Treating pulmonary hypertension post cardiopulmonary bypass in pigs: milrinone vs. sildenafil analog

Author:

Urdaneta F1,Lobato EB1,Beaver T2,Muehlschlegel JD3,Kirby DS4,Klodell C2,Sidi A3

Affiliation:

1. Department of Anesthesiology, University of Florida College of Medicine, and Anesthesia Service; Malcom Randall Veterans Administration Medical Center, Gainesville, Florida

2. Department of Surgery, University of Florida College of Medicine, and Anesthesia Service

3. Department of Anesthesiology, University of Florida College of Medicine, and Anesthesia Service

4. Malcom Randall Veterans Administration Medical Center, Gainesville, Florida

Abstract

Procedures using cardiopulmonary bypass (CPB) and aortic cross-clamping are associated with a variable degree of ischemia/reperfusion of the lungs, leading to acute pulmonary hypertension (PHT). The purpose of this study was to compare the effects of the sildenafil analog (UK343-664), a phosphodiesterase type V(PDEV) inhibitor, with milrinone, a PDE type III inhibitor, in a porcine model of acute PHT following CPB. After the pigs were anesthetized, pressure-tipped catheters were placed in the right ventricle and carotid and pulmonary arteries. Cardiac output was measured with an ultrasound probe on the ascending aorta. After heparinization and placement of aortic and right atrial cannulae, non-pulsatile CPB was instituted and cardioplegia administered following aortic cross-clamping. After 30 minutes, the clamp was removed and the animals re-warmed and separated from CPB in sinus rhythm. The animals were randomized to 3 groups, and 16 animals were studied to completion: milrinone (n=5) 50 μg/kg; sildenafil-analog (n=5) 500 μg/kg; and normal saline (NS) (n=6). Hemodynamic data were collected at baseline pre-CPB and, following termination of CPB, at baseline, 5, 10 and 30 minutes after administration of the drug. Pulmonary hypertension was present in all groups following CPB. After administration of the drugs, mean pulmonary artery pressure decreased in all 3 groups; however, only in the sildenafil-analog group did pulmonary vascular resistance(PVR) decrease by 35%, from 820 to 433 dynes · cm · sec-5at 5 minutes (p<0.05), and continued to be decreased at 10 minutes by 26% (P<0.05). Pulmonary selectivity was demonstrated with sildenafil-analog, because there were no similar changes in systemic vascular resistance(SVR) and no significant changes in systemic hemodynamics. Sildenafil-analog, a PDEV inhibitor, shows a promising role for managing the PVR increases that occur following CPB.

Publisher

SAGE Publications

Subject

Advanced and Specialised Nursing,Cardiology and Cardiovascular Medicine,Safety Research,Radiology Nuclear Medicine and imaging,General Medicine

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1. Pharmacology of the Pulmonary Circulation;Principles and Practice of Anesthesia for Thoracic Surgery;2019

2. A Specific and Sensitive HPLC–MS/MS Micromethod for Milrinone Plasma Levels Determination After Inhalation in Cardiac Patients;Therapeutic Drug Monitoring;2014-10

3. Acute Right Ventricular Failure;The Right Ventricle in Health and Disease;2014-09-13

4. Retraction Statement;Perfusion;2011-10-25

5. Pharmacology of the Pulmonary Circulation;Principles and Practice of Anesthesia for Thoracic Surgery;2011

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