Sodium Hydroxide Pinpoint Pressing Permeation Method for the Animal Modeling of Sick Sinus Syndrome

Abstract

Sodium hydroxide pinpoint pressing permeation (SHPPP) was investigated in order to build a rat model of sick sinus syndrome (SSS), which is easy to operate and control the degree of damage, with fewer complications and applicable for large and small animals.Thirty healthy Wistar rats (15 males and 15 females, weighing 250-350 g) were randomly divided into 3 groups, namely a formaldehyde thoracotomy wet compressing group (FTWC), formaldehyde pinpoint pressing permeation group (FPPP) group, and SHPPP group. The number of surviving rats, heart rate (HR), sinoatrial node recovery time (SNRT), corrected SNRT (CSNRT), and sinoatrial conduction time (SACT) were recorded 3 days, one week, and two weeks after modeling.The achievement ratio of modeling was 10% in the FTWC group, 40% in the FPPP group, and 70% in the SHPPP group, and the differences were statistically significant (χ(2) = 7.250, P = 0.007). Meanwhile, the HR was reduced by about 37% in these 3 groups 3 days after modeling, while the reduction was maintained only in SHPPP (P > 0.05) and the HR was re-elevated in the FTWC and FPPP groups 2 weeks after modeling (P < 0.05). Additionally, the SNRT, cS-NRT, and SACT were significantly prolonged compared with pre-modeling in all 3 groups (P < 0.01).SHPPP was the best method with which to build an SSS model with stable and lasting low HR and high success rate of modeling, which might be helpful for further studies on the SSS mechanisms and drugs.

Development of a Rat Model of Sick Sinus Syndrome Using Pinpoint Press Permeation

“…The extent of reduced heart rate to establish a functional animal SSS model remains unclear. In a previously reported SSS model, a 30–50% decrease in heart rate, sinus arrest, sinoatrial blockage, or nodal escape was significant outcomes [8, 9]. However, the number, size, location, and morphology of SAN cells vary between animals, indicating that SAN function and tolerance to low heart rate might vary between animal models.…”

“…In a previous report describing a less invasive method, a SSS rat model was established using a custom-made mapping catheter that carried a small cotton ball dipped in 20% sodium hydroxide sans respiratory support. The cotton ball was inserted close to the right edge of the second intercostal sternum, and the location was ensured by observing changes with an electrocardiogram in vitro, eliminating the need to remove a rib or open the chest, yielding a success rate of 70% [9]. Anatomically, the SAN region in a rat is covered by thymus tissue and the right atrial appendage, and the thymus tissue is further wrapped in a layer of epicardium, while the medial part of the right lung is located above the thymus tissue, which is close to the lateral edge in particular (Figure 6, left).…”

“…Thus, the method described above, we argue, carries a higher risk of in-procedure damage to the lung tissue, potentially leading to pneumothorax. Due to the anatomical restrictions described above, a custom-made syringe carrying a cotton ball cannot reach the SAN area [9] without causing certain damage to the lung and thymus tissue. In addition, the thin epicardium wrapping of the SAN area can only be separated by direct observation.…”

The cellular function and molecular mechanism of formaldehyde in cardiovascular disease and heart development

“…Arrhythmia is caused by abnormal electrical signalling within or exterior to the sinus node (SN), leading to slow signal conduction, blockage, or conduction through abnormal channels, which ultimately results in abnormal heartbeat frequency and rhythm. Studies have found that formaldehyde may have a potential role in causing arrhythmia including sick sinus syndrome (SSS), 8 atrioventricular block, 27 ventricular tachycardia, ventricular fibrillation 27 and atrial fibrillation (AF) 28 . In particular, cardiomyocytes, which comprise excitatory cells that conduct electrical signals and undergo contraction, are extremely sensitive to the toxic effects of formaldehyde.…”

“…Accordingly, the International Agency for Research on Cancer (IARC) classifies formaldehyde as a known human carcinogen 2 . Moreover, owing to its toxicity, formaldehyde also participates in the onset of neurodegenerative diseases such as ageing and Alzheimer's disease 6 and can cause cardiovascular diseases (CVD) such as atherosclerosis (AS), 7 arrhythmia 8 and stroke 9 as well. In addition, the exposure of pregnant women to formaldehyde mainly through pre‐pregnancy or during pregnancy not only damages the body of the pregnant woman but also endangers the growth and development of the foetus.…”