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
1 Children’s Heart Center, Nevada3131 La Canada, Suite 230, Las Vegas, NV 89169, USA
2 Department of Pediatrics, University of Nevada Las Vegas, School of Medicine, 2040 W Charleston Blvd Ste. 402, Las Vegas, NV 89109, USA
3 Vascular BioSciences, 72 Santa Felicia Dr, Goleta, CA 93117, USA

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© 2023 Rothman et al.

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: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address corresponding to this author at the Children’s Heart Center Nevada 3131 La Canada St. Suite 230, Las Vegas NV 89169 USA; Tel: (702) 732-1290; Fax: (702) 732-1385; E-mail:



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.


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.


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).


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.

Keywords: Animal research, CAR, Homing peptide, Fasudil, Pulmonary hypertension, Swine.