The differential effects of systemic vasoconstrictors on human pulmonary artery tension.
OBJECTIVE
Acute pulmonary hypertension following cardiac surgery can have a significant effect on postoperative morbidity and mortality. However, limited data are available on the efficacy and potency of clinically used systemic vasopressors on the pulmonary vasculature. The aim of this study was to use human pulmonary artery to characterize the pharmacological effects of clinically used vasopressors on the human pulmonary vasculature.


METHODS
Fifty-seven pulmonary artery rings of internal diameter 2-4 mm and 2 mm long, mounted in a multiwire myograph system, were used to measure changes in isometric tension. We constructed concentration response curves by cumulative addition to the myograph chambers of KCl, noradrenaline (NA), adrenaline (AD), vasopressin, endothelin-1 (ET-1) and prostaglandin F2a (PGF2a).


RESULTS
AD, NA, ET-1, PGF2a and KCl caused dose-dependent vasoconstriction in the pulmonary artery samples (EC50 246 nM [95% confidence interval, CI, 153-394 nM], 150 nM [95% CI 51-447 nM], 1.46 nM [95% CI 0.69-3.1 nM], 6.35 µM [95% CI 3.58-11.2 µM] and 17.24 mM [95% CI 12.43-24.07 mM], respectively), whereas vasopressin had no significant effect. The order of efficacy was KCl = PGF2a > AD > NA > ET-1 and the order of potency was ET-1 T-AD = NA > PGF2a > KCl.


CONCLUSIONS
This study demonstrated the efficacy and potency of clinically used vasopressors and endogenous vasopressors on human pulmonary vascular tone. PGF2a and KCl equally caused maximal amounts of constriction, whereas ET-1 had less effect and vasopressin had no effect. These effects may need to be taken into account in the clinical setting because they might result in the development of pulmonary hypertension.
Department of Cardiothoracic Surgery, Castle Hill Hospital, Cottingham, UK.
Azar
A
Hussain
Department of Cardiothoracic Surgery, Castle Hill Hospital, Cottingham, UK.
Rob
R
Bennett
Department of Cardiothoracic Surgery, Castle Hill Hospital, Cottingham, UK.
Yama
Y
Haqzad
Department of Cardiothoracic Surgery, Castle Hill Hospital, Cottingham, UK.
Syed
S
Qadri
Department of Cardiothoracic Surgery, Castle Hill Hospital, Cottingham, UK.
Mubarak
M
Chaudhry
Department of Cardiothoracic Surgery, Castle Hill Hospital, Cottingham, UK.
Michael
M
Cowen
Department of Cardiothoracic Surgery, Castle Hill Hospital, Cottingham, UK.
Mahmoud
M
Loubani
Department of Respiratory Medicine, Castle Hill Hospital, Cottingham, UK.
Alyn
A
Morice
D000328:Adult; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008955:Models, Cardiovascular; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014667:Vasopressins; D011189:Potassium Chloride
Human; In vitro; Pulmonary artery rings; Pulmonary hypertension; Vasoconstrictor