Effects of perindopril on the swallowing reflex
in a rat dysphagia model induced by ligation ofbilateral common carotid arteries (BCAO)○ Yuuji Murata, Chengjun Ma, Takashi Tashiro, Kousuke Morizumi, Seiichi Katayama,

Naoyuki Hironaka, Katsuhide Nishi

Summary in Japanese

Objective
Dysphagia, as one cause of aspiration pneumonia is still to be amajor complication in the patients with such pathologicalconditions as cerebrovascular disease, Parkinson's disease,aging, and overdose of antipsychotic drugs. To evaluate theeffects of the chemicals on dysphagia, we established a rat
dysphagia model by ligation of bilateral common carotid
arteries (BCAO).

In this study, we investigated the protective effects of perindopril
against the dysfunction of the swallowing reflex in the BCAO
ligation model rats.

Materials and Methods

誤 嚥 性 肺炎の原因の 一つである嚥 下障害は，脳 血管疾 患，パーキンソン病，加 齢，抗精神病薬の過剰摂取の患者にとって，依然として主要な合併症である．化合物の嚥下障害に対する効果を評価するために，両側総頚動脈（BCAO）の結紮によるラット嚥下障害モデルを作製した．

この研究では，ラットのBCAOにおける嚥下反射の機能不全に対するペリンドプリルの効果を検討した．BCAOラットは，イソフルラン吸入による麻酔下で，両側総頚動脈を結紮して作製し，嚥下障害を誘発した．BCAOラットにペリンドプリルを4週間反復経口投与し，BCAOまたは偽手術後 29日目に顎舌骨筋の筋電図（EMG）を記録することによって嚥下反射を測定した．BCAOラットでは，ペリンドプリルの4週間経口投与により，嚥下反射の減少が改善された．これらの結果は，BCAO によって嚥下障害モデルが確立され，ラットの BCAO 誘発嚥下障害モデルを用いて嚥下反射に対する化合物の効果を評価できることが示している．

Results● Animal

Experiment 1

Crl:CD(SD), ♂, 7w● Model preparation and evaluation method
Experiment 1

Study on the elicitation of swallowing reflexes in normal rats

Swallowing reflexes were elicited by infusion of water for injection or
citric acid and were determined by recording electromyogram (EMG) ofmylohyoid muscle in normal rats.
Experiment 2

Evaluation of the effects of perindopril in BCAO rats

BCAO rats were prepared by ligation of bilateral common carotid
arteries to induce dysphagia under anesthesia with isoflurane
inhalation. Perindopril was continuously administered orally for 4 weeks,
and the swallowing reflex was determined by recording EMG ofmylohyoid muscle at 29 days post-BCAO or sham-operation.
Test Group

Dose level

Sham group-BCAO group(Control)

0Animalnumber

Dose volume Dose route-

5 mL/kg

Perindopril group 0.4 mg/kg

p.o.

Ligation ofBCAO-1 Ｗ
Quarantine andAcclimatization0W2W

3W

Administration (p.o.) of
perindopril or water for injection
at 1 time/day for 29 days

● Image diagram of swallowing reflex measurement

Infusion tube

For inducing
swallowing reflex

Citric acid
(30 mM)

Experiment 2

##86

**

4
20Sham(n=7)

Control(n=11)

Perindopril(n=12)

Figure 2 Elicitation by water for injection**p<0.01 vs sham group (Student’s t-test) ; ## p<0.01 vs Control group (Student’s t-test)

Conclusion

Mylohyoid muscle
Electrode

Citric acid(10 mM)**p<0.01 vs water for injection group; ## p<0.01 vs Citric acid 10mM group (Student’s t-test)

104W

Water forinjection

Figure 1 Elicitation by water for injection or Citric acid11

Measurement ofswallowing reflex
1W

1012

● Experimental schedule**20712##300

Number of swallows● Group composition

Number of swallows

40

Electromyogram(1) In the rats stimulated by citric acid, the number of theswallowing reflexes was significantly increased compared tothose stimulated by water for injection.

(2) The number of the swallowing reflexes was significantly
decreased in the BCAO (control) group compared to the shamgroup. By administration of perindopril, the number ofswallowing reflexes was significantly increased compared tothe control group.

In conclusion, BCAO treatment induced dysphagia in rats.
Perindopril improved the swallowing reflexes in theBCAO-induced dysphagia in rats, indicating that BCAO-induced
dysphagia model in rats is useful in the development oftherapeutic drugs on dysphagia.