Application of superior vena cava spectrum in evaluation of therapeutic effects of monocrotaline-induced pulmonary arterial hypertension in rats

doi:10.3877/cma.j.issn.1672-6448.2016.02.015

Abstract

Abstract:

Objective

To investigate the value of spectrum of superior vena cava (SVC) in estimation of curative effect of monocrotaline induced pulmonary hypertension in rats.

Methods

One hundred and sixty-eight (weight 180-220 g) healthy adult male SD rats were included, with 10 rats as normal controls. Pulmonary hypertension rat models (pulmonary artery systolic pressure greater than 30 mmHg, 1 mmHg = 0.133 kPa) were established by intraperitoneal injection of 2% monocrotaline 50 mg/kg. In twenty-eighth days, 8/103 rats were randomly selected to assess the efficacy of the model. The rest rats were randomly treated with beraprost, sildenafil, bosentan (24 rats/group) and placebo (23 rats), accordingly divided into four groups. After 2 weeks of treatment, SVC Doppler ultrasound and right ventricular pressure, pulmonary arterial systolic pressure measured with right heart catheter were compared.

Results

Pulmonary arterial hypertension model was successfully established in 55 rats and they all underwent SVC ultrasound examination. AR/S ratio of the right SVC and S velocity of both the left and right SVCs had a good correlation with the pulmonary arterial pressures. SVC Doppler flow showed significantly increased AR/S and decreased S wave compared with the control group (P<0.01). Pulmonary artery systolic pressure was significantly correlated the right SVC AR/S ratio (AR/S of right SVC: Y=50.07X+24.62, R²=0.302, P<0.01; AR/S of left SVC: r=0.491, P<0.01). Drug efficacy analysis: on analysis of natural mortality after administration, dead rats in each group appeared hydrothorax, ascites and pericardial effusion, which was more severe in placebo and bosentan groups. Bosentan group had the highest mortality. But there was no significant difference among groups (P>0.05). The lung tissue pathology examination showed varied degrees of membrane thickening, lumen narrowing and smooth muscle hyperplasia in all groups.

Conclusion

The pulmonary arterial hypertension model could be successfully established by intraperitoneal injection of 2% MCT. There was no statistically significant difference in the short-term efficacy of beraprost, sildenafil and bosentan. AR/S of right SVC correlated well with the pulmonary artery systolic pressure and it may be used as one of Doppler ultrasound parameters for evaluation of pulmonary hypertension and its therapeutic effects.

Key words: Vena cava, superior, Monocrotaline, Hypertension, pulmonary, Rats

Ying Hou, Lijun Yuan, Yuemin Wang, Juan Li, Lei Shi, Jingxi Du, Yunyou Duan. Application of superior vena cava spectrum in evaluation of therapeutic effects of monocrotaline-induced pulmonary arterial hypertension in rats[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2016, 13(02): 154-160.

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References 18

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组别	鼠数（只）	RVSP（mmHg）	PASP（mmHg）	NO（μmol/L）	体重（g）	RV/IVS+LV	RV/BW（mg/g）
肺动脉压力正常	13	27.79±5.29	21.74±5.77	12.14±6.71	370.00±52.12	0.27±0.03	0.42±0.18
肺动脉高压	42	70.95±22.27	63.72±20.72	18.27±10.64	287.68±61.63	0.59±0.15	0.84±0.65
t值	?	-10.55	-10.77	-2.19	4.33	-12.13	-3.62
P值	?	<0.01	<0.01	<0.05	<0.01	<0.01	<0.01
组别	鼠数（只）	RSVC-S（cm/s）	RSVC-AR（cm/s）	RAR/S	LSVC-S（cm/s）	LSVC-AR（cm/s）	LAR/S
肺动脉压力正常	13	38.19±6.23	14.50±5.43	0.38±0.16	46.81±16.45	15.16±6.12	0.33±0.12
肺动脉高压	42	24.28±15.92	13.40±8.14	0.63±0.25	23.72±15.25	14.78±6.11	0.77±0.35
t值	?	4.53	0.54	-3.34	4.36	0.19	-6.99
P值	?	<0.01	>0.05	<0.01	<0.01	>0.05	<0.01

组别	鼠数（只）	RVSP（mmHg）	PASP（mmHg）	NO（μmol/L）	体重（g）	RV/IVS+LV	RV/BW（mg/g）
肺动脉压力正常	13	27.79±5.29	21.74±5.77	12.14±6.71	370.00±52.12	0.27±0.03	0.42±0.18
肺动脉高压	42	70.95±22.27	63.72±20.72	18.27±10.64	287.68±61.63	0.59±0.15	0.84±0.65
t值	?	-10.55	-10.77	-2.19	4.33	-12.13	-3.62
P值	?	<0.01	<0.01	<0.05	<0.01	<0.01	<0.01
组别	鼠数（只）	RSVC-S（cm/s）	RSVC-AR（cm/s）	RAR/S	LSVC-S（cm/s）	LSVC-AR（cm/s）	LAR/S
肺动脉压力正常	13	38.19±6.23	14.50±5.43	0.38±0.16	46.81±16.45	15.16±6.12	0.33±0.12
肺动脉高压	42	24.28±15.92	13.40±8.14	0.63±0.25	23.72±15.25	14.78±6.11	0.77±0.35
t值	?	4.53	0.54	-3.34	4.36	0.19	-6.99
P值	?	<0.01	>0.05	<0.01	<0.01	>0.05	<0.01

组别	鼠数（只）	PVSP（mmHg）	PASP（mmHg）	NO（μmol/L）	体重（g）	RV/IVS+LV	RV/BW（mg/g）
对照组	10	28.37±5.63	21.74±6.62	12.54±7.38	359.00±52.16	0.28±0.03	0.41±0.21
贝前列素组	10	64.00±22.41^b	58.60±21.19^b	20.25±16.08	299.40±65.31	0.57±0.19^b	0.90±0.69
西地那非组	12	70.20±28.24^b	63.20±27.50^b	16.43±8.49	307.75±79.69	0.53±0.17^b	1.04±0.67
波生坦组	10	84.40±26.08^b	74.40±20.91^b	13.56±6.93	266.00±55.02^b	0.64±0.14^b	0.77±0.63
安慰剂组	5	53.40±24.13^a	47.30±22.77^a	13.79±7.69	343.20±68.04	0.54±0.20^b	0.60±0.53
模型组	8	57.33±9.12^a	50.58±9.03^a	25.10±4.72	276.00±50.26^a	0.50±0.18^a	0.37±0.39
F值	?	6.528	6.930	1.401	2.759	5.343	1.786
P值	?	<0.01	<0.01	>0.05	<0.05	<0.01	>0.05
组别	鼠数（只）	RSVC-S（cm/s）	RSVC-AR（cm/s）	RAR/S	LSVC-S（cm/s）	LSVC-AR（cm/s）	LAR/S
对照组	10	38.17±7.01	14.06±5.34	0.36±0.16	42.00±13.41	14.06±6.16	0.33±0.14
贝前列素组	10	30.16±20.36	15.13±7.50	0.60±0.22	37.89±19.43	18.19±3.94	0.61±0.33
西地那非组	12	31.68±15.11	17.39±12.10	0.61±0.34	33.06±21.42	18.25±8.02	0.72±0.31^b
波生坦组	10	15.10±9.73^b	9.69±3.15	0.65±0.25	13.79±5.32^b	10.58±5.01	0.86±0.45^b
安慰剂组	5	28.46±16.28	12.91±2.59	0.57±0.27	27.52±15.71	12.86±3.06	0.57±0.26
模型组	8	18.80±9.37^b	11.12±5.25	0.61±0.16^a	16.00±4.84^b	13.59±3.68	0.90±0.35^b
F值	?	3.418	1.455	1.699	5.272	2.985	3.841
P值	?	<0.05	>0.05	>0.05	<0.01	<0.05	<0.01

组别	鼠数（只）	PVSP（mmHg）	PASP（mmHg）	NO（μmol/L）	体重（g）	RV/IVS+LV	RV/BW（mg/g）
对照组	10	28.37±5.63	21.74±6.62	12.54±7.38	359.00±52.16	0.28±0.03	0.41±0.21
贝前列素组	10	64.00±22.41^b	58.60±21.19^b	20.25±16.08	299.40±65.31	0.57±0.19^b	0.90±0.69
西地那非组	12	70.20±28.24^b	63.20±27.50^b	16.43±8.49	307.75±79.69	0.53±0.17^b	1.04±0.67
波生坦组	10	84.40±26.08^b	74.40±20.91^b	13.56±6.93	266.00±55.02^b	0.64±0.14^b	0.77±0.63
安慰剂组	5	53.40±24.13^a	47.30±22.77^a	13.79±7.69	343.20±68.04	0.54±0.20^b	0.60±0.53
模型组	8	57.33±9.12^a	50.58±9.03^a	25.10±4.72	276.00±50.26^a	0.50±0.18^a	0.37±0.39
F值	?	6.528	6.930	1.401	2.759	5.343	1.786
P值	?	<0.01	<0.01	>0.05	<0.05	<0.01	>0.05
组别	鼠数（只）	RSVC-S（cm/s）	RSVC-AR（cm/s）	RAR/S	LSVC-S（cm/s）	LSVC-AR（cm/s）	LAR/S
对照组	10	38.17±7.01	14.06±5.34	0.36±0.16	42.00±13.41	14.06±6.16	0.33±0.14
贝前列素组	10	30.16±20.36	15.13±7.50	0.60±0.22	37.89±19.43	18.19±3.94	0.61±0.33
西地那非组	12	31.68±15.11	17.39±12.10	0.61±0.34	33.06±21.42	18.25±8.02	0.72±0.31^b
波生坦组	10	15.10±9.73^b	9.69±3.15	0.65±0.25	13.79±5.32^b	10.58±5.01	0.86±0.45^b
安慰剂组	5	28.46±16.28	12.91±2.59	0.57±0.27	27.52±15.71	12.86±3.06	0.57±0.26
模型组	8	18.80±9.37^b	11.12±5.25	0.61±0.16^a	16.00±4.84^b	13.59±3.68	0.90±0.35^b
F值	?	3.418	1.455	1.699	5.272	2.985	3.841
P值	?	<0.05	>0.05	>0.05	<0.01	<0.05	<0.01

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