Blockade of endothelin-converting enzyme reduces pulmonary hypertension after cardiopulmonary bypass and circulatory arrest.
BACKGROUND
Pulmonary dysfunction associated with elevated pulmonary vascular resistance is a significant problem after cardiopulmonary bypass (CPB) and circulatory arrest. Mediators of the pulmonary hypertensive response to CPB have not been fully elucidated. The purpose of this study was to examine the contribution of the endothelium-derived vasoconstrictor endothelin-1 to postbypass pulmonary hypertension.


METHODS
Twelve 1-month-old piglets were instrumented with left atrial and pulmonary artery (PA) micromanometers and a PA flow probe. Phosphoramidon (Phos, n = 6) pigs received a 30 mg/kg bolus of Phos, an endothelin converting enzyme inhibitor. Controls (n = 6) received saline solution. All animals were placed on CPB and underwent a 60-minute period of circulatory arrest. The indexed pulmonary vascular resistance (PVRI) was calculated at baseline for controls, both before and 10 minutes after drug infusion in the Phos group, and 15 minutes after separation from CPB in both groups.


RESULTS
Pre-CPB, mean PA pressure, and PVRI were not different between the control and Phos groups (14.6 +/- 1.1 versus 14.5 +/- 1.1 mm Hg and 7322 +/- 1269 versus 7260 +/- 947 dyne/sec/kg/cm-5, respectively). After CPB mean PA pressure was significantly higher in control than Phos animals (32.1 +/- 1.1 versus 22.5 +/- 1.3 mm Hg, p = 0.0003). PVRI was also significantly higher in the controls (30896 +/- 4714 versus 14972 +/- 1710, dyne/sec/kg/cm-5, p = 0.02).


CONCLUSIONS
Production of endothelin-1 during CPB and circulatory arrest is a mediator of postbypass pulmonary hypertension.
Kirshbom
P M
PM
Division of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Tsui
S S
SS
DiBernardo
L R
LR
Meliones
J N
JN
Schwinn
D A
DA
Ungerleider
R M
RM
Gaynor
J W
JW
D000818:Animals; D001158:Arteries; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D002315:Cardiopulmonary Bypass; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000502:physiology*; D005740:Gases / Q000097:blood; D006020:Glycopeptides / Q000494:pharmacology; D006324:Heart Arrest, Induced; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000209:etiology*; D008666:Metalloendopeptidases; D011183:Postoperative Complications; D011652:Pulmonary Circulation / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D016232:Endothelins; D005740:Gases; D006020:Glycopeptides; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon