Even though rodents are accessible model animals, their electrophysiological properties are deeply different from those of humans, making the translation of rat studies to humans rather difficult. We compared the mechanisms of ventricular repolarization in various animal models to those of humans by measuring cardiac ventricular action potentials from ventricular papillary muscle preparations using conventional microelectrodes and applying selective inhibitors of various potassium transmembrane ion currents. Inhibition of the I_K1 current (10 µmol/L barium chloride) significantly prolonged rat ventricular repolarization, but only slightly prolonged it in dogs, and did not affect it in humans. On the contrary, I_Kr inhibition (50 nmol/L dofetilide) significantly prolonged repolarization in humans, rabbits, and dogs, but not in rats. Inhibition of the I_Kur current (1 µmol/L XEN-D0101) only prolonged rat ventricular repolarization and had no effect in humans or dogs. Inhibition of the I_Ks (500 nmol/L HMR-1556) and I_to currents (100 µmol/L chromanol-293B) elicited similar effects in all investigated species. We conclude that dog ventricular preparations have the strongest translational value and rat ventricular preparations have the weakest translational value in cardiac electrophysiological experiments.

The present study was designed to test the hypothesis that the selectivity of blocking the late Na⁺ current (I_NaL) over the peak Na⁺ current (I_NaP) is related to the fast offset kinetics of the Na⁺ channel inhibitor. Therefore, the effects of 1 µM GS967 (I_NaL inhibitor), 20 µM mexiletine (I/B antiarrhythmic) and 10 µM quinidine (I/A antiarrhythmic) on I_NaL and I_NaP were compared in canine ventricular myocardium. I_NaP was estimated as the maximum velocity of action potential upstroke (V⁺_max). Equal amounts of I_NaL were dissected by the applied drug concentrations under APVC conditions. The inhibition of I_NaL by mexiletine and quinidine was comparable under a conventional voltage clamp, while both were smaller than the inhibitory effect of GS967. Under steady-state conditions, the V⁺_max block at the physiological cycle length of 700 ms was 2.3% for GS967, 11.4% for mexiletine and 26.2% for quinidine. The respective offset time constants were 110 ± 6 ms, 456 ± 284 ms and 7.2 ± 0.9 s. These results reveal an inverse relationship between the offset time constant and the selectivity of I_NaL over I_NaP inhibition without any influence of the onset rate constant. It is concluded that the selective inhibition of I_NaL over I_NaP is related to the fast offset kinetics of the Na⁺ channel inhibitor.

Myxosarcomas are rare malignant tumors of soft connective tissues, classified into various subtypes, including myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyosarcoma. In this study, we proposed to study the demographic, tumor characteristics, and overall survival rate and compared the treatment modalities between these cancers. Patient data collected based on locoregional metastasis presentation of the abovementioned tumors with a cutoff study of survival duration up to 10 years were obtained from the SEER database during 1975‐2016. Our results indicated that elderly patients and females were more in locoregional myxoid leiomyosarcoma than myxoid liposarcoma and myxoid chondrosarcoma with locoregional metastasis. The white race represented the most patients who suffered from these cancers than other races. The heart is the primary site for the abovementioned cancers, in addition to the female genitals to the myxoid leiomyosarcoma. Myxoid liposarcoma and myxoid chondrosarcoma patients with locoregional metastasis were suffering from grade II, while locoregional myxoid leiomyosarcoma patients with blank grading were due to missed data. Surgery was the most common treatment modality in this study compared with radiotherapy and chemotherapy. Kaplan‐Meier analysis showed a significant difference in survival time between the three subtypes by using histology, and myxoid leiomyosarcoma showed prolonged survival than others. Elderly, female, white, unknown grade, surgery, no radiation, and no chemotherapy variables were independent factors associated with overall survival among these cancers. Multivariate analysis also showed significant differences in overall survival between the three tumors by histology, and myxoid leiomyosarcoma was with a better prognosis than others. Multivariate analysis of locoregional myxoid leiomyosarcoma showed the statistical significance of black race, grade, and radiotherapy, indicating them as independent prognostic factors of locoregional myxoid leiomyosarcoma. We conclude that surgery was the primary treatment modality against these cancers than radiotherapy and chemotherapy. And the locoregional myxoid leiomyosarcomas showed a better prognosis and higher survival rate than locoregional myxoid liposarcoma and locoregional myxoid chondrosarcoma.