Beardrich5414
NAD-based therapeutic strategies are encouraged against obesity and heart disease. Our study, therefore, aimed to investigate the effects of nicotinamide riboside (NR), isolated or combined with caloric restriction (CR), both approaches well-known for stimulating NAD levels, on adiposity parameters, cardiometabolic factors and cardiac oxidative stress in rats submitted to cafeteria diet (CAF).
After 42days of CAF-induced obesity (hypercaloric and ultra-processed foods common to humans), we examined the effects of oral administration of NR (400mg/kg for 28days), combined or not with CR (-62% kcal, for 28days), on anthropometric, metabolic, tissue, and cardiac oxidative stress parameters in obese male Wistar rats.
In obese rats, treatment with NR alone mitigated final body weight gain, reduced adiposity (visceral and subcutaneous), improved insulin resistance, and decreased TG/HDL ratio and heart size. In cardiac OS, treatment with NR increased the antioxidant capacity via glutathione peroxidase and catalase enzymes (in rats under CR) as well as reduced the pro-oxidant complex NADPH oxidase (in obese and lean rats). Hyperglycemia, hypertriglyceridemia and elevated levels of TBARS in the heart were state-dependent adverse effects, induced by treatment with NR.
This is the first study to report effects of nicotinamide riboside on cardiac oxidative stress in an obesity model. Nicotinamide riboside, a natural dietary compound, presented antiobesity effects and cardiometabolic benefits, in addition to positively modulating oxidative stress in the heart, in a state-dependent manner.
This is the first study to report effects of nicotinamide riboside on cardiac oxidative stress in an obesity model. Nicotinamide riboside, a natural dietary compound, presented antiobesity effects and cardiometabolic benefits, in addition to positively modulating oxidative stress in the heart, in a state-dependent manner.Troponin is the Ca2+ molecular switch that regulates striated muscle contraction. In the heart, troponin Ca2+ sensitivity is also modulated by the PKA-dependent phosphorylation of a unique 31-residue N-terminal extension region of the Troponin I subunit (NH2-TnI). However, the detailed mechanism for the propagation of the phosphorylation signal through Tn, which results in the enhancement of the myocardial relaxation rate, is difficult to examine within whole Tn. Several models exist for how phosphorylation modulates the troponin response in cardiac cells but these are mostly built from peptide-NMR studies and molecular dynamics simulations. Here we used a paramagnetic spin labeling approach to position and track the movement of the NH2-TnI region within whole Tn. Through paramagnetic relaxation enhancement (PRE)-NMR experiments, we show that the NH2-TnI region interacts with a broad surface area on the N-domain of the Troponin C subunit. This region includes the Ca2+ regulatory Site II and the TnI switch-binding site. Phosphorylation of the NH2-TnI both weakens and shifts this region to an adjacent site on TnC. Interspin EPR distances between NH2-TnI and TnC further reveal a phosphorylation induced re-orientation of the TnC N-domain under saturating Ca2+ conditions. We propose an allosteric model where phosphorylation triggered cooperative changes in both the interaction of the NH2-TnI region with TnC, and the re-orientation of the TnC interdomain orientation, together promote the release of the TnI switch-peptide. Enhancement of the myocardial relaxation rate then occurs. Knowledge of this unique role of phosphorylation in whole Tn is important for understanding pathological processes affecting the heart.
Although not formalized into current risk assessment models, frailty has been associated with negative postoperative outcomes in many specialties. Using administrative coding, we evaluated the impact of frailty on in-hospital mortality, complications and resource use in a nationally representative cohort of patients undergoing isolated coronary artery bypass grafting (CABG).
Patients ≥ 18 years who underwent isolated CABG across the United States were identified using the 2005-2016 National Inpatient Sample. Frailty was defined using a derivative of the validated Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator. Mortality, length of stay, inflation-adjusted costs, and postoperative complications were evaluated using multi-level multivariable regression.
Of an estimated 2,137,618 patients undergoing isolated CABG, 85,879 (4.0%) were considered frail. The proportion of frail patients increased over the study period (NP-trend=0.002), while annual mortality rates declined (NP-trend<0.001). Frail patients were older (68.9±10.7 years vs. 65.0±10.6 years, P<0.001), and more commonly female (32.8% vs. 26.2%, P<0.001). After adjustment, frailty was associated with increased odds of in-hospital mortality (adjusted odds ratio, AOR 2.49, 95% confidence interval, 95% CI 2.30-2.70, P<0.001), major complications (AOR 2.55, 95% CI 2.39-2.71, P<0.001), increased length of stay (AOR 1.40, 95% CI 1.09-2.11, P<0.001), and costs (AOR 1.03, 95% CI 1.02-1.07, P<0.001).
Frailty as identified by administrative coding serves as strong independent predictor of death and complications following CABG. Incorporation of frailty into risk models may aid in counseling patients about operative risk and benchmarking outcomes.
Frailty as identified by administrative coding serves as strong independent predictor of death and complications following CABG. Incorporation of frailty into risk models may aid in counseling patients about operative risk and benchmarking outcomes.
Clinical studies have demonstrated improved gradients after AVR with the Trifecta (TR) as compared to the Magna Ease (ME). Clinical benefits of this strategy have not been demonstrated.
Patients undergoing AVR for severe AS with either valve were included. Patients were excluded if they underwent concomitant procedures other than CABG. Inverse proportion treatment weighting was used in the analysis. The primary outcome was a composite of cardiac mortality, need for re-intervention, freedom from first CHF. Secondary outcomes included a) all-cause mortality b) the composite components and c) cumulative CHF admission. Follow-up echocardiograms were assessed in a cohort of patients to assess structural valve degeneration (SVD).
There were 331 patients in the TR group and 360 patients in the ME group. The TR group had more females (48% vs 32%, p<0.001) with smaller roots (LVOT diameter [TR 2.11, ME 2.17 cm, p<0.001]). After weighting, there was no significant difference in the composite measure between groups (p>0.05). There was no difference in all-cause mortality (HR 0.82 95% CI(0.42, 1.59), p=0.56) and five-year survival was 91.9% in ME and 93.4% in the TR group. There was no difference in cardiac death, re-intervention or first onset of CHF or incidence of SVD. There was no difference in the rate of admissions for CHF per 100 patients between the two valve types (p=0.19).
Early hemodynamic benefits have not translated into differences in medium-term clinical outcomes between these two valves and long-term follow-up is necessary.
Early hemodynamic benefits have not translated into differences in medium-term clinical outcomes between these two valves and long-term follow-up is necessary.Here we present our technique of aortic valve replacement through a reversed C-shaped ministernotomy in 36 patients operated between 2017 and 2019. All patients had a preoperative computed tomography that guided the surgical approach. The sternum was incised at the level of the first and third or the second and fourth intercostal spaces. Cross-clamp time was of 65.2 ± 15.9 minutes. Median extubation time was of 2 hours. There was no postoperative 30-day mortality. Because the upper and lower parts of the sternum remain intact, this approach may improve postoperative thoracic stability.
Hyponatremia is an unrecognized risk factor for adverse outcomes after cardiac surgery. We sought to study the prevalence of preoperative hyponatremia and its impact in short-term and long-term outcomes after cardiac surgery.
Patients who had CABG, valve, or CABG and valve procedures from 2000 to 2016 and available preoperative serum sodium within 30 days of the index procedure were included in the study. The effect of preoperative sodium on short and long-term outcomes was analyzed as a continuous and as a binary (hyponatremia (Na+<135mEq/L) vs. no hyponatremia) predictor variable in multivariable regression models.
Preoperative hyponatremia was present in 9.9% of 16,238 patients with available sodium levels. Comorbidities were more common in patients with hyponatremia. Hyponatremia was independently associated with operative mortality (OR 1.80, 95% CI 1.38 - 2.34, p<0.001), long term mortality (HR 1.31, 95% CI 1.21 - 1.40, p<0.001), longer post-operative length of stay (HR 1.35, 95% CI 1.28 - 1.43, p<0.001), renal failure (OR 1.52, 95% CI 1.20- 1.93, p<0.001), prolonged ventilation (OR 1.52, 95% CI 1.30 - 1.78, p<0.001), and stroke or TIA (OR 1.48, 95% CI 1.09 - 2.02, p=0.013). Severity of hyponatremia, as measured by sodium level, was similarly associated with increased risk of death and post-operative complications.
Preoperative hyponatremia is relatively common and is associated with adverse short- and long-term outcomes after cardiac surgery. Preoperative hyponatremia can be used independently from standard risk factors to identify high risk patients for cardiac surgery.
Preoperative hyponatremia is relatively common and is associated with adverse short- and long-term outcomes after cardiac surgery. Preoperative hyponatremia can be used independently from standard risk factors to identify high risk patients for cardiac surgery.
Previous studies suggest that birth prior to 39 weeks gestational age (GA) is associated with higher perioperative mortality and morbidity after congenital heart surgery. The optimal approach to timing of surgery in premature infants remains unclear. We investigated the impact of GA at birth and corrected GA at surgery on post-operative outcomes using the Pediatric Cardiac Critical Care Consortium (PC
) database.
Infants undergoing selected index cardiac operations before the end of the neonatal period were included (n=2,298). GA at birth and corrected GA at the time of index cardiac surgery were used as categorical predictors and fitted as a cubic spline to assess non-linear relationships. The primary outcome was hospital mortality. Multivariable logistic regression models assessed the association between predictors and outcomes while adjusting for confounders.
Late-preterm birth (34-36 weeks) was associated with increased odds of mortality compared to full-term (39-40 weeks) birth while early-term birth (37-38 weeks) was not associated with increased mortality. Corrected GA at surgery of 34-37 weeks compared to 40-44 weeks was associated with increased mortality. When analyzing corrected GA at surgery as a continuous predictor of outcome, odds of survival improve as patients approach 39 weeks corrected GA.
Contrary to previous literature, we did not find an association between early-term birth and hospital mortality at PC
hospitals. Our analysis of the relationship between corrected GA and mortality suggests that operating closer to full-term corrected GA may improve survival.
Contrary to previous literature, we did not find an association between early-term birth and hospital mortality at PC4 hospitals. Our analysis of the relationship between corrected GA and mortality suggests that operating closer to full-term corrected GA may improve survival.