Selective vasodilation by nitric oxide inhalation during sustained pulmonary hypertension following recurrent microembolism in pigs.
OBJECTIVE
This study establishes a new model of sustained pulmonary hypertension induced by recurrent microembolism in pigs and evaluates the effects of nitric oxide (NO) inhalation in this model.


METHODS
Fourteen pigs were embolized under general anesthesia with 300-microm microspheres intravenously three times over a period of 7 weeks. Four pigs served as untreated controls. Hemodynamic and gas exchange measurements were performed on days 1 and 7 after the last embolization.


RESULTS
Recurrent microembolism caused sustained pulmonary hypertension (mean pulmonary artery pressure [MPAP] 26 +/- 2 and 18 +/- 1 mm Hg on days 1 and 7, respectively) compared with the control group (MPAP 13 +/- 1 mm Hg each for days 1 and 7; P < .05, respectively). Right heart hypertrophy was present at autopsy as indicated by an increase in minimal myocyte diameter. Inhaled NO (5 and 40 parts per million [ppm]) was administered on days 1 and 7. On both days, inhaled NO significantly reduced MPAP and pulmonary vascular resistance without affecting systemic hemodynamics. There were no differences in responses to 5 and 40 ppm inhaled NO.


CONCLUSIONS
We conclude that recurrent microembolization in pigs provides a reliable model of sustained pulmonary hypertension. In this model inhaled NO is a selective pulmonary vasodilator, indicating that active vasoconstriction significantly contributes to sustained pulmonary hypertension after recurrent microembolism.
Weimann
J
J
Department of Anesthesiology, Institute of Pathology, Ruprecht-Karls-University, Heidelberg, Germany.
Zink
W
W
Schnabel
P A
PA
Jakob
H
H
Gebhard
M M
MM
Martin
E
E
Motsch
J
J
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004617:Embolism / Q000150:complications; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008863:Microspheres; D009569:Nitric Oxide / Q000627:therapeutic use*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012138:Respiratory Therapy / Q000379:methods*; D013552:Swine; D014665:Vasodilator Agents / Q000627:therapeutic use*
D014665:Vasodilator Agents; D009569:Nitric Oxide