N. Potocnik

Protective effects of fullerenol C60(OH)24 against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer

The effects of fullerenol C60(OH)24 (Frl) at doses of 25, 50, and 100mg/kg/week (for a time-span of 3 weeks) on heart and liver tissue after doxorubicin (Dox)-induced toxicity in rats with colorectal cancer were investigated. In the present study, we used an in vivo Wistar male rat model to explore whether Frl could protect against Dox-induced (1.5mg/kg/week for 3 weeks) chronic cardio- and hepato- toxicity and compared the effect with a well-known antioxidant, vitamin C (100mg/kg/week for 3 weeks). According to macroscopic, microscopic, hematological, biochemical, physiological, pharmacological, and pharmacokinetic results, we confirmed that, at all examined doses, Frl exhibits a protective influence on the heart and liver tissue against chronic toxicity induced by Dox.

Non-invasive beat-to-beat determination of changes in the small artery compliance after smoking

Abstract We investigated the response of the small arterial compliance on smoking in 5 occasional smokers before, during and after inhaling the first cigarette in the day. For this purpose we used a non-invasive method based on interpretation of the oscillometric signal from the finger cuff coupled to the signal from photoplethysmograph. This system enables on-line determination of the finger artery compliance as function of transmural pressure (ptm) between 0 and 120 mmHg, where each heart beat is presented by a set of compliance values in the range of the pulse pressure reduced by the cuff pressure. This procedure allowed construction of time course of the arterial compliance. When comparing the compliance value at ptm of 40 mmHg, we found its fluctuations around the steady value during the rest and immediate lowering of the compliance after smoking, accompanied by the increase of blood pressure and heart rate.

Cardiac autonomic modulation induced by doxorubicin in a rodent model of colorectal cancer and the influence of fullerenol pretreatment

The very effective anticancer drug doxorubicin (DOX) is known to have cardiotoxic side effects, which could be accompanied by autonomic modulation. Autonomic disbalance might even be an initiating mechanism underlying DOX-induced cardiotoxicity and can be studied noninvasively by the analysis of heart rate variability (HRV). A number of strategies have been assessed to predict chemotherapy-induced cardiac dysfunction while HRV, a potential detecting tool, has not yet been tested. Thus, we aimed to determine the effect of DOX treatment on HRV in a rat model of colorectal cancer. While pretreatment with fullerenol (Frl) acts protectively on DOX-induced cardiotoxicity, we aimed to test the effect of Frl pretreatment on DOX-induced HRV alterations. After the induction of colorectal cancer, adult male Wistar rats were treated with saline (n = 7), DOX (1.5 mg/kg per week, n = 7) or DOX after pretreatment with Frl (25 mg/kg per week, n = 7) for three weeks (cumulative DOX dose 4.5 mg/kg). One week after treatment rats were anaesthetized, standard ECG was measured and HRV was analyzed in time and frequency domain. During autopsy the intestines and hearts were gathered for biochemical analysis and histopathological examination. DOX treatment significantly decreased parasympathetically mediated high-frequency component (p<0.05) and increased the low-frequency component of HRV (p<0.05), resulting in an increased LF/HF ratio (p<0.05) in cancerous rats. When pretreated with Frl, DOX-induced HRV alterations were prevented: the high-frequency component of HRV increased (p<0.01), the low-frequency decreased (p<0.01), LF/HF ratio decreased consequently (p<0.01) compared to DOX only treatment. In all DOX-treated animals, disbalance of oxidative status in heart tissue and early myocardial lesions were found and were significantly reduced in rats receiving Frl pretreatment. Autonomic modulation accompanied the development of DOX-induced cardiotoxicity in rat model of colorectal cancer and was prevented by Frl pretreatment. Our results demonstrated the positive prognostic power of HRV for the early detection of DOX-induced cardiotoxicity.

The reversible displacement of the passive diastolic p-V curve in the isolated guinea pig left ventricle.

We studied viscoelastic behaviour of the isolated diastolic guinea pig left ventricle (LV), manifested in changes of the hysteresis loop of the pressure-volume (p-V) diagram, produced by acute volume loading. Specifically, we investigated how the width of the hysteresis depends on the way LV volume loading, and whether changes in the hysteresis width are reversible. Each of 11 LV was instrumented with a catheter for injection and withdrawal of saline, and a micromanometer (Millar, 2F) to measure LV pressure. LV were loaded by the computer controlled injection of saline in 6–8 sequential injection steps of 100 µl each with a pause of 5 s, followed by a similar withdrawal pattern. In protocol A (N=5), a 100 µl higher maximal LV volume (LVVmax) was reached during injection than in the control run, and in protocol B (N=6), the time spent at LVVmax was longer (20 vs. 5 s pause). In both protocols a reproducible displacement of the passive p-V curve during volume unloading was observed, reflected in the increase of the hysteresis width by 23±8 % in protocol A, and 12±3 % in protocol B. Reversible displacement of the passive diastolic p-V curve after large aperiodic volume change suggests participation of reversible phenomena, like extracellular fluid filtration, and may in part provide an answer to the phenomenon of preconditioning.