Pulmonary hypertension (PH) unresponsive to pharmacological intervention is considered a contraindication for orthotopic heart transplantation (OHTX) due to risk of postoperative right-heart failure. In this prospective study, we describe our experience with a treatment strategy of improving severe PH in heart transplant candidates by means of ventricular assist device (VAD) implantation and subs equent OHTX. In 11 heart transplantation candidates with severe PH unresponsive to pharmacological intervention we implanted VAD with the aim of achieving PH to values acceptable for OHTX. In all patients we observed significant drop in pulmonary pr essures, PVR and TPG (p<0.001 for all) 3 months after VAD implantation to values sufficient to allow OHTX. Seven patients underwent transplantation (mean duration of support 216 days) while none of patients suffered right-side heart failure in postoperative period. Two patients died after transplantation and five patients are living in very good condition with a mean duration of 286 days after OHTX. In our opinion, severe PH is not a contraindication for orthotopic heart transplantation any more., J. Kettner ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Interesting and stimulating data about the effect of the perivascular adipose tissue size on atherogenesis are based mainly on CT findings. We studied this topic by directly analyzing perivascular adipose tissue in explanted hearts from patients undergoing transplantation. Ninety -six consecutive patients were included, including 58 with atherosclerotic coronary heart disease (CHD) and 38 with dilation cardiomyo pathy (DCMP). The area of perivascular fat, area of the coronary artery wall, and ratio of CD68 -positive macrophages within the perivascular fat and within the vascular wall were quantified by immunohistochemistry. There was no significant difference in th e perivascular adipose tissue size between the two groups. Nevertheless, there was a significantly higher number of macrophages in the coronary arterial wall of CHD patients. In addition, we found a close relationship between the ratio of macrophages in th e arterial wall and adjacent perivascular adipose tissue in the CHD group, but not in the DCMP group . According to our data interaction between macrophages in the arterial wall and macrophages in surrounding adipose tissue could be more important mechanism of atherogenesis than the size of this tissue itself., I. Kralova Lesna, Z. Tonar, I. Malek, J. Maluskova, L. Nedorost, J. Pirk, J. Pitha, V. Lanska, R. Poledne., and Obsahuje bibliografii
Despite the widespread use of potent immunosuppressive drugs, such as cyclosporin A and mycophenolate mofetil, ongoing and recurrent cellular rejection remain a common problem after heart transplantation. We aimed to describe the long-term effects of conversion from cyclosporine A to tacrolimus in patients with ongoing and recurrent cellular rejection. This was a single-centre retrospective analysis of 17 heart transplant recipients who were switched from cyclosporine A to tacrolimus due to ongoing (5 patients) or recurrent cellular rejection (12 patients). We studied long-term efficacy and safety of this approach. 167 endomyocardial biopsies were performed during a mean followup of 69.1±12.7 months. Thirteen biopsies (7.8 %) in eight patients (47 %) revealed higher grades of acute cellular rejection (Banff 2). However, they were not hemodynamically significant and did not require intravenous antirejection therapy. The mean rejection score was reduced significantly. Conversion to tacrolimus was tolerated in 82 % pts without any significant side effects during a long-term follow-up. In conclusion, the conversion to tacrolimus in heart transplant recipients with ongoing or recurrent acute cellular rejection was safe and effective also during a long-term follow-up., B. Skalická ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Solid organ transplantation is an established treatment modality in patients with end-stage organ damage in cases where other therapeutic options fail. The long-term outcomes of solid organ transplant recipients have improved considerably since the introduction of the first calcineurin inhibitor (CNI) - cyclosporine. In 1984, the potent immunosuppressive properties of another CNI, tacrolimus, were discovered. The immunosuppressive effects of CNIs result from the inhibition of interleukin-2 synthesis and reduced proliferation of T cells due to calcineurin blockade. The considerable side effects that are associated with CNIs therapy include arterial hypertension and nephrotoxicity. The focus of this article was to review the available literature on the pathophysiological mechanisms of CNIs that induce chronic nephrotoxicity and arterial hypertension. CNIs lead to activation of the major vasoconstriction systems, such as the reninangiotensin and endothelin systems, and increase sympathetic nerve activity. On the other hand, CNIs are known to inhibit NO synthesis and NO-mediated vasodilation and to increase free radical formation. Altogether, these processes cause endothelial dysfunction and contribute to the impairment of organ function. A better insight into the mechanisms underlying CNI nephrotoxicity could assist in developing more targeted therapies of arterial hypertension or preventing CNI nephrotoxicity in organ transplant recipients, including heart transplantation., L. Hošková, I. Málek, L. Kopkan, J. Kautzner., and Obsahuje bibliografii
In some patients, heart failure (HF) is associated with increased pulmonary vascular resistance (PVR). The magnitude and the reversibility of PVR elevation affect the HF management. Sildenafil has been recently recognized as potent PVR-lowering drug in HF. The aim of the study was to compare hemodynamic effects and pulmonary selectivity of sildenafil to prostaglandin E1(PGE1). Right-heart catheterization was performed in 13 euvolemic advanced HF patien ts with elevated PVR (6.3±2 Wood's units). Hemodynamic parameters were measured at the baseline, during i.v. infusion of PGE1 (alprostadil 200 ng·kg-1·min-1 ) and after 40 mg oral do se of sildenafil. Both drugs similarly reduced systemic vascular resistance (SVR), but sildenafil had higher effect on PVR (-28 % vs. -49 %, p=0.05) and transpulmonary pressu re gradient than PGE1. The PVR/SVR ratio - an index of pulmonary se lectivity, did not change after PGE1(p=0.7) but it decreased by -32 % (p=0.004) after sildenafil. Both drugs similarly reduced pulmonary artery mean and wedge pressures and increa sed cardiac index (+27 % and +28 %). Sildenafil led more often to transplant-acceptable PVR while causing smaller drop of mean systemic pressure than PGE1. In conclusion, vasodilatatory effects of sildenafil in patients with heart failure are more pronounced in pulmonary than in systemic circulation., H. Al-Hiti ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy