Randomized, prospective trial of oxygen, continuous positive airway pressure, and bilevel positive airway pressure by face mask in acute cardiogenic pulmonary edema.

OBJECTIVE: To compare the effects of oxygen, continuous positive airway pressure (CPAP), and bilevel positive airway pressure (bilevel-PAP) on the rate of endotracheal intubation in patients with acute cardiogenic pulmonary edema. DESIGN: Randomized, controlled trial. SETTING: Tertiary hospital emergency room. PATIENTS: We randomly assigned 80 patients with severe cardiogenic acute pulmonary edema into three treatment groups. Patients were followed for 60 days after the randomization. INTERVENTIONS: Oxygen applied by face mask, CPAP, and bilevel-PAP. MEASUREMENTS AND MAIN RESULTS: The rate of endotracheal intubation as well as vital signs and blood gases was recorded during the first 24 hrs. Mortality was evaluated at 15 days, at 60 days, and at hospital discharge. Complications related to respiratory support were evaluated before hospital discharge. Treatment with CPAP or bilevel-PAP resulted in significant improvement in the PaO2/FiO2 ratio, subjective dyspnea score, and respiratory and heart rates compared with oxygen therapy. Endotracheal intubation was necessary in 11 of 26 patients (42%) in the oxygen group but only in two of 27 patients (7%) in each noninvasive ventilation group (p = .001). There was no increase in the incidence of acute myocardial infarction in the CPAP or bilevel-PAP groups. Mortality at 15 days was higher in the oxygen than in the CPAP or bilevel-PAP groups (p < .05). Mortality up to hospital discharge was not significantly different among groups (p = .061). CONCLUSIONS: Compared with oxygen therapy, CPAP and bilevel-PAP resulted in similar vital signs and arterial blood gases and a lower rate of endotracheal intubation. No cardiac ischemic complications were associated with either of the noninvasive ventilation strategies.

Redox processes underlying the vascular repair reaction.

Accumulating evidence indicates that vascular dysfunction in atherosclerosis, hypertension, and diabetes is either caused by or accompanied by oxidative stress in the vessel wall. In particular, the role of redox processes as mediators of vascular repair and contributors to post-angioplasty restenosis is increasingly evident. Yet the pathophysiology of such complex phenomena is still unclear. After vascular injury, activation of enzymes such as NADPH oxidase leads to a marked increase in superoxide generation, proportional to the degree of injury, which rapidly subsides. Such early superoxide production is significantly greater after stent deployment, as compared to balloon injury. Recent data suggest the persistence of low levels of oxidant stress during the vascular repair reaction in neointimal and medial layers. Despite the compensatory increase in expression of iNOS and nNOS, nitric oxide bioavailability is reduced because of increased reaction rates with superoxide, yielding as by-products reactive nitrogen/oxygen species that induce protein nitration. Concurrently, the activity of vascular superoxide dismutases exhibits a sustained decrease following injury. This decreased activity appears to be a key contributor to vasoconstrictive remodeling and a major determinant of the occurrence of nitrative/oxidative stress. Replenishment of superoxide dismutase (SOD), as well as treatment with vitamins C and E or the lipid-lowering drug probucol and its analogs, led to decrease in constrictive remodeling and improved vessel caliber. Better understanding of the redox pathophysiology of vascular repair should help clarify the pathogenesis of many other vascular conditions and may provide novel therapeutic strategies to prevent vascular lumen loss.

Sustained decrease in superoxide dismutase activity underlies constrictive remodeling after balloon injury in rabbits.

OBJECTIVE: The redox pathophysiology of vascular repair is incompletely understood. We assessed the role of vascular superoxide dismutase (SOD) activity in oxidative/nitrative stress and caliber loss postinjury (PI). METHODS AND RESULTS: Rabbits submitted to iliac artery balloon overdistension were followed for 14 days PI. Significant decrease in vascular SOD activity occurred at 7 and 14 days PI (by 45% and 34%, respectively, versus control, 96+/-1 U/mg, P<0.05). Separation in concanavalin-A column showed that both extracellular SOD (ecSOD) and CuZn SOD activities were reduced, whereas Western analysis showed normal or augmented protein expression. Immunoreactivity to nitrotyrosine, neuronal NO synthase (NOS), and inducible NOS (iNOS) increased in media and neointima PI; iNOS mRNA also augmented. Administration of ecSOD from days 7 to 14 PI corrected the SOD activity decrease and minimized caliber loss by 59% (P=0.007) despite unaltered neointima. Nitrate levels markedly increased with ecSOD in injured artery homogenates (26+/-5 versus 4+/-0.3 micromol/L per mg, P=0.001). Such increase was 70% inhibited by specific iNOS antagonist 1400w. Nitrotyrosine and neuronal NOS expression decreased after ecSOD. CONCLUSIONS: Sustained low vascular SOD activity has a key role in constrictive remodeling after injury, promoting oxidative/nitrative stress and impairment of iNOS-derived NO bioavailability. SOD function may critically determine whether iNOS induction is beneficial or deleterious in vivo.