Coenzyme Q10 depletion and mitochondrial energy disturbances in rejection development in patients after heart transplantation.

UNLABELLED: Sixty endomyocardial biopsies (EMB) and whole blood or plasma samples from 34 patients after heart transplantation (HTx-pts) were studied. Acute rejection of the transplanted heart was histologically graded as: 0 (without), 0-1 (incipient), 1 (mild), 2 (moderate). The level of coenzyme Q10 (CoQ10) in 28 EMB was estimated by HPLC. Mitochondrial respiratory chain function and energy production were measured in 60 EMB. This study is the first report showing a correlation between: (a) histological signs of rejection in the human transplanted heart and (b) CoQ10 level of EMB, CoQ10 blood level, and mitochondrial bioenergetic processes: inhibition in FAD-part, but not in NAD-part of respiratory chain. In all patients after heart transplantation (HTx-pts) the dynamic balance between total antioxidant status and degree of oxidative stress was disturbed. CONCLUSIONS: CoQ10 level and mitochondrial bioenergetic functions of EMB contribute to the explanation of pathobiochemical mechanisms of origin and development rejection of human transplanted heart. We suppose that estimation of EMB CoQ10 level could be used as a bioenergetic marker of rejection development in human transplanted heart. CoQ10 therapy could contribute to the prevention of rejection of the transplanted heart.

[Preparation for heart transplantation in Slovakia 1994-1997]. / Príprava transplantácie srdca na Slovensku v rokoch 1994-1997.

The authors present the process of introduction heart transplant programme in the years 1994-1997 in Slovakia. A short historical review about heart transplantation is given in the article. Fundamental requirements for heart transplantation realization, activities of Working group "Heart transplantation", methods of follow-up of patients after heart transplantation and selection of candidates for transplantation, are discussed. The authors also deal with surgical and anaesthesiological prerequisites for this programme realization. In conclusion they claim that the requirements for regular programme of heart transplantation are accomplished. (Tab. 2, Fig. 3, Ref. 21.)

[Hyperlipoproteinemia in patients after heart transplantation]. / Hyperlipoproteinémie u chorých po transplantácii srdca.

Hyperlipidaemia is one of the most frequent metabolic disorders after heart transplantation (HTx). The significance of hyperlipidaemia is stressed mainly in relation to graft vascular disease (GVD) which is the leading cause of death more than one year after transplantation. Recently the evidence on the role of hyperlipidaemia (HLP) in the pathogenesis of GVD is growing. Total cholesterol (TC), triglycerides (TAG) HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) were analysed cross-sectionally in 35 patients (30 males), aged 20-64 (median 40) years, more than one year after HTx. In 25 patients HTx was performed because of dilated cardiomyopathy (D-KMP), in 10 because of coronary artery disease (CAD). TC more than 5.6 mmol/l was detected in 29 (83%), TAG > 2.3 mmol/l in 15 (43%), LDL-C >3.6 mmol/l in 28 (80%) and HDL-C < 1.4 mmol/l in 25 (75%) of patients. There were no statistically significant differences in evaluated parameters found between the groups of patients operated on because of CAD and D-CMP, with and without glucose tolerance disorder and groups treated with higher (> 5 mg/D) and lower (.5 mg/D) dose of prednisone. Significant linear correlation of body mass index (BMI) and TAG or BMI and HDL/C resp. was confirmed. Pathogenesis of HLP after HTx is complex. Except of obesity, no unambiguous evidence of the role of glucose tolerance disorder or prednisone dose in immunosuppressive treatment were found. (Tab. 2, Fig. 3, Ref. 21.)

[Diagnosis and therapy of acute rejection in patients after orthotopic heart transplantation]. / Diagnostika a liecba akútnej rejekcie u pacientov po ortotopickej transplantácii srdca.

OBJECTIVE: In organ allotransplantation represents a serious problem acute rejection, which is the reaction of recipient organism aimed to reject the transplanted organ. AIM: To obtain experience in the field of routine long term are of patients after heart transplantation living in Slovakia. METHOD: 33 patients after orthotopic heart transplantation (HTx) were included in our long term care by the 1. June 1996. According to the accepted protocol we make the whole set of examinations is performed. This includes endomyocardial biopsy which is the only reliable method for the detection of rejection and also the criterion of sufficiency of immunosuppressive therapy. RESULTS: Acute rejection was revealed in 14 (43%) patients. CONCLUSIONS: Tactics of therapy and the length of the interval to subsequent biopsy were determined according to the histological findings of preceding biopsy, the clinical status and the combination of immunosuppression therapy. (Tab. 2, Ref. 13.)

Participation of coenzyme Q10 in the rejection development of the transplanted heart: a clinical study.

Coenzyme Q10 and alpha-tocopherol concentrations were assessed in 28 endomyocardial biopsies from 22 patients and in 61 blood samples from 31 patients after heart transplantation with histologically confirmed signs of rejection. The values were compared to the group of 14 patients with cardiomyopathies of unclear etiology as candidates for heart transplantation. Blood analyses were also compared with 50 healthy persons. Myocardial and blood coenzyme Q10 concentrations were already significantly decreased in the incipient phase of rejection (degree 0-1) and also in rejection phase 1 and 2. In patients without rejection signs myocardial and blood coenzyme Q10 values were similar to those of cardiomyopathic patients. No significant differences were found in alpha-tocopherol concentrations in relation to signs of rejection. Increased plasma lipid peroxidation quantified as malondialdehyde production was detected in all groups of transplanted patients. The results contribute to the explanation of some pathobiochemical mechanisms participating in the rejection development of the transplanted heart.

[Dilated cardiomyopathy and heart transplantation]. / Dilatacná kardiomyopatia a transplantácia srdca.

Authors compare selected demographic, clinical, methodological and laboratory parameters in 20 patients who underwent heart transplantation (HTx) because of dilated cardiomyopathy (DKMP) with those, who have had HTx because of progressive and otherwise unresolved coronary artery disease (KCH). Patients operated because of DKMP were younger than those who underwent HTx for KCH. Women were only in the group of DKMP. Otherwise there were no differences between these two groups. The global analysis showed, that the majority of patients after HTx were asymptomatic. However, high incidence of obesity, hyperlipoproteinemia, cytopoenia, renal and hepatal dysfunction were found. Finally the authors presented an overview of standard chronic therapy after HTx and proposed some approaches to undesirable habits and disorders which aggravated the prognosis of the patients after HTx.

[Quality of life after heart transplantation--psychosocial aspects]. / Kvalita zivota po transplantácii srdca--psychosociálne aspekty.

The aim of this study was to evaluate psychosocial quality of life after heart transplantation. We examined 29 patients (25 M and 4 F), average age was 43.5 y (18-62 y). The age at time of heart transplantation was 43 years (17-55 y). The time after heart transplantation was 3.3 year (0.3-9 y). Spielberger's Questionnaire of Anxiety, Knobloch's inventory of neuroticism, Freiburg's Personality Inventory and Quality of Life Inventory were used, 33% of patients demonstrated increasing frequency and 29% of patients increasing intensity of neurotic symptoms. 23% of patients presented increasing levels of anxiety (as a state). The personality dimensions (depression, excitability and low emotional stability) displayed high frequency. The results showed that patients were more satisfied with family support, with sexual activities, and less satisfied with financial situation, social activities, social isolations, sleep, memory, excitability, fatigue. 41.5% of patients returned back to work. The results indicate that these psychosocial factors play an important role in quality of life after heart transplantation. That is why if is necessary to dedicate an increasing attention to them. (Tab. 1, Fig. 6, Ref. 14.)

[Coenzyme Q10 and alpha-tocopherol in patients after heart transplantation]. / Koenzým Q10 a alfatokoferol u pacientov po transplantácii srdca.

Pathobiochemical mechanisms which participate in the rejection of transplanted heart are not fully clarified. A significant role in this process can be played by endogenous antioxidants, especially coenzyme Q10 which aside from its antioxidative properties is inevitable for cellular bioenergy. The authors investigated the concentration of Q10 alpha-tocopherol in endomyocardial biopsies in the blood in 11 patients from 1 to 9 years of age after transplantation of the heart (HTx-pat) examined in UKVCH in Bratislava who were compared with the group of 13 patients with cardiopathies of unclear origin (KPNP-pat) as possible candidates for transplantation. They detected a decreased concentration of coenzyme Q10 in the myocardium and blood of HTx-patients. Levels of alpha-to-copherol in the myocardium were identical in both groups, in plasma they were higher in patients after HTx. The authors suppose that the levels of coenzyme Q10 in patients after HTx can be influenced by an increased production of free oxygen radicals during rejection episodes, as well as immunosuppressive therapy, and indicate to the possible consequences of this decrease. The presented results provide the first information on the levels of coenzyme Q14 and alpha-tocopherol in patients after transplantation of the heart, registered and controlled in the Slovak Republic. They can contribute to the clarification of some pathobiochemical mechanisms of rejection, respectively to their therapeutic effect. (Fig. 2, Ref. 16.).

[Mitochondrial bioenergetics in patients before and after heart transplantation]. / Bioenergetika mitochondrií u pacientov pred transplantáciou a po transplantácii srdca.

BACKGROUND: The results of the study of biochemical and genetic characteristics of mitochondria in human medicine become widely used in practice. This is confirmed also by the Nobel Symposium which took place in 1994, and was dedicated to the problem of mitochondrial diseases and the effect of their therapy. Relatively rare is the information on the pathobiochemistry of heart muscle mitochondria in patients with cardiomyopathies. No information, so far, is available on oxidative phosphorylation in cases of myocardium transplantation in patients. MAIN PURPOSE AND OBJECTIVES: To bring early metabolic changes in mitochondria within EMB (endomyocardial biopsy) under control in patients after transplantation of the heart (Htx). These detected metabolic changes can contribute to the clarification of the mechanisms participating in the rejection of the transplanted myocardium. PATIENTS AND METHODS: The investigated group of patients included: a) patients with cardiopathies of unclear origin (NYHA II, NYHAIII) b) patients after transplantation of the heart (NYHAI-II) The authors assessed the properties of the respiratory chain and ATP production in mitochondria of EMB. CONCLUSIONS: The new methodical approach to the study of bioenergy of mitochondria of the myocardium in patients allows an early recognition of pathobiochemical changes in myocardium. Supplementing studies are going to reveal wether the presented methodical approach bear diagnostic value. (Fig. 3, Ref. 25.).

[Cardiopathies of unknown origin--a cooperative interdisciplinary study]. / Kardiopatie nejasného pôvodu--kooperatívna interdisciplinárna stúdia.

The authors described aim. objectives, design and criteria of the study which is oriented to the clinical and research problems of heart diseases of uncertain origin. The paper presents the preliminary experience with invasive cardiological techniques in this field. At the same time the authors discuss the potential impact of the basic research on the prevention and effective treatment of cardiopathy which is until now of unknown origin.

[Clinical aspects of cardiopathy of unknown origin]. / Klinický obraz kardiopatií nejasného pôvodu.

Frequently even physical and noninvasive examinations with laboratory analysis do not determine the final aetiology of cardiac symptoms, and it is necessary to complete them with an invasive examination with the aim of ascertaining the primary cause. Our article gives information about the results of clinical, laboratory and noninvasive examinations in the group of patients suspected of cardiopathy of unknown origin.

[Angiocardiography of cardiopathy of unknown origin]. / Angiokardiografia kardiopatií nejasného pôvodu.

Authors described their experiences with angiocardiography, (selective coronarography and left ventriculography), in 41 patients aged from 32 to 59 years with the preliminary diagnosis of cardiopathy of unknown origin. The patients with diagnosis of cardiopathy of unknown origin were those, who cannot be assigned to any of the known and acknowledge diagnostic categories, not even by using complex clinical, laboratory and noninvasive cardiological diagnostic procedures. Angiocardiography enabled to produce new and unexpected data of diagnostic value three patients with heart disease (all of the three mentioned patients had significant changes of the coronary supply, i.e. the reduction in lumen diameter of the coronary vessel being of more than 50% with local or total wall motion abnormalities). The other thirty-eight patients had normal findings of the coronary supply. One patient had a normal coronarographic findings, normal left ventricular wall motion and also the subsequent histological examination from the endomyocardial bioptic sample of the heart tissue, did not confirm pathological abnormalities. Selective coronarography and left ventriculography is a useful and safe clinical diagnostic procedure in exactly defined groups of patients.

[Echocardiography of cardiopathies]. / Echokardiografia kardiopatií.

The authors deal with the relation of echocardiography and diseases of the cardiac muscle, draftly classified as cardiopathies. The author's starting point is issued from the presumption that heart diseases which lack the characteristic diagnostic signs in echocardiographic picture affect the heart's systolic and diastolic functions. Echocardiography enables to quantify the extent of affliction of both functions. On the basis of analysis of a set of 22 prospectively examined patients the authors judge as to wether the results of individual volume measurements by means of echocardiographic imaging (one dimensional, two dimensional, Doppler) are correct. In the frame of systolic and diastolic functions examination they highlight the Doppler evaluation due to its technical simplicity and good correlations with literal documents dealing with invasive examinations.

[Metabolic study of mitochondria in myocardial biopsies in patients with cardiopathy of unknown origin]. / Metabolické stúdie mitochondrií v biopsiách myokardu u pacientov s kardiopatiami nejasného pôvodu.

BACKGROUND: Mitochondrial cardiomyopathies are being studied as metabolic diseases of the cardiac muscle which represents a new approach in metabolic studies. The development of mitochondrial diseases is concomited by an impairment in complexes of mitochondrial respiratory chain, which so far could have been possibly studied exclusively on experimental animals. The method of skinned? fibers enables to measure the pathobiochemical processes in mitochondria in a small amount of bioptic myocardial tissue of patients. AIM: The study is aimed at: applying the method of skinned fibers in biopsy of myocardium in patients, trying to localize the impaired loci of the mitochondrial respiratory chains, prospective early and fast assessment of the diagnosis of mitochondrial cardiomyopathy in patients. CONCLUSIONS: The study brings the first information on the possibility of performing more value measurements of mitochondrial respiratory chains per one bioptic sample from the myocardium in patients. The preliminary results indicate to the prospective possibility of early and fast assessment of the diagnosis of mitochondrial cardio(myo)pathies. The presented results require complementary studies involving the development of "mitochondrial medicine".

[Determination of coenzyme Q10 and alpha-tocopherol levels in patients with cardiopathies of unknown origin: perspectives in diagnosis]. / Stanovenie hladín koenzýmu Q10 a alfatokoferolu u pacientov s kardiopatiami nejasného pôvodu: perspektívne diagnostické moznosti.

The coenzyme Q10 (ubiquinone) plays an important role in bioenergetic conditions in myocardiac cells and together with alpha-tocopherol they act as endogenous antioxidants. Decreased levels in coenzyme Q10 were confirmed in some types of cardiomyopathies and in failing myocardium. Insufficiency of E vitamin is a risk factor in cardiovascular diseases. The study investigates the levels of coenzyme Q10 and alpha-tocopherol in the blood and in bioptic samples of the myocardium in patients with cardiopathies of unknown origin and it is aimed at their application as an auxiliary diagnostic method. The authors have introduced a method of coenzyme Q10 and alpha-tocopherol assessment from the bioptic samples of the myocardium, from the blood and plasma of these patients by means of high-performance liquid chromatography (HPLC). The authors detected decreased levels of coenzyme Q10 in the myocardium and blood of patients with cardiopathies. The dependence on the functional state of the myocardium according to NYHA was not confirmed due to the small number of patients. The plasmatic alpha-tocopherol levels decreased in dependence on the severeness of the disease. A more significant dependence was detected between the levels of alpha-tocopherol in the myocardium and its functional state. The average myocardial level of alpha-tocopherol in patients of the NYHA II group was almost ten-fold higher than in the NYHA II group. The gained results appoint to the meaning of investigation of the coenzyme Q10 and alpha-tocopherol in patients with cardiopathies of unknown origin and give a hint of prospective possibilities for application in the diagnosis assessment.

[Endomyocardial biopsy in cardiopathy of unknown origin]. / Endomyokardiálna biopsia u kardiopatií nejasného pôvodu.

The authors described their experiences with endomyocardial biopsy (EMB) in 21 adult patients aged from 18 to 59 years with the preliminary diagnosis of cardiopathy of uncertain origin (CPUO). Their definition of CPUO is as symptoms and/or findings of cardiac disease, which cannot be exactly identify using even complex clinical and noninvasive cardiological diagnostic procedures. Diagnostic value of EMB was substantial in two of their patients (in one hypereosinophilia of myocardium, and in another amyloidosis), non specific results were found in 18 patients, and 1 patient had normal pattern of the biopsy. EMB is useful and safe clinical diagnostic procedure in exactly defined groups of patients.

[Blood levels of Fe, Zn, Br and Rb determined by radionuclide x-ray fluorescence analysis in patients with dilated cardiomyopathy]. / Sledovanie koncentrácií Fe, Zn, Br a Rb v krvi pacientov s diagnózou dilatacná kardiomyopatia metódou rádionuklidovej röntgenofluorescencnej analýzy.

In 68 patients (50 men between the age of 18-59, 18 women between the age of 20-53) inflicted by dilatation cardiomyopathy in the stage of severe decompensation (functional NYHA group III-IV, the concentrations of Fe, Zn, Br, and Rb in whole blood were determined by means of radionuclide X-ray-fluorescence analysis. The Fe concentration (X = 401.26 +/- 14.58) was significantly lower (alpha = 0.074), the Zn concentration (X = 8.20 +/- 0.95) was not significantly altered, the trace elements concentration Br (X = 32.30 +/- 4.61) and Rb (X = 4.58 +/- 0.38) were remarkably and significantly higher (alpha = 2.10(-16), resp. alpha < or = 1.10(-16)) when compared with concentrations of these elements in healthy controls. The method of radionuclide X-ray-fluorescence analysis is suitable for element analysis of blood. Its advantages reside in its rapidness, polycomponence, sample nondestructiveness and low requirement of material. (Tab. 3, Fig. 4, Ref. 17.)

[Non-invasive assessment of the efficacy of long-term vasodilator therapy of cardiac decompensation in patients with dilated cardiomyopathy]. / Neinvazívne sledovanie úcinnosti dlhodobej vazodilatacnej liecby srdcovej dekompenzácie u pacientov s dilatacnými kardiomyopatiami.

In 18 patients (14 men, 4 women, in the age of 37-52 years, mean = 43 years) with dilated cardiomyopathy allocated into NYHA functional classification groups III-IV, the efficacy of ambulatory long term (mean = 6 years) vasodilator therapy by means of non-invasive methods was evaluated. NITRO-MACK retard (venodilator) in the dosage of 20 mg per day and DIHYDRALAZIN (arteriodilator) in the dosage of 100-200 mg per day were combined simultaneously with continuous administration of cardiotonics and diuretics. Vasodilator therapy had a favourable effect on systolic and diastolic function of the left ventricle with the mostly marked effect at the beginning of treatment. Amidst non-invasive parameters, the diastolic amplitude time index and left ventricular hypertrophy-dilatation index had the greatest prognostic value regarding the treatment efficacy and survival of patients. This objective evidence of the efficacy of vasodilator therapy in patients with dilated cardiomyopathy coincided with the improvement of clinical status, subjective relief, moderation of decompensation, and thus with the improvement of life quality. (Fig. 1, Tab. 4, Ref. 24.).

Incidence of Coxsackie virus infection in patients with dilated cardiomyopathy.

A total of 127 patients, divided into two groups, were examined; one was made up by patients with dilated cardiomyopathy (D-CMP) (n: 32), the other one by patients with myocarditis and pericarditis ("other cardiopathies") (n: 95). A control group of healthy subjects (n: 278) consisted of blood donors. Infection with Coxsackie viruses (B1, B2, B3, B4, B5, B6, A7, A9) was followed up serologically using virus-neutralizing antibodies and/or IgM class virus-specific antibodies. Actual Coxsackie virus infection was demonstrated in almost half of patients. Seventeen (53.1%) out of the 32 D-CMP patients (with a negative history of Coxsackie virus infection) had a positive serological finding. The most frequently isolated Coxsackie virus was, B4. In the group of "other cardiopathies", a positive serological finding was in 42 patients (44.2%) with the incidence of B1 and B4 viruses being the highest and identical. Compared with data obtained in healthy controls, the incidence of Coxsackie virus infection in the two follow-up groups of patients was statistically highly significant (p less than 0.001).