CORRELATION OF PLASMA ENDOTHELIN-1 LEVELS WITH PULMONARY HYPERTENSION AFTER INHALED NITRIC OXIDE THERAPY
Abstract
Background: Variable response to inhaled nitric oxide (iNO) therapy in patients with mitral stenosis(MS) having pulmonary hypertension (PH) has been documented in early studies. The objectives of this
study were to measure plasma Endothelin-1 (ET-1) levels in those patients and to correlate them with
pulmonary vascular indices after iNO therapy. It was Quesi-experimental study. Methods: Thirty
patients with mitral or mixed mitral and aortic valve disease with severe pulmonary hypertension and
enrolled for valve replacement surgery were included. Before the replacement, baseline pulmonary
vascular indices and cardiac output were recorded. After the surgery, 10-20 ppm iNO was administered
for 1 hour and all the parameters were again recorded. Patients were grouped into responders and non
responders on the basis of % reduction in Pulmonary Vascular Resistance (PVR) after iNO therapy.
Plasma ET-1 levels were measured in both groups by ELISA before and after the iNO therapy. Paired
sample t-test was used to compare mean values for significance. The correlations between variables
were then calculated by using Pearson's coefficient. Results: The plasma ET-1 levels were very high in
all patients. They reduced in responders after iNO therapy; non-responders paradoxically showed
significant increase in the levels of ET-1 after iNO therapy. Moreover, a positive correlation was
observed in plasma ET-1 levels and post operative levels of PVR. Conclusion: The correlation of
changes in PVR and plasma ET-1 levels in responders suggests that high plasma ET-1 is a key
mediator of poor response in PH secondary to MS, after iNO therapy.
Keywords: Mitral Stenosis, Pulmonary Hypertension, Inhaled Nitric Oxide
References
Palmer RM, Ferrige AG, Moncada S. Nitric oxide release
accounts for the biological activity of endothelium- derived
relaxing factor. Nature 1987;327:524-6.
Ichinose F, Roberts JD, Zapol WM. Inhaled Nitric Oxide: A
selective pulmonary vasodilator: current uses and therapeutic
potential. Circulation 2004;109;3106-11.
Rich GF, Murphy GD, Roos CM, Johns RA. Inhaled nitric
oxide: selective pulmonary vasodilator in cardiac surgical
patients.Anesthesiology1993;78:1028-35.
Razzaq Z, Aslam M, Hussain MM, Naqvi S, Zameer M, Badar
Ahmed. Variable response to inhaled nitric oxide in post
operative patient of motral stenosis with pulmonary hypertension.
J Ayub Med Coll Abbottabad 2009;21(1):98-102.
Giaid A, Yanagisawa M, Langleben D, Miche RPl, Levy R,
Shennib H et al. Expression of endothelin-1 in the lungs of
patients with pulmonary hypertension. N Engl J Med
;328:1732-9.
Giaid A. Nitric Oxide and Endothelin-1 in Pulmonary
Hypertension. Chest 1998;114(3 Suppl):208-12
Dupuis J, Goresky CA, Rose CP, Stewart DJ, Cernacek P,
Schwab AJ, et al. Endothelin-1 myocardial clearance,
production, and effect on capillary permeability in vivo. Am
J Physiol 1997;273:H1239-45.
Cody RJ, Haas GJ, Binkley PF, Capers Q, Kelley R. Plasma
endothelin correlates with the extent of pulmonary
hypertension in patients with chronic congestive heart failure.
Circulation. 1992;85:504-9.
Nootens M, Kaufmann E, Rector T, Toher C, Judd D, Francis
GS, et al. Neurohormonal activation in patients with right
ventricular failure from pulmonary hypertension: relation to
hemodynamic variables and endothelin levels. J Am Coll
Cardiol 1995;26:1581-5.
Dupuis J, Rouleau JL, Cernacek P. Reduced pulmonary
clearance of endothelin-1 contributes to the increase of
circulating levels in heart failure secondary to myocardial
infarction. Circulation 1998;98:1684-7.
Chen MC, Wu CJ, Yip HJ, Cheng HW, Chen CJ, Yu TH, et
al. Increased circulating endothelin-1 in mitral stenosis:
Irrelevance of left atrial and pulmonary artery pressure Chest
;125:390-6.
Snopek G, Pogorzelska H, Korewicki J. Influence of valve
replacement on plasma endothelin-1 level in mitral stenosis..
J Heart Valve Dis2000;9(1);82-7.
Kinoshita O, Yoshimi H, Nagata S. Ishikura F, Kimura K,
Yamabe T et al. Rapid increase in plasma endothelin
concentrations during percutaneous balloon dilatation of the
J Ayub Med Coll Abbottabad 2009;21(3)
http://www.ayubmed.edu.pk/JAMC/PAST/21-3/Zubia.pdf
mitral valve in patients with mitral stenosis. Br Heart J
;69:322-6.
William E. Truog WE, Norberg M, Thibeault DW. Effect of
Inhaled Nitric Oxide in Endothelin-1-Induced Pulmonary
Hypertension. Biol Neonate 1998;73:246-53.
Wagner F, Buz S, Neumeyer HH, Hetzer R, Hocher B. Nitric
oxide inhalation modulates endothelin-1 plasma
concentration gradients following left ventricular assist
device implantation. J Cardiovasc Pharmacol 2004;44:89-91.
Kinoshita M, Mabuchi N, Tsutamoto T, Wada A, Ohnishi M,
Maeda K, et al. Relationship between interleukin-6 production
in the lungs and pulmonary vascular resistance in patients with
congestive heart failure. Chest 2002;121:1195-202.
Rubens C, Ewert R, Halank M, Wensel R, Orzechowski HD,
Schultheiss HP, et al. Big endothelin-1 and endothelin-1
plasma levels are correlated with the severity of primary
pulmonary hypertension. Chest 2001;120:1562-9.
Yamamoto K, Ikeda U, Mito H, Fujikawa H, Sekiguchi H,
Shimada K. Endothelin production in pulmonary circulation
of patients with mitral stenosis. Circulation 1994;89:2093-8.
Snopek G, Pogorzelska H, Rywik TM, Browarek A, Janas J,
Korewicki J. Usefulness of endothelin-1 concentration in
capillary blood in patients with mitral stenosis as a predictor
of regression of pulmonary hypertension after mitral valve
replacement or valvuloplasty. Am J Cardiol 2002;90:188-9.
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