The differential in vitro effects of clinically used vasoactive drugs on small human pulmonary vessels

Hussain, Azar

July 2017

Thesis or dissertation

© 2017 Azar Hussain. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.

Pulmonary hypertension (PH) is an important prognostic factor in cardiac surgery and is associated with increased morbidity and mortality. The mechanism of the underlying pathophysiology is complex and PH may exist prior to surgery or might develop during or after surgery. Different models are used to explore the underlying cellular and molecular mechanism of lung disease especially pulmonary vascular disease. Isolation of human pulmonary artery and measurement of pulmonary vascular tension are vital to understand the pathophysiology of human pulmonary vessels. The aim of this study was to characterize the effects of clinically used pharmacological agents on the human pulmonary vasculature.

Patients undergoing lung resection were consulted and consented for their resected lung tissue to be included in the study. Pulmonary arteries (PA) dissected from disease free areas of lung resection and PA rings of internal diameter 2-4 mm and 2 mm long were prepared. Integrity of the endothelium was confirmed with 1μM acetylcholine (ACh) and 37.6 μM (EC₈₀) potassium chloride (KCl) was used to check the contractility of PA rings. Multiwire myograph system was used to mount the PA rings under physiological conditions in modified Krebs solution. Concentration response curves were constructed to pharmacological agents by cumulative addition to the myograph chambers.

Both the multi-wire myograph and organ bath system have demonstrated identical conclusions and confirmed that the most efficient resting tension for human PA rings of internal diameter 2-4 mm is 1.61 gf Vasopressin had no vasoconstrictive effect on the small human pulmonary arteries and hence may be safe to use for systemic vasoconstriction in patients with pulmonary hypertension. The prostacyclin analogues were the most potent and efficacious vasodilators in the isolated human pulmonary arteries.

The current study is the only in vitro study that demonstrated the efficacy and potency of clinically used vasopressors, prostacyclin analogues, sodium nitroprusside and phosphodiesterase inhibitors on human pulmonary vascular reactivity. These effects may inform the use of these drugs in the clinical setting as prostacyclin analogues provide better results. Fully blinded randomized control trials are needed to show the potential bench to bed effect of this study.

Hull York Medical School, The University of Hull and University of York
Morice, Alyn H.; Loubani, Mahmoud
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