Use of sildenafil in a liver transplant recipient with acute pulmonary embolism

Bonatti, Hugo; Sawyer, Robert G.; Hagspiel, Klaus D.

doi:10.1007/s10353-010-0511-8

Cited by 5 publications

(4 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study therefore adds novel insights to the growing body of preclinical data, suggesting that NO-sGC-cGMP stimulation may be safe and beneficial in intermediate-risk pulmonary embolism. 3,[14][15][16][17][18][19][20][21][22][23] While case reports and smaller series also show promising effects, [6][7][8][9][10][11][12] the first, recently published, randomized clinical trial failed to reduce the combined, primary end point of normalization of RV function, evaluated by echocardiography and biomarkers of RV strain. 13 Inhaled NO did, however, attenuate RV dilatation and hypokinesia, indicating a beneficial effect as seen in the present study.…”

Section: Effects Of No-sgc-cgmp Stimulationmentioning

confidence: 99%

“…While case reports and smaller series have shown promising results, the first, recently published, randomized clinical trial failed to prove a significant benefit of inhaled NO. [6][7][8][9][10][11][12][13] Experimental data are promising but studies have been performed in models of acute pulmonary embolism using artificial plastic spheres or models of nonpulmonary embolism-related or chronic pulmonary hypertension. 3,[14][15][16][17][18][19][20][21][22][23] It is currently unknown whether the pulmonary vasodilatory effects found in these studies translate to the more physiological setting of acute pulmonary embolism caused by larger thromboemboli.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Riociguat, sildenafil and inhaled nitric oxide reduces pulmonary vascular resistance and improves right ventricular function in a porcine model of acute pulmonary embolism

Schultz

Andersen

Gade

et al. 2019

European Heart Journal: Acute Cardiovascular Care

View full text Add to dashboard Cite

Background: Pulmonary vasodilators as add-on to current treatment strategies in acute pulmonary embolism may improve right ventricular unloading and hence improve patient outcome. We aimed to investigate whether stimulation of the nitric oxide (NO)–soluble guanylate cyclase (sGC)–cyclic guanosine monophosphate (cGMP) pathway with riociguat, sildenafil or inhaled NO causes pulmonary vasodilation and improves right ventricular function in a porcine model of acute intermediate risk pulmonary embolism. Methods: Two large autologous blood clots were administered to the pulmonary circulation of 28 pigs (60 kg). Animals were randomized to four increasing, clinically equivalent doses of riociguat ( n=6), sildenafil ( n=6), inhaled NO ( n=6) or vehicle ( n=6). Sham animals ( n=4) did not receive pulmonary embolism or treatment. Haemodynamic responses were evaluated at baseline, after pulmonary embolism and after each dose using invasive pressure measurements, transoesophageal echocardiography, respiratory parameters and blood analysis. Results: Pulmonary embolism caused a three-fold increase in pulmonary vascular resistance compared with baseline (pulmonary embolism: 352±29 vs. baseline: 107±6 dynes, p<0.0001). All treatments lowered pulmonary vascular resistance compared with vehicle (riociguat: –158±35, sildenafil: –224±35, inhaled NO: –156±35 dynes, p<0.0001). Sildenafil, but neither inhaled NO nor riociguat, caused a decrease in systemic vascular resistance (sildenafil 678±41 vs. vehicle 1081±93 dynes, p=0.02) and increased cardiac output (sildenafil 8.8±0.8 vs. vehicle: 5.9±0.2 L/min, p<0.001). Systemic blood pressure was unaltered in all treatment groups. Conclusion: Stimulation of the NO–sGC–cGMP pathway by riociguat, sildenafil and inhaled NO reduces pulmonary vascular resistance in a porcine model of acute pulmonary embolism without lowering systemic blood pressure.

show abstract

Section: Effects Of No-sgc-cgmp Stimulationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Riociguat, sildenafil and inhaled nitric oxide reduces pulmonary vascular resistance and improves right ventricular function in a porcine model of acute pulmonary embolism

Schultz

Andersen

Gade

et al. 2019

European Heart Journal: Acute Cardiovascular Care

View full text Add to dashboard Cite

show abstract

“…98,135–137 In a patient with congenital heart disease and acute-in-chronic PE, sildenafil dramatically improved oxygenation. 109 The use of sildenafil made withdrawal of inotropes possible shortly after treatment, 135,138 whereas another case report measures the effects of sildenafil on the following day. 139 This was, however, a severely ill patient with five-day history of saddle PE and in cardiogenic shock.…”

Section: Resultsmentioning

confidence: 99%

“…Sildenafil showed promising effects in both acute post-operative PE and acute-in-chronic PE. 98,[135][136][137] In a patient with congenital heart disease and acute-in-chronic PE, sildenafil dramatically improved oxygenation. 109 The use of sildenafil made withdrawal of inotropes possible shortly after treatment, 135,138 whereas another case report measures the effects of sildenafil on the following day.…”

Section: Endothelin Antagonismmentioning

confidence: 98%

Pulmonary vasodilation in acute pulmonary embolism – a systematic review

et al. 2020

View full text Add to dashboard Cite

Acute pulmonary embolism is the third most common cause of cardiovascular death. Pulmonary embolism increases right ventricular afterload, which causes right ventricular failure, circulatory collapse and death. Most treatments focus on removal of the mechanical obstruction caused by the embolism, but pulmonary vasoconstriction is a significant contributor to the increased right ventricular afterload and is often left untreated. Pulmonary thromboembolism causes mechanical obstruction of the pulmonary vasculature coupled with a complex interaction between humoral factors from the activated platelets, endothelial effects, reflexes and hypoxia to cause pulmonary vasoconstriction that worsens right ventricular afterload. Vasoconstrictors include serotonin, thromboxane, prostaglandins and endothelins, counterbalanced by vasodilators such as nitric oxide and prostacyclins. Exogenous administration of pulmonary vasodilators in acute pulmonary embolism seems attractive but all come with a risk of systemic vasodilation or worsening of pulmonary ventilation-perfusion mismatch. In animal models of acute pulmonary embolism, modulators of the nitric oxide-cyclic guanosine monophosphate-protein kinase G pathway, endothelin pathway and prostaglandin pathway have been investigated. But only a small number of clinical case reports and prospective clinical trials exist. The aim of this review is to give an overview of the causes of pulmonary embolism-induced pulmonary vasoconstriction and of experimental and human investigations of pulmonary vasodilation in acute pulmonary embolism.

show abstract

Sildenafil improves the beneficial hemodynamic effects exerted by atorvastatin during acute pulmonary thromboembolism

Neto-Neves

Dias‐Junior

Uzuelli

et al. 2011

European Journal of Pharmacology

View full text Add to dashboard Cite

We investigated whether atorvastatin has beneficial hemodynamic effects during acute pulmonary thromboembolism (APT) and whether sildenafil improves these effects. We studied the involvement of oxidative stress, matrix metalloproteinases (MMPs), and neutrophil activation. APT was induced with autologous blood clots (500 mg/kg) in anesthetized male lambs pretreated with atorvastatin (10 mg/kg/day, subcutaneously; 1 week) or vehicle (dimethyl sulfoxide 10% subcutaneously). Sildenafil (0.7 mg/kg intravenously) or saline infusions were performed 60 min after APT induction. Non-embolized control animals received saline. APT significantly increased pulmonary vascular resistance index (PVRI) and mean pulmonary artery pressure (MPAP) by approximately 310% and 258% respectively. While atorvastatin pretreatment attenuated these increases (~150% and 153%, respectively; P < 0.05), its combination with sildenafil was associated with lower increases in PVRI and MPAP (~32% and 36%, respectively). Gelatin zymography showed increased MMP-9 and MMP-2 levels in the bronchoalveolar lavage, and increased MMP-9 levels in plasma from embolized animals. Atorvastatin pretreatment attenuated bronchoalveolar lavage MMP-2 increases. The combination of drugs blunted the MMPs increases in bronchoalveolar lavage and plasma (P < 0.05). Neutrophils accumulated in bronchoalveolar lavage after APT, and atorvastatin pretreatment combined with sildenafil (but not atorvastatin alone) attenuated this effect (P < 0.05). APT increased lung lipid peroxidation and total protein concentrations in bronchoalveolar lavage, thus indicating oxidative stress and alveolar-capillary barrier damage, respectively. Both increases were attenuated by atorvastatin pretreatment alone or combined with sildenafil (P < 0.05). We conclude that pretreatment with atorvastatin protects against the pulmonary hypertension associated with APT and that sildenafil improves this response. These findings may reflect antioxidant effects and inhibited neutrophils/MMPs activation.

show abstract

Use of sildenafil in a liver transplant recipient with acute pulmonary embolism

Cited by 5 publications

References 23 publications

Riociguat, sildenafil and inhaled nitric oxide reduces pulmonary vascular resistance and improves right ventricular function in a porcine model of acute pulmonary embolism

Riociguat, sildenafil and inhaled nitric oxide reduces pulmonary vascular resistance and improves right ventricular function in a porcine model of acute pulmonary embolism

Pulmonary vasodilation in acute pulmonary embolism – a systematic review

Sildenafil improves the beneficial hemodynamic effects exerted by atorvastatin during acute pulmonary thromboembolism

Contact Info

Product

Resources

About