In our previous studies, a decreased blood pressure was reported in children treated by anthracycline (AC). The aim of this study was to assess the long-term effects of AC anticancer therapy in 45 subjects aged 13-22 years by repeated 24-hour Holter monitoring of blood pressure. Sixty four aged-matched subjects served as controls. The differences between mean values of systolic (SBP) and diastolic blood pressure (DBP) in each hour of both groups were evaluated by Mann-Whitney test. Also the parameters of the least-squares fit of the sinusoidal curve in each subject were estimated (M - mesor, midline-estimating, a mean value of sinusoidal curve corresponds to 24-hours mean pressure; A - amplitude, double amplitude corresponds to nightday difference; Acr - acrophase is a time of maximal value of a sinusoidal curve). SBP and DBP was significantly lower only during night hours in anthracycline patients 19-22 years old. Also M was lower in this age subgroup of patients comparing to age matched controls (SBP: 112±6 mm Hg versus 117±7 mm Hg, p<0.05; DBP: 67±3 mm Hg versus 69±6 mm Hg, p<0.05), A was not different, Acr in patients was shifted one hour earlier (SBP: 2.4 p.m. versus 3.6 p.m., p<0.05; DBP: 2.1 p.m. versus 3.3 p.m., p<0.01). This corresponds to the shift of the morning blood-pressure increase seen on 24-hours blood pressure profiles. M correlated with age in controls (SBP: r=0.374, p<0.01; regression coefficient b=1.34 mm Hg/1 year; DBP: r=0.365, p<0.01; b=0.95 mm Hg/1 year), but not in patients (SBP: r=0.182, DBP: r=0.064). A and Acr were age-independent in all subjects. It is concluded that blood pressure in 19-22 years old AC patients is lower during night hours, the age-dependent increase of blood pressure seen in healthy controls between 13 and 22 years of age does not occur in patients. This finding is consistent with the long-lasting impairment of the sympathetic nervous system caused by anthracyclines., Z. Nováková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The matrix metalloproteinases (MMPs) play a key role during cardiac remodeling. The aim of the study was to investigate the changes in collagenous proteins and MMPs in the model of non-ischemic, anthracycline-induced chronic cardiomyopathy in rabbits using both biochemical and histological approaches. The study was carried out in three groups of Chinchilla male rabbits: 1) daunorubicin (3 mg/kg, once weekly for 10 weeks), 2) control (saline in the same schedule), 3) daunorubicin with the cardioprotectant dexrazoxane (60 mg/kg, before each daunorubicin). Morphological changes in the myocardium of daunorubicin-treated animals were characterized by focal myocardial interstitial fibrosis of different intensity. The subsequent proliferation of the fibrotic tissue was marked by an increased content of both collagen types I and III, which resulted in their typical coexpression in the majority of bundles of fibers forming either smaller or larger scars. Biochemical analysis showed a significantly increased concentration of hydroxyproline, mainly in the pepsin-insoluble fraction of collagenous proteins, in the daunorubicin-treated group (1.42±0.12 mg/g) as compared with the control (1.03±0.04 mg/g) and dexrazoxane (1.07±0.07 mg/g) groups. Dexrazoxane co-administration remarkably reduced the cardiotoxic effects of daunorubicin to the extent comparable with the controls in all evaluated parameters. Using zymography, it was possible to detect only a gelatinolytic band corresponding to MMP-2 (MMP-9 activity was not detectable). However, no significant changes in MMP-2 activity were determined between individual groups. Immunohistochemical analysis revealed increased MMP-2 expression in both cardiomyocytes and fibroblasts. Thus, this study has revealed specific alterations in the collagen network in chronic anthracycline cardiotoxicity in relationship to the expression and activity of major MMPs., M. Adamcová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Anthracycline cardiotoxicity represents a serious risk of anticancer chemotherapy. The aim of the present pilot study was to compare the potential of both the left ventricular (LV) filling pattern evaluation and cardiac troponin T (cTnT) plasma levels determination for the early detection of daunorubicin-induced cardiotoxicity in rabbits. The echocardiographic measurements of transmitral LV inflow as well as cTnT determinations were performed weekly for 10 weeks in daunorubicin (3 mg/kg weekly) and control groups (n=5, each). Surprisingly, no significant changes in LV-filling pattern were observed through the study, most likely due to the xylazine-containing anesthesia, necessary for appropriate resolving of the E and A waves. In contrast to the echographic measurement, the dP/dt min index obtained invasively at the end of the study revealed a significant im pairment in LV relaxation, which was further supported by observed disturbances in myocardial collagen content and calcium homeostasis. However, at the same time cTnT plasma levels were progressively rising in the daunorubicin-treated animals from the 5th week (0.024±0.008 μg/l) until the end of the experiment (0.186±0.055 μg/l). Therefore, in contrast to complicated non-invasive evaluation of diastolic function, cTnT is shown to be an early and sensitive marker of anthracycline-induced cardiotoxicity in the rabbit model., M. Štěrba, T. Šimůnek, O. Popelová, A. Potáčová, M. Adamcová, Y. Mazurová, M. Holečková, V. Geršl., and Obsahuje bibliografii a bibliografické odkazy
The aim of this study was to analyze the ECG time intervals in the course of the development of chronic anthracycline cardiomyopathy in rabbits. Furthermore, this approach was employed to study the effects of a model cardioprotective drug (dexrazoxane) and two novel iron chelating compounds - salicylaldehyde isonicotinoyl hydrazone (SIH) and pyridoxal 2-chlorobenzoyl hydrazone (o-108). Repeated daunorubicin administration induced a significant and progressive prolongation of the QRS complex commencing with the 8th week of administration. At the end of the study, we identified a significant correlation between QRS duration and the contractility index dP/dtmax (r=-0.81; P<0.001) as well as with the plasma concentrations of cardiac troponin T (r=0.78; P<0.001). In contrast, no alterations in ECG time intervals were revealed in the groups co-treated with either dexrazoxane or both novel cardioprotective drugs (SIH, o-108). Hence, in this study, the QRS duration is for the first time shown as a parameter suitable for the non-invasive evaluation of the anthracycline cardiotoxicity and cardioprotective effects of both well established and investigated drugs. Moreover, our results strongly suggest that novel iron chelators (SIH and o-108) merit further study as promising cardioprotective drugs against anthracycline cardiotoxicity., A. Potáčová, M. Adamcová, H. Čajnáková, L. Hrbatová, M. Štěrba, O. Popelová, T. Šimůnek, P. Poňka, V. Geršl., and Obsahuje bibliografii a bibliografické odkazy
Anthracyclines represent one of the important classes of anti-cancer drugs; however, their major disadvantage is their profound cardiovascular toxicity. This study aimed to evaluate influence of anthracyclines on cardiovascular stiffness parameters estimated from pulse wave (PW). PW was measured in 59 cancer survivors treated with anthracyclines in childhood and in 248 healthy age-matched controls. Both patients and controls were divided into three age groups (13 – 15, 16 – 18 and 19 – 24 years). Central PW augmentation index (C-AI75) and augmentation pressure (C-AP75), both normalized to heart rate 75 bpm, were calculated as parameters of arterial wall stiffness. Central Buckberg sub-endocardial viability ratio (SEVR) was calculated as a parameter of diastolic function. Patients and controls were compared in each age group. C-AI75 and C-AP75 were significantly increased in patients in age groups 16 – 18 and 19 – 24 years. SEVR was decreased in patients in the oldest age group. Our results suggest that although toxic influence of
anthracyclines to arterial wall and heart are developing during childhood and puberty, they can be detected rather in the adulthood. These changes are yet subclinical; however, their presence indicates potentially increased cardiovascular risk in childhood cancer survivors treated with anthracyclines during childhood.