Biomedical subjects

Richard N Pierson

Publications and source records attributed to Richard N Pierson.

At least 37 records · Page 2Linked to original sources

PubMed2005

Hyperacute lung rejection in the pig-to-human model 4: evidence for complement and antibody independent mechanisms.

BACKGROUND: We assessed whether the combination of complement regulation and depletion of xenoreactive antibodies improves the outcome of pulmonary xenografts compared with either strategy alone. METHODS: Lungs from pigs heterozygous (hDAF(+/-)) or homozygous (hDAF(+/+)) for the human decay accelerating factor transgene (hDAF) or their nontransgenic litter mates (hDAF(-/-)) were perfused with heparinized whole human blood. In additional groups, xenoreactive natural antibodies (XNA) were depleted by pig lung perfusion (hDAF(-/-)/AbAbs, hDAF(+/-)/AbAbs) before the experiment. This combined approach was augmented by adding soluble complement receptor 1 (sCR1) to the perfusate in one further group (hDAF(+/-)/AbAbs/sCR1). RESULTS: HDAF(-/-) lungs perfused with unmodified human blood were rejected after 32.5 min (interquartile range, IQR 5 to 210). HDAF(+/-) lungs survived for 90 min (IQR 10 to 161, P = 0.54). Both groups showed a rapid rise in pulmonary vascular resistance (PVR), which is a characteristic feature of hyperacute rejection (HAR). This phenomenon was blunted in the hDAF(+/+) group, although survival (48 min, IQR 14 to 111) was not further prolonged. Antibody depletion (AbAbs) led to a significant increase in survival time (hDAF(-/-)/AbAbs: 315 min, IQR 230 to 427; hDAF(+/-)/AbAbs: 375 min, IQR 154 to 575), reduced PVR and less complement production. Addition of sCR1 reduced complement elaboration but did not further improve survival (200 min, IQR 128 to 580) and surprisingly tended to increase PVR. CONCLUSIONS: Depletion of xenoreactive antibodies is more effective than membrane-bound complement regulation to blunt hyperacute rejection of pulmonary xenografts, but even the combined approach including soluble-phase complement inhibition is not sufficient to reliably prevent organ failure within hours. It therefore seems likely that other factors independent of antibody and complement contribute to HAR in this model.

Animals↗

PubMed2005

Extracellular water: greater expansion with age in African Americans.

Aging is associated with the onset of chronic diseases that lead to pathological expansion of the extracellular water (ECW) compartment. Healthy aging, in the absence of disease, is also reportedly accompanied by a relative expansion of the ECW compartment, although the studies on which this observation is based are few in number, applied different ECW measurement methods, included small ethnically homogeneous subject samples, and failed to adjust ECW for non-age-related influencing factors. The aim of the current study was to examine, in a large (n = 1,538) ethnically diverse [African American (AA), Asian, Caucasian, Hispanic] subject group the cross-sectional relationships between ECW and age after controlling first for other potential factors that may influence fluid distribution. ECW and intracellular water (ICW) were derived from measured total body water (isotope dilution) and potassium (40K whole body counting). The cross-sectional relationships between ECW, ICW, and ECW/ICW (E/I), and age were developed using multiple regression modelling methods. Body weight, weight squared, height, age, sex, race, and interactions were all significant ECW predictors. The slope of the observed race x age interaction was significantly greater in AA (beta = 0.0005, P = 0.005) than in the three other race groups. Race, sex, and age differences in fluid distribution persisted after adjusting for body composition in a subgroup (n = 994) with dual-energy X-ray absorptiometry lean soft tissue and fat measurements. A relative ECW expansion (i.e., E/I) was present with greater age in most sex-race groups, although the effect was not significantly larger in AA males (P > 0.05) compared with the other race groups, except Asians (P < 0.05). For females, a larger E/I-age effect was found in AA compared with the other race groups, but only the comparison against Hispanics was significant (P < 0.05). The ECW compartment and E/I are thus variably larger, according to race, in healthy older subjects independent of sex, lean soft tissue, and fat mass.

Black or African American↗

PubMed2005

Body mass index and outcomes after left ventricular assist device placement.

BACKGROUND: Although extremes of body mass index (BMI) are associated with decreased survival after cardiac transplantation, its association with outcomes after left ventricular assist device (LVAD) implantation is not known. This issue is especially important as LVADs are now approved as destination therapy for advanced heart failure patients who are not transplant candidates. In this study, we assess the association between BMI and outcomes after LVAD implantation. METHODS: A total of 222 patients who underwent LVAD placement (190 bridge-to-transplant [BTT] and 32 destination therapy) were divided into four groups based on BMI (kg/m2) quartiles (group 1, <22.9; group 2, 22.9 to 26.3; group 3, 26.4 to 29.4; and group 4, >29.4) and were compared for outcomes. RESULTS: Eighty-four patients died on LVAD support. Six- and 12-month survival on LVAD for the four groups was 35%, 60%, 65%, and 73%, and 26%, 34%, 50%, and 66% (both p < 0.01), respectively. Similar trends were seen for the composite endpoint of survival on LVAD and within 30 days posttransplant among BTT patients. Infectious, neurological, respiratory, or bleeding complications were not related to BMI. Patients with higher BMI tended to have a greater risk of reoperations (43%, 49%, 53%, and 61%, p = 0.06) and renal complications (16%, 33% 23%, 43%, p = 0.03). Age and history of thoracotomy were independently associated with mortality whereas higher BMI was not. Survival was worst for patients with lowest BMI. CONCLUSIONS: Higher BMI did not adversely affect survival after LVAD implantation and therefore relative obesity should not be considered a contraindication for LVAD placement. Further work is needed to understand and manage risks for low BMI patients.

Adult↗

PubMed2005

Disruption of graft endothelium correlates with early failure after off-pump coronary artery bypass surgery.

BACKGROUND: Saphenous vein graft failure after coronary artery bypass surgery may be as high as 5% to 10% in the first postoperative week. We hypothesized that identifying damage sustained by saphenous vein endothelium before grafting predicts early graft attrition after off-pump coronary artery bypass graft surgery. METHODS: Intraoperative graft flow, platelet function, and endothelial integrity were analyzed in 125 patients undergoing off-pump coronary artery bypass graft surgery. Endothelial integrity was assessed in an excess vein segment from each graft using immunohistochemistry (CD31 staining). Platelet function was monitored just before and immediately after revascularization and on postoperative days 1 and 3 using whole blood aggregometry, thrombelastography, and platelet activated clotting time. Platelet activation was monitored using flow cytometry. Intraoperative conduit blood flow, measured by transit time ultrasonography, was used to detect and rectify anastomotic problems. Early graft patency was determined on postoperative day 5 using gated multichannel computed tomography angiography. RESULTS: In 106 patients undergoing postoperative computed tomography evaluation, 10 vein grafts in 10 patients were discovered to have developed early thrombosis, representing 4% (10 of 217) of all vein grafts. Endothelial integrity was 10.75% +/- 17.56% in 10 grafts that failed early compared with 51.45% +/- 36.29% in patent grafts (p = 0.04). Perioperative platelet function and graft flow did not differ significantly between the two groups. CONCLUSIONS: Although endothelial disruption predicts early failure of bypass grafts, the importance of a hypercoaguable state and low graft flow as a cause of early graft thrombosis after off-pump coronary artery bypass graft surgery was not supported by our preliminary results. A means to assess, prevent, and treat intraoperative vein graft damage will likely improve early graft patency.

Aged↗

PubMed2005

A novel approach to tricuspid valve replacement: the upside down stentless aortic bioprosthesis.

BACKGROUND: Tricuspid valve replacement (TVR) is a rarely needed operation. Choices between mechanical and biological prosthesis still generate controversy. We present our initial clinical experience with a stentless aortic root placed inverted in the tricuspid annulus. METHODS: Between August 2000 and September 2003, TVR for severe tricuspid insufficiency was performed in 8 patients. Indications were infective endocarditis (7) and iatrogenic damage (1). Mean age was 42.2 years old (20 to 58 years old). Five patients were male and 3 patients had a concomitant procedure (mitral valvuloplasty, coronary bypass grafting, and aortic valve replacement). A stentless aortic root, size 27 mm (n = 5) or 29 mm (n = 3) was placed inverted in the tricuspid position after the valsalva sinuses were scalloped. Interrupted 4-0 polypropylene sutures were used between the tricuspid valve annulus and the sewing ring. The struts equivalent on the stentless valve were anchored to the septal, anterior and posteroinferior wall of the right ventricle using 5-0 PTFE pledgeted sutures. RESULTS: Hospital survival was 100% and mean hospital stay was 12.5 days (3 to 18 days). Intraoperative and follow-up echocardiograms revealed no stenosis or insufficiency. Mean follow-up was 17.2 months (1-38 months). There were 3 late deaths due to continued IV drug use (n = 2) and end-stage renal failure (n = 1). CONCLUSIONS: This is a novel surgical alternative for a very high risk population. Potential advantages over current options include minimization of blood contact with nonbiological surfaces, preservation of annular motion, freedom from anticoagulation, and a theoretical lower rate of calcification.

Adult↗

PubMed2005

A multi-institutional experience with the CryoMaze procedure.

BACKGROUND: The Cox Maze III operation remains the gold standard for the surgical treatment of atrial fibrillation (AF). We report our experience using a flexible argon-powered metal cryoprobe for creation of the complete Cox-Maze III lesion set in patients with AF (the CryoMaze operation). METHODS: Beginning July 2002, 38 patients underwent the CryoMaze operation. Two patients had isolated CryoMaze procedures, whereas 36 patients had the CryoMaze performed in combination with coronary, valvular, or aortic surgery. All patients had electrocardiographic follow-up. Atrial fibrillation was continuous in 79%. Mean duration of AF before operation was 48 months. RESULTS: There were no complications related to the use of cryoenergy. There was 1 hospital death (2.6%) and no late deaths. At a mean follow-up of 12 months, 35 of 37 patients (95%) were in normal sinus rhythm. One patient required pacemaker implantation 3 months after surgery, and 1 patient refused follow-up. There have been no early or late thromboembolic events. CONCLUSIONS: The CryoMaze operation reliably cures atrial fibrillation at medium term follow-up, with rates identical to those reported for the classic Cox-Maze III operation.

Adult↗

PubMed2005

Diabetes and outcomes after left ventricular assist device placement.

BACKGROUND: Patients with diabetes have poorer outcomes after surgery in general. In this study, we assess the impact of diabetes on outcomes after left ventricular assist devices (LVAD) placement. METHODS AND RESULTS: Data on 222 patients (57 diabetics) who underwent Novacor LVAD placement between 1996 and 2003 were compared for outcomes among patients who did and did not have diabetes. Significant differences between the diabetics versus nondiabetics included age (56 +/- 8 versus 49 +/- 1 years, P < .01), ischemic heart failure etiology (61% versus 44%, P = .04), history of hypertension (56% versus 30%, P < .01), thoracotomy (42% versus 30%, P = .08), stroke (14% versus 5%, P = .03), and body weight (86 +/- 16 kg versus 80 +/- 17 kg, P = .03), respectively. Eighty-four patients died on LVAD support, 28 of whom were diabetic. Thirty, 180, and 365-day survival for diabetic versus nondiabetic patients was: 76.6%, 45.6%, and 30.4% for diabetics and 86.7%, 62.4%, and 47.1% for nondiabetics (P = .02 for 180 and 365-day morality). After controlling for other variables, patients with diabetes were at a higher risk of mortality (OR 1.76, 95%CI 1.05-2.94). No significant difference in survival was noted between insulin-dependent versus non-insulin-dependent diabetics. CONCLUSION: Patients with diabetes are at a higher risk of mortality after LVAD implantation.

Adult↗

PubMed2005

Pre-transplant reversible pulmonary hypertension predicts higher risk for mortality after cardiac transplantation.

BACKGROUND: Pre-transplant fixed pulmonary hypertension is associated with higher post-transplant mortality. In this study, we assessed the significance of pre-transplant reversible pulmonary hypertension in patients undergoing cardiac transplantation. METHODS: Overall, we studied 182 patients with baseline normal pulmonary pressures or reversible pulmonary hypertension, defined as a decrease in pulmonary vascular resistance (PVR) to < or =2.5 Wood units (WU), who underwent cardiac transplantation. Multiple recipient and donor characteristics were assessed to identify independent predictors of mortality. RESULTS: The average duration of follow-up was 42 +/- 28 months. Forty patients (22%) died during the follow-up period. Baseline hemodynamics for alive vs dead patients were as follows: pulmonary artery systolic (PAS) 42 +/- 15 vs 52 +/- 15 mm Hg; PA diastolic 21 +/- 9 vs 25 +/- 9 mm Hg; PA mean 28 +/- 11 vs 35 +/- 10 mm Hg; transpulmonary gradient (TPG) 9 +/- 4 vs 11 +/- 7 mm Hg (all p < 0.05); total pulmonary resistance 7.7 +/- 4.8 vs 8.8 +/- 3.2 WU (p = 0.08); and PVR 2.3 +/- 1.5 vs 2.9 +/- 1.6 WU (p = 0.06). In an unadjusted analysis, patients with PAS >50 mm Hg had a higher risk of death (odds ratio [OR] 5.96, 95% confidence interval [CI] 1.46 to 19.84 as compared with PAS < or =30 mm Hg). There was no significant difference in survival among patients with baseline PVR <2.5, 2.5 to 4.0 or >4.0 WU, but patients with TPG > or =16 had a higher risk of mortality (OR 4.93, 95% CI 1.84 to 13.17). PAS pressure was an independent predictor of mortality (OR 1.04, 95% CI 1.02 to 1.06). Recipient body mass index, history of sternotomy; and donor ischemic time were the other independent predictors of mortality. CONCLUSION: Pre-transplant pulmonary hypertension, even when reversible to a PVR of < or =2.5 WU, is associated with a higher mortality post-transplant.

Adult↗

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

Bioelectrical impedance analysis: population reference values for phase angle by age and sex.

BACKGROUND: Phase angle is an indicator based on reactance and resistance obtained from bioelectrical impedance analysis (BIA). Although its biological meaning is still not clear, phase angle appears to have an important prognostic role. OBJECTIVE: The aim of this study was to estimate population averages and SDs of phase angle that can be used as reference values. DESIGN: BIA and other methods used to evaluate body composition, including hydrodensitometry and total body water, were completed in 1967 healthy adults aged 18-94 y. Phase angle was calculated directly from body resistance and reactance, and fat mass (FM) was estimated from the combination of weight, hydrodensitometry, and total body water by using the 3-compartment Siri equation. Phase angle values were compared across categories of sex, age, body mass index (BMI), and percentage FM. RESULTS: Phase angle was significantly (P < 0.001) smaller in women than in men and was lower with greater age (P < 0.001). Phase angle increased with an increase in BMI and was significantly inversely associated with percentage fat in men. Phase angle was significantly predicted from sex, age, BMI, and percentage FM in multiple regression models. CONCLUSIONS: Phase angle differs across categories of sex, age, BMI, and percentage fat. These reference values can serve as a basis for phase angle evaluations in the clinical setting.

Adult↗

PubMed2005

Body fat redistribution after weight gain in women with anorexia nervosa.

BACKGROUND: Body image distortions are a core feature of anorexia nervosa (AN). Increasing evidence suggests that the fat distribution immediately after weight restoration in patients with AN differs from the distribution typical of healthy adult women. OBJECTIVE: The purpose of this study was to assess body fat distribution before and shortly after normalization of weight in women with AN. DESIGN: Body composition and fat distribution were assessed by anthropometry, dual-energy X-ray absorptiometry, and whole-body magnetic resonance imaging in 29 women with AN before and after weight normalization and at a single time point in 15 female control subjects. Hormone concentrations were also evaluated in patients and control subjects. RESULTS: During approximately 10.1 +/- 2.9 wk (range: 4-17.3 wk) of treatment, patients with AN gained 12.2 +/- 3.6 kg, and refed weight (54.1 +/- 4.2 kg) did not differ significantly from that of control subjects (54.7 +/- 4.4 kg). Waist-to-hip circumference ratio (P < 0.006), total trunk fat (P < 0.003), visceral adipose tissue (P < 0.006), and intramuscular adipose tissue (P < 0.003) were significantly greater in the weight-recovered patients than in the control subjects. In contrast, after refeeding, total subcutaneous adipose tissue and skeletal muscle mass did not differ significantly between the patients and control subjects. In patients with AN, serum cortisol decreased and serum estradiol increased significantly with refeeding but not to control concentrations. CONCLUSIONS: In women with AN, normalization of weight in the short term is associated with an abnormal distribution of body fat. The implications of these findings for the long-term psychological and physical health of women with AN are unknown.

Absorptiometry, Photon↗

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

Co-stimulation blockade targeting CD154 and CD28/B7 modulates the induced antibody response after a pig-to-baboon cardiac xenograft.

BACKGROUND: The induced antibodies against Galalpha1,3Gal (Gal) and non-Gal epitopes may contribute to delayed xenograft rejection (DXR). We asked whether blockade of the CD40/CD154 and CD28/B7 co-stimulatory pathways modulates the baboon elicited antibody response to pig Gal and non-Gal antigens. METHODS: Eighteen baboons received heterotopic heart transplants from pigs transgenic for human decay-accelerating factor (n = 13) or membrane cofactor protein (n = 5). Ten reference ''conventional therapy'' animals received cyclosporin A, cyclophosphamide and mycophenolate mofetil, with (n = 4) or without (n = 6) anti-CD20. Eight ''co-stimulation blockade'' animals received anti-CD154 mAb (IDEC-131) and anti-thymocyte globulin, with (n = 4) or without (n = 4) anti-CD20; two of these animals also received CTLA4-Fc. Anti-alphaGal IgG and IgM, anti-non-Gal antibodies and graft histology were assessed serially. RESULTS: Excluding two early graft failures, median graft survival with conventional therapy was 15 days (range 6 to 36 days, n = 8). Anti-Gal IgG antibody remained low through day 6 to 10, only one graft failure was accompanied by significant rise in anti-Gal IgG, and the anti-non-Gal response was weak (n = 2) or absent (n = 7). However many recipients succumbed with infection (n = 4) or coagulopathy (n = 2); DXR and ICOS+ T cells were prevalent in long-surviving grafts. With co-stimulation blockade, excluding three early graft failures, median graft survival was 7 days (range 6 to 11 days, n = 5). This regimen was very well tolerated, but increased anti-Gal antibody titer within 14 days was associated with graft failure in four of six animals. Although an anti-non-Gal response was present in three of six animals during IDEC-131 monotherapy (one strong, two weak), it was absent in both cases with additional CTLA4-Fc treatment. CONCLUSIONS: As used here, CD154 blockade alone does not completely prevent induction of Gal and non-Gal anti-pig antibodies. Our preliminary data suggest that other co-stimulation pathways, including CD28/B7 and ICOS, are sufficient to mediate high-titer anti-non-Gal antibody to porcine antigens in baboons, and contribute significantly to the pathogenesis of DXR.

Anemia↗

PubMed2005

Humoral immunity to vimentin is associated with cardiac allograft injury in nonhuman primates.

Immunity to autologous protein has not previously been described following nonhuman primate cardiac transplant. Native hearts and cardiac allografts from cynomolgus monkeys were assessed by immunohistology for vimentin, a highly conserved intermediate filament protein. IgM and IgG to vimentin were measured in serial sera from untreated (n = 4) or cyclosporine (CsA)-treated (n = 8, 2 with ATG) cardiac allograft recipients, and in groups treated with anti-CD154 antibody with (n = 6) or without ATG (n = 28). IgM or IgG reactive with vimentin was elaborated within 30 days with unmodified acute rejection (3/4) or in CsA-treated animals (5/6). CD154 blockade did not prevent anti-vimentin IgM (14/28) but tended to delay the IgG response during therapy (anti-CD154: 8/28, p = 0.10 vs. CsA; anti-CD154+ATG: 2/6). CAV and alloantibody were seen in 25 of 26 animals with grafts surviving over 30 days, including seven animals without increasing anti-vimentin antibody. Anti-vimentin antibodies and vascular complement deposition were found in rejected hearts. Acute and chronic alloimmunity disrupt modulation of autoreactivity to vimentin through pathways, which are resistant to CsA, but may be partially regulated by CD154.

Animals↗

PubMed2005

Four commonly used dual-energy X-ray absorptiometry scanners do not identically classify subjects for osteopenia or osteoporosis by T-score in four bone regions BIz11.5.

We investigated whether four commonly used dual-energy X-ray absorptiometry (DXA) scanners (DPX, DPX-L,and Prodigy by GE Lunar, and Delphi-A by Hologic) could classify identical subjects as osteopenic or osteoporotic using the T-score for bone mineral density in four regions of interest: PA spine (L1-L4), femur (total), forearm (total),and 33% radius in 77 adults (38 females) free of treatment for bone metabolic disease (age range 20-81 yr). There were no significant differences between T-score means for posterior-anterior spine by DPX, DPX-L, and Prodigy, but they were higher than the mean T-score by Delphi-A (p < 0.05). Prodigy gave the lowest and DPX and Delphi-A gave the highest T-score for 33% radius (p < 0.05). No subject was classified as osteoporotic in the femur region by the four scanners, although other classifications varied by region and scanner. No two scanners classified subjects identically for osteopenia in any of the four regions. These results indicate that classification of bone density in individual subjects using T-scores varies by different DXA scanners, even the scanners were made by the same manufacturer.

Absorptiometry, Photon↗

PubMed2005

Beyond antibody-mediated rejection: hyperacute lung rejection as a paradigm for dysregulated inflammation.

The use of animal organs for transplantation in humans is seen as a potential solution to the short supply of human donor organs available for clinical transplantation. However, to develop this therapeutic option as clinical reality will require surmounting formidable obstacles. The primary immunologic barrier to pig-to-human xenotransplantation is hyperacute rejection (HAR), a phenomenon previously characterized as resulting from antibody binding and complement activation. This article will first review recent progress in the development of specific strategies to overcome hyperacute lung rejection (HALR), through production of genetically engineered pig organs, modification of the host innate immunity and control of antibody and complement. Additional therapeutic targets identified in HALR are reviewed, with particular emphasis on recent studies describing a critical role for the coagulation cascade in HAR.

Acute Disease↗

PubMed2004

Selection of patients for heart transplantation in the current era of heart failure therapy.

OBJECTIVES: We sought to assess the relationship between survival, peak exercise oxygen consumption (VO(2)), and heart failure survival score (HFSS) in the current era of heart failure (HF) therapy. BACKGROUND: Based on predicted survival, HF patients with peak VO(2) <14 ml/min/kg or medium- to high-risk HFSS are currently considered eligible for heart transplantation. However, these criteria were developed before the widespread use of beta-blockers, spironolactone, and defibrillators-interventions known to improve the survival of HF patients. METHODS: Peak VO(2) and HFSS were assessed in 320 patients followed from 1994 to 1997 (past era) and in 187 patients followed from 1999 to 2001 (current era). Outcomes were compared between these two groups of patients and those who underwent heart transplantation from 1993 to 2000. RESULTS: Survival in the past era was 78% at one year and 67% at two years, as compared with 88% and 79%, respectively, in the current era (both p < 0.01). One-year event-free survival (without urgent transplantation or left ventricular assist device) was improved in the current era, regardless of initial peak VO(2): 64% vs. 48% for peak VO(2) <10 ml/min/kg (p = 0.09), 81% vs. 70% for 10 to 14 ml/min/kg (p = 0.05), and 93% vs. 82% for >14 ml/min/kg (p = 0.04). Of the patients with peak VO(2) of 10 to 14 ml/min/kg, 55% had low-risk HFSS and exhibited 88% one-year event-free survival. One-year survival after transplantation was 88%, which is similar to the 85% rate reported by the United Network for Organ Sharing for 1999 to 2000. CONCLUSIONS: Survival for HF patients in the current era has improved significantly, necessitating re-evaluation of the listing criteria for heart transplantation.

Algorithms↗

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↗