Author:
Rothman Abraham,Restrepo Humberto,Evans William N.,Sarukhanov Valeri,Mann David
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.
Publisher
Bentham Science Publishers Ltd.
Subject
Pulmonary and Respiratory Medicine
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