Table 1.

Vasodilation through the NO-sGC-cGMP pathway in acute pulmonary embolism.

Treatment	Experimental microsphere/glass beads/air PE	Experimental autologous (blood, fat, muscle, collagen) PE	Case reports	Clinical trials	Guideline recommendation
Nitric oxide	Lowers PVR, mPAP but not MAP.66,68–71,73,80,84–86 No effect on mPAP but increase in CO.87	Lowers PVR, mPAP, increases CO.51,65,67,72,74–76,79,81–83 Lowers cardiac damage.65,76,77 No hemodynamic effects.78 Decreased stroke volume88 or MAP/SVR79,83	18 PE cases with mostly positive effects92–94,96,108 Five cases in combination with thrombolysis, thrombectomy or embolectomy97,99–102 Five cases of post-operative PE98,107 Two PE cases in patients with PFO or VSD106,109 One post-partum patient with PE95 Four pediatric cases103–105 One case of autoimmune hemolytic anaemia47 One PE case with deterioration on iNO110	Eight patients, single arm. Safe. Trend towards improvement.112 iNOPE trial, double-blinded, 78 patients with intermediate-high-risk PE randomized to iNO + O2 or placebo. Neutral on both endpoints111	Either no recommendations16 or “Inhalation of nitric oxide may improve the hemodynamic status (…) no evidence for its clinical efficacy or safety”4
sCG stimulators/ activators	Lowers mPAP and PVR. Risk of decreased MAP.84,118–120	Lowers PVR and mPAP and increases CO75	None	None	No recommendations4,16
PDE-5 inhibitors	Lowers mPAP and PVR, no effect on MAP84,86,126–131	Lowers mPAP and PVR75,124,125	Three PE cases136,138,139 One case of acute-on-chronic PE137 One case with congenital VSD109 Two cases of post-operative PE98,135 One child with non-thrombotic PE140	None	No recommendations4,16

Note: Summary of review of the NO-sGC-cGMP pathway to induce pulmonary vasodilation in acute pulmonary embolism. Divided by treatment option, animal or clinical data and guideline recommendation. Please see text for further details.

CO: cardiac output; iNO: inhaled nitric oxide; MAP: mean arterial pressure; mPAP: mean pulmonary arterial pressure; NO: nitric oxide; PAP: pulmonary artery pressure; PE: pulmonary embolism; PFO: persistent foramen ovale; PVR: pulmonary vascular resistance; SVR: systemic vascular resistance; VSD: ventricular septal defect.