RESEARCH ARTICLE
CAR Selectively Enhances the Pulmonary Vasodilatory Effect of Fasudil in a Microsphere Model of Pulmonary Hypertension
Abraham Rothman1, 2, *, Humberto Restrepo1, 2, William N. Evans1, 2, Valeri Sarukhanov1, David Mann3
Article Information
Identifiers and Pagination:
Year: 2023Volume: 17
E-location ID: e187430642303160
Publisher ID: e187430642303160
DOI: 10.2174/18743064-v17-e230404-2022-19
Article History:
Received Date: 15/10/2022Revision Received Date: 17/01/2023
Acceptance Date: 02/03/2023
Electronic publication date: 27/04/2023
Collection year: 2023
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
