Abstract
BackgroundElectrochemotherapy (ECT) is a combined treatment in which high voltage electroporation (EP) pulses are used to facilitate the uptake of a chemotherapeutic drug into tumor cells, thus increasing antitumor effectiveness of the drug. The effect of ECT of deep-seated tumors located close to the heart on functioning of the heart has not been previously investigated. In this study, we investigate the effects of intra-abdominal ECT of colorectal liver metastases on functioning of the heart during the early post-operative care period.MethodsFor ECT high voltage EP pulses with amplitudes of up to 3000 V and 30 A were delivered in synchronization with electrical activity of the heart. Holter electrocardiographic (ECG) signals were obtained from 10 patients with colorectal liver metastases treated with ECT. ECG was recorded during the periods of 24 hours before and after the surgical procedure involving ECT. Four-hour long night-time ECG segments from both periods exhibiting the highest level of signal stationarity were analyzed and compared. Changes in several ECG and heart rate variability (HRV) parameters were evaluated.ResultsNo major heart rhythm changes (i.e., induction of extrasystoles, ventricular tachycardia or fibrillation) or pathological morphological changes (i.e., ST segment changes) indicating myocardial ischemia were found. However, we found several minor statistically significant but clinically irrelevant changes in HRV parameters after ECT procedures: a decrease in median values of the mean NN interval, a decrease in the low-frequency and in the normalized low-frequency component, and an increase in the normalized high-frequency component.ConclusionsOnly minor effects of intra-abdominal ECT treatment on functioning of the heart were found. They were expressed as statistically significant but clinically irrelevant changes in heart rate and long-term HRV parameters and were as such not life-threatening to the patients. The nature of these changes is such that they can be attributed to the known effects of the drugs given to the patients in the post-operative care. Further investigation is still warranted to unambiguously resolve whether ECT with high voltage EP pulses applied in immediate vicinity of the heart is responsible for the observed effects.
Highlights
Electrochemotherapy (ECT) is a combined treatment in which high voltage electroporation (EP) pulses are used to facilitate the uptake of a chemotherapeutic drug into tumor cells, increasing antitumor effectiveness of the drug
The analysis of ECG signals recorded before and after ECT procedure showed no increase in appearance of abnormal heartbeats in ECG signals recorded after ECT even in cases where abnormal heartbeats were present in ECG signal before ECT (Table 3)
ECG signals recorded in patients number 6, 9 and 10 contained large amounts of high-frequency noise either before or after ECT procedure, which rendered a reliable determination of ppQTc intervals impossible (Table 3)
Summary
Electrochemotherapy (ECT) is a combined treatment in which high voltage electroporation (EP) pulses are used to facilitate the uptake of a chemotherapeutic drug into tumor cells, increasing antitumor effectiveness of the drug. Electroporation-based techniques, like electrochemotherapy (ECT), gene electrotransfection and non-thermal irreversible electroporation, are becoming a viable option for treatment of internal, deep-seated tumors and tissues (e.g., in bones, brain, liver, lung, prostate, kidney, colon and esophagus). In such cases, surgical, percutaneous or endoscopic procedures are used to gain access to the treatment area [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18]. If the electric field distribution is such that the heart lies in the reversibly electroporated area, premature action potentials are generated causing cardiac arrhythmias [8]
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