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
| Autor: | Piet Claus, Patrick Wouters, Wolfgang Buhre, Steffen Rex, C Missant |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Cardiac output PROSTACYCLIN Hypertension Pulmonary Sus scrofa Critical Care and Intensive Care Medicine Ventricular Function Left Contractility SYSTOLIC FUNCTION CARDIAC-FUNCTION Internal medicine medicine.artery PRESSURE-OVERLOAD Administration Inhalation medicine Animals Iloprost Prospective Studies Cardiac Output IN-VIVO Pressure overload NITRIC-OXIDE business.industry Research medicine.disease Pulmonary hypertension CONDUCTANCE CATHETER Preload Disease Models Animal DOGS Heart failure Anesthesia Pulmonary artery Acute Disease Cardiology cardiovascular system Ventricular Function Right HEART-FAILURE lipids (amino acids peptides and proteins) business ARTERY HYPERTENSION medicine.drug |
| Zdroj: | Critical Care Critical care 12(5), R113-R113 (2008). doi:10.1186/cc7005 CRITICAL CARE |
| ISSN: | 1466-609X 1364-8535 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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