Cardiometric assessment of toxicity of the experimental antitumor chemotherapy and the cardio-protective effect made by L-carnitine

Abstract

The aim is to conduct a cardiometric assessment of formation of acute and late toxic disorders in experimental animals with Guerin's carcinoma during carboplatin chemotherapy against the background of L-carnitine medication.

Materials and methods

The study was performed using 43 white outbred male rats weighing 200-230 g, 16 of them intact (without a tumor) and 27 with inoculated Guerin's carcinoma, who were administered chemotherapy drug Carboplatin-Teva (CP) intraperitoneally at a dose of 50 mg/kg of body weight twice at an interval of 5 days. L-carnitine was administered per os using a gastric tube in an amount of 0.3 ml of the solution. ECG was recorded using hemodynamic PC-assisted analyzer CARDIOCODE (ST LLC CARDIOCODE, Taganrog, Russia) in anesthesia-free animals fixed onto the operating table in the back position. The recording was performed for 15 seconds with skin surface mini-electrodes.

Results

24 hours after the administration of carboplatin to intact animals and tumor-bearing rats, early symptoms of cardiotoxicity appeared in the form of an initial P-wave response as a marker of an increase in the load on the atria and a slowdown in its pumping function. The further delayed effect of carboplatin demonstrated the smoothing of the P wave on the ECG, which indicated a stable effect of increasing the tonus of the atrial walls. A pronounced sign of cardiomyopathy was a decrease in the amplitude of the QR phase and an attenuation of QRS, reflecting a decrease in the energetic potential of cardiomyocytes. The corrective effect of L-carnitine in animals with tumor chemotherapy was manifested in the restoration of the P wave duration to the initial level of 0.019 s, and the duration of the PQ and QRS intervals began to correspond to intact animals without cytostatic administration, 0.03 s and 0.09 s, respectively. That was an evidence for the effect of the cardioprotector on the supression of the carboplatin toxic action.

Conclusions

Studies with the use of the model of malignant tumor growth and antitumor therapy with carboplatin indicate that there are manifestations of early and late symptoms of cardiotoxicity in the form of pathological shifts in some ECG phase constants. The possibility of correcting disorders can be provided by cardioprotector L-carnitine as a participant in the energy supply to the cardiac mitochondria.

Imprint

Alla I. Shikhlyarova, Mikhail Y.Rudenko, Yulia Y. Arapova, Ivan A. Popov, Galina V. Zhukova, Elena M. Frantsiyants, Elena A. Dzhenkova, Irina V. Kaplieva, Valerija A. Bandovkina, Irina V. Neskubina, Natalya A. Maksimova, Yulianna S. Shatova, Elena A. Sheiko, Botir А. Yuldashev, Malika D. Murodova. Cardiometric assessment of toxicity of the experimental antitumor chemotherapy and the cardioprotective effect made by L-carnitine. Cardiometry; Issue 18; May 2021; p.24-32; DOI: 10.18137/cardiometry.2021.18.2432; Available from: http://www.cardiometry.net/issues/no18-may-2021/cardiometric-assessment-of-toxicity