Impaired Cardiovascular Function Research Articles

Sleep-related breathing disorders in patients with schistosomal cor-pulmonale

Schistosmiasis has long been an endemic disease in Egypt and an important cause of pulmonary hypertension. ObjectivesWe aimed to investigate the clinical and polysomnographic features of sleep-related breathing disorders (SRBD) in patients with schistosomal cor-pulmonale and to evaluate their effects on pulmonary hemodynamics. Patients and methodsWe studied 10 stable patients diagnosed with schistosomal pulmonary hypertension (7 males and 3 females their mean age was 43.7±8.04) and 10 healthy volunteers matched for age, sex and BMI. Patients’ exclusion criteria were: smoking, morbid obesity, other secondary causes of pulmonary hypertension, systemic hypertension, ischemic or rheumatic heart disease or left heart failure. All patients underwent overnight polysomnography or ambulatory cardiorespiratory sleep studies, spirometry, ECG and echocardiography. Daytime sleepiness was also assessed using the Epworth sleepiness scale (ESS). ResultsThe mean AHI in patients group was 20.0±11.34/h while in the control group it was 2.3±1.16/h. 80% of the patients were found to have an AHI>10/h and 60% had moderate to severe sleep apnea (AHI⩾15/h). In addition, the majority of the patients (80%) spent>30% of the night with an arterial oxygen saturation <90%. SRBD were not correlated with anthropometric measures, spirometry nor with the typical symptoms of SA such as excessive sleepiness as assessed by ESS. More importantly, SRBD were significantly associated with measures of pulmonary hypertension severity, and patients with moderate to severe SA had more impaired cardiovascular function as indicated by more severe right ventricular dilatation (p=0.036) than patients with mild sleep apnea. ConclusionSRBD are highly prevalent in patients with schistosomal pulmonary hypertension (PH). Also, the SA severity was correlated with more advanced PH and more severe cardiovascular impairment. Therefore in the evaluation of patients with schistosomal PH, polysomnography or an ambulatory cardiorespiratory sleep study seems justified to identify potentially treatable SRBD that may additionally challenge the already compromised cardiovascular system in these patients.

A Rating Scale for the Functional Assessment of Patients with Familial Dysautonomia (Riley Day Syndrome)

To develop a reliable rating scale to assess functional capacity in children with familial dysautonomia, evaluate changes over time, and determine whether severity within a particular functional category at a young age affected survival. Ten functional categories were retrospectively assessed in 123 patients with familial dysautonomia at age 7 years ± 6 months. Each of the 10 Functional Severity Scale categories (motor development, cognitive ability, psychological status, expressive speech, balance, oral coordination, frequency of dysautonomic crisis, respiratory, cardiovascular, and nutritional status) were scored from 1 (worst or severely affected) to 5 (best or no impairment). Changes over time were analyzed further in 22 of the 123 patients who were also available at ages 17 and 27 years. Severely impaired cardiovascular function and high frequency of dysautonomic crisis negatively affected survival (P < .005 and P < .001, respectively). In the 22 individuals followed up to age 27 years, psychological status significantly worsened (P = .01), and expressive speech improved (P = .045). From age 17 to 27 years, balance worsened markedly (P = .048). The Functional Severity Scale is a reliable tool to measure functional capacity in patients with familial dysautonomia. The scale may prove useful in providing prognosis and as a complementary endpoint in clinical trials.

Role of Physical Training in Heart Failure with Preserved Ejection Fraction

About 50% or more of heart failure (HF) patients living in the community have preserved left ventricular ejection fraction (HFpEF), and the proportion is higher among women and the very elderly. A cardinal feature of HFpEF is reduced aerobic capacity, measured objectively as peak exercise pulmonary oxygen uptake (peak VO(2)), that results in decreased quality of life. Specifically, peak VO(2) of HFpEF patients is 30-70% lower than age-, sex-, and comorbidity-matched control patients without HF. The mechanisms for the reduced peak VO(2) are due to cardiovascular and skeletal muscle dysfunction that results in reduced oxygen delivery to and/or utilization by the active muscles. Currently, four randomized controlled exercise intervention trials have been performed in HFpEF patients. These studies have consistently demonstrated that 3-6 months of aerobic training performed alone or in combination with strength training is a safe and effective therapy to increase aerobic capacity and endurance and quality of life in HFpEF patients. Despite these benefits, the physiologic mechanisms underpinning the improvement in peak exercise performance have not been studied; therefore, future studies are required to determine the role of physical training to reverse the impaired cardiovascular and skeletal muscle function in HFpEF patients.

Disassociation of Muscle Insulin Signaling and Insulin-Stimulated Glucose Uptake during Endotoxemia

Lipopolysaccharide (LPS) elicits a strong immune response, which leads to the release of inflammatory cytokines. Increased cytokine production has been shown to impair insulin-mediated glucose disposal. LPS can alter other factors, such as muscle blood flow and insulin signaling in the myocyte,that can influence glucose disposal. We hypothesize that LPS induced impairments in cardiovascular function contribute to the associated impairments in insulin action in vivo. Male wild-type C57BL/6J mice had a catheter implanted in the jugular vein for infusions and the carotid artery for sampling 5 days prior to the hyperinsulinemic-euglycemic clamp. Mice were treated with vehicle, low-(1 ug/gBW) or high-dose (10 ug/gBW) LPS 4 hours prior to the clamp. Muscle glucose uptake (MGU) was assessed using [2-14C] deoxyglucose. While both low- and high-dose LPS inhibited insulin-stimulated MGU compared to vehicle-treated mice, the impairment was more significant with the high-dose treatment (∼25% in soleus and ∼70% in both gastrocnemius and vastus lateralis). Interestingly, insulin signaling through the PI3-kinase pathway in the muscle was not affected by this treatment suggesting that the decrease in MGU is not directly due to impairments in muscle insulin action. Echocardiography demonstrated that high-dose LPS treatment significantly decreased stroke volume (∼30%), heart rate (∼35%), and cardiac output (∼50%). These observations were not seen with vehicle or low-dose LPS treatment. High-dose LPS treatment also significantly decreased muscle blood flow (∼70%) and whole body oxygen consumption (∼50%). Thus, in vivo acute endotoxemia does not impair insulin signaling through the PI3-kinase pathway in skeletal muscle and decreased tissue blood flow likely plays a central role in the impairment of glucose uptake in the muscle.

Increase of ATP-sensitive potassium (KATP) channels in the heart of type-1 diabetic rats

BackgroundAn impairment of cardiovascular function in streptozotocin (STZ)-diabetic rats has been mentioned within 5 days-to-3 months of induction. ATP-sensitive potassium (KATP) channels are expressed on cardiac sarcolemmal membranes. It is highly responsive to metabolic fluctuations and can have effects on cardiac contractility. The present study attempted to clarify the changes of cardiac KATP channels in diabetic disorders.MethodsStreptozotocin-induced diabetic rats and neonatal rat cardiomyocytes treated with a high concentration of glucose (a D-glucose concentration of 30 mM was used and cells were cultured for 24 hr) were used to examine the effect of hyperglycemia on cardiac function and the expression of KATP channels. KATP channels expression was found to be linked to cardiac tonic dysfunction, and we evaluated the expression levels of KATP channels by Western blot and Northern blot analysis.ResultsThe result shows diazoxide produced a marked reduction of heart rate in control group. Furthermore, the methods of Northern blotting and Western blotting were employed to identify the gene expression of KATP channel. Two subunits of cardiac KATP channel (SUR2A and kir 6.2) were purchased as indicators and showed significantly decreased in both diabetic rats and high glucose treated rat cardiac myocytes. Correction of hyperglycemia by insulin or phlorizin restored the gene expression of cardiac KATP in these diabetic rats.ConclusionsBoth mRNA and protein expression of cardiac KATP channels are decreased in diabetic rats induced by STZ for 8 weeks. This phenomenon leads to result in desensitization of some KATP channel drugs.

Cardiac and vascular phenotypes in the apolipoprotein E-deficient mouse

Cardiovascular death is frequently associated with atherosclerosis, a chronic multifactorial disease and a leading cause of death worldwide. Genetically engineered mouse models have proven useful for the study of the mechanisms underlying cardiovascular diseases. The apolipoprotein E-deficient mouse has been the most widely used animal model of atherosclerosis because it rapidly develops severe hypercholesterolemia and spontaneous atherosclerotic lesions similar to those observed in humans. In this review, we provide an overview of the cardiac and vascular phenotypes and discuss the interplay among nitric oxide, reactive oxygen species, aging and diet in the impairment of cardiovascular function in this mouse model.

Links between metabolic syndrome and cardiovascular autonomic dysfunction.

Background. Type 2 diabetes (T2D) might occur within metabolic syndrome (MbS). One of the complications of T2D is an impaired (imp) cardiovascular autonomic function (CAF). Aims. In subjects with T2D and age ≤ 55 years, the prevalence of impCAF and its relationship with BMI, waist, HbA1c values, MbS, hypertension, and family history of T2D and/or hypertension were analysed. Methods. 180 subjects consecutively undergoing a day hospital for T2D were studied. The IDF criteria were used to diagnose MbS. To detect impCAF, 5 tests for the evaluation of CAF were performed with Cardionomic (Meteda, Italy). Univariate and multivariate analyses were performed. Results. The prevalence of impCAF and MbS were 33.9% and 67.8%, respectively. Among diabetics with impCAF, 86.9% had MbS. ImpCAF was significantly associated with MbS, overweight, and HbA1c > 7%. Both logistic (P = 0.0009) and Poisson (P = 0.0113) models showed a positive association between impCAF and MbS. The degree of ImpCAF showed a positive linear correlation with BMI and HbA1c values. Conclusions. The study demonstrates that glycaemic control and overweight influence CAF and that T2D + MbS is more strongly associated with impCAF than isolated T2D. We suggest that MbS not only increases the cardiovascular risk of relatively young subjects with T2D but is also associated with impCAF.

Autonomic Nervous System, Inflammation, and Diabetes: Mechanisms and Possible Interventions

It is well known that cardiac autonomic neuropathy increases morbidity and mortality and is associated with prognosis of cardiovascular events in diabetes. Indeed, autonomic imbalance between the sympathetic and parasympathetic nervous system regulation of cardiovascular function is markedly associated with mortality among patients with both type 1 and type 2 diabetes [1]. The published evidence supports a common pathogenesis for IHD, hypertension, and diabetes based on a sympathetic homeostatic shift, and the usefulness of prevention based on improving the risk/prevention balance by using standard pharmaceutical and lifestyle preventative measures [2]. In addition, autonomic nervous system has been indicated as an important element in the bidirectional communication between the brain and the immune system, allowing the central control of immune status and inflammation [3]. This special issue includes 9 papers on autonomic mechanisms, inflammation, and interventions being one of them a review. In fact, J. Petrofsky et al. examine the influence of autonomic dysfunction associated with aging and type 2 diabetes on daily life activities concentrating on how autonomic impairment alters normal daily activities. Impairments include the response of the blood vessels to heat, sweating, heat transfer, whole body heating, orthostatic intolerance, balance, and gait. In addition, the effects of ageing were examined. In the submitted research papers, D. Senador et al. demonstrate that the effects of high-fructose diet in producing cardiovascular and metabolic pathologies depend on the timing of fructose intake, while G. Garruti and colleagues in a clinical study examine the links between metabolic syndrome and cardiovascular autonomic dysfunction. The authors suggest that metabolic syndrome not only increases the cardiovascular risk of relatively young subjects with T2D but is also associated with impaired cardiovascular autonomic function. In a very interesting research paper, D. C. Lieb et al. concluded that cardiac autonomic imbalance and adipose tissue-derived inflammation in newly diagnosed and established type 2 diabetes are interrelated. In the following papers, F. G. Shiraishi et al. have shown that in patients with diabetes and chronic kidney disease, aerobic capacity was associated with inflammatory state independently of diabetes presence. On the other hand, L. Jorge and colleagues demonstrate that a single bout of dynamics aerobic exercise was able to improve hemodynamic and autonomic function as expressed by baroreflex sensitivity control of heart rate in experimental diabetes. In other interventional research paper, P. Fiorino et al. examined cardiac autonomic modulation and metabolic response in streptozotocin diabetic rats treated with green tea. The authors concluded that the green tea reduced hyperglycemia and prevented renal injury and autonomic dysfunction in experimental diabetes. Finally, S. N. Xue et al. have shown that MMP9 deters the healing of diabetic foot ulcers by inhibiting the biological behaviors of skin fibroblasts, while M. Zhang et al. have suggested that LYR motif containing 1 gene may be an important mediator in the development of obesity-related insulin resistance since the expression of LYRM1 mRNA is affected by a variety of factors that are related to insulin sensitivity. The purpose of the present special issue was to discuss the role of autonomic nervous system not only in cardiovascular control but also in other pathophysiological mechanisms associated with inflammation and tissue damage, believing that sympathetic and parasympathetic balance may influence the risk and prevention equilibrium in diabetes. In conclusion, restoration of autonomic balance must be the aim of the prevention programs including therapeutic lifestyle changes and other pharmacologic approaches. M. C. Irigoyen Dulce Elena Casarini Mariana Morris Nicola Montano

Cardiovascular Autonomic Nervous System Function and Aerobic Capacity in Type 1 Diabetes

Impaired cardiovascular autonomic nervous system (ANS) function has been reported in type 1 diabetes (T1D) patients. ANS function, evaluated by heart rate variability (HRV), systolic blood pressure variability (SBPV), and baroreflex sensitivity (BRS), has been linked to aerobic capacity (VO2peak) in healthy subjects, but this relationship is unknown in T1D. We examined cardiovascular ANS function at rest and during function tests, and its relations to VO2peak in T1D individuals. Ten T1D patients (34 ± 7 years) and 11 healthy control (CON; 31 ± 6 years) age and leisure-time physical activity-matched men were studied. ANS function was recorded at rest and during active standing and handgrip. Determination of VO2peak was obtained with a graded cycle ergometer test. During ANS recordings SBPV, BRS, and resting HRV did not differ between groups, but alpha1 responses to maneuvers in detrended fluctuation analyses were smaller in T1D (active standing; 32%, handgrip; 20%, medians) than in CON (active standing; 71%, handgrip; 54%, p < 0.05). VO2peak was lower in T1D (36 ± 4 ml kg−1 min−1) than in CON (45 ± 9 ml kg−1 min−1, p < 0.05). Resting HRV measures, RMSSD, HF, and SD1 correlated with VO2peak in CON (p < 0.05) and when analyzing groups together. These results suggest that T1D had lower VO2peak, weaker HRV response to maneuvers, but not impaired cardiovascular ANS function at rest compared with CON. Resting parasympathetic cardiac activity correlated with VO2peak in CON but not in T1D. Detrended fluctuation analysis could be a sensitive detector of changes in cardiac ANS function in T1D.

Soluble Guanylate Cyclase Stimulation Prevents Fibrotic Tissue Remodeling and Improves Survival in Salt-Sensitive Dahl Rats

BackgroundA direct pharmacological stimulation of soluble guanylate cyclase (sGC) is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521), have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO) and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension.Methods and ResultsMortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d) for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1.ConclusionsStimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions.

Cultured neonatal rat cardiomyocytes display differences in glucose uptake and sensitivity to dexamethasone related to maternal diet.

Feeding a low protein (LP) diet in rat pregnancy is associated with impaired cardiovascular health and function, possibly as a result of tissue remodelling. To assess whether cardiomyocytes retain differences induced by protein restriction, cells from neonatal rats exposed to control or LP diets in utero were cultured for a period of 10 days. At the end of this period, no differences in cell size, proliferation differentiation or metabolic function were noted. When treated with dexamethasone (0.1-10 μM) for 2 days, it was noted that insulin-stimulated glucose uptake was enhanced, but only in cells from LP rats. Increased glucocorticoid sensitivity of cardiomyocytes from LP rats could not be explained by differential expression of the glucocorticoid receptor or the glucose transporters, GLUT1 and GLUT4. The findings of the study suggest that sensitivity to endocrine signals may be permanently programmed by undernutrition through mechanisms that are preserved in vitro.

Impaired cardiovascular autonomic nervous system function in patients with Churg–Strauss syndrome

Objectives: Although peripheral nervous system involvement in patients with Churg–Strauss syndrome (CSS) has been described, little is known about its autonomic part. Autonomic nervous system (ANS) function can be assessed by studying heart rate variability (HRV) and a decrease in the spectrum of HRV correlates with ANS impairment.Methods: Out of 24 CSS patients we chose 12 (four males, eight females, aged 40 ± 8.3 years) in disease remission and without cardiac involvement. Twelve age- and sex-matched healthy volunteers served as a control group. All underwent 24-h electrocardiogram (ECG) Holter recordings. HRV was calculated from 1-h segments, including: total power (TP), ultra-low frequency (ULF), very low frequency (VLF), low frequency (LF), and high frequency (HF) powers as well as normalized LF (LF%) and HF (HF%) powers and the LF to HF power ratio (LF/HF).Results: The CSS patients showed decreased HRV parameters in the 1-h domains: TP (2038 vs. 3622 ms2, p = 0.001), HF (561 vs. 1574 ms2, p < 0.001), LF (672 vs. 1050 ms2, p < 0.01), and VLF (544 vs. 738 ms2, p = 0.016). However, LF% and LF/HF ratio were markedly higher in CSS patients than in controls (53.4% vs. 39%, p < 0.001 and 1.1 vs. 0.64, p < 0.001), whereas HF% was lower in CSS than in controls (46.6% vs. 61%, p < 0.001). These results were independent of duration of the disease, eosinophil count, corticosteroids, or peripheral nerve involvement in the past.Conclusions: The CSS patients show impaired HRV parameters, indicating parasympathetic ANS dysfunction in addition to peripheral nervous system involvement.

P086 Characteristics and Socioeconomic Status of Patients undergoing Percutaneous Coronary Intervention with Stent Choice based on Patients' Willingness-to-Pay

Objective: To investigate peripheral arterial elasticity and wave intensity (WI) changes in patients with coronary artery disease (CAD). Methods: 26 cases of CAD patients with heart failure (HF group); 42 cases of non-heart failure patients (NHF group) and 40 healthy volunteers (control group) were involved in this study. ALOKA prosound a10 was employed to measure the indexes of the common carotid artery, including the first peak of carotid arterial (W1), the second peak (W2), the negative area of WI between the first and second peaks (NA), interval between the R wave of the ECG and the first peak (R-1st), interval between the first and second peaks (1st–2nd), Elasticity modulus (Ep), Stiffness parameter (b), Arterial Compliance (AC), Augmentation index (AI) and Pulse wave velocity (PWV). Comparison among the groups used the analysis of variance (ANOVA). Results: Elasticity of the carotid arteries in the NHF group and HF group were decreased. Compared with the control group, Ep, b and PWV were lower, AC was higher, and the differences were statistically significant (p 0.05). Conclusion: WI is a noninvasively obtained, clinically useful parameter for the evaluation of LV systolic and early diastolic performance, and WI reflected impaired cardiovascular function in CAD patients with a new perspective.

Age related decreases in thermoregulation and cardiovascular function in horses

Older horses have an increased risk of hyperthermia due to impaired cardiovascular function. While many studies have investigated thermoregulation in horses during exercise, none have investigated the effects of ageing. To test the hypothesis that there is a difference in thermoregulation during exercise and plasma volume (PV) in young and old horses. Study 1: 6 young (Y, 7.7 ± 0.5 years) and 5 old (O, 26.0 ± 0.8 years) unfit Standardbred mares (507 ± 11 kg, mean ± s.e.) ran on a treadmill (6% grade, velocity calculated to generate a work rate of 1625 watts) until core temperature reached 40 °C. Core (CT), skin (ST), rectal temperature (RT) and heart rate (HR) were measured every min until 10 min post exertion. Packed cell volume (HCT), lactate (LA) and plasma protein (TP) were measured in blood samples collected before, at 40 °C and every 5 min until 10 min post exercise. Sweat loss was estimated using bodyweight. Study 2: Plasma volume was measured in 26 young (8.2 ± 0.7 years) and 8 old (26.6 ± 0.7 years) Standardbred mares (515 ± 12 kg) using Evans Blue dye. Pre-exercise blood (rBV) and red cell (rRCV) volumes were calculated using PV and HCT. Data analysis utilised repeated measures ANOVA and t tests and data are expressed as mean ± s.e. Old horses reached 40 °C faster (998 ± 113 vs. 1925 ± 259 s; P < 0.05) with a greater HR at 40 °C (184 ± 6 vs. 140 ± 5 beats/min; P < 0.05) and greater sweat losses (P < 0.05). Heart rate did not differ (P > 0.05) post exercise. Age did not alter (P > 0.05) CT, ST, RT, LA, HCT or TP. Plasma volume was greater in Y vs. O horses (P < 0.05, 28.5 ± 1.4 vs. 24.1 ± 1.6 l) as was rBV (41.3 ± 2.0 vs. 35.3 ± 2.3 l) and rRCV (13.3 ± 0.6 vs. 11.1 ± 0.8 l). Ageing compromises the ability to handle the combined demand of exercise and thermoregulation in part due to decreased absolute pre-exercise PV.

Resting cardiovascular function improvements in adult men following resistance training

Impaired cardiovascular function increases the risk for fatal and non-fatal cardiovascular disease, renal disease and all-cause mortality. Research has demonstrated an inverse relationship between these cardiovascular impairments and exercise. However, previous research has mainly focused on aerobic training since regular resistance-trained men tend to display higher blood pressures due to decreased arterial compliance and increased arterial stiffness. Thus, the aim of the study was to determine the effects of eight weeks of progressive resistance training on cardiovascular functioning as depicted by resting heart rate (RHR), systolic blood pressure (RSBP), diastolic blood pressure (RDBP), rate-pressure product (RRPP) and mean arterial pressure (RMAP). Twenty eight inactive men were assigned to either a resistance training group (ResG) (n = 13) or non-exercising control group (ConG) (n = 15). Eight weeks of resistance training resulted in significant (p < 0.05) changes in cardiovascular parameters, which are: RSBP (p < 0.001), RDBP (p < 0.001), RMAP (p < 0.001) and RRPP (p < 0.001), but not RHR (p = 0.441). This study indicates that resistance training improves cardiovascular function in adult men possibly resulting in cardioprotective benefits.Key words: Blood pressure, heart rate, hemodynamic responses, strength training, vascular function.

GLP-1 signaling preserves cardiac function in endotoxemic Fischer 344 and DPP4-deficient rats

Glucagon-like peptide-1 (GLP-1) is rapidly cleaved by widely expressed dipeptidyl peptidase-4 (DPP4) enzyme. Both DPP4 inhibitors and GLP-1 analogue are being developed as a novel class of oral antihyperglycemic agent in the treatment of diabetes. However, the benefits of both agents on the cardiovascular function of endotoxemic animals remains poorly understood. In this study, the cardiac function of wild-type and DPP4-deficient rats was evaluated by pressure-volume loops in control and 4h after lipopolysaccharide (LPS, 10mg/kg, i.v.) treatment. LPS-induced suppression of cardiovascular function in wild-type rats was associated with a significant reduction in cardiac cAMP level, phosphorylation of phospholamban, and attenuation of aortic contractile response to phenylephrine. DPP4-deficient rats had better preservation of cardiovascular function than wild-type rats during endotoxemia, which was correlated with a more prominent elevation of GLP-1 signaling. These findings coincided with the pretreatment of GLP-1 analogue, exendin-4, where the deterioration of cardiovascular function during endotoxemia was significantly reversed in wild-type rats. Furthermore, the benefit of DPP4 deficiency or GLP-1 analogue not only preserved cardiovascular function but also alleviated multiple organ injury and improved survival rate during endotoxemia. In summary, this study demonstrated that the resistance to LPS in DPP4-deficient rats seems to be derived from the higher GLP-1 production, and exendin-4 prevents cardiac dysfunction in wild-type rats with endotoxemia. This study proves that GLP-1 agonists or DPP4 inhibitor may possibly be used as a preventive or even as a novel therapeutic agent in septic shock.

Influence of Beverage Temperature on Exercise Performance in the Heat: A Systematic Review

Increased core temperature (T(c)), impaired cardiovascular function, and dehydration contribute to fatigue during prolonged exercise in the heat. Although many studies have examined mechanisms addressing these factors, few have investigated the effect of cold beverage temperature on thermoregulation and exercise performance in the heat. Citations from MEDLINE (Ovid), Sport Discus (EBSCOhost), AUSPORT and AusportMed (Informit), Web of Science, and SCOPUS were identified from the earliest record until September 2008 using the search terms: drink temperature, beverage temperature, fluid temperature, water temperature, and cold fluid combined with body temperature and thermoregulation. To be included, studies needed to assess core or rectal temperature during exercise in moderate or hot environmental conditions. After quality rating was completed by two reviewers, the difference in mean Tc and exercise performance was calculated. Ten studies meeting search inclusion criteria were available for analysis. Three were excluded because sufficient detail or statistical data were not reported. A meta-analysis was not performed because the studies were deemed too different to group. Three of the remaining 7 studies found modulated T(c) with cold beverage consumption, and from the 4 that conducted exercise performance tests, performance improved by 10% with cold fluids. Cold fluid may attenuate T(c) rise and improve exercise performance in the heat; however, study findings are mixed. Research using well-trained athletes and fluid-ingestion protocols replicating competition scenarios is required. Potential sensory effects of cold fluid in maintaining motivation also need to be assessed as a mechanism underpinning improved performance.

Nebivolol in chronic heart failure: current evidence and future perspectives

Importance of the field: Chronic activation of the sympathetic nervous system leads to deterioration of cardiovascular function in heart failure patients. In systolic heart failure, β-blockers were proven to be effective in decreasing the number of deaths and improving morbidity. However, β-blockers are a heterogeneous drug group, consisting of agents with different selectivity for adrenergic receptors and/or additional effects in heart or peripheral circulation.Areas covered in the review: We describe the role of the sympathetic nervous system, β-blockers and specifically nebivolol in chronic heart failure.What the reader will gain: Nebivolol is a third-generation β-blocker, with high β1/β2 selectivity. Moreover, it has important vasodilating properties, by stimulating the production of nitric oxide. Smaller studies have already shown beneficial effects of nebivolol treatment on surrogate end points in heart failure patients. The recently published SENIORS (Phase III) study in an elderly heart failure population demonstrated a decreased number of clinical events in patients treated with nebivolol. Importantly, this effect was observed in patients with both impaired and preserved left ventricular systolic function.Take home message: Specific β-blockers may have distinct effects in various subgroups of heart failure patients. So far, nebivolol is the only β-blocker to have been shown effective in elderly heart failure patients, regardless of their left ventricular ejection fraction.

L‐Carnitine Attenuates Cardiac Remodelling rather than Vascular Remodelling in Deoxycorticosterone Acetate‐Salt Hypertensive Rats

L-carnitine is an important co-factor in fatty acid metabolism by mitochondria. This study has determined whether oral administration of L-carnitine prevents remodelling and the development of impaired cardiovascular function in deoxycorticosterone acetate (DOCA)-salt hypertensive rats (n = 6-12; #p < 0.05 versus DOCA-salt). Uninephrectomized rats administered DOCA (25 mg every 4th day s.c.) and 1% NaCl in drinking water for 28 days developed cardiovascular remodelling shown as systolic hypertension, left ventricular hypertrophy, increased thoracic aortic and left ventricular wall thickness, increased left ventricular inflammatory cell infiltration together with increased interstitial collagen and increased passive diastolic stiffness and vascular dysfunction with increased plasma malondialdehyde concentrations. Treatment with L-carnitine (1.2% in food; 0.9 mg/g/day in DOCA-salt rats) decreased blood pressure (DOCA-salt 169 +/- 2; + L-carnitine 148 +/- 6# mmHg), decreased left ventricular wet weights (DOCA-salt 3.02 +/- 0.07; + L-carnitine 2.72 +/- 0.06# mg/g body-wt), decreased inflammatory cells in the replacement fibrotic areas, reduced left ventricular interstitial collagen content (DOCA-salt 14.4 +/- 0.2; + L-carnitine 8.7 +/- 0.5# % area), reduced diastolic stiffness constant (DOCA-salt 26.9 +/- 0.5; + L-carnitine 23.8 +/- 0.5# dimensionless) and decreased plasma malondialdehyde concentrations (DOCA-salt 26.9 +/- 0.8; + L-carnitine 21.2 +/- 0.4# micromol/l) without preventing endothelial dysfunction. L-carnitine attenuated the cardiac remodelling and improved cardiac function in DOCA-salt hypertension but produced minimal changes in aortic wall thickness and vascular function. This study suggests that the mitochondrial respiratory chain is a significant source of reactive oxygen species in the heart but less so in the vasculature in DOCA-salt rats, underlying the relatively selective cardiac responses to L-carnitine treatment.

Cerebrovascular reactivity and dynamic autoregulation in tetraplegia

Humans with spinal cord injury have impaired cardiovascular function proportional to the level and completeness of the lesion. The effect on cerebrovascular function is unclear, especially for high-level lesions. The purpose of this study was to evaluate the integrity of dynamic cerebral autoregulation (CA) and the cerebrovascular reactivity in chronic tetraplegia (Tetra). After baseline, steady-state hypercapnia (5% CO(2)) and hypocapnia (controlled hyperventilation) were used to assess cerebrovascular reactivity in 6 men with Tetra (C5-C7 lesion) and 14 men without [able-bodied (AB)]. Middle cerebral artery blood flow velocity (MCAv), cerebral oxygenation, arterial blood pressure (BP), heart rate (HR), cardiac output (Q; model flow), partial pressure of end-tidal CO(2) (Pet(CO(2))), and plasma catecholamines were measured. Dynamic CA was assessed by transfer function analysis of spontaneous fluctuations in BP and MCAv. MCAv pulsatility index (MCAv PI) was calculated as (MCAv(systolic) - MCAv(diastolic))/MCAv(mean) and standardized by dividing by mean arterial pressure (MAP). Resting BP, total peripheral resistance, and catecholamines were lower in Tetra (P < 0.05), and standardized MCAv PI was approximately 36% higher in Tetra (P = 0.003). Resting MCAv, cerebral oxygenation, HR, and Pet(CO(2)) were similar between groups (P > 0.05). Although phase and transfer function gain relationships in dynamic CA were maintained with Tetra (P > 0.05), coherence in the very low-frequency range (0.02-0.07 Hz) was approximately 21% lower in Tetra (P = 0.006). Full (hypo- and hypercapnic) cerebrovascular reactivity to CO(2) was unchanged with Tetra (P > 0.05). During hypercapnia, standardized MCAv PI reactivity was enhanced by approximately 78% in Tetra (P = 0.016). Despite impaired cardiovascular function, chronic Tetra involves subtle changes in dynamic CA and cerebrovascular reactivity to CO(2). Changes are evident in coherence at baseline and MCAv PI during baseline and hypercapnic states in chronic Tetra, which may be indicative of cerebrovascular adaptation.