Journal of pharmacological and toxicological methods · 2025
Optimization strategy for modeling sick sinus syndrome in rats: Balancing effect and animal care.
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He Liming, Shi Xinxin, Wang Yucheng, Huang Shuwei
Аннотация
OBJECTIVE: This study aimed to validate the feasibility of establishing a sick sinus syndrome (SSS) rat model by injecting 3 % sodium hydroxide (NaOH) into the jugular vein at a rate of 0.01 mL/s, and to assess reductions in animal mortality and vascular injury.
RESULTS: Compared with the conventional 10 % NaOH method, the modified 3 % NaOH approach yielded a significantly higher modeling success rate (78 % vs. 44 %), substantially lower mortality (15 % vs. 48 %), and reduced jugular vein injury. Electrophysiological evaluations demonstrated a time-dependent decrease in post-modeling heart rate (HR), characterized by widened P-waves and prolonged PR intervals. Additionally, heart rate variability (HRV) analysis revealed a notable increase in the standard deviation of normal-to-normal intervals (SDNN) 2 weeks post-modeling. Histopathological analysis (HE staining) indicated more pronounced necrosis and fibrosis in sinus node P-cells, accompanied by elevated levels of hydroxyproline (HYP) and transforming growth factor β1 (TGF-β1). Furthermore, assessments of pacing-related ion channels showed downregulated transcription and expression of hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and reduced SCN5A transcription, aligning with observed electrophysiological abnormalities.
CONCLUSION: The modified 3 % NaOH method effectively establishes an SSS rat model, offering advantages in simplicity, cost-efficiency, and animal welfare. This model provides a practical platform for fundamental SSS research, especially in resource-limited laboratories.
RESULTS: Compared with the conventional 10 % NaOH method, the modified 3 % NaOH approach yielded a significantly higher modeling success rate (78 % vs. 44 %), substantially lower mortality (15 % vs. 48 %), and reduced jugular vein injury. Electrophysiological evaluations demonstrated a time-dependent decrease in post-modeling heart rate (HR), characterized by widened P-waves and prolonged PR intervals. Additionally, heart rate variability (HRV) analysis revealed a notable increase in the standard deviation of normal-to-normal intervals (SDNN) 2 weeks post-modeling. Histopathological analysis (HE staining) indicated more pronounced necrosis and fibrosis in sinus node P-cells, accompanied by elevated levels of hydroxyproline (HYP) and transforming growth factor β1 (TGF-β1). Furthermore, assessments of pacing-related ion channels showed downregulated transcription and expression of hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and reduced SCN5A transcription, aligning with observed electrophysiological abnormalities.
CONCLUSION: The modified 3 % NaOH method effectively establishes an SSS rat model, offering advantages in simplicity, cost-efficiency, and animal welfare. This model provides a practical platform for fundamental SSS research, especially in resource-limited laboratories.