Effects of chronic carbon monoxide exposure on fetal growth and development in mice

<p>Abstract</p> <p>Background</p> <p>Carbon monoxide (CO) is produced endogenously, and can also be acquired from many exogenous sources: ie. cigarette smoking, automobile exhaust. Although toxic at high levels, low level production or exposure lends to normal physiologic functions: smooth muscle cell relaxation, control of vascular tone, platelet aggregation, anti- inflammatory and anti-apoptotic events. In pregnancy, it is unclear at what level maternal CO exposure becomes toxic to the fetus. In this study, we hypothesized that CO would be embryotoxic, and we sought to determine at what level of chronic CO exposure in pregnancy embryo/fetotoxic effects are observed.</p> <p>Methods</p> <p>Pregnant CD1 mice were exposed to continuous levels of CO (0 to 400 ppm) from conception to gestation day 17. The effect on fetal/placental growth and development, and fetal/maternal CO concentrations were determined.</p> <p>Results</p> <p>Maternal and fetal CO blood concentrations ranged from 1.12- 15.6 percent carboxyhemoglobin (%COHb) and 1.0- 28.6%COHb, respectively. No significant difference was observed in placental histological morphology or in placental mass with any CO exposure. At 400 ppm CO vs. control, decreased litter size and fetal mass (p < 0.05), increased fetal early/late gestational deaths (p < 0.05), and increased CO content in the placenta and the maternal spleen, heart, liver, kidney and lung (p < 0.05) were observed.</p> <p>Conclusions</p> <p>Exposure to levels at or below 300 ppm CO throughout pregnancy has little demonstrable effect on fetal growth and development in the mouse.</p

Results of matching valve and root repair to aortic valve and root pathology

ObjectiveFor patients with aortic root pathology and aortic valve regurgitation, aortic valve replacement is problematic because no durable bioprosthesis exists, and mechanical valves require lifetime anticoagulation. This study sought to assess outcomes of combined aortic valve and root repair, including comparison with matched bioprosthesis aortic valve replacement.MethodsFrom November 1990 to January 2005, 366 patients underwent modified David reimplantation (n = 72), root remodeling (n = 72), or valve repair with sinotubular junction tailoring (n = 222). Active follow-up was 99% complete, with a mean of 5.6 ± 4.0 years (maximum 17 years); follow-up for vital status averaged 8.5 ± 3.6 years (maximum 19 years). Propensity-adjusted models were developed for fair comparison of outcomes.ResultsThirty-day and 5-, 10-, and 15-year survivals were 98%, 86%, 74%, and 58%, respectively, similar to that of the US matched population and better than that after bioprosthesis aortic valve replacement. Propensity-score–adjusted survival was similar across procedures (P > .3). Freedom from reoperation at 30 days and 5 and 10 years was 99%, 92%, and 89%, respectively, and was similar across procedures (P > .3) after propensity-score adjustment. Patients with tricuspid aortic valves were more likely to be free of reoperation than those with bicuspid valves at 10 years (93% vs 77%, P = .002), equivalent to bioprosthesis aortic valve replacement and superior after 12 years. Bioprostheses increasingly deteriorated after 7 years, and hazard functions for reoperation crossed at 7 years.ConclusionsValve preservation (rather than replacement) and matching root procedures have excellent early and long-term results, with increasing survival benefit at 7 years and fewer reoperations by 12 years. We recommend this procedure for experienced surgical teams

Carbon Monoxide Prevents Hypertension and Proteinuria in an Adenovirus sFlt-1 Preeclampsia-Like Mouse Model

Preeclampsia (PE) remains a leading cause of maternal and neonatal morbidity and mortality worldwide. Smoking cigarettes is associated with a decreased incidence of PE. Based on this observation and previous work, we hypothesize that women who smoke have a lower risk of developing PE because of elevated levels of carbon monoxide (CO) in their blood. The objective of this study was to determine if low-dose CO in ambient air could attenuate the late pregnancy hypertension (HTN) and proteinuria in the Adenovirus (Ad) sFlt-1 PE-like mouse model. Continuous low-dose CO treatment (250 ppm) was started on E10.5 and maintained until E17.5. Compared to control and Ad empty vector, AdsFlt-1 mice displayed late-gestation HTN (E14.5–17.5) (P,0.05), proteinuria (P,0.05) and reduced Bowman’s space which were all prevented with CO treatment. Use of the Ad (with/without sFlt-1) or CO had no effect (p.0.05) on litter size, fetal resorption numbers and fetal or placental weights. This study shows that treatment with CO can prevent HTN and proteinuria in a mouse model of PE. It provides a possible mechanism for the reduced incidence of PE in smoking women, and supports the possibility of using CO as a future treatment for PE

Tail-vein injection of AdsFlt-1 significantly increased maternal plasma sFlt-1 levels compared to control and AdEV groups.

<p>All maternal mouse sFlt-1 plasma levels (ng/ml ± SEM) were 0±1.23 at GD0.5 of pregnancy, but at term, both control and AdEV sFlt-1 levels were increased to levels observed in normal pregnancy. Mice injected with AdsFlt-1 measured with significant increases in plasma sFlt-1 levels, and this was not difference when exposed to CO. Similar letters represent data that is not statistically different.</p

Maternal sFlt-1 –induced hypertension (HTN) in late stage pregnancy is completely normalized when mice are exposed to CO.

<p>No difference in BP throughout pregnancy was noted in control ± CO or AdEV ± CO groups throughout pregnancy. The injection of AdsFlt-1 led to HTN at the end of pregnancy (P<0.05), which was completed attenuated in mice exposed to CO and not different from control or AdEV groups (P>0.05).</p

Comparison of maternal blood carbon monoxide levels between groups of mice.

<p>Similar letters denote no difference between groups, using a p-value of 0.05.</p><p>Comparison of maternal blood carbon monoxide levels between groups of mice.</p

Comparison of maternal plasma sFlt-1 concentration and percentage of fetal loss for mice injected with high to low AdsFlt-1 concentrations.

<p>Comparison of maternal plasma sFlt-1 concentration and percentage of fetal loss for mice injected with high to low AdsFlt-1 concentrations.</p