Establishment of a Rabbit Heart-failure Model Using Transverse Aortic Constriction

doi:10.12300/j.issn.1674-5817.2022.020

Abstract

Abstract:

Objective To investigate the method and feasibility of establishing a rabbit heart-failure model using transverse aortic constriction (TAC). Methods Twenty-five healthy male Japanese white rabbits were randomly divided into an operation group (n=15) and a sham-operation group (n=10). The animals in the operation group underwent TAC to establish the rabbit model of heart failure. The sham-operation group underwent thoracotomy but no narrowing operation. Cardiac function was evaluated using ultrasound at 4 and 8 weeks after operation. Eight weeks after operation, the descending aortic flow velocity was detected using cardiac ultrasound, combined with molecular biological indexes and pathological observations to verify the feasibility and stability of TAC in establishing the rabbit heart-failure model. Results Eight weeks after operation, 13 rabbits in the operation group and 10 in the sham-operation group survived. The blood flow velocities at the constriction in the operation group were >2.20 m/s. Compared with the sham-operation group, the following outcomes in the operation group increased significantly (P<0.05): heart rate, ascending aortic diameter, left atrial end-diastolic diameter, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter. Left ventricular ejection fraction decreased significantly (P<0.05). Compared with the sham-operation group, the contents of left ventricular N-terminal pro B type natriuretic peptide (NT-proBNP) and β-myosin heavy chain (β-MHC) significantly increased in the operation group (P<0.05). Pathological sections showed that 8 weeks after TAC, cardiomyocytes in the operation group were hypertrophic and disordered, and myocardial fiber bundles widened. Interventricular septal end-diastolic thickness and left ventricular posterior wall end-diastolic thickness significantly increased in the operation group (P<0.05), compared to those in the sham-operation group at 4 weeks. Conclusion It is effective and feasible to establish an experimental rabbit heart-failure model using TAC. Cardiac ultrasound is an effective method to evaluate and determine the degree of aortic arch constriction and the success of heart-failure modeling. Rabbits in the operation group showed myocardial decompensation at 8 weeks after TAC, resulting in irreversible heart failure.

Key words: Ultrasound, Transverse aortic constriction, Heart failure, Rabbits

CLC Number:

Q95-33

Qingyi LUO, Tiling ZHANG, Yunchuan DING, Jian CHEN, Li ZHAO, Qinghui WANG. Establishment of a Rabbit Heart-failure Model Using Transverse Aortic Constriction[J]. Laboratory Animal and Comparative Medicine, 2022, 42(5): 401-408.

Figures/Tables 6

Figure 1 Sites of surgical ligation of the transverse aortic constriction (TAC) in rabbitsNote：A, Schematic diagram of the site of coarctation of the aorta in TAC; the black circle indicates the ligation site. B, Intraoperative opration diagram of TAC; the arrow shows the ligation site.

Figure 2 Flow velocity of the descending aorta in rabbitsNote： A, The flow velocity at the coarctation of the descending aorta measured in the suprasternal fossa was 2.25 m/s at 8 weeks after transverse aortic constriction operation (n=13); B, The velocity of the descending aorta measured in the suprasternal fossa section was 0.22 m/s (n=10) at 8 weeks after operation in rabbits in the sham-operated group; C, Bar graph comparing the descending aortic flow velocity between the two groups, *P<0.05.

Table 1 Changes in cardiac ultrasound parameters at 4 and 8 weeks after operation

项目 Items	假手术组 Sham-operation group		TAC手术组 TAC operation group
项目 Items	4周 4 weeks	8周 8 weeks	4周 4 weeks		8周 8 weeks
心率HR/(次·min^-1)	218.00±18.00	225.00±15.00	251.00±15.00	300.00±20.00^*
升主动脉内径AAOd/mm	4.31±0.74	4.52±0.91	4.72±0.77	7.57±0.88^*
左房舒张末期内径LADd/mm	3.56±0.84	3.75±0.55	3.84±0.92	4.94±0.42^*
左室舒张末期内径LVEDd/mm	11.04±1.70	12.15±1.51	12.55±1.84	15.45±1.66^*
左室收缩末期内径LVEDs/mm	4.64±0.75	4.89±0.68	5.14±0.92	8.83±0.72^*
左室舒张末期室间隔厚度IVSd/mm	1.73±0.34	1.87±0.26	2.95±0.41^*	1.51±0.32
左室后壁舒张末期厚度LVPWd/mm	1.55±0.32	1.76±0.24	2.65±0.56^*	1.23±0.41
左室射血分数LVEF/%	57.33±7.24	60.16±11.97	58.31±8.74	40.29±7.62^*

Figure 3 Doppler echocardiography shows the apical four-chamber view of each groupNote： A, Apical four-chamber view of the sham-operation group 4 weeks after operation; B, Apical four-chamber view of the sham-operation group 8 weeks after operation; C, Apical four-chamber view of the operation group 4 weeks after transverse aortic constriction operation; D, Apical four-chamber view of the operation group 8 weeks after transverse aortic constriction operation.

Figure 4 Changes in the contents of left ventricular heart failure markets 8 weeks after TAC detected by real-time quantitative PCRNote：A, NT-proBNP content at 8 weeks after operation; B， β-MHC content at 8 weeks after operation. Compared with the sham-operation，*P<0.05； n=3.

Figure 5 HE staining and Masson staining of experimental rabbit myocardial tissues in the operation and sham-operation groupsNote： A, HE stained sections of the sham-operation group and the transverse aortic constriction (TAC) operation group at 8 weeks after operation (upper, ×20; lower, ×40); B, Masson’s trichrome stained sections of the sham-operation group and the TAC operation group at 8 weeks after operation (upper, ×40; lower, ×100).

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