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

2019 ◽  
Vol 9 (4) ◽  
pp. 293-301
Author(s):  
Jacob Schultz ◽  
Asger Andersen ◽  
Inger Lise Gade ◽  
Benedict Kjaergaard ◽  
Jens Erik Nielsen-Kudsk
Keyword(s):  
Pulmonary Embolism ◽  
Right Ventricular ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Acute Pulmonary Embolism ◽  
Porcine Model ◽  
Systemic Blood Pressure ◽  
Systemic Blood ◽  
Inhaled No ◽  
Stimulation Of

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.

Inhaled nitric oxide has pulmonary vasodilator efficacy both in the immediate and prolonged phase of acute pulmonary embolism

2020 ◽  
pp. 204887262091871 ◽  
Author(s):  
Anders Kramer ◽  
Christian Schmidt Mortensen ◽  
Jacob Gammelgaard Schultz ◽  
Mads Dam Lyhne ◽  
Asger Andersen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Embolism ◽  
Right Ventricular ◽  
Acute Pulmonary Embolism ◽  
Porcine Model ◽  
Inhaled Nitric Oxide ◽  
Intermediate Risk ◽  
Ventricular Afterload ◽  
Pulmonary Vasodilator ◽  
Acute Pe

Background Inhaled nitric oxide (iNO) effectively reduces right ventricular afterload when administered in the immediate phase of acute pulmonary embolism (PE) in preclinical animal models. In a porcine model of intermediate-risk PE, we aimed to investigate whether iNO has pulmonary vasodilator efficacy both in the immediate and prolonged phase of acute PE. Methods Anesthetized pigs ( n = 18) were randomized into three subgroups. An acute PE iNO-group ( n = 6) received iNO at 40 ppm at one, three, six, nine and 12 hours after onset of PE. Vehicle animals ( n = 6) received PE, but no active treatment. A third group of sham animals ( n = 6) received neither PE nor treatment. Animals were evaluated using intravascular pressures, respiratory parameters, biochemistry and intracardiac pressure-volume measurements. Results The administration of PE increased mean pulmonary artery pressure (mPAP) (vehicle vs sham; 33.3 vs 17.7 mmHg, p < 0.0001), pulmonary vascular resistance (vehicle vs sham; 847.5 vs 82.0 dynes, p < 0.0001) and right ventricular arterial elastance (vehicle vs sham; 1.2 vs 0.2 mmHg/ml, p < 0.0001). Significant mPAP reduction by iNO was preserved at 12 hours after the onset of acute PE (vehicle vs iNO; 0.5 vs –3.5 mmHg, p < 0.0001). However, this response was attenuated over time ( p = 0.0313). iNO did not affect the systemic circulation. Conclusions iNO is a safe and effective pulmonary vasodilator both in the immediate and prolonged phase of acute PE in an in-vivo porcine model of intermediate-risk PE.

Ventricular Outflow Dynamics in the Lizard, Varanus Niloticus: Responses to Hypoxia, Hypercarbia and Diving

1974 ◽  
Vol 60 (3) ◽  
pp. 871-880 ◽  
Author(s):  
R. W. MILLARD ◽  
K. JOHANSEN
Keyword(s):  
Blood Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pressure Rise ◽  
Systemic Blood Pressure ◽  
Aortic Pressure ◽  
Systemic Resistance ◽  
Systemic Blood ◽  
Normal Breathing ◽  
The Right

1. Blood flow and blood pressure have been measured in the right aorta and left pulmonary artery of the semi-aquatic lizard, Varanus niloticus, during normal breathing, during hypercarbic and hypoxic breathing and during voluntary diving. 2. Mean pulmonary blood pressure during normal breathing was 19.5±2.0 cmH2O while right aortic pressure was 118.0±3.0 cmH2O. The high systemic blood pressure and high ratio of systemic to pulmonary vascular resistance (4.0-6.0) stand out among reptiles and approach values in homeotherm vertebrates. 3. Pulmonary pressure rise preceded right aortic pressure rise by 120 msec at a heart rate of 25/min. Pulmonary ejection lasted 50% of the cardiac cycle compared to 25% for aortic ejection during normal breathing. 4. CO2 breathing increased right aortic vascular resistance by 120% while pulmonary resistance increased moderately by 30%. Carotid vascular resistance decreased during CO2 breathing. The pulmonary blood pressure increase was however much higher than the systemic, but at no time did systemic and pulmonary blood pressures overlap. 5. Hypoxic breathing increased pulmonary blood pressure to 36.0±4.0 cmH2O while right aortic pressure fell to 100.0±10.0 cmH2O. Ejection time remained unchanged in the right aorta while pulmonary flow became continuous. Overall pulmonary vascular resistance increased markedly while systemic resistance changed little. 6. Voluntary diving increased pulmonary blood pressure while the systemic blood pressure fell markedly. 7. The results obtained are discussed in the light of ventricular outflow distribution in reptiles. Directional shunting of blood inside the heart of V. niloticus during cardiac systole must be reduced or absent. Intracardiac shunting during cardiac filling or by systolic residual volumes is small, placing varanid lacertilians haemodynamically closer to homoetherm vertebrates than other reptiles studied.

Pulmonary Vascular Versus Right Ventricular Function Changes During Targeted Therapies of Pulmonary Hypertension – An Argument for Upfront Combination Therapy?

2012 ◽  
Vol 8 (3) ◽  
pp. 209
Author(s):  
Wouter Jacobs ◽  
Anton Vonk-Noordegraaf ◽  
◽  
Keyword(s):  
Combination Therapy ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Meta Analysis ◽  
Right Heart Failure ◽  
Functional Class ◽  
Pulmonary Vasculature ◽  
The Right

Pulmonary arterial hypertension is a progressive disease of the pulmonary vasculature, ultimately leading to right heart failure and death. Current treatment is aimed at targeting three different pathways: the prostacyclin, endothelin and nitric oxide pathways. These therapies improve functional class, increase exercise capacity and improve haemodynamics. In addition, data from a meta-analysis provide compelling evidence of improved survival. Despite these treatments, the outcome is still grim and the cause of death is inevitable – right ventricular failure. One explanation for this paradox of haemodynamic benefit and still worse outcome is that the right ventricle does not benefit from a modest reduction in pulmonary vascular resistance. This article describes the physiological concepts that might underlie this paradox. Based on these concepts, we argue that not only a significant reduction in pulmonary vascular resistance, but also a significant reduction in pulmonary artery pressure is required to save the right ventricle. Haemodynamic data from clinical trials hold the promise that these haemodynamic requirements might be met if upfront combination therapy is used.

Shape-based analysis of right ventricular dysfunction associated with acute pulmonary embolism

2012 ◽  
Author(s):  
Nima Tajbakhsh ◽  
Wenzhe Xue ◽  
Hong Wu ◽  
Jianming Liang ◽  
Eileen M. McMahon ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Right Ventricular ◽  
Acute Pulmonary Embolism ◽  
Ventricular Dysfunction ◽  
Right Ventricular Dysfunction
Sign in / Sign up

Export Citation Format

Share Document