHODS: P-gp activity was measured by rhodamine efflux in T-cell subsets from bronchoalveolar lavage (BAL) of five healthy volunteers and 27 lung allograft recipients. The effect of T-cell activation on P-gp activity was modeled by stimulation of peripheral blood mononuclear cells with staphylococcal enterotoxin B. RESULTS: Most BAL T cells expressed memory-effector markers. Patients had a lower proportion of CD4 T cells (P = 0.005), whereas control subjects had CD4-to-CD8 ratios similar to peripheral blood. In controls, basal P-gp activity was greatly increased in both CD4 (35% P-gp active) and CD8 (63%) lung T cells compared with peripheral T cells. Basal P-gp activity was elevated in patient BAL T cells but was lower than control BAL activity (CD4, P = 0.07; CD8, P = 0.03). Lung T cells from transplant patients had modest (CD4) or marked (CD8) increases in substrate-induced P-gp activity compared with normal lung, indicating that P-gp was not irreversibly inhibited. Patients with acute cellular rejection (ACR) had reduced P-gp activity in CD4, but not CD8, BAL T cells compared with patients without ACR (P = 0.004). To determine the relationship between T-cell activation on P-gp modulation, P-gp activity was measured in staphylococcal enterotoxin B-stimulated peripheral blood mononuclear cells. P-gp activity was abrogated in CD71 cycling cells but remained high in a persistent but minor population of resting naive T cells. CONCLUSIONS: Lung T cells have increased in vivo P-gp activity and therefore may eliminate substrate drugs, resulting in local resistance to immunosuppressive therapy. However, P-gp function is reduced during T-cell activation, providing a window of susceptibility to treatment during ACR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Optimizing donor heart outcome after prolonged storage with endothelial function analysis and continuous perfusion.

BACKGROUND: By minimizing tissue ischemia, continuous perfusion (CP) during organ transport may increase the safety of "marginal donors." My colleagues and I investigated whether an analysis of donor heart viability predicts recovery of grafts challenged with a 24-hour preservation interval. METHODS: Dog hearts underwent cold static storage (CS) for 8 hours (n = 8) or 24 hours (n = 2) or CP for 24 hours with cold asanguinous, oxygenated solution (n = 8). Myocardial systolic and diastolic function and oxygen and lactate consumption were assessed at base line, during CP, and after Langendorff blood reperfusion. Base line endothelial function was evaluated by the percentage transcoronary change ([coronary sinus - aorta]/aorta) in myeloperoxidase and by platelet function and coronary flow reserve after 20 seconds of coronary artery occlusion. During CP, the endothelium was assessed by transcoronary protein release and coronary resistance. Edema was assessed by weight gain and histology. RESULTS: Base line systolic and metabolic functions showed no relation to post-Langendorff function. Compared with CS, CP resulted in a greater recovery in systolic function (87% +/- 35% vs 65% +/- 15% of baseline; p = 0.05) and a shorter interval required for lactate consumption to exceed production (7.0 +/- 6.8 minutes vs 15.0 +/- 8.9 minutes; p = 0.06). Endothelial function was heterogeneous: coronary flow reserve, 2.7 +/- 0.7; percentage change in myeloperoxidase, -8.4% +/- 6.8%; and change in platelet function, 4.3% +/- 3.5%, as determined by thromboelastography angle at base line. Protein release during CP for 24 hours was 8.3 +/- 7.1 g. Two factors predicted more than 75% systolic pressure generation recovery: use of CP and normal endothelial function (p = 0.05; Fisher's exact test). However, CP led to edema according to histology, weight gain (72 +/- 29 g), and impaired diastolic function versus CS (end-diastolic pressure-volume relationship, 1.4 +/- 0.4 mm Hg/mL vs 0.8 +/- 0.3 mm Hg/mL; p = 0.08). CONCLUSIONS: Better systolic function despite 16 hours' more preservation than cold storage corroborates the idea that CP supports aerobic metabolism at physiologically important levels. Viability analysis focused on endothelial function and identified organs that were able to tolerate this 24-hour preservation interval.

Aerobiosis↗
PubMed2004

An internet-based intervention to improve psychosocial outcomes in heart transplant recipients and family caregivers: development and evaluation.

BACKGROUND: Although quality of life (QOL) is generally improved by heart transplantation, medical noncompliance and mental health and QOL limitations often emerge and persist. Transplant teams' ability to address these issues is hampered because many patients reside long distances from the transplant program. We therefore conducted the first empirical evaluation of an internet-based psychosocial intervention for heart recipients and their families. METHODS: Based on focus group work and previous research, a multifaceted web-based intervention was developed with stress and medical regimen management workshops; monitored discussion groups; access to electronic communication with the transplant team; and information on transplant-related health issues. Intervention effectiveness was evaluated with 20 patients and family caregivers who used the website for 4 months (plus usual clinical care). Pre- and post-intervention assessments of mental health, QOL and medical compliance were performed. Comparison groups of 40 patients and their caregivers who received only usual care were similarly assessed. RESULTS: Relative to the comparison groups, intervention patients' depressive and anxiety symptoms, and caregivers' anxiety and hostility symptoms declined significantly (P < 0.05). QOL in social functioning significantly improved. Mental health and QOL benefits were greater among more frequent users of the website. Overall, intervention patients' medical compliance did not change. However, the sub-group using the website's medical regimen workshop showed significantly better compliance at follow-up than all other patients in attending clinic appointments, completing blood work and following diet. CONCLUSIONS: These preliminary findings suggest that a web-based intervention could have a vital role in follow-up care and in patients' and families' adjustment to heart transplantation.

Adaptation, Psychological↗
PubMed2004

HLA-specific antibodies are associated with high-grade and persistent-recurrent lung allograft acute rejection.

BACKGROUND: The impact of HLA-specific antibodies is not well established in the acute rejection of lung allografts. Acute rejection represents the most important risk factor for the development of chronic lung allograft dysfunction. METHODS: We analyzed the pattern of HLA antibodies before and after transplantation in 54 patients, and correlated our data with the presence and frequency of high-grade and persistent-recurrent acute rejection, during the first 18 post-operative months. The diagnosis of acute rejection was based on histologic International Society for Heart and Lung Transplantation (ISHLT)-published criteria. RESULTS: Ten of 54 patients had a positive enzyme-linked immunoassay (ELISA) post-transplantation. In 90% of ELISA-positive patients, the presence of HLA antibodies was associated with persistent-recurrent acute rejections, compared with 34% in the ELISA-negative group (p < 0.005). There were 28 high-grade acute rejection episodes in the ELISA-positive group, compared with 36 in the ELISA-negative group (p < 0.0001). The ELISA-positive patients required a greater intensity of immunosuppressive therapy. The patients with ELISA-detected anti-HLA antibodies were at least 3-fold more likely to develop high-grade acute rejection and persistent-recurrent acute rejection, and 7-fold more likely to develop multiple episodes of persistent-recurrent acute rejection, compared with ELISA-negative patients. CONCLUSIONS: ELISA-based screening for the development of HLA antibodies is a reliable method that can identify lung transplant recipients at increased risk for high-grade and persistent-recurrent acute rejection. Although bronchiolitis obliterans appears as a point of no return in the evolution of lung-transplanted patients, early detection of risk factors for acute rejection could indirectly decrease the incidence of bronchiolitis obliterans. These lung-transplanted patients may benefit from an altered strategy of immunosuppression.

Acute Disease↗
PubMed2004

Optimal timing of cardiac transplantation after ventricular assist device implantation.

OBJECTIVE: We sought to determine the influence of the interval from ventricular assist device implantation to cardiac transplantation on end-organ function and posttransplantation survival. METHODS: United Network for Organ Sharing data on 2692 heart transplantations performed in adult patients in the United States between October 1999 and March 2001 were reviewed. RESULTS: Seventeen percent (466) of adult heart transplant recipients were bridged to transplantation with a ventricular assist device. Almost half of patients with ventricular assist devices undergoing transplantation were upgraded to status 1A as a result of ventricular assist device-related complications occurring more than 30 days after ventricular assist device implantation. Creatinine and total bilirubin levels were less in patients undergoing transplantation after 2 to 4 weeks of mechanical support. One-year survival was higher in the nonventricular assist device than in the ventricular assist device group (85.7% vs 79.7%, P =.0004). Within the ventricular assist device group, survival was lower for patients undergoing transplantation within 2 weeks of ventricular assist device implantation compared with those undergoing transplantation later (74.2% vs 84.2 %, P =.03). One-year survival among patients supported with a ventricular assist device for more than 30 days without complications was 91.4%. Multivariate analysis demonstrated a significant independent effect of the time interval from ventricular assist device implantation to transplantation on posttransplantation mortality and suggested that a period of lowest risk might exist between 1 and 3 months after implantation. CONCLUSIONS: Survival after cardiac transplantation is influenced by the time interval from ventricular assist device insertion to transplantation. Survival is significantly lower when performed within 2 to 4 weeks of ventricular assist device implantation.

Adult↗
PubMed2004

Interleukin-10 production genotype protects against acute persistent rejection after lung transplantation.

BACKGROUND: Our previous studies demonstrated that cytokine gene polymorphisms are related to acute rejection in pediatric heart transplantation; a decreased tumor necrosis factor (TNF)-alpha production genotype combined with an increased or intermediate interleukin (IL)-10 production genotype was associated with the smallest incidence of acute rejection. The objective of this study was to determine whether cytokine genotypes TNF-alpha, IL-10, IL-6, interferon-gamma, and transforming growth factor beta were associated with acute persistent rejection after lung transplantation. METHODS: Cytokine genotyping was performed in 119 adult lung transplantation recipients who underwent surveillance transbronchial biopsies during their first year after transplantation. We categorized recipients with acute persistent rejection if they had 2 consecutive biopsy specimens at >/=Grade A2 despite anti-rejection treatment. We performed cytokine genotyping using the polymerase chain reaction-sequence specific primers technique, with a commercially available kit. RESULTS: We analyzed the IL-10 genotype in 116 patients. For the increased IL-10 production genotype, 7 of 20 patients (35%) were persistent rejecters. In comparison, 57 of 96 patients (59%) with intermediate or decreased IL-10 production genotype had acute persistent rejection (p = 0.046). For IL-10 haplotypes associated with intermediate IL-10 production, 30 of 45 patients with GCC/ACC haplotype (67%) had acute persistent rejection compared with 10 of 22 patients with GCC/ATA (45%). In the patients with intermediate IL-10 production, 17 of 22 (77%) with IL-10 GCC/ACC and IL-6 G/C had acute persistent rejection, whereas only 2 of 7 patients (29%) with IL-10 GCC/ATA and IL-6 G/G had acute persistent rejection (p = 0.018). CONCLUSIONS: In lung transplant recipients, the increased IL-10 production genotype protects against acute persistent rejection when compared with the intermediate or decreased IL-10 production genotypes. The intermediate IL-10 production genotype in lung transplant recipients can be differentiated into 2 haplotype responses, with the GCC/ACC haplotype associated more with acute persistent rejection. In lung transplant recipients, the immunomodulatory effects of IL-6 are differentiated in the G/C and G/G alleles in conjunction with IL-10 haplotypes, with G/C being associated with more acute persistent rejection in conjunction with the IL-10 GCC/ACC haplotype. Future pharmacogenomic models may incorporate these associations with acute persistent rejection in lung transplant recipients to formulate individualized therapeutic regimens.

Acute Disease↗
PubMed2004

Tacrolimus dosing in adult lung transplant patients is related to cytochrome P4503A5 gene polymorphism.

Tacrolimus is a potent immunosuppressive agent used in lung transplantation and is a substrate for both P-glycoprotein (P-gp, encoded by the gene MDR1) and cytochrome (CYP) P4503A. A previous study by the authors identified a correlation between the tacrolimus blood level per dose with CYP3A5 and MDR1 gene polymorphisms in pediatric heart transplant patients. The objective of this study was to confirm the influence of these polymorphisms on tacrolimus dosing in adult lung transplant patients. Adult lung transplant patients who had been followed for at least 1 year after lung transplantation were studied. Tacrolimus blood level (ng/mL) per dose (mg/day) at 1, 3, 6, 9, and 12 months after transplantation was calculated as [L/D]. DNA was extracted from blood. MDR1 3435 CC, CT, and TT; MDR1 2677 GG, GT, and TT; and CYP3A5*1 (expressor) and *3 (nonexpressor) genotypes were determined by PCR amplification, direct sequencing, and sequence evaluation. Eighty-three patients were studied. At 1, 3, 6, 9, and 12 months after the transplant, a significant difference in [L/D] was found between the CYP3A5 expressor versus nonexpressor genotypes (mean +/- SD of 1.49 +/- 0.88 vs. 3.11 +/- 4.27, p = 0.01; 1.23 +/- 0.82 vs. 3.44 +/- 8.97, p = 0.05; 1.32 +/- 0.96 vs. 3.81 +/- 6.66, p = 0.005; 0.95 +/- 1.19 vs. 3.74 +/- 5.98, p = 0.0015; and 0.45 +/- 0.2 vs. 3.76 +/- 6.75, p = 0.0001, respectively). MDR1 G2677T and C3435T genotypes had only minimal effects on [L/D] at 1 and 3 months after transplantation. This study confirms the relationship of CYP3A5 polymorphisms to tacrolimus dosing in organ transplant patients. CYP3A5 expressor genotypes required a larger tacrolimus dose to achieve the same blood levels than the CYP3A5 nonexpressors at all time points during the first posttransplant year. This was not uniformly true for MDR1. The authors therefore conclude that tacrolimus dosing in adult lung transplant patients is associated with CYP3A5 gene polymorphisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Blood soluble drag-reducing polymers prevent lethality from hemorrhagic shock in acute animal experiments.

Over the past several decades, blood-soluble drag reducing polymers (DRPs) have been shown to significantly enhance hemodynamics in various animal models when added to blood at nanomolar concentrations. In the present study, the effects of the DRPs on blood circulation were tested in anesthetized rats exposed to acute hemorrhagic shock. The animals were acutely resuscitated either with a 2.5% dextran solution (Control) or using the same solution containing 0.0005% or 5 parts per million (ppm) concentration of one of two blood soluble DRPs: high molecular weight (MW=3500 kDa) polyethylene glycol (PEG-3500) or a DRP extracted from Aloe vera (AVP). An additional group of animals was resuscitated with 0.0075% (75 ppm) polyethylene glycol of molecular weight of 200 kDa (PEG-200), which possesses no drag-reducing ability. All of the animals were observed for two hours following the initiation of fluid resuscitation or until they expired. We found that infusion of the DRP solutions significantly improved tissue perfusion, tissue oxygenation, and two-hour survival rate, the latter from 19% (Control) and 14% (PEG-200) to 100% (AVP) and 100% (PEG-3500). Furthermore, the Control and PEG-200 animals that survived required three times more fluid to maintain their blood pressure than the AVP and PEG-3500 animals. Several hypotheses regarding the mechanisms underlying these observed beneficial hemodynamic effects of DRPs are discussed. Our findings suggest that the drag-reducing polymers warrant further investigation as a potential clinical treatment for hemorrhagic shock and possibly other microcirculatory disorders.

Acute Disease↗
PubMed2003

Smooth muscle cell hypertrophy of renal cortex arteries with chronic continuous flow left ventricular assist.

BACKGROUND: Pathophysiology of long-term continuous flow left ventricular assist is not well described. With many of these devices becoming available, it is important to examine for possible pathologic effects. In this study we examined the relationship between diminished pulsatility and pathologic changes in renal cortical arteries. METHODS: Twenty-nine calves were implanted with various continuous flow left ventricular assist systems in a left ventricle-descending thoracic aorta bypass configuration. Pulsatility was quantified by pulse pressure and pulsatility index. Pathologic changes of the renal cortex arteries were described and evaluated by medial thickness, medial/vascular cross-sectional area ratio, and smooth muscle cell count, to quantify hypertrophy or hyperplasia. Seven calves, which underwent a sham-implant, were used as controls. RESULTS: Systolic arterial pressure, pulse pressure, and pulsatility index were significantly lower and diastolic pressure was significantly higher than before implant in pump-implanted animals. Twenty-three of 29 pumpimplanted calves (79.3%) had medial smooth muscle cell hypertrophy in renal cortex arteries, whereas none of sham-implanted calves had any abnormal lesions. When the pump-implanted calves were grouped according to the presence of smooth muscle cell hypertrophy, there was a clear trend toward lower pump flow rate in calves with lesions. Renal function was within the normal range in all calves. CONCLUSIONS: There appears to be a relationship between smooth muscle cell hypertrophy in renal cortex arteries and continuous flow left ventricular assist. Furthermore, although the pathologic changes are likely multifactorial, these lesions appear to be related to lower pump assist rates.

Animals↗
PubMed2003

Effect of aneurysm on the tensile strength and biomechanical behavior of the ascending thoracic aorta.

BACKGROUND: Rupture of an ascending thoracic aortic aneurysm (ATAA), which is associated with significant mortality, occurs when the mechanical forces acting on the aneurysm exceed the strength of the degenerated aortic wall. The purpose of this study was to evaluate changes in biomechanical properties of the aortic wall related to ATAA formation. METHODS: Ascending thoracic aortic aneurysm tissue was obtained from surgery; control (nonaneurysmal) aorta was obtained from autopsy. Tissue strips with longitudinal (LONG) or circumferential (CIRC) orientation were stretched to failure. Maximum tissue stiffness and tensile strength were determined from plots of stress (normalized force) versus strain (normalized deformation). Student's t test was used for all comparisons. RESULTS: Tensile strength of LONG (nATAA = 17, n(control) = 7) and CIRC (nATAA = 23, n(control) = 7) ATAA specimens were 29% and 34% less than that of control tissue, respectively (p < 0.05). Maximum tissue stiffness was 72% stiffer for LONG ATAA (p < 0.05) and 44% stiffer for CIRC ATAA (p = 0.06) than for control tissue, respectively. CONCLUSIONS: The data suggest that ATAA formation is associated with stiffening and weakening of the aortic wall, which may potentiate aneurysm rupture.

Aged↗
PubMed2003

Distal thoracic aorta hemodynamics during exercise with continuous flow left ventricular assist system.

OBJECTIVES: Continuous flow left ventricular assist systems (LVAS) are being discussed as a destination therapy. LVAS patients will have expanded activity of daily life, including exercise. In this study, we analyzed the effects of exercise on blood flow in the distal thoracic aorta of LVAD implanted animals. METHODS: Five calves with a continuous flow LVAS exercised on treadmill at two different pump flow rates (PFR), 60-80% (high PFR) and 25-30% (low PFR) of pulmonary artery flow rate. Pump, pulmonary artery and descending thoracic aorta flow waves were recorded before, during and after exercise. Systolic and diastolic flow volume in each cardiac cycle in pump and descending thoracic aorta flow was calculated. RESULTS: (1) Average flow rates - Pulmonary artery and descending thoracic aorta flow rates increased with heart rate during exercise and there was no difference between groups. (2) Pump flow wave - Pump regurgitation increased temporally during exercise at both PFRs, but sustained incidences of regurgitation after exercise were only observed at low PFR. Systolic and diastolic pump flow volume decreased during exercise at both PFRs, but systolic volume increased and diastolic volume decreased significantly after exercise at low PFR. (3) Descending thoracic aorta flow wave - At high PFR, systolic volume of descending thoracic aorta increased but diastolic flow volume decreased during exercise. At low PFR, both systolic and diastolic volume of the descending thoracic aorta decreased during exercise, but systolic volume increased and diastolic volume decreased after exercise. Systolic volume of the descending thoracic aorta in low PFR was significantly greater and diastolic volume was less than those in high PFR during and after exercise. CONCLUSION: Exercise temporarily increases pump regurgitation with continuous flow LVAS support. Average flow rate of the descending thoracic aorta was maintained by compensation from increased heart rate, although the diastolic flow of the descending thoracic aorta decreased after exercise at the lower pump flow rate. Further study will be needed to evaluate whether or not this flow decrease causes hemodynamic and/or an oxygen delivery mismatch to peripheral tissue.

Animals↗
PubMed2003

LVAD bloodstream infections: therapeutic rationale for transplantation after LVAD infection.

INTRODUCTION: Patients who have ventricular assist devices (VADs) and experience bloodstream infection (BSI) have high mortality. We addressed 2 questions raised by the United Network for Organ Sharing (UNOS) priority policy for this problem: 1) Are organs wasted on this ultra-high-risk group? 2) Can device-related BSI be differentiated from transient BSI? METHODS: Patients with VADs who underwent heart transplantation from 1987 to 2001, who had BSI during VAD support, and who had positive cultures at VAD explant (device-related BSI, n = 10) were compared with those with negative cultures at explant (non-device-related BSI, n = 11). RESULTS: Patients with device-related BSI had an 80% (8/10) rate of persistent bacteremia; 30 days and 1 year after transplantation, mortality was 14% and 26%, respectively. Non-device-related BSI (n = 11) persisted in 18% (2/11); peri-operative and 1-year mortalities were 9% and 13%. Duration of VAD support predicted infection (132 vs 48 days, p < 0.001); hypo-albuminemia (2.9 +/- 0.5 mg/dl vs 3.3 +/- 0.8 mg/dl, p < 0.05), and a resistant organism predicted a device-related BSI. These patients had increased intubation requirements and had increased creatinine concentration during the first post-operative week, with no difference in liver function, blood loss, transfusions (packed red blood cells, fresh frozen plasma, or platelets), or hemodynamic stability vs patients with non-device BSI. Despite decreased immunosuppression, we found no difference in acute rejection events with device-related BSI. Re-infection with the pre-operative organism occurred in only 1 patient per group. CONCLUSIONS: These data suggest that urgent (Status 1A) cardiac transplantation is effective in stable patients with device-related BSI, and these data support the current UNOS policy. However, an extra-device source of BSI should be excluded by considering the isolated organism, the baseline nutritional status, and other risk factors.

Bacteremia↗
PubMed2003

Lung deposition and pharmacokinetics of cyclosporine after aerosolization in lung transplant patients.

PURPOSE: Aerosolized cyclosporine (aCsA) has proven to be an effective therapy for refractory acute and chronic rejection in lung transplant (LTx) patients. The objective of this study is to evaluate the lung deposition and systemic absorption of aCsA after aerosolized cyclosporine administration in LTx patients in the immediate postoperative period. METHOD: Cyclosporine (CsA) was administered intravenously (1.0 mg/kg) to eight LTx patients, and multiple blood samples were collected over 24 h. At least 24 h later, aCsA (300 mg in propylene glycol) was administered to the same patients using nebulization and multiple blood samples were obtained again. Five patients had an additional inhalational gamma scintigraphy study with aCsA and 99MTc-labeled albumin to measure drug deposition. RESULTS: Peak blood concentrations of CsA after aerosol administration ranged from 119-402 ng/ml, and concentrations at 24 h ranged from 9-48 ng/ml. The rate of decline in drug concentration in blood in the apparent elimination phase was notably slower after administration of aCsA than after IV infusion. Terminal disposition half life (t 1/2 lambda(z)) values ranged from 4.1-9.9 h (mean 6.5 h) following IV administration and from 23.1 to 65.2 h (mean 40.7 h) following pulmonary administration, suggesting that drug absorption occurred throughout the 24-h sampling period following pulmonary administration. Deconvolution analysis indicated biphasic absorption of CsA from the lung in all patients, characterized by rapid initial absorption (absorption half-life 0.73 +/- 0.38 h) over the first 4 to 6 h followed by slower, sustained absorption throughout the remainder of the sampling period (absorption half-life 16.2 +/- 13.2 h). The absolute bioavailability of CsA after aerosol administration ranged from 5.4-11.2% (mean 8.2%) of the dose placed in the nebulizer. The total dose delivered to the lung estimated from scintigraphy ranged from 17.8-39.3 mg, and was in approximate agreement with the amount of drug absorbed, estimated using deconvolution. Essentially all drug deposited in the lungs was systemically absorbed. CONCLUSIONS: This study documents that cyclosporine can be effectively delivered by aerosolization to the lung of transplant patients in the early postoperative period. Part of the cyclosporine deposited in the lung is absorbed rapidly into systemic circulation and a portion is absorbed slowly but completely over a prolonged period.

Administration, Inhalation↗
PubMed2003

In vivo evaluation of a MPC polymer coated continuous flow left ventricular assist system.

The aim of this study was the evaluation of the thrombogenicity and the biocompatibility of the SunMedical EVAHEART left ventricular assist system (LVAS) coated with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer compared to a diamond-like carbon (DLC) coating. Four calves were implanted with the MPC polymer-coated LVAS. Eight calves were implanted with DLC coated LVAS. The thrombogenicity and biocompatibility of the pumps were evaluated. At explant, 60.0 +/- 37.2% (5-85%) of the pump surface area was still coated with MPC polymer after the duration of 45.0 +/- 32.0 days. In 1 out of 4 MPC and 2 out of 8 DLC coated pumps, there was a very small amount of thrombus around the seal ring; otherwise the blood contacting surfaces were free of thrombus. Major organs were normal except for a few lesions in kidneys from both groups. The MPC polymer coated EVAHEART LVAS seems to have low thrombogenicity and high biocompatibility similar to the DLC coated system. The current study demonstrated that the MPC polymer coating shows great promise for being used as an antithrombogenic substrate for the LVAS due to its ease of application, significant cost benefit, and reduction in anticoagulation therapy in acute postoperative period.

Animals↗