CAR Selectively Enhances the Pulmonary Vasodilatory Effect of Fasudil in a Microsphere Model of Pulmonary Hypertension.

Q3 Medicine Open Respiratory Medicine Journal Pub Date : 2023-04-27 eCollection Date: 2023-01-01 DOI:10.2174/18743064-v17-e230404-2022-19
Abraham Rothman, Humberto Restrepo, William N Evans, Valeri Sarukhanov, David Mann
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Abstract

Background: Despite the approval of several medications for pulmonary hypertension, morbidity and mortality are unacceptably high. Systemic hypotension may limit the use of pulmonary hypertension medications.

Objectives: This study aimed to assess whether the homing peptide CAR (CARSKNKDC) improves the vasodilatory selectivity of fasudil in the pulmonary circulation or systemic circulation in a porcine pulmonary hypertension model.

Materials and methods: Pulmonary hypertension (to approximately 2/3-3/4 systemic pressure levels) was induced by chronic and acute administration of microspheres in 3 micro Yucatan pigs (mean weight 19.9 kg, mean age 4.3 months). Fasudil (0.3 mg/kg) was administered without and with CAR (1.5 mg/kg), and the effect on aortic (Ao) and right ventricular (RV) pressure was recorded with indwelling catheters.

Results: Immediately after fasudil administration, there was a decrease in Ao pressure followed by prompt recovery to baseline. The RV pressure decrease was progressive and sustained. Fasudil alone resulted in a 12% decrease in RV pressure, whereas co-administration of CAR with fasudil resulted in a 22% decrease in RV pressure (p < 0.0001). Fasudil alone caused an average decrease of 34% in the RV/Ao pressure ratio, and fasudil + CAR caused an average decrease of 40% in the RV/Ao pressure ratio (p < 0.0001).

Conclusion: The homing peptide CAR selectively enhanced the acute vasodilatory effects of fasudil on the pulmonary vascular bed in a porcine experimental model of pulmonary hypertension.

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CAR选择性地增强法舒地尔在肺动脉高压微球模型中的肺血管扩张作用
尽管已经批准了几种治疗肺动脉高压的药物,但发病率和死亡率高得令人无法接受。系统性低血压可能限制肺动脉高压药物的使用。本研究旨在评估归巢肽CAR(CARSKNKDC)是否能改善猪肺动脉高压模型中法舒地尔在肺循环或体循环中的血管舒张选择性。在3头尤卡坦微型猪(平均体重19.9kg,平均年龄4.3个月)中,通过慢性和急性给药微球诱导肺动脉高压(达到约2/3-3/4的全身压力水平)。Fasudil(0.3 mg/kg)在无CAR和有CAR的情况下给药(1.5 mg/kg),并用留置导管记录对主动脉(Ao)和右心室(RV)压力的影响。法舒地尔给药后,Ao压力立即下降,随后迅速恢复到基线。RV压力的下降是渐进和持续的。Fasudil单独用药可使RV压力降低12%,而CAR与Fasudil联合用药可使右心室压力降低22%(p<0.0001)。Fasudil单药可使RV/Ao压力比平均降低34%,在猪肺动脉高压实验模型中,归巢肽CAR选择性增强了法舒地尔对肺血管床的急性血管舒张作用。
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来源期刊
Open Respiratory Medicine Journal
Open Respiratory Medicine Journal Medicine-Pulmonary and Respiratory Medicine
CiteScore
1.70
自引率
0.00%
发文量
17
期刊介绍: The Open Respiratory Medicine Journal is an Open Access online journal, which publishes research articles, reviews/mini-reviews, letters and guest edited single topic issues in all important areas of experimental and clinical research in respiratory medicine. Topics covered include: -COPD- Occupational disorders, and the role of allergens and pollutants- Asthma- Allergy- Non-invasive ventilation- Therapeutic intervention- Lung cancer- Lung infections respiratory diseases- Therapeutic interventions- Adult and paediatric medicine- Cell biology. The Open Respiratory Medicine Journal, a peer reviewed journal, is an important and reliable source of current information on important recent developments in the field. The emphasis will be on publishing quality articles rapidly and making them freely available worldwide.
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