Landiolol modulates sodium 1.5 ion and connexin-43 to reduce sepsis ventricular arrhythmias

Figure 1 Schematic diagram of the rat sepsis model protocol.

Figure 2 Comparison of tumor necrosis factor-α and interleukin-6 expression levels among the three groups. ^aP < 0.05 vs control, ^bP < 0.05 vs sepsis group, n = 8. TNF-α: Tumor necrosis factor-α; IL-6: Interleukin-6.

Figure 3 Comparison of the electrocardiogram in the three groups. A: Control group; B: Sepsis model group; C: Sepsis model + landiolol group.

Figure 4 Landiolol inhibits the production of inflammatory cells in the ventricular myocardium of sepsis rats and reduces myocardial cell apoptosis, thereby inhibiting fibrosis. A: Comparison of hematoxylin and eosin staining results in rat hearts; B: Quantitative comparison of Masson-stained myocardial fibrosis degree in the different experimental groups; C: Subcellular alterations in myocardial cells observed by confocal microscopy. From left to right in each column: Full-field view → FITC channel (green, target protein) → 4’-6-diamidino-2-phenylindole channel (blue, nuclei). Original magnification: 20 ×, n = 3.

Figure 5 Landiolol reverses the abnormal conduction velocity of ventricular myocytes in septic rats, and significantly reduces conduction dispersion and heart rate. A: Electrocardiographic recordings from isolated perfused hearts of rats in each experimental group; B: Comparison of various interval durations (PR, QT, QTS) and heart rates in isolated perfused hearts among the three groups; C: Comparative analysis of conduction time and conduction velocity in isolated perfused hearts in the experimental groups, left ventricular active time, left ventricular contraction velocity; D: Comparative analysis of conduction dispersion in isolated perfused hearts across the experimental groups. Black represents the control group, red represents the sepsis model group, green represents the sepsis model group treated with low-dose (0.1 mg/minute) landiolol, dark blue represents the sepsis model group treated with medium-dose (0.2 mg/minute) landiolol, light blue represents the sepsis model group treated with high-dose (0.4 mg/minute) landiolol, and pink represents the landiolol washout group. n = 3. HR: Heart rates; LV-AT: Left ventricular active time; LV-CV: Left ventricular contraction velocity.

Figure 6 Comparative analysis of connexin-43 expression via immunohistochemistry across the experimental groups. A: Immunohistochemical staining results of connexin-43 (Cx43) channel protein in ventricular myocardial tissues of rats; B: Quantitative analysis of Cx43 expression levels in ventricular myocardial tissues; C: Immunohistochemical staining results of sodium 1.5 ion (Nav1.5) channel protein in ventricular myocardial tissues of rats; D: Quantitative analysis of Nav1.5 channel expression levels in ventricular myocardial tissues; E and F: Protein expression levels of Cx43/Nav1.5 channel in rat ventricular myocardial tissue were detected by western blot, with glyceraldehyde-3-phosphate dehydrogenase as the internal control. Quantitative analysis of the above protein expressions was conducted. ^aP < 0.05 vs control, ^bP < 0.05 vs sepsis group, ^cP < 0.01 vs control, ^dP < 0.001 vs control, ^eP < 0.001 vs sepsis group and n = 3. Original magnification was 20 ×, n = 3. All data are expressed as mean ± SD. Cx43: Connexin-43; Nav1.5: Sodium 1.5 ion; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase.

Figure 7 Schematic representation of gap junctions between myocardial cells. The cell membrane contains a hemichannel composed of six connexins, with the left and right sides remaining unconnected hemichannels, while the central portion consists of two hemichannels that interconnect to form a complete gap junction channel. This channel allows direct molecular passage, facilitating the transfer of substances between adjacent cells.