Cyclosporine-related posterior reversible encephalopathy syndrome after heart transplantation: should we withdraw or reduce cyclosporine?: case reports.

Cyclosporine (CsA) related encephalopathy has not been well documented after heart transplantation. We report 2 cases of posterior reversible encephalopathy syndrome (PRES). The first case was a 68-year-old woman who underwent heart transplantation and received immunosuppression with mycophenolate mofetil, prednisone, and CsA. On day 14, she developed arterial hypertension, headache, visual disturbances, and generalized seizures. Fluid-attenuated inversion recovery magnetic resonance imaging (MRI) of the brain showed diffuse and bilateral high signals in the frontal posterior and the occipital areas. The second case was a 19-year-old man with a heart transplant receiving immunosuppression with prednisone and CsA. On day 44, he developed acute headache and generalized seizures. T2-weighted MRI of the brain showed diffuse high signals in the cerebellum, right lenticular and occipital areas. In both cases blood CsA concentration was therapeutic. Both cases recovered but in the first case neurologic findings were reversed only after CsA withdrawal.

Identification and characterization of two genes (MIP-1beta, VE-CADHERIN) implicated in acute rejection in human heart transplantation: use of murine models in tandem with cDNA arrays.

BACKGROUND: Genes and mechanisms of action involved in human acute rejection after allogeneic heart transplantation remain to be elucidated. The use of a murine allograft model in tandem with cDNA arrays and quantitative real-time polymerase chain reaction (Q-PCR) can greatly help in identifying key genes implicated in human heart acute rejection. METHODS AND RESULTS: Hearts from Balb/c mice were either not transplanted or transplanted heterotopically in the abdomen of Balb/c (isografts) and C57BL/6 (allografts) mice. Histological analysis showed acute rejection only in allografts. Total RNA was extracted from isografts (n=3), allografts (n=4), and not transplanted hearts (n=4); reverse transcribed; and labeled with P32. Each probe was hybridized to cDNA macroarrays. Eight genes were overexpressed and 7 genes were underexpressed in allografts compared with isografts. Macrophage inflammatory protein-1beta (MIP-1beta), an overexpressed gene, and VE-cadherin, an underexpressed gene, were validated by immunohistochemistry and Q-PCR in the murine models. Genes of interest, validated in the 3 murine groups, were then investigated in human heart tissues. Immunohistochemistry and Q-PCR performed on endomyocardial biopsies after heart transplantation showing no rejection (n=10) or grade IB (n=10) or IIIA (n=10) rejection, according to International Society of Heart and Lung Transplantation criteria, confirmed the results obtained from the murine model. CONCLUSIONS: We have demonstrated that the upregulation of MIP-1beta and downregulation of VE-cadherin may strongly participate in human acute heart rejection.

Alteration of the left ventricular contractile reserve in heart transplant patients: a dobutamine stress strain rate imaging study.

BACKGROUND: Strain rate imaging (SRI), a recently developed Doppler-derived process, allows quantification of myocardial systolic function. We investigate whether SRI quantifies the contractile reserve during dobutamine stress tests in heart transplant patients (HT), when compared with normal individuals. METHODS: An incremental dobutamine test (5 to 40 microg/kg per minute) was performed in 10 HT and 15 control subjects, all of whom displayed normal coronary angiography. Gray-scale and color myocardial Doppler data were acquired in standard B-mode views at baseline, low-dose, peak, and recovery. Longitudinal SR was processed from the myocardial velocities for each segment. The changes in maximal systolic SR were used to quantify myocardial contractile reserve. RESULTS: Dobutamine infusion failed to induce clinical symptoms or electrocardiographic (ECG) changes in either group. Visually determined wall motion score was considered normal in all segments for each stage of the dobutamine stress. Heart rate was augmented similarly in both groups during dobutamine infusion. In controls, systolic SR increased gradually with incremental dobutamine dose and returned to baseline values upon recovery. Conversely, in HT patients, the increase in systolic SR was blunted at peak dobutamine, at which point it was significantly different vs controls. CONCLUSIONS: Quantitative assessment of myocardial function using SRI during dobutamine stress revealed an impaired contractile reserve in HT patients with normal coronary angiography. These subtle changes in regional myocardial function could not be identified using visual wall motion scoring. Additional studies are necessary to evaluate whether SR imaging detection of contractile reserve impairment will improve clinical efficiency or event prediction in this population.