We used P-32 as a radioactive source to irradiate normal myocardial tissue, and the immediate effects on cardiomyocytes were not obvious. At 30 days after the procedure, the voltage mapping results showed that P-32 internal radiotherapy can significantly reduce the local myocardial potential and produce different degrees of fibrosis in the irradiated myocardium. Specifically, 13 mCi of radiation for 60 min or 26 mCi of radiation for 30 min can result in complete transmural damage. However, 13 mCi of radiation for 30 min exhibited obvious damage only to the endocardium, not to the epicardium, which indicated that upregulation of the radiation dose of P-32 internal radiotherapy will increase the range of myocardial damage, even to the extent of transmural damage. Therefore, if P-32 internal radiotherapy is used to irradiate the origin of tachyarrhythmia or the key isthmus, it could also cause effective damage, thereby potentially playing a role in the treatment of tachyarrhythmia.
P-32 has been used as a radioactive source for skin keloids, rheumatoid arthritis, hemangioma, and myeloma. It is a relatively safe radioactive source with a short radiation distance and good controllability. Additionally, the half-life of P-32 is only 14.3 days. Therefore, compared with other radionuclides, there are fewer long-term adverse effects, and the post‑processing of radionuclide waste is easier. During the experiments, the pigs did not experience any serious complications, thus indicating the good safety of P-32 internal radiotherapy.
We also found that P-32 internal radiotherapy had little effect on the coronary artery and femoral artery. Therefore, it may have an important role in the treatment of tachyarrhythmia originating from around the coronary artery and may be preferable compared to RFCA.
P-32 internal radiotherapy has several advantages. First, P-32 internal radiotherapy did not cause significant damage to the arteries. Immediately after the procedure, the gross specimen showed no fibrotic damage or acute or chronic thrombosis at the local coronary arteries in the irradiated area. It is suggested that the sensitivity of P-32 internal radiotherapy to the coronary artery is lower than that of myocardial tissue. The relative selectivity of different tissues also increases the advantages of P-32 internal radiotherapy compared with conventional RFCA. If the radiofrequency ablation sites are close to the coronary arteries, then RFCA may cause acute coronary artery damage, leading to acute myocardial infarction. P-32 internal radiotherapy may have an unparalleled advantage because the diameter of the radiotherapy catheter is 6 Fr. If it is extended into the coronary artery for irradiation, then it will cause acute myocardial infarction. Therefore, it is impossible to directly verify the coronary artery damage caused by P-32. The histopathological structures of the pig femoral artery and coronary artery are relatively similar, thereby making it more convenient and easier to explore the safety of P-32 in arteries. Therefore, to indirectly verify coronary artery damage caused by P-32 internal radiotherapy, we subjected the femoral arteries of pigs 4 to 7 to 26 mCi of radiation for 30 min. At 30 days later, femoral artery angiography showed that the femoral artery did not exhibit stenosis or serious damage and had an intact vascular structure under microscopy. Furthermore, the safe use of coronary radioactive stents (with the same mechanism as P-32, which can emit β-rays) also proved that the damage caused by internal radiotherapy to the coronary artery is controllable. Ventricular tachycardia originates from some specific anatomic regions, such as the summit area, where the coronary artery distributes widely, or the epicardium, where adipose tissue is covered. RFCA can easily cause coronary injury that can result in acute myocardial infarction. With other methods, the radiofrequency energy can hardly penetrate the epicardium during routine endocardial ablation. Therefore, P-32 internal radiotherapy may have an important role in solving the shortcomings of RFCA. For example, internal radiotherapy can control the damage to the coronary artery. Additionally, unlike radiofrequency energy, β-rays can penetrate adipose tissue and affect arrhythmia originating from the epicardium of the left ventricle.
RFCA uses radiofrequency energy to damage the myocardium, thus causing local myocardial necrosis to treat ventricular arrhythmia. It requires a radiofrequency ablation catheter to be closely attached to the ventricular wall. If the attachment is not sufficient, then the radiofrequency energy cannot appropriately affect the myocardium, thereby causing damage. For tachyarrhythmia originating from some specific structures, such as the papillary muscles, the difficulty of routine RFCA is high and there are many requirements that must be fulfilled by the operator. In contrast to radiofrequency energy, P-32 internal radiotherapy can release β-rays to damage the cardiomyocyte DNA. Although poor adhesion reduces the effects of β-rays on the irradiation area per unit of time, compared with radiofrequency energy, there are fewer effects. Therefore, there are fewer requirements for P-32 internal radiotherapy catheter attachment than there are for radiofrequency ablation catheter attachment, which makes the catheter attachment procedure less difficult. This can be advantageous for patients who experienced failed RFCA because of insufficient catheter attachment.
Patients may feel better during internal radiotherapy. The immediate effects and tissue damage caused by P-32 internal radiotherapy are minimal. During the procedure, patients do not experience the adverse reactions caused by conventional radiofrequency ablation, such as nausea, vomiting, chest tightness, chest pain, and pericardial tamponade.
This study has some shortcomings. First, the number of experimental animals is relatively small, and the effects of different doses on cardiomyocytes have not been investigated in detail. Second, the time effect of tissue damage after internal radiotherapy is not fully understood. We plan to perform another study in which we will adjust the observation time gradient to find the exact time point at which the maximum effects of internal radiotherapy appear. Third, the distance and direction of irradiation are not presently controllable. Fourth, the radioactive catheter used during this study was independently designed and manufactured. It has a titanium tip surface, a length of 8 mm, and a diameter of 0.8 mm. The hardness of the tip may be greater than that of the radiofrequency ablation catheter, which may result in a hematoma on the endocardial surface of the myocardium at some of the irradiation points.