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Effects of inhaled iloprost on right ventricular contractility, right ventriculo-vascular coupling and ventricular interdependence: a randomized placebo-controlled trial in an experimental model of acute pulmonary hypertension

(2008) CRITICAL CARE. 12(5).
Author
Organization
Abstract
Introduction Prostacyclin inhalation is increasingly used to treat acute pulmonary hypertension and right ventricular failure, although its pharmacodynamic properties remain controversial. Prostacyclins not only affect vasomotor tone but may also have cAMP-mediated positive inotropic effects and modulate autonomic nervous system tone. We studied the role of these different mechanisms in the overall haemodynamic effects produced by iloprost inhalation in an experimental model of acute pulmonary hypertension. Methods In this prospective, randomized, placebo-controlled animal study, twenty-six pigs (mean weight 35 +/- 2 kg) were instrumented with biventricular conductance catheters, a pulmonary artery flow probe and a high-fidelity pulmonary artery pressure catheter. The effects of inhaled iloprost (50 mu g) were studied in the following groups: animals with acute hypoxia-induced pulmonary hypertension, and healthy animals with and without blockade of the autonomic nervous system. Results During pulmonary hypertension, inhalation of iloprost resulted in a 51% increase in cardiac output compared with placebo (5.6 +/- 0.7 versus 3.7 +/- 0.8 l/minute; P = 0.0013), a selective reduction in right ventricular afterload (effective pulmonary arterial elastance: 0.6 +/- 0.3 versus 1.2 +/- 0.5 mmHg/ ml; P = 0.0005) and a significant increase in left ventricular end-diastolic volume (91 +/- 12 versus 70 +/- 20 ml; P = 0.006). Interestingly, right ventricular contractility was reduced after iloprost-treatment (slope of preload recruitable stroke work: 2.2 +/- 0.5 versus 3.4 +/- 0.8 mWatt-s/ml; P = 0.0002), whereas ventriculo-vascular coupling remained essentially preserved (ratio of right ventricular end-systolic elastance to effective pulmonary arterial elastance: 0.97 +/- 0.33 versus 1.03 +/- 0.15). In healthy animals, inhaled iloprost had only minimal haemodynamic effects and produced no direct effects on myocardial contractility, even after pharmacological blockade of the autonomic nervous system. Conclusions In animals with acute pulmonary hypertension, inhaled iloprost improved global haemodynamics primarily via selective pulmonary vasodilatation and restoration of left ventricular preload. The reduction in right ventricular afterload is associated with a paradoxical decrease in right ventricular contractility. Our data suggest that this reflects an indirect mechanism by which ventriculo-vascular coupling is maintained at the lowest possible energetic cost. We found no evidence for a direct negative inotropic effect of iloprost.
Keywords
HEART-FAILURE, IN-VIVO, CARDIAC-FUNCTION, SYSTOLIC FUNCTION, PRESSURE-OVERLOAD, ARTERY HYPERTENSION, CONDUCTANCE CATHETER, NITRIC-OXIDE, PROSTACYCLIN, DOGS

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MLA
Rex, S. et al. “Effects of Inhaled Iloprost on Right Ventricular Contractility, Right Ventriculo-vascular Coupling and Ventricular Interdependence: a Randomized Placebo-controlled Trial in an Experimental Model of Acute Pulmonary Hypertension.” CRITICAL CARE 12.5 (2008): R113. Print.
APA
Rex, S., Missant, C., Claus, P., Buhre, W., & Wouters, P. (2008). Effects of inhaled iloprost on right ventricular contractility, right ventriculo-vascular coupling and ventricular interdependence: a randomized placebo-controlled trial in an experimental model of acute pulmonary hypertension. CRITICAL CARE, 12(5), R113.
Chicago author-date
Rex, S., C. Missant, P. Claus, W Buhre, and Patrick Wouters. 2008. “Effects of Inhaled Iloprost on Right Ventricular Contractility, Right Ventriculo-vascular Coupling and Ventricular Interdependence: a Randomized Placebo-controlled Trial in an Experimental Model of Acute Pulmonary Hypertension.” Critical Care 12 (5): R113.
Chicago author-date (all authors)
Rex, S., C. Missant, P. Claus, W Buhre, and Patrick Wouters. 2008. “Effects of Inhaled Iloprost on Right Ventricular Contractility, Right Ventriculo-vascular Coupling and Ventricular Interdependence: a Randomized Placebo-controlled Trial in an Experimental Model of Acute Pulmonary Hypertension.” Critical Care 12 (5): R113.
Vancouver
1.
Rex S, Missant C, Claus P, Buhre W, Wouters P. Effects of inhaled iloprost on right ventricular contractility, right ventriculo-vascular coupling and ventricular interdependence: a randomized placebo-controlled trial in an experimental model of acute pulmonary hypertension. CRITICAL CARE. CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND: BIOMED CENTRAL LTD,; 2008;12(5):R113.
IEEE
[1]
S. Rex, C. Missant, P. Claus, W. Buhre, and P. Wouters, “Effects of inhaled iloprost on right ventricular contractility, right ventriculo-vascular coupling and ventricular interdependence: a randomized placebo-controlled trial in an experimental model of acute pulmonary hypertension,” CRITICAL CARE, vol. 12, no. 5, p. R113, 2008.
@article{529326,
  abstract     = {Introduction Prostacyclin inhalation is increasingly used to treat acute pulmonary hypertension and right ventricular failure, although its pharmacodynamic properties remain controversial. Prostacyclins not only affect vasomotor tone but may also have cAMP-mediated positive inotropic effects and modulate autonomic nervous system tone. We studied the role of these different mechanisms in the overall haemodynamic effects produced by iloprost inhalation in an experimental model of acute pulmonary hypertension.
Methods In this prospective, randomized, placebo-controlled animal study, twenty-six pigs (mean weight 35 +/- 2 kg) were instrumented with biventricular conductance catheters, a pulmonary artery flow probe and a high-fidelity pulmonary artery pressure catheter. The effects of inhaled iloprost (50 mu g) were studied in the following groups: animals with acute hypoxia-induced pulmonary hypertension, and healthy animals with and without blockade of the autonomic nervous system.

Results During pulmonary hypertension, inhalation of iloprost resulted in a 51% increase in cardiac output compared with placebo (5.6 +/- 0.7 versus 3.7 +/- 0.8 l/minute; P = 0.0013), a selective reduction in right ventricular afterload (effective pulmonary arterial elastance: 0.6 +/- 0.3 versus 1.2 +/- 0.5 mmHg/ ml; P = 0.0005) and a significant increase in left ventricular end-diastolic volume (91 +/- 12 versus 70 +/- 20 ml; P = 0.006). Interestingly, right ventricular contractility was reduced after iloprost-treatment (slope of preload recruitable stroke work: 2.2 +/- 0.5 versus 3.4 +/- 0.8 mWatt-s/ml; P = 0.0002), whereas ventriculo-vascular coupling remained essentially preserved (ratio of right ventricular end-systolic elastance to effective pulmonary arterial elastance: 0.97 +/- 0.33 versus 1.03 +/- 0.15). In healthy animals, inhaled iloprost had only minimal haemodynamic effects and produced no direct effects on myocardial contractility, even after pharmacological blockade of the autonomic nervous system.

Conclusions In animals with acute pulmonary hypertension, inhaled iloprost improved global haemodynamics primarily via selective pulmonary vasodilatation and restoration of left ventricular preload. The reduction in right ventricular afterload is associated with a paradoxical decrease in right ventricular contractility. Our data suggest that this reflects an indirect mechanism by which ventriculo-vascular coupling is maintained at the lowest possible energetic cost. We found no evidence for a direct negative inotropic effect of iloprost.},
  author       = {Rex, S. and Missant, C. and Claus, P. and Buhre, W and Wouters, Patrick},
  issn         = {1466-609X},
  journal      = {CRITICAL CARE},
  keywords     = {HEART-FAILURE,IN-VIVO,CARDIAC-FUNCTION,SYSTOLIC FUNCTION,PRESSURE-OVERLOAD,ARTERY HYPERTENSION,CONDUCTANCE CATHETER,NITRIC-OXIDE,PROSTACYCLIN,DOGS},
  language     = {eng},
  number       = {5},
  publisher    = {BIOMED CENTRAL LTD,},
  title        = {Effects of inhaled iloprost on right ventricular contractility, right ventriculo-vascular coupling and ventricular interdependence: a randomized placebo-controlled trial in an experimental model of acute pulmonary hypertension},
  url          = {http://dx.doi.org/10.1186/cc7005},
  volume       = {12},
  year         = {2008},
}

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