Stable Heart Transplant Recipients Research Articles

Relationship between cerebral blood flow and blood pressure in long-term heart transplant recipients.

Heart transplant recipients are at an increased risk for cerebral hemorrhage and ischemic stroke; yet, the exact mechanism for this derangement remains unclear. We hypothesized that alterations in cerebrovascular regulation is principally involved. To test this hypothesis, we studied cerebral pressure-flow dynamics in 8 clinically stable male heart transplant recipients (62±8 years of age and 9±7 years post transplant, mean±SD), 9 male age-matched controls (63±8 years), and 10 male donor controls (27±5 years). To increase blood pressure variability and improve assessment of the pressure-flow dynamics, subjects performed squat-stand maneuvers at 0.05 and 0.10 Hz. Beat-to-beat blood pressure, middle cerebral artery velocity, and end-tidal carbon dioxide were continuously measured during 5 minutes of seated rest and throughout the squat-stand maneuvers. Cardiac baroreceptor sensitivity gain and cerebral pressure-flow responses were assessed with linear transfer function analysis. Heart transplant recipients had reductions in R-R interval power and baroreceptor sensitivity low frequency gain (P<0.01) compared with both control groups; however, these changes were unrelated to transfer function metrics. Thus, in contrast to our hypothesis, the increased risk of cerebrovascular complication after heart transplantation does not seem to be related to alterations in cerebral pressure-flow dynamics. Future research is, therefore, warranted.

Growth Differentiation Factor 15 Is Related to Anemia and Iron Metabolism in Heart Allograft Recipients and Patients With Chronic Heart Failure

BackgroundGrowth differentiation factor (GDF) 15 was recently identified as a hepcidin-suppression factor that is expressed at high levels in patients with ineffective erythropoiesis. Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. The aim of this study was to assess GDF15 levels and its correlation with iron parameters in 134 stable heart transplant recipients compared with 157 patients with chronic heart failure (CHF). MethodsComplete blood count, urea, creatinine, lipids, fasting glucose, and iron status were studied with the use of standard laboratory methods. We assessed GDF15, hepcidin, and soluble transferrin receptor (sTfR) with commercially available assays. ResultsMean levels of GDF15 and hepcidin were significantly higher in heart allograft recipients compared with patients with chronic heart failure (P < .001). GDF15 was significantly higher in patients with anemia compared with nonanemic counterparts in both groups. In univariate analysis in heart transplant recipients, GDF15 was related to kidney function, age, time after transplantation, hepcidin, sTfR, hemoglobin, transferrin saturation, ejection fraction (EF), and New York Heart Association functional class. GDF15 was not related to serum iron or ferritin in both groups. In multivariate analysis, sTfR, creatinine, and age were found to be predictors of GDF15. In univariate analysis in CHF patients, GDF15 was related to creatinine, erythrocyte count, hemoglobin, hepcidin, and total iron binding capacity and tended to correlate with EF. In multivariate analysis, hepcidin, creatinine, and EF were found to be predictors of GDF15 in CHF. ConclusionsGDF15, by affecting iron status, might be involved in the pathogenesis of anemia in patients with cardiovascular pathology.

Fibroblast Growth Factor 23 and Klotho as Cardiovascular Risk Factors in Heart Transplant Recipients

BackgroundFibroblast growth factor (FGF) 23 is one of the most recently discovered FGFs. This phosphaturic hormone produced in bones is a risk factor for cardiovascular diseases and thus mortality. Klotho is an essential coreceptor for FGF23 and at the same time it is known as a “longevity” hormone. There are no data considering FGF23 and Klotho roles in heart transplant (HT) recipients. The aim of this study was to assess Klotho and FGF23 serum concentration in heart transplant recipients depending on immunosuppressive therapy regimen and comorbidities. MethodsEighty-four stable heart transplant recipients were enrolled in the study; 22 healthy volunteers served as control subjects. FGF23 and Klotho protein concentration, markers of renal function, such as cystatin C and neutrophil gelatinase–associated lipocalin (NGAL), and heart failure markers, such as copeptine and N-termiinal pro–B-type natriuretic peptide (NT-proBNP), were evaluated. ResultsFGF23 concentration was significantly higher in the HT group whereas Klotho protein was significantly lower. FGF23 correlated with creatinine level (r = 0.72; P < .001), estimated glomerular filtration rate (eGFR; r = −0.32; P < .01), cystatin C (r = 0.36; P < .01), NGAL (r = 0.51; P < .001), hemoglobin (r = −0.39; P < .001), NT-proBNP (r = 0.51; P < .001), high-density lipoprotein (HDL; r = 0.27; P < .05), intraventricular septum thickness (r = 0.42; P < .01) and right ventricular systolic pressure (r = 0.34; P < .05). Klotho protein correlated only with age (r = −0.21; P < .05), creatinine (r = −0.21; P < .05), and eGFR (r = −0.31; P < .01). FGF23 concentration was significantly higher in patients with eGFR <60 mL/min whereas Klotho protein was significantly lower. FGF23 predictors were renal function (creatinine concentration; β = 0.45; P = .0001), HDL (β = 0.33; P = .003), intraventricular septum thickness (β = 0.38; P = .0003), and right ventricular systolic pressure (β = 0.34; P = .003), explaining 70% of FGF23 variability. ConclusionsFGF23/Klotho system disorders in HT recipients are related to cardiovascular system function and kidney failure and could cause increased risk of cardiovascular disease.

Zonulin and Iron Metabolism in Heart Transplant Recipients

BackgroundIn patients after heart transplantation, anemia is relatively common and is associated with impaired kidney function, subclinical inflammatory state, and immunosuppressive treatment. Zonulin-prehaptoglibin-2 is newly discovered protein with poorly defined function. Hemoglobin binds haptoglobin, and this stable complex prevents oxidative stress caused by hemoglobin. Zonulin is necessary for integrity of intracellular tight junction in the gut. Taking into consideration iron metabolism, including its absorption in the gut, the aim of this study was to assess zonulin levels in heart transplant recipients and their possible correlations with iron status, immunosuppressive therapy, and kidney function. MethodsThe study was performed with 80 stable heart transplant recipients and 22 healthy volunteers. Zonulin, iron status, and inflammatory markers were assessed with the use of commercially available kits. ResultsZonulin correlated with intraventricular diameter (r = 0.30; P < .05), right ventricle systemic pressure (r = 0.27; P < .05), and hemoglobin (r = 0.21; P < .05). There were no correlations between zonulin and iron status. Zonulin was significantly lower in heart transplant recipients than in healthy volunteers (P < .001). Kidney function, immunosuppressive regimen, New York Heart Association functional class, sex, and presence of anemia did not affect zonulin level. ConclusionsZonulin, despite its effect on the absorption of different nutrients and other substances and hypothethic role in oxidative stress, seems not to play a role in the pathogenesis of anemia in heart transplant recipients. Its physiologic role remains obscure.

(16) - A Randomized Trial of Everolimus Initiation and Calcineurin Inhibitor (CNI) Elimination in Stable Heart Transplant Recipients With Impaired Renal Function

s S15 Conclusion: This was the first study to demonstrate a lower rate of CMV infection in patients treated with Tac vs. those treated with CsA after HTx.

(15) - Increased Plasma Levels of Graft-Derived Cell-Free DNA Correlate with Rejection in Heart Transplant Recipients

Purpose: Circulating graft-derived cell-free DNA (cfDNA) isolated from plasma is a potential biomarker of acute cellular rejection in organ transplant recipients. We sought to investigate if plasma levels of either total or graft derived cfDNA correlate with clinically proven rejection in heart transplant patients. Methods: 118 samples from 76 subjects from the CARGO and CARGO II studies were selected for this cohort study. Levels of total cfDNA were determined by quantitative real-time PCR (qRT-PCR) using assays for HBA, HBB, 18S and PDCD1 genes. Initial investigation of the value of graft-derived cfDNA took advantage of the gender difference in female recipients with a heart from a male donor. Proportions of graft-derived cfDNA relative to total cfDNA were determined in these subjects by qRT-PCR using an assay for the male-specific TSPY-1 gene. Results: Levels of total cfDNA are not different between stable heart transplant recipients and subjects with biopsy-confirmed rejection. Interestingly, heart transplant recipients have higher levels of total cfDNA compared to non-transplant controls. Graft-derived cfDNA proportion is significantly increased in subjects with biopsy-confirmed rejection compared to stable subjects (median difference 10-fold in CARGO and 5-fold in CARGO II subjects older than 15 years and at least 55 days post transplant). Conclusion: Graft-derived cfDNA is a useful biomarker of heart transplant rejection. This non-invasive test may aid in the identification of patients with acute cellular rejection and may be applicable to monitoring other organ transplants, such as lung or kidney. This study was funded by XDx.

Interval training does not modulate diastolic function in heart transplant recipients

Objectives. This study investigates the effect of aerobic interval training on diastolic function at rest and during exercise in stable heart transplant (HTx) recipients. Design. Twenty-three stable HTx recipients (74% males, mean age 50 ± 14.9 years) were recruited to a training programme. Intervention was 8 weeks intensive training or control in a randomized controlled design. Results. At baseline, participants had normal or mild diastolic dysfunction at rest. During exercise, mean E/e′ increased from 9.0 (± 2.8) to 12.8 (± 7.7) (p = 0.09), E/A increased from 2.1 (± 0.6) to 2.6 (± 0.7) (p = 0.02), and deceleration time decreased by over 50 ms, all markers of increased filling pressure. There were no correlations between diastolic function and VO2peak at baseline. After intervention VO2peak increased from 23.9 (± 4.5) to 28.3(± 6) ml/kg/min in the training group (difference between groups p = 0.0018). No consistent pattern of improvement in diastolic function at rest or during exercise was seen. Conclusion. The study does not support a role of diastolic dysfunction in the limited exercise capacity of HTx recipients and suggests that in these patients peripheral factors are of greater importance.

One year of high-intensity interval training improves exercise capacity, but not systemic arterial function in stable heart transplant recipients

One year of high-intensity interval training improves exercise capacity, but not systemic arterial function in stable heart transplant recipients

Sildenafil Improves Small Artery Elasticity in Heart Transplant Recipients

Purpose Small artery elasticity (SAE) derived from radial artery pulse wave contour analysis is a measurement of endothelial function and a predictor of cardiovascular events in the general population. We have previously shown that SAE is reduced in heart transplant recipients (HTR) and is associated with cardiac allograft vasculopathy. In this study, we evaluated the effect of sildenafil on SAE in HTR. Methods and Materials We enrolled 11 stable HTR without recent history of rejection, infection, renal disease or CAV. SAE was measured prior to and one hour after administration of 50mg of oral sildenafil. Paired sample t-test was performed to compare SAE pre- and post-sildenafil. Results Median age was 62 yrs (range 44-72), 88% were male, median duration of transplant was 1 yr (range 1-3), and mean BMI was 26.5 ±3.72 kg/m2. 66% had prior ischemic cardiomyopathy. Mean baseline SAE was 3.7±1.1 ml/mmHgX10. One hour following administration of sildenafil, SAE increased significantly by 38% on average. The mean SAE after sildenafil was 5.2±2.3 ml/mmHgX10 (p= 0.032). [ figure 1 ] Conclusions Acute sildenafil treatment improves small artery elasticity in heart transplant recipients. Further studies are warranted to determine whether modification of endothelial function has clinical implications in heart transplant recipients.

One year of high-intensity interval training improves exercise capacity, but not left ventricular function in stable heart transplant recipients: A randomised controlled trial

Heart transplant recipients have lower exercise capacity and impaired cardiac function compared with the normal population. High-intensity interval training (HIIT) improves exercise capacity and cardiac function in patients with heart failure and hypertension, but the effect on cardiac function in stable heart transplant recipients is not known. Thus, we investigated whether HIIT improved cardiac function and exercise capacity in stable heart transplant recipients by use of comprehensive rest- and exercise-echocardiography and cardiopulmonary exercise testing. Fifty-two clinically stable heart transplant recipients were randomised either to HIIT (4 × 4 minutes at 85-95% of peak heart rate three times per week for eight weeks) or to control. Three such eight-week periods were distributed throughout one year. Echocardiography (rest and submaximal exercise) and cardiopulmonary exercise testing were performed at baseline and follow-up. One year of HIIT increased VO 2peak from 27.7 ± 5.5 at baseline to 30.9 ± 5.0 ml/kg/min at follow-up, while the control group remained unchanged (28.5 ± 7.0 vs. 28.0 ± 6.7 ml/kg per min, p < 0.001 for difference between the groups). Systolic and diastolic left ventricular functions at rest and during exercise were generally unchanged by HIIT. Whereas HIIT is feasible in heart transplant recipients and effectively improves exercise capacity, it does not alter cardiac systolic and diastolic function significantly. Thus, the observed augmentation in exercise capacity is best explained by extra-cardiac adaptive mechanisms.

Generic Cyclosporine A in Stable Heart Transplant Recipients

Generic Cyclosporine A in Stable Heart Transplant Recipients

Left ventricular twist in clinically stable heart transplantation recipients: A speckle tracking echocardiography study

Background and aimCavity twist is an integral part of LV function and its pattern in transplanted hearts is not well known. This study aimed at exploring LV twist in clinically stable heart transplant (HT) recipients with no evidence for rejection. MethodsWe studied 32 HT patients (54±24months after HT), 34 other cardiac surgery (CS) patients and compared them with 35 health controls using speckle tracking echocardiography, measuring peak twist angle, time-to-peak twist, and untwist rate. ResultsLV twist angle was smaller in the HT group (6.2±3.3°) in comparison with the CS group and controls (13.2±3.5° and 13.1±4.5°, respectively; p<0.0001 for all) and untwist rate was reduced (HT group: −74±30°/s; CS group: −118±43°/s; controls: −116±39°/s; p<0.0001 for all). Time-to-peak twist was not different between groups. Time after HT was the main independent predictor of both LV twist angle and untwist rate (β=0.8, p<0.0001). ConclusionThough clinically stable, LV twist dynamics are significantly impaired in HT recipients, even in comparison with patients who underwent other cardiac surgery.

Cardiac allograft hypertrophy is associated with impaired exercise tolerance after heart transplantation

Exercise performance, an important aspect of quality of life, remains limited after heart transplantation (HTx). This study examines the effect of cardiac allograft remodeling on functional capacity after HTx. The total cohort of 117 HTx recipients, based on echocardiographic determination of left ventricle mass and relative wall thickness at 1 year after HTx, was divided into 3 groups: (1) NG, normal geometry; (2) CR, concentric remodeling; and (3) CH, concentric hypertrophy. Cardiopulmonary exercise testing was performed 5.03 ± 3.08 years after HTx in all patients. Patients with acute rejection or significant graft vasculopathy were excluded. At 1 year post-HTx, 30% of patients had CH, 55% had CR and 15% had NG. Exercise tolerance, measured by maximum achieved metabolic equivalents (4.62 ± 1.44 vs 5.52 ± 0.96 kcal/kg/h), normalized peak Vo(2) (52 ± 14% vs 63 ± 12%) and Ve/Vco(2) (41 ± 17 vs 34 ± 6), was impaired in the CH group compared with the NG group. A peak Vo(2) ≤14 ml/kg/min was found in 6%, 22% and 48% of patients in the NG, CR and CH groups, respectively (p = 0.01). The CH pattern was associated with a 7.4-fold increase in relative risk for a peak Vo(2) ≤14 ml/kg/min compared with NG patients (95% confidence interval 1.1 to 51.9, p = 0.001). After multivariate analysis, a 1-year CH pattern was independently associated with a reduced normalized peak Vo(2) (p = 0.018) and an elevated Ve/Vco(2) (p = 0.035). The presence of CH at 1 year after HTx is independently associated with decreased normalized peak Vo(2) and increased ventilatory response in stable heart transplant recipients. The identification of CH, a potentially reversible mechanism of impairment in exercise capacity after HTx, may have major clinical implications.

Pharmacokinetics in stable heart transplant recipients after conversion from twice-daily to once-daily tacrolimus formulations

A prolonged-release formulation of tacrolimus for once-daily administration (tacrolimus QD) has been developed. This phase II, open-label, multicenter, prospective single-arm study compared the pharmacokinetics (PK) of tacrolimus in stable heart transplant patients before and after conversion from twice-daily tacrolimus (tacrolimus BID) to tacrolimus QD. Heart transplant recipients (≥6 months after transplant), previously maintained on tacrolimus BID-based therapy, received tacrolimus BID from Days 1 to 7 and were converted on a 1:1 (mg/mg) basis to tacrolimus QD. Five 24-hour PK profiles were collected (Days 1, 7, 8, 14, 21). Safety parameters were also evaluated. Of 85 patients, 45 (50.6%) completed all 5 evaluable PK profiles. Steady-state tacrolimus area under the curve, 0 to 24 hours (AUC(0-24)) and minimum concentration (C(min)) were comparable for both formulations, with treatment ratio means of 90.5% (90% confidence intervals [CI], 86.4%-94.6%) and 87.4% (95% CI, 82.9%-92.0%), respectively (acceptance interval, 80%-125%). There was good correlation between AUC(0-24) and C(min) for tacrolimus QD (r = 0.94) and BID (r = 0.91). The relationship between these 2 parameters was also similar. This study provides evidence for successful conversion from tacrolimus BID to QD on a 1:1 (mg/mg) total daily dose basis. Approximately one-third of patients may require dose adjustments. Both formulations were well tolerated, with stable renal function during the study. Adverse events were reported by approximately one-tenth of patients receiving tacrolimus BID and a quarter of those who received QD.

Outcome of Treatment With Pegylated Interferon and Ribavirin in Heart Transplant Recipients With Chronic Hepatitis C

Background/aim The combination of pegylated interferon (PEG-IFN) and ribavirin (RBV) is the current treatment for chronic hepatitis C (CHC). The treatment is thought to suppress viral replication and induce viral clearance via immunomodulatory effects. For this reason, concern exists for the use of this treatment in recipients of a solid organ transplantation. We sought to evaluate the safety and efficacy of PEG-IFN/RBV in heart transplant recipients with CHC. Methods From June 2005 to September 2009, we treated three CHC patients with heart transplantation. PEG-IFN alpha2b and RBV doses and treatment duration were set according to the hepatitis C virus (HCV) genotype and body weight as per current recommendations. Dose reductions were dictated by individual patient tolerability. Cardiac safety was monitored by clinical examinations, echocardiography, and measurement of troponin I and B-type natriuretic peptide, as well as endomyocardial biopsies. Results All three patients, displayed HCV genotype 1b infection, viral loads of >5 logs, and a Scheuer fibrosis score ≥ 2. Two of them completed the prescribed treatment course becoming sustained virological responders. The other patient had an initial complete virological response, but subsequently experienced a viral breakthrough after reduction of PEG-IFN and withdrawal of RBV due to severe anemia. We observed no cardiovascular adverse events nor rejection episodes. Posttreatment clinical history and examination, electrocardiography, and echocardiography did not show any sign of graft dysfunction. Conclusions Treatment with PEG-IFN/RBV may be safely offered to stable heart transplant recipients with CHC and signs of liver disease progression. Close monitoring of treatment safety is mandatory.

Reduced levels of both circulating CD4+CD25+CD127low/neg and CD4+CD8neg invariant natural killer regulatory T cells in stable heart transplant recipients

A cross-regulation between two regulatory T cell (T(reg) ) subsets [CD4(+) CD25(+) and invariant natural killer (NK) T - iNK T] has been described to be important for allograft tolerance induction. However, few studies have evaluated these cellular subsets in stable recipients as correlates of favourable clinical outcome after heart transplantation. T(reg) and iNK T cell levels were assayed by flow cytometry in peripheral blood samples from 44 heart transplant recipients at a 2-year interval in 38 patients, and related to clinical outcome. Multi-parameter flow cytometry used CD4/CD25/CD127 labelling to best identify T(reg) , and a standard CD3/CD4/CD8/Vα24/Vβ11 labelling strategy to appreciate the proportions of iNK T cells. Both subtypes of potentially tolerogenic cells were found to be decreased in stable heart transplant recipients, with similar or further decreased levels after 2 years. Interestingly, the patient who presented with several rejection-suggesting incidents over this period displayed a greater than twofold increase of both cell subsets. These results suggest that CD4(+) CD25(+) CD127(low/neg) T(reg) and iNK T cells could be involved in the local control of organ rejection, by modulating immune responses in situ, in clinically stable patients. The measurement of these cell subsets in peripheral blood could be useful for non-invasive monitoring of heart transplant recipients, especially in the growing context of tolerance-induction trials.

What they say versus what we see: “Hidden” distress and impaired quality of life in heart transplant recipients

Quality of life (QoL) studies in heart transplant recipients generally rely on quantifiable self-report questionnaires and have shown that approximately 20% of patients undergo distress and poor QoL not clearly related to medical variables. Building on existing qualitative research, we used a phenomenologically informed audiovisual method to explore the nature of "distress" in heart transplant recipients. Focused open-ended interviews were conducted in non-clinical settings with 27 medically stable heart transplant recipients (70% male, mean age 53 ± 13 years, range 18 to 72 years; mean time since transplant 4.1 ± 2.4 years). Interviews were audio/videotaped and transcribed verbatim. A qualitative software program (NVIVO8) was used to code interview transcripts and videotaped bodily gestures and "expressive artifacts" as well as vocal tone and volume. Distress was displayed by 88% of patients during the interview, and 52% displayed a profound disjunct between the words they used to describe their quality of life (e.g., "wonderful") and their embodied expressions of the same (e.g., protective body posturing, distressed facial expression). Most also expressed significant distress when discussing issues such as the donor and their "gift of life," as well as a disrupted sense of bodily integrity and identity that they felt could only be appreciated by fellow heart recipients. Increased awareness of this distress and disruption related to bodily integrity and identity after heart transplant may allow transplant professionals and researchers to see beyond "words" to more effectively reduce distress and improve quality of life.

493: Reduced Dose-Adapted MMF Exposure under Proton Pump Inhibitor Co-Medication in Stable Heart Transplant Recipients

493: Reduced Dose-Adapted MMF Exposure under Proton Pump Inhibitor Co-Medication in Stable Heart Transplant Recipients

Exercise Training Improves Aerobic Capacity and Skeletal Muscle Function in Heart Transplant Recipients

The aim of this study was to examine the effects of 12 weeks of supervised aerobic and strength training (SET) versus no-training (NT) on peak aerobic power (VO2peak), submaximal exercise left ventricular (LV) systolic function, peripheral vascular function, lean tissue mass and maximal strength in clinically stable heart transplant recipients (HTR). Forty-three HTR were randomly assigned to 12 weeks of SET (n = 22; age: 57 +/- 10 years; time posttransplant: 5.4 +/- 4.9 years) or NT (n = 21; age: 59 +/- 11 years; time posttransplant: 4.4 +/- 3.3 years). The change in VO2peak (3.11 mL/kg/min, 95% CI: 1.2-5.0 mL/kg/min), leg and total lean tissue mass (0.78 kg, 95% CI: 0.31-1.3 kg and 1.34 kg, 95% CI: 0.34-2.3 kg, respectively), chest-press (10.4 kg, 95% CI: 5.2-15.5 kg) and leg-press strength (34.7 kg, 95% CI: 3.7-65.6 kg) were significantly higher after SET versus NT. No significant change was found for submaximal exercise LV systolic function or brachial artery endothelial-dependent or -independent vasodilation. Supervised exercise training is an effective intervention to improve VO2peak, lean tissue mass and muscle strength in HTR. This training regimen did not improve exercise LV systolic function or brachial artery endothelial function.

Pharmacokinetics of Mycophenolic Acid and its Phenolic-Glucuronide and Acyl Glucuronide Metabolites in Stable Thoracic Transplant Recipients

Mycophenolate mofetil is an immunosuppressant commonly used in solid organ transplantation. Its active metabolite, mycophenolic acid (MPA), is metabolized to the inactive 7-O-mycophenolic acid glucuronide (MPAG) and the active acyl glucuronide (AcMPAG). Most pharmacokinetic (PK) studies have been focused on MPA, but not its metabolites, in kidney transplant recipients. Pharmacokinetic studies of MPA and its metabolites in thoracic transplant recipients are scarce. Because neither the heart nor lung is involved in MPA metabolism or excretion, the thoracic transplant population may exhibit unique PKs. This open-label study aimed to characterize and compare PKs of MPA and its metabolites in stable lung or heart transplant recipients. Fifty thoracic (27 lung, 23 heart) transplant recipients were recruited. Subjects were also taking cyclosporine (11 lung, 14 heart) or tacrolimus (16 lung, nine heart), and prednisone (27 lung, one heart). Blood samples were obtained at 0, 20, 40, 60, and 90 minutes and 2, 4, 6, 8, 10, and 12 hours postdose. Plasma was used for drug level analysis (MPA, MPAG, and AcMPAG) by a high-performance liquid chromatography-ultraviolet detection method; in a subset of subjects, free MPA concentrations were also determined. Conventional PK parameters (dose-normalized) were determined by noncompartmental methods. There was wide interpatient variability of MPA, MPAG, and AcMPAG PKs with coefficients of variation exceeding 70% for most PK parameters measured. Other findings (P < 0.05) included: lower MPA area under the curve, maximum concentration, and minimum concentration; higher apparent clearance and MPAG/MPA metabolic ratio in the lung versus heart transplant group; lower MPA area under the curve and minimum concentration, and higher apparent clearance and MPAG/MPA metabolic ratio in lung transplant recipients concurrently taking cyclosporine versus tacrolimus; and lower minimum concentration in heart transplant recipients taking cyclosporine versus tacrolimus. Despite large interpatient variability in the PKs of MPA, MPAG, and AcMPAG among thoracic transplant recipients, there appear to be significant differences between lung and heart patients, which warrant further study.