Lower HR Research Articles

Chemoreflex and baroreflex alterations in Parkinsonism induced by 6-OHDA in unanesthetized rats

Parkinson’s disease (PD) is mainly characterized by motor signals. However, non-motor signals also affect and decrease the quality of life of PD patients. Among these non-motor signs are cardiovascular disorders as orthostatic hypotension, postprandial hypotension and cardiac arrhythmias, which may be due to the involvement of both central nervous system and peripheral autonomic nervous system. In the present study we investigated the cardiovascular function, evaluating cardiovascular reflexes (chemoreflex and baroreflex), in an animal model of Parkinsonism induced by bilateral infusion of the toxin 6-hydroxydopamine (6-OHDA), in the substantia nigra pars compacta (SNpc). The results showed that the animals induced to Parkinsonism had lower arterial pressure (AP) and heart rate HR) compared to control animals. We showed that after activation of the baroreceptors by phenylephrine (Phe) and sodium nitroprusside (SNP), the baroreflex sensitivity index was not changed between the groups. However, there was a greater increase in the AP when stimulated with Phe and greater tachycardia when stimulated with SNP in 6-OHDA animals. After activation of the peripheral chemoreceptors through KCN injection (cytotoxic hypoxia), there was a higher increase in pressor and bradycardic response in injured animals with bilateral 6-OHDA. These changes in the cardiovascular reflexes may be important adjustments mechanisms to maintain the cerebral blood flow in those animals, and may be a result of denervation supersensitivity to catecholamines in autonomic targets.

Bedtime ingestion of hypertension medications reduces the risk of new-onset type 2 diabetes: a randomised controlled trial

We investigated whether therapy with the entire daily dose of ≥ 1 hypertension medications at bedtime exerts greater reduction in the risk of new-onset diabetes than therapy with all medications upon awakening. We conducted a prospective, randomised, open-label, blinded endpoint trial of 2,012 hypertensive patients without diabetes, 976 men and 1,036 women, 52.7 ± 13.6 years of age. Patients were randomised, using a computer-generated allocation table, to ingest all their prescribed hypertension medications upon awakening or the entire daily dose of ≥ 1 of them at bedtime. Investigators blinded to the hypertension treatment scheme of the patients assessed the development of new-onset diabetes. During a 5.9-year median follow-up, 171 participants developed type 2 diabetes. Patients of the bedtime, compared with the morning-treatment group, showed: (1) significantly lower asleep BP mean, greater sleep-time relative BP decline and attenuated prevalence of non-dipping at the final evaluation (32% vs 52%, p < 0.001); and (2) significantly lower HR of new-onset diabetes after adjustment for the significant influential characteristics of fasting glucose, waist circumference, asleep systolic BP mean, dipping classification and chronic kidney disease (CKD) (unadjusted HR 0.41 [95% CI 0.29, 0.58]; adjusted HR 0.43 [0.31, 0.61]; event-rate 4.8% vs 12.1% with bedtime and morning treatment, respectively; p < 0.001). Greater benefit was observed for bedtime compared with awakening treatment with angiotensin receptor blockers (ARBs) (HR 0.39 [0.22, 0.69]; p < 0.001), ACE inhibitors (0.31 [0.12, 0.79], p = 0.015) and β-blockers (0.35 [0.14, 0.85], p = 0.021). In hypertensive patients without diabetes, ingestion of ≥ 1 BP-lowering medications at bedtime, mainly those modulating or blocking the effects of angiotensin II, compared with ingestion of all such medications upon awakening, results in improved ambulatory BP (ABP) control (significant further decrease of asleep BP) and reduced risk of new-onset diabetes. ClinicalTrials.gov NCT00295542. This independent investigator-promoted research was supported by unrestricted grants from Ministerio de Ciencia e Innovación (SAF2006-6254-FEDER; SAF2009-7028-FEDER); Xunta de Galicia (PGIDIT03-PXIB-32201PR; INCITE07-PXI-322003ES; INCITE08-E1R-322063ES; INCITE09-E2R-322099ES; 09CSA018322PR); and Vicerrectorado de Investigación, University of Vigo.

Role of 5-HT(2B) Serotonin Receptor Agonist in the Regulation of Pumping Function of the Heart.

The effect of α-methyl-5-hydroxytryptamine maleate, an agonist of 5-HT2B serotonin receptors, on the pumping function of the heart was examined in rats with forced motor behavior. At rest, swim-trained rats demonstrated lower HR and greater stroke volume and cardiac output than untrained rats. The agonist decreased HR, stroke volume, and cardiac output in 21- and 70-day-old swim-trained rats, but not in 100- and 200-day-old rats.

21-gene recurrence score assay (RS) and impact on adjuvant chemotherapy (CTx) use among lobular (L) and ductal (D) histology hormone receptor positive (HR+) early breast cancers (EBC).

543 Background: RS identifies lower risk HR+ EBCs that may avoid adjuvant CTx. L histology may influence CTx use in intermediate RS cancers given its association with high HR+ expression and hormon...

Effect of salt diet on beat-to-beat blood pressure and heart rate dynamics in hypertensive and non-hypertensive rats

mm Hg (SD: 12). Upon repeat BP measurement, the systolic BP decreased by a mean of 11 mm Hg (95% CI: 8.3 13.7, p<0.001) with 63 (86.3%) patients experiencing a lower systolic reading. Similarly, the diastolic BP decreased by a mean of 5 mm Hg (95% CI: 3.3 7.1, p<0.001) as 54 (74.0%) patients developed a lower diastolic reading. There were 48 (65.8%) patients who experienced reduction in both systolic and diastolic BP, and whose baseline characteristics did not significantly differ from the remaining patients. Repeating the HR measurement led to reduction in the pulse reading by a mean of 6.2 beats per minute (95% CI: 4.7 7.8, p<0.001) with 61 (83.6%) patients experiencing lower HR. Conclusion: Among a high-risk population of hypertensive patients, repeating measurements during the clinic appointment leads to significantly lower BP and HR readings. Our findings suggest that the repeated BP may be more representative of hypertensive status, illustrating a component of white coat hypertension. We propose the concept of ‘‘first pass’’ white coat hypertension to refer to the difference between first and second BP readings during an individual office visit. ‘‘Second pass’’ white coat hypertension may then refer to the phenomenon of persistently high BP readings in the office but normal readings at home. Recognizing the utility of obtaining a repeat set of BP and HR measurements may have significant impact on management decisions.

Efficacy of Surgery and Further Treatment of Progressive Glioblastoma

Treatment options for patients with glioblastoma at progression have remained controversial, and selection criteria for the appropriate type of intervention remain poorly defined. The objectives were to determine which factors favor the decision for second surgery and which factors are associated with overall survival (OS) and to evaluate the National Institutes of Health (NIH) recurrent glioblastoma scale. The scale includes tumor involvement of eloquent brain regions, functional status, and tumor volume. A retrospective single-center analysis of patients with newly diagnosed glioblastoma undergoing initial surgery between January 2007 and December 2011 was performed. Patients were separated into two groups: those with versus those without second resection surgery at disease progression. OS was compared using the multiple logistic regression model, Cox proportional hazard regression, and Kaplan-Meier survival analysis. The data of 98 patients were statistically analyzed. Among the patients, 58 had initial surgery only (age 61.27 years; median OS [mOS] 14.81 months) and 40 underwent second surgery at disease progression (age 55 years; mOS 18.86 months). Age was the only predictor for repeated surgery (P= 0.012; odds ratio 0.94). At the time of tumor progression, administration of alkylating chemotherapy (P= 0.004; hazard ratio [HR] 0.24) or bevacizumab (P= 0.001; HR 0.23) was associated with longer OS. Reoperation was associated with a lower HR (P= 0.134; HR 0.66). The NIH recurrent glioblastoma scale showed statistically significant improvement of prognosis prediction with the addition of age. Surgery of progressive glioblastoma and postoperative treatment at the time of progression is associated with improved OS in some patients. The addition of age may improve survival prediction of the NIH recurrent glioblastoma scale.

Difference of catecholamine responses to exercise in men with trisomy 21, with or without chronotropic incompetence

ObjectiveOur purpose was to analyse if catecholamine responses to exercise would be different in Down syndrome (DS) with or without chronotropic incompetence. Research design and methodsTwenty five men with DS (mean age 22.2±3.2) and twenty six controls (CONT, mean age 22.5±1.4) participated in the study, and are divided into 3 groups: CONT, DS with chronotropic incompetence (DS+) and DS without chronotropic incompetence (DS−). During two treadmill incremental tests, blood samples were collected for the determination of hormonal and metabolic variables. ResultsTen out of 25 DS had chronotropic incompetence whereas no CONT. At rest, compared to CONT, despite similar physical activity, DS with chronotropic incompetence had significantly higher subcutaneous fat mass (p<0.001), lower epinephrine concentration (p<0.01), and higher leptin (p<0.01) and insulin concentrations (p<0.05). At peak exercise, all DS had lower heart rate, oxygen uptake and blood lactate concentrations than controls (p<0.001). During a ‘Submaximal incremental test’, DS with chronotropic incompetence had lower HR and lactate values (p<0.001) compared to CONT and DS without chronotropic incompetence (p<0.01). They also had blunted epinephrine and impaired norepinephrine responses to exercise compared to DS without chronotropic incompetence and CONT (p<0.01 and p<0.05 respectively). ConclusionsOur results indicate that catecholamine adaptations to exercise are not adequate in DS+ and are associated with exercise intolerance. Thus, this endocrine profile at rest and during exercise may limit endurance performance of DS.

Autonomic regulation in fetuses with congenital heart disease

BackgroundExposure to antenatal stressors affects autonomic regulation in fetuses. Whether the presence of congenital heart disease (CHD) alters the developmental trajectory of autonomic regulation is not known. Aims/Study DesignThis prospective observational cohort study aimed to further characterize autonomic regulation in fetuses with CHD; specifically hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and tetralogy of Fallot (TOF). SubjectsFrom 11/2010 to 11/2012, 92 fetuses were enrolled: 41 controls and 51 with CHD consisting of 19 with HLHS, 12 with TGA, and 20 with TOF. Maternal abdominal fetal electrocardiogram (ECG) recordings were obtained at 3 gestational ages: 19–27 weeks (F1), 28–33 weeks (F2), and 34–38 weeks (F3). Outcome measuresFetal ECG was analyzed for mean heart rate along with 3 measures of autonomic variability of the fetal heart rate: interquartile range, standard deviation, and root mean square of the standard deviation of the heart rate (RMSSD), a measure of parasympathetic activity. ResultsDuring F1 and F2 periods, HLHS fetuses demonstrated significantly lower mean HR than controls (p<0.05). Heart rate variability at F3, as measured by standard deviation, interquartile range, and RMSSD was lower in HLHS than controls (p<0.05). Other CHD subgroups showed a similar, though non-significant trend towards lower variability. ConclusionsAutonomic regulation in CHD fetuses differs from controls, with HLHS fetuses most markedly affected.

HOW MOTIVATIONAL AND CALM MUSIC MAY AFFECT THE PREFRONTAL CORTEX AREA AND EMOTIONAL RESPONSES: A FUNCTIONAL NEAR-INFRARED SPECTROSCOPY (fNIRS) STUDY.

Using functional near-infrared spectroscopy, the present study investigated how listening to differently valenced music is associated with changes in hemoglobin concentrations in the prefrontal cortex area, indicating changes in neural activity. Thirty healthy people (15 men; M age = 24.8 yr., SD = 2.4; 15 women; M age = 25.2 yr., SD = 3.1) participated. Prefrontal cortex activation, emotional responses (heart rate variability), and self-reported affective ratings were measured while listening to calm and motivational music. The songs were presented in a random counterbalanced order and separated by periods of white noise. Mixed-model repeated-measures analysis of variance (ANOVA) evaluated the relationships for main effects and interactions. The results showed that music was associated with increased activation of the prefrontal cortex area. For both sexes, listening to the motivational song was associated with higher vagal withdrawal (lower HR) than the calm song. As expected, participants rated the motivational song with greater affective valence and higher arousal. Effects persisted longer in men than in women. These findings suggest that both the characteristics of music and sex differences may significantly affect the results of emotional neuroimaging in samples of young adults.

Abstract 18907: Relationships Between Renal Haemodynamics With Cardiac and Aortic Haemodynamics in the Early Stages of Essential Hypertension

Introduction: The relationship of renal haemodynamics with cardiac and aortic hameodynamics is still unclear. Hypothesis: We evaluated the relationship of increased renal resistive index (RRI) with Augmentation index (AIx) and cardiac haemodynamics by means of mitral annular early diastolic velocity (E/Ea) in untreated patients with essential hypertension. Methods: 76 newly diagnosed untreated non diabetic patients with stage I-II essential hypertension [35 males, aged 50 years, office blood pressure (BP) = 143/ 91 mm Hg], underwent ABPM, complete echocardiographic study for determination of E/Ea and blood sampling for assessment of metabolic profile. Moreover, data on renal resistive index (RRI), obtained by Doppler ultrasound sampling of the intrarenal arteries, as well as augmentation index (AIx), were retrospectively analyzed. Results: Based on the mean value of RRI (0.60), hypertensives were classified into those with high and low RRI. Hypertensives with high RRI values compared to those with low values were older (55.6±9.8 vs 44.4±11.6 years, p &lt; 0.001), had lower 24-hour diastolic BP (77.5±7.7 vs 84.3±6.7 mmHg, p &lt; 0.001), lower 24-hour HR (71.2±10.3 vs 76.2±9.2 bpm, p &lt; 0.05), higher levels of AIx (27.2±8.2 vs 17.8±14.8 %, p &lt; 0.01), and higher values of E/Ea (lateral) (7.7±1.8 vs 6.2±2.3, p &lt; 0.05). In the total population, RRI was negatively related to 24-hour diastolic BP (r = -0.523, p &lt; 0.001) and 24-hour HR (r = -0.281, p &lt; 0.05), while it was positively associated with CRP (r = 0.335, p &lt; 0.05), TChol (r = 0.296, p &lt; 0.01), age (r = 0.443, r &lt; 0.001), AIx (r = 0.413, p = 0.001) and E/Ea(lateral) (r = 0.465, p &lt; 0.05). Multiple regression analysis revealed that 24-hour diastolic BP and E/Ea (lateral) were independent associated with RRI (R2 = 0.434, p &lt; 0.05). Conclusions: Increased vascular resistance of intrarenal arteries is associated with impaired aortic and cardiac haemodynamics, as reflected by increased AIx and E/Ea (lateral) values. RRI may be considered a useful surrogate of haemodynamics in essential hypertension.

Cycling time trial performance may be impaired by whey protein and L-alanine intake during prolonged exercise.

Previous studies reported that adding protein (PRO) to carbohydrate (CHO) solutions enhances endurance performance. The ergogenic effect may be a function of additional protein/amino acid calories, but this has not been examined. In addition, although supplemental L-alanine (ALA) is readily oxidized during exercise, the subsequent impact on metabolism and prolonged endurance performance is unknown. The purpose of this investigation was to independently gauge the impact of whey PRO hydrolysate and ALA supplementation on performance and various physiological parameters. Eight cyclists (age: 22.3 ± 5.6 yr, weight: 70.0 ± 8.0 kg, VO2max: 59.4 ± 4.9 ml · kg(-1) · min(-1)) performed 120 min of constant-load cycling (55% of peak power) followed by a 30-km time trial (TT) under placebo (PLA), PRO, and ALA conditions. Magnitude-based qualitative inferences were applied to evaluate treatment differences and data are presented as percent difference between treatments ± 90% confidence limit. Both ALA (2.1 ± 2.7%) and PRO intake (-2.1 ± 2.2%) possibly harmed performance compared with PLA. Of interest, heart rate was possibly lower with ALA than PLA at 20- (-2.7 ± 3.4%) and 120-min (-1.7 ± 2.9%) of constant-load cycling and the serum interleukin-6 (IL-6) response to 120 min of cycling was likely attenuated with PRO compared with PLA (PLA, 6.6 ± 3.7 fold vs. PRO, 2.9 ± 1.8 fold). In addition, blood glucose levels were lower with PRO than PLA at 20- (-8.8 ± 2.3%; very likely) and 120-min (-4.9 ± 4.6%; likely) of constant-load cycling. Although ALA intake appears to lower HR and PRO ingestion dampens the IL-6 response to exercise, the ingestion of PRO (without CHO) or ALA does not enhance, and may actually impair, performance following prolonged cycling.

ABSTRACT 814

Background and aims: WHO based protocol and the Pediatric Advanced Life Support approach have been used for the treatment of hypovolemic shock in Guatemala City. WHO is based in clinical findings and do not has any goal in the treatment. Aims: Identifies if in patients with severe hypovolemia, ischemia, metabolic acidosis and with absence of central pulses the fluid deficit will be higher and underestimated. Methods: Prospective, descriptive, University Hospital, hypovolemic shock related to diarrhea. Rapid cardiopulmonary evaluation of the PALS course was performed, Blood lactate was measured 0 min and 60 min after starting the fluid recovery. The goal directed therapy restore pulses, extremities warmth, capillary refill < 2 seconds, heart rate decrease, and increase in blood pressure. Monitoring for the appearance of congestive rales, hepatomegaly after the hydratation, severe edema or increment of the intrabdominal pressure. Decisions were based in perfusion restoration instead of the WHO protocol. Data processed SPSS 22;a t test for independent samples with a significant value of p < 0.05. Results: 82 children, age of 21.5 ± 34.5 months, 57 survived and 25 died. All decreased mental status. Survivors had lower HR at admission and 1 hour after, (p<0.05), higher MAP, higher pH (p<0.001), lower lactate. higher lactate depuration and base excess correction (p<0.001) All the nutritional indexes were lower in patients who died (p<0.05). Conclusions: Survivors received in the first hour 97.7 ± 42.2 ml/kg, this represents 49% more than the recommendations of the WHO protocol (p<0.001).

A comparison of bolus injection of landiolol versus oral administration of propranolol before cardiac computed tomography

Heart rate (HR) reduction is essential to achieve good image quality for cardiac computed tomography (CCT). We evaluated the efficacy of a bolus injection of landiolol, an ultra-short acting β-blocker, without the administration of oral β-blocker to reduce HR prior to CCT. We enrolled 678 consecutive patients who underwent CCT from December 2011 to March 2012 and divided them into three groups, which were a propranolol group (n = 277), a low-dose landiolol group (n = 188), and a high-dose landiolol group (n = 213). Patients in the propranolol group received oral propranolol (10–20 mg) prior to CCT. Patients in the low-dose and high-dose landiolol groups were administered a bolus injection of landiolol (0.125 mg/kg), while the high-dose group received an additional 3.75 mg of landiolol if the baseline HR was ≥75/min. Although the average HR was significantly lower in the propranolol group (61.6 ± 8.0/min) than in the low-dose landiolol group (64.1 ± 7.4/min, P < 0.001), there was no significant difference in the image quality (P = 0.91). Among patients with baseline HR ≥75/min, the average HR tended to be lower in the high-dose landiolol group (67.2 ± 6.9/min) compared with the low-dose landiolol group (69.0 ± 6.9/min, P = 0.10), and there was a corresponding difference in image quality between these two groups (P = 0.02). In conclusion, Although the decrease of HR was significantly larger in the propranolol group than in the landiolol groups, the image quality was similar. Among the patients who received landiolol, a higher dose was associated with a lower HR and better image quality. Further investigation to assess higher-dose bolus injection of landiolol or bolus injection following oral administration of a β-blocker would be needed.

Land Versus Water Treadmill Running: Lactate Threshold

The lactate threshold (LT) is a valuable parameter for setting appropriate exercise intensities. Whether the intensity where the LT occurs is similar in water vs. land treadmill exercise has not been determined. The purpose of this study was to determine LT during aquatic vs. land treadmill running. On separate days, on land and in water (submerged at the xiphoid process), 15 participants performed on a multistage graded exercise treadmill LT test in random order. LT was determined using the DMax method. At LT, no statistically significant differences were identified for running speed (195.3 ± 31.5 m·min -1 land vs. 188.1 ± 22.9 m·min-1 water), lactate concentration (2.6 ± 0.8 land vs. 2.7 ± 0.8 water mmol·L-1). At LT, there were statistically lower (p < .004) water vs. land VO2 values (37.9 ± 5.4 land vs. 35.0 ± 5.4 water ml·kg-1·min-1), and heart rate (HR; 171 ± 14 land vs 159 ± 18 water bpm). The lower VO2 and HR in water may reflect a lower energy requirement due to a decreased body weight support in the water. This is beneficial for those using aquatic treadmills and desiring to achieve threshold-intensity training while lowering the joint-stress caused by land running.

Body Composition and Cardiorespiratory Response of Male and Female Soldiers during a Simulated Attack Maneuver

The study of organic response during combat is poorly reported in specific literature, despite being essential to improve soldiers training. The aim of the present research was to study the body composition and organic response during a treadmill test simulating the attack maneuver of a light infantry company, studying the differences between soldiers gender. Body composition and organic response in the treadmill test were analyzed in 27 healthy professional soldiers. Body weight was lower and fat mass was higher in female soldiers, and height and muscle mass were higher in male soldiers. In treadmill test, values of maximal oxygen uptake (VO2), oxygen uptake at anaerobic threshold and maximal heart rate (HR) and HR at anaerobic threshold, were higher in male soldiers (male vs. female: 51.9±1.2 vs. 50.4±1.3 ml/kg/min; 3278.9±93.9 vs. 2721.8 ml/min; 194.2±1.9 vs. 184.0±6.6 bpm; 181.3±1.8 vs. 171.4±1.7 bpm respectively). During simulated attack maneuver female soldiers presented lower VO2 and higher HR than male soldiers, showing a worse physical fitness level. These data could be used by military coach to improve specific combat training. It is also recommended a decrease in the weigh carried by soldiers and to improve their aerobic performance to maximize the efficiency in last phases of combat maneuvers.

The burden, distribution and risk factors for cervical oncogenic human papilloma virus infection in HIV positive Nigerian women

BackgroundThe expected reduction in cervical cancer incidence as a result of increased access to antiretroviral therapy is yet to be seen. In this study we investigated the effect of HIV infection and treatment on high-risk (hr) human papilloma virus (HPV) prevalence and distribution.MethodsCervical cells from 515 (220 HIV positive and 295 HIV negative) women, recruited during community cervical cancer screening programme in states of Ogun and Lagos and at the cervical cancer screen clinic, Nigerian Institute of Medical Research Lagos were evaluated for the presence of 13 hr HPV genotypes by polymerase chain reaction based assay.ResultsThe prevalence of high-risk HPV was 19.6% in the studied population. HPV 16 (3.9%), 35 (3.5%), 58 (3.3%) and 31 (3.3%) were the most common hr HPV infections detected. We observed that the prevalence of hr HPV was higher in HIV positives (24.5%) than 15.9% in HIV negative women (OR = 1.7; 95% CI: 1.1-2.7). A multivariate logistic regression analysis showed a lower hr HPV prevalence in HIV positive women on antiretroviral drugs (OR = 0.4; 95% CI: 0.3-0.5) and with CD4 count of 500 and above (OR = 0.7; 95% CI: 0.5-0.8). A higher prevalence of hr HPV was also noted in HIV positive women with CD4 count < 200 cells/mm3 (OR = 2.4; 95% CI: 1.7-5.9).ConclusionHPV 16, 35, 58 and 31 genotypes were the most common hr HPV infection in our study group, which could be regarded as high risk general population sample; with higher prevalence of HPV 16 and 35 in HIV positive women than in HIV negative women. The use of antiretroviral drugs was found to be associated with a lower prevalence of hr HPV infection, compared to those not on treatment. This study raises important issues that should be further investigated to enable the development of robust cervical cancer prevention and control strategies for women in our setting.

Degree of Beta-Blockade and Outcomes in Patients with Acute Coronary Syndrome

Objective: We sought to determine if the outcome benefit of beta blockade in the ACS population is associated with baseline HR, discharge HR, or a reduction in HR. Background: ACC guidelines recommend a resting HR goal of 50 to 60 bpm in ACS patients. This recommendation is not based on study outcomes, but rather on expert opinion. Evidence-based clinical trials investigating ideal target heart rate of beta blocker (BB) therapy in the ACS population are lacking. Methods: A retrospective analysis was performed of all ACS patients who underwent coronary angiography (with or without percutaneous coronary intervention) at Providence Hospital from September 2006 to August 2011 excluding patients with any contraindication to BB therapy. Discharge HR was used as the predictor variable for outcomes in these patients. Results: A total of 912 patients (403 ST elevation myocardial infarction MI (STEMI) and 509 Non STEMI patients were included. Discharge HR was divided into quintiles: quintile 1 (48 - 64 bpm), quintile 2 (65 - 70), quintile 3 (71 - 76), quintile 4 (77 - 83) and quintile 5 (84 - 119). There was a statistically significant difference seen between the quintile 1 composite endpoint and the other quintile endpoints. (p value <0.05) No differences were seen across quintiles in median TIMI risk index score at admission, systolic and diastolic blood pressure or beta-blocker dose at discharge. Patients in quintile 1 fared better overall with the observation of worse outcomes in patients with a discharge heart rate less than 55. Conclusion: In those with ACS, particularly STEMI and NSTEMI, a lower discharge HR conferred a decreased composite endpoint at 24 months with the best outcomes seen at a resting HR between 55-65. Further studies are needed to investigate the clinical benefit of optimal HR reduction in this population beyond 2 years.

Abstract B109: The role of SIRT6 in drug resistance and cellular senescence in cancer.

Abstract Introduction: The Sirtuin family consists of 7 members. They comprize highly conserved NAD+-dependent deacetylases that play an important role in a board spectrum of cellular processes, including metabolism, differentiation, survival and cellular senescence. It has also been suggested that these proteins are central to cancer development and drug resistance. Recent studies have documented that SIRT6, a nuclear chromatin-associated protein, has a key role in genomic stability and degenerative pathologies associated with ageing. Moreover, SIRT6 has been reported to have a function in the regulation of DNA damage repair. Therefore, this research aims to investigate the role of SIRT6 in drug resistance and cellular senescence in cancer cells. Methods: Cell lines that we have used in this research consist of sensitive and resistant breast cancer cells, Hela cells and mouse embryonic fibroblasts (MEFs). To investigate the role of SIRT6 in drug resistance, we treated cells with either epirubicin or paclitaxel, then performed immunofluorescent, comet and repair assays to investigate DNA damage repair. Clonogenic and beta-galactosidase assays were also used to investigate long-term survival and cellular senescence. Results: We found that SIRT6 is elevated in drug resistant cells compared to drug sensitive parental cells and that SIRT6 mediates drug resistance by increasing DNA damage repair. Sirt6-/- MEFs have lower levels of γH2AX accumulation compared to WT MEFs. These higher levels of SIRT6 are also associated with the lower activities of p53 and FOXO3a which are two important cell cycle/survival regulators. Here, we show that depletion of SIRT6 in cancer cells results in a decrease in long-term survival and lower HR and NHEJ DNA repair activity. SIRT6-deficeint cells also exhibit the induction of senescence-associated β-galactosidase activity and flat cell morphology. Conclusion: Our results suggest a novel role of SIRT6 in epirubicin and paclitaxel treatment resistance and cellular senescence. SIRT6 could be a potential biomarker for identifying tumors that are likely to be resistant to these chemotherapeutic agents. It might be also a useful therapeutic target for the prevention of acquired drug resistance and for improving the efficiency of drug treatment. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B109. Citation Format: Mattaka Khongkow, Eric Lam. The role of SIRT6 in drug resistance and cellular senescence in cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B109.

150 minutes of vigorous physical activity per week predicts survival and successful ageing: a population-based 11-year longitudinal study of 12 201 older Australian men

BackgroundPhysical activity has been associated with improved survival, but it is unclear whether this increase in longevity is accompanied by preserved mental and physical functioning, also known as healthy ageing....

Frequency of Mentally Stimulating Activities Modifies the Relationship Between Cardiovascular Reactivity and Executive Function in Old Age

Recent evidence suggests that younger and middle-age adults who show greater cardiovascular reactivity (CVR) to acute mental stress demonstrate better reasoning and memory skills. The purpose of this study was to examine whether older adults would exhibit a similar positive association between CVR and executive function and whether regular engagement in mentally stimulating activities (MSA) would moderate this association. Secondary cross-sectional analysis. Three clinical research centers in the Midwest and on the West Coast and East Coast. A total of 487 older adults participating in an ongoing national survey. Heart rate (HR) and low-frequency (LF) and high-frequency (HF) domains of heart rate variability (HRV) were measured at baseline and in response to standard mental stress tasks (Stroop color word task and mental arithmetic). Executive function was measured separately from the stress tasks by using five neuropsychological tests. MSA was measured by self-reported frequency of six common MSA. Higher HR reactivity was associated with better executive function after controlling for demographic and health characteristics and baseline HR, and the interaction between HR reactivity and MSA was significant for executive function. Higher LF-HRV reactivity was also associated with executive function, but subsequent analyses indicated that frequency of MSA was the strongest predictor of executive function in models that included LF-HRV or HF-HRV. Higher HR reactivity to acute psychological stress is related to better executive function in older adults. For those with lower HR reactivity, engaging frequently in MSA produced compensatory benefits for executive function.