Beta Receptor Blockade Fails to Recover Ventricular Function Despite Increased Pre-Synaptic Sympathetic Nervous System Function in Experimental Pulmonary Arterial Hypertension
| Autor: | Jennifer M. Renaud, Ali Ahmadi, R. deKemp, Rob S. Beanlands, Lisa Mielniczuk, Jason G.E. Zelt |
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| Rok vydání: | 2019 |
| Předmět: |
Pulmonary and Respiratory Medicine
Transplantation medicine.medical_specialty Sympathetic nervous system Ejection fraction Adrenergic receptor business.industry Hypoxia (medical) Blockade Subcutaneous injection Blood pressure medicine.anatomical_structure Internal medicine medicine Cardiology Surgery medicine.symptom Cardiology and Cardiovascular Medicine business Carvedilol medicine.drug |
| Zdroj: | The Journal of Heart and Lung Transplantation. 38:S97 |
| ISSN: | 1053-2498 |
| DOI: | 10.1016/j.healun.2019.01.226 |
| Popis: | Purpose Neurohormonal dysfunction has been implicated in pulmonary arterial hypertension (PAH), and therefore may be an important modifiable target. Despite β-blocker's proven efficacy in left heart failure, their use in PAH and RV failure is less established. The objectives of the study were twofold, to determine the effects of β-receptor blockade on 1) ventricular function; and 2) myocardial sympathetic nervous system (SNS) function in an animal model of PAH. Methods PAH was induced in male Sprague-Dawley rats (200g; n=36) by a single subcutaneous injection of Sugen 5416 (20mg/kg) followed by 3 weeks of hypoxia (10% O2). At week 5 post-injection, PAH rats were randomized to receive carvedilol (15 mg/kg/day oral; n=18) or vehicle (n=18) for 4 weeks. At 9 weeks, myocardial SNS function was assessed with [11C]-meta-hydroxephedrine (HED) positron emission tomography. Results Four weeks of carvedilol treatment did not decrease PAH severity, with no changes in RV systolic pressure compared to vehicle. RV ejection fraction (EF) was significantly lower in both PAH groups compared to healthy control (↓17-21%; p Conclusion In experimental PAH, carvedilol treatment may worsen ventricular function. The decrease in heart function was observed despite the increased presynaptic SNS function in the LV observed with carvedilol. Together, these results may caution against the use of β-receptor blockade in patients with PAH induced RV failure. |
| Databáze: | OpenAIRE |
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