NCT03748082

Effects of Nitric Oxide on the Endothelium During Hemolysis.

Effects of Nitric Oxide on Vascular Responsiveness and on Endothelial Cells During Hemolysis in Patients With Pre-operative Endothelial Dysfunction Undergoing Prolonged Cardiopulmonary Bypass.

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Massachusetts General Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is an ancillary (add-on) study to the clinical trial entitled "Effect of Nitric Oxide in Cardiac Surgery Patients With Endothelial Dysfunction", which has Clinical Trials.gov identifier NCT02836899. NCT02836899 trial randomizes cardiac surgical patients to receive either Nitric Oxide (NO) or a placebo during and after cardiac surgery. This ancillary study aims to assess the effects of Nitric Oxide on vascular responsiveness and on endothelial function during hemolysis in patients with pre-operative endothelial dysfunction undergoing cardiac surgery requiring prolonged cardiopulmonary bypass.

Detailed description

Endothelial cells regulate tissue perfusion by releasing nitric oxide (NO), a potent endogenous dilator of vascular smooth muscle cells, which modifies vascular tone. Under normal physiological conditions, vascular NO is released by endothelial NO synthase (eNOS). Impairment of the eNOS, as seen in patients with atherosclerosis, peripheral vascular disease, hypertension, obesity, and diabetes, is a feature of endothelial dysfunction.The inability to increment eNOS activity is particularly evident in conditions of decreased vascular NO bioavailability, such as during hemolysis associated with prolonged cardiopulmonary bypass (CPB\>90 min). During hemolysis, ferrous plasma free hemoglobin (Oxy-Hb) is released into the circulation and can be injurious for the endothelial cells by exerting an oxidative and proinflammatory effect. Moreover, plasma free Oxy-Hb can scavenge vascular NO, reducing its bioavailability as ferrous Oxy-Hb is transformed into ferric methemoglobin (Met-Hb). The clinical results of reduced bioavailability of vascular NO have been found to be associated with both systemic and pulmonary vasoconstriction, ultimately leading to reduced tissue perfusion. The exogenous administration of NO has been shown to prevent the scavenging of endogenous NO by inactivating the highly oxidative-reactive ferrous plasma Oxy-Hb to ferric Met-Hb. Our group is conducting a randomized controlled trial at Massachusetts General Hospital (Boston, USA) in patients with signs and symptoms of endothelial dysfunction, undergoing cardiac surgery requiring prolonged CPB and randomized to receive NO or placebo. However, the mechanisms underlying the beneficial systemic effects of NO administration have still to be determined. This is an ancillary study that aims to (I) assess the effects of hemolysis on vascular responsiveness and on endothelial function in patients with pre-operative endothelial dysfunction and (II) to determine the vascular protective effects of NO administration.

Conditions

• Endothelial Dysfunction
• Hemolysis Intravascular
• Cardiovascular Diseases
• Cardiovascular Risk Factor

Interventions

Type	Name	Description
DRUG	Nitric Oxide	Inhaled nitric oxide (iNO) will be administered via the CPB machine and after CPB via the inspiratory limb of the anesthetic or ventilator circuit, and thereafter via the mechanical ventilator in the ICU. Test gas administration will commence at the onset of CPB and last for 24 hours. At the end of 24 hours, iNO will be weaned and discontinued.
DIAGNOSTIC_TEST	Reactive Hyperemia Index	Vascular responsiveness will be assessed with peripheral arterial tonometry which measures the transient increase in forearm blood flow (Reactive Hyperemia Index, RHI) in response to a five-minute occlusion of the brachial artery with a pressure cuff.
PROCEDURE	Endothelial Cells Collection	Endothelial cells are collected before and after surgery from a peripheral vessel using a soft J-shaped wire inserted through an intravascular catheter.

Timeline

• Start date: 2018-12-05
• Primary completion: 2023-11-01
• Completion: 2023-11-01
• First posted: 2018-11-20
• Last updated: 2025-12-02

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study