Xie, Wenping; Zhang, Wenpeng; Ren, Juan; Li, Wentao; Zhou, Lili; Cui, Yuan; Chen, Huiming; Yu, Wenlian; Zhuang, Xiaomei; Zhang, Zhenqing; Shen, Guolin; Li, Haishan
2018-02-14
Triclocarban (TCC) has been identified as a new environmental pollutant that is potentially hazardous to human health; however, the effects of short-term TCC exposure on cardiac function are not known. The aim of this study was to use metabonomics and molecular biology techniques to systematically elucidate the molecular mechanisms of TCC-induced effects on cardiac function in mice. Our results show that TCC inhibited the uptake, synthesis, and oxidation of fatty acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic glycolysis levels in heart tissue after short-term TCC exposure. TCC also inhibited the nuclear peroxisome proliferator-activated receptor α (PPARα), confirming its inhibitory effects on fatty acid uptake and oxidation. Histopathology and other analyses further confirm that TCC altered mouse cardiac physiology and pathology, ultimately affecting normal cardiac metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful effects on mouse cardiac metabolism and function from a new perspective, using metabonomics and bioinformatics analysis data.
Stembridge, Mike; Ainslie, Philip N; Shave, Rob
2015-11-01
What is the topic of this review? At high altitude, the cardiovascular system must adapt in order to meet the metabolic demand for oxygen. This review summarizes recent findings relating to short-term and life-long cardiac adaptation to high altitude in the context of exercise capacity. What advances does it highlight? Both Sherpa and lowlanders exhibit smaller left ventricular volumes at high altitude; however, myocardial relaxation, as evidenced by diastolic untwist, is reduced only in Sherpa, indicating that short-term hypoxia does not impair diastolic relaxation. Potential remodelling of systolic function, as evidenced by lower left ventricular systolic twist in Sherpa, may facilitate the requisite sea-level mechanical reserve required during exercise, although this remains to be confirmed. Both short-term and life-long high-altitude exposure challenge the cardiovascular system to meet the metabolic demand for O2 in a hypoxic environment. As the demand for O2 delivery increases during exercise, the circulatory component of oxygen transport is placed under additional stress. Acute adaptation and chronic remodelling of cardiac structure and function may occur to facilitate O2 delivery in lowlanders during sojourn to high altitude and in permanent highland residents. However, our understanding of cardiac structural and functional adaption in Sherpa remains confined to a higher maximal heart rate, lower pulmonary vascular resistance and no differences in resting cardiac output. Ventricular form and function are intrinsically linked through the left ventricular (LV) mechanics that facilitate efficient ejection, minimize myofibre stress during contraction and aid diastolic recoil. Recent examination of LV mechanics has allowed detailed insight into fundamental cardiac adaptation in high-altitude Sherpa. In this symposium report, we review recent advances in our understanding of LV function in both lowlanders and Sherpa at rest and discuss the potential consequences for exercise capacity. Collectively, data indicate chronic structural ventricular adaptation, with adult Sherpa having smaller absolute and relative LV size. Consistent with structural remodelling, cardiac mechanics also differ in Sherpa when compared with lowlanders at high altitude. These differences are characterized by a reduction in resting systolic deformation and slower diastolic untwisting, a surrogate of relaxation. These changes may reflect a functional cardiac adaptation that affords Sherpa the same mechanical reserve seen in lowlanders at sea level, which is absent when they ascend to high altitude. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.
Redetzke, Rebecca A.; Gerdes, A. Martin
2012-01-01
Thyroid hormones (THs) play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV) contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH). LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function. PMID:23056390
Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying ...
Weltman, Nathan Y.; Ojamaa, Kaie; Savinova, Olga V.; Chen, Yue-Feng; Schlenker, Evelyn H.; Zucchi, Riccardo; Saba, Alessandro; Colligiani, Daria; Pol, Christine J.
2013-01-01
Thyroid hormones (THs) play a pivotal role in regulating cardiovascular homeostasis. To provide a better understanding of the coordinated processes that govern cardiac TH bioavailability, this study investigated the influence of serum and cardiac TH status on the expression of TH transporters and cytosolic binding proteins in the myocardium. In addition, we sought to determine whether the administration of T3 (instead of T4) improves the relationship between THs in serum and cardiac tissue and cardiac function over a short-term treatment period. Adult female Sprague Dawley rats were made hypothyroid by 7 weeks treatment with the antithyroid drug 6-n-propyl-2-thiouracil (PTU). After establishing hypothyroidism, rats were assigned to 1 of 5 graded T3 dosages plus PTU for a 2-week dose-response experiment. Untreated, age-matched rats served as euthyroid controls. PTU was associated with depressed serum and cardiac tissue T3 and T4 levels, arteriolar atrophy, altered TH transporter and cytosolic TH binding protein expression, fetal gene reexpression, and cardiac dysfunction. Short-term administration of T3 led to a mismatch between serum and cardiac tissue TH levels. Normalization of serum T3 levels was not associated with restoration of cardiac tissue T3 levels or cardiac function. In fact, a 3-fold higher T3 dosage was necessary to normalize cardiac tissue T3 levels and cardiac function. Importantly, this study provides the first comprehensive data on the relationship between altered TH status (serum and cardiac tissue), cardiac function, and the coordinated in vivo changes in cardiac TH membrane transporters and cytosolic TH binding proteins in altered TH states. PMID:23594789
Gayda, Mathieu; Ribeiro, Paula A B; Juneau, Martin; Nigam, Anil
2016-04-01
In this review, we discuss the most recent forms of exercise training available to patients with cardiac disease and their comparison or their combination (or both) during short- and long-term (phase II and III) cardiac rehabilitation programs. Exercise training modalities to be discussed include inspiratory muscle training (IMT), resistance training (RT), continuous aerobic exercise training (CAET), and high-intensity interval training (HIIT). Particular emphasis is placed on HIIT compared or combined (or both) with other forms such as CAET or RT. For example, IMT combined with CAET was shown to be superior to CAET alone for improving functional capacity, ventilatory function, and quality of life in patients with chronic heart failure. Similarly, RT combined with CAET was shown to optimize benefits with respect to functional capacity, muscle function, and quality of life. Furthermore, in recent years, HIIT has emerged as an alternative or complementary (or both) exercise modality to CAET, providing equivalent if not superior benefits to conventional continuous aerobic training with respect to aerobic fitness, cardiovascular function, quality of life, efficiency, safety, tolerance, and exercise adherence in both short- and long-term training studies. Finally, short-interval HIIT was shown to be useful in the initiation and improvement phases of cardiac rehabilitation, whereas moderate- or longer-interval (or both) HIIT protocols appear to be more appropriate for the improvement and maintenance phases because of their high physiological stimulus. We now propose progressive models of exercise training (phases II-III) for patients with cardiac disease, including a more appropriate application of HIIT based on the scientific literature in the context of a multimodal cardiac rehabilitation program. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Kumarapeli, Asangi R K; Horak, Kathleen; Wang, Xuejun
2010-01-01
Molecular chaperones represent the first line of defense of intracellular protein quality control. As a major constituent of molecular chaperones, heat shock proteins (HSP) are known to confer cardiomyocyte short-term protection against various insults and injuries. Previously, we reported that the small HSP αB-crystallin (CryAB) attenuates cardiac hypertrophic response in mice subjected to 2 weeks of severe pressure overload. However, the long-term role of small HSPs in cardiac hypertrophy and failure has rarely been studied. The present study investigates the cardiac responses to chronic severe pressure overload in CryAB/HSPB2 germ line ablated (KO) and cardiac-specific CryAB overexpressingtransgenic (TG) mice. Pressure overload was induced by transverse aortic constriction in KO, TG, and non-transgenic wild type (NTG) control mice and 10 weeks later molecular, cellular, and whole organ level hypertrophic responses were analyzed. As we previously described, CryAB/HSPB2 KO mice showed abnormal baseline cardiac physiology that worsened into a restrictive cardiomyopathic phenotype with aging. Severe pressure overload in these mice led to rapid deterioration of heart function and development of congestive cardiac failure. Contrary to their short term protective phenotype, CryAB TG mice showed no significant effects on cardiac hypertrophic responses and very modest improvement of hemodynamics during chronic systolic overload. These findings indicate that small HSPs CryAB and/or HSPB2 are essential to maintain cardiac structure and function but overex-pression of CryAB is not sufficient to confer a sustained protection against chronic systolic overload. PMID:20733949
Kumarapeli, Asangi R K; Horak, Kathleen; Wang, Xuejun
2010-07-21
Molecular chaperones represent the first line of defense of intracellular protein quality control. As a major constituent of molecular chaperones, heat shock proteins (HSP) are known to confer cardiomyocyte short-term protection against various insults and injuries. Previously, we reported that the small HSP alphaB-crystallin (CryAB) attenuates cardiac hypertrophic response in mice subjected to 2 weeks of severe pressure overload. However, the long-term role of small HSPs in cardiac hypertrophy and failure has rarely been studied. The present study investigates the cardiac responses to chronic severe pressure overload in CryAB/HSPB2 germ line ablated (KO) and cardiac-specific CryAB overexpressingtransgenic (TG) mice. Pressure overload was induced by transverse aortic constriction in KO, TG, and non-transgenic wild type (NTG) control mice and 10 weeks later molecular, cellular, and whole organ level hypertrophic responses were analyzed. As we previously described, CryAB/HSPB2 KO mice showed abnormal baseline cardiac physiology that worsened into a restrictive cardiomyopathic phenotype with aging. Severe pressure overload in these mice led to rapid deterioration of heart function and development of congestive cardiac failure. Contrary to their short term protective phenotype, CryAB TG mice showed no significant effects on cardiac hypertrophic responses and very modest improvement of hemodynamics during chronic systolic overload. These findings indicate that small HSPs CryAB and/or HSPB2 are essential to maintain cardiac structure and function but overex-pression of CryAB is not sufficient to confer a sustained protection against chronic systolic overload.
Kobara, Miyuki; Furumori-Yukiya, Akiko; Kitamura, Miho; Matsumura, Mihoko; Ohigashi, Makoto; Toba, Hiroe; Nakata, Tetsuo
2015-08-01
Caloric restriction (CR) prevents senescent changes, in which reactive oxygen species (ROS) have a critical role. Left ventricular (LV) hypertrophy is a risk factor for cardiovascular diseases. We examined whether CR alters cardiac redox state and hypertrophy from chronic pressure overload. Male c57BL6 mice were subjected to ascending aortic constriction (AAC) with ad libitum caloric intake (AL + AAC group) or 40% restricted caloric intake (CR + AAC group). CR was initiated 2 weeks before AAC and was continued for 4 weeks. Two weeks after constriction, AAC increased LV wall thickness, impaired transmitral flow velocity, and augmented myocyte hypertrophy and fibrosis, in association with enhancement of BNP and collagen III expressions in the AL + AAC group. In the AL + AAC group, oxidative stress in cardiac tissue and mitochondria were enhanced, and NADPH oxidase activity and mitochondrial ROS production were elevated. These changes were significantly attenuated in the CR + AAC group. Additionally, in antioxidant systems, myocardial glutathione peroxidase and superoxide dismutase activities were enhanced in the CR + AAC group. Chronic pressure overload increased cardiac oxidative damage, in association with cardiac hypertrophy and fibrosis. Short-term CR suppressed oxidative stress and improved cardiac function, suggesting that short-term CR could be a useful strategy to prevent pressure overload-induced cardiac injury. Copyright © 2015 Elsevier Inc. All rights reserved.
The role of 17-beta estradiol in ischemic preconditioning protection of the heart.
Babiker, Fawzi A; Hoteit, Lamia J; Joseph, Shaji; Mustafa, Abu Salim; Juggi, Jasbir S
2012-09-01
The protective effects of 17-beta estradiol (E2) on cardiac tissue during ischemia/reperfusion (I/R) injury have not yet been fully elucidated. To assess the protective effects of short- and long-term E2 treatments on cardiac tissue exposed to I/R, and to assess the effects of these treatments in combination with ischemic preconditioning (IPC) on cardiac protection from I/R injury. SPRAGUE DAWLEY RATS WERE ASSIGNED TO THE FOLLOWING TREATMENT PROTOCOLS: control (no preconditioning); IPC (isolated hearts were subjected to two cycles of 5 min global ischemia followed by 10 min of reperfusion); E2 preconditioning (E2PC; isolated hearts were subjected to E2 pharmacological perfusion for 15 min); short-term in vivo E2 pretreatment for 3 h; long-term in vivo E2 pretreatment or withdrawal (ovariectomy followed by a six-week treatment with E2 or a placebo); combined IPC and E2PC; combined IPC and short- or long-term E2 pretreatments or withdrawal. All hearts were isolated and stabilized for at least 30 min before being subjected to 40 min of global ischemia followed by 30 min of reperfusion; left ventricular function and vascular hemodynamics were then assessed. IPC, E2PC and short-term E2 pretreatment led to the recovery of left ventricle function and vascular hemodynamics. Long-term E2 and placebo treatments did not result in any protection compared with untreated controls. The combination of E2PC or short-term E2 treatments with IPC did not block the IPC protection or result in any additional protection to the heart. Long-term E2 treatment blocked IPC protection; however, placebo treatment did not. Short-term treatment with E2 protected the heart against I/R injury through a pathway involving the regulation of tumour necrosis factor-alpha. The combination of short-term E2 treatment with IPC did not provide additional protection to the heart. Short-term E2 treatment may be a suitable alternative for classical estrogen replacement therapy.
Mendes, Renata Gonçalves; Simões, Rodrigo Polaquini; De Souza Melo Costa, Fernando; Pantoni, Camila Bianca Falasco; Di Thommazo, Luciana; Luzzi, Sérgio; Catai, Aparecida Maria; Arena, Ross; Borghi-Silva, Audrey
2010-01-01
Coronary artery bypass grafting (CABG) is accompanied by severe impairment of cardiac autonomous regulation (CAR). This study aimed to determine whether a short-term physiotherapy exercise protocol post-CABG, during inpatient cardiac rehabilitation (CR), might improve CAR. Seventy-four patients eligible for CABG were recruited and randomised into physiotherapy exercise group (EG) or physiotherapy usual care group (UCG). EG patients underwent a short-term supervised inpatient physiotherapy exercise protocol consisting of an early mobilisation with progressive exercises plus usual care (respiratory exercises). UCG only received respiratory exercises. Forty-seven patients (24 EG and 23 UGC) completed the study. Outcome measures of CAR included linear and non-linear measures of heart rate variability (HRV) assessed before discharge. By hospital discharge, EG presented significantly higher parasympathetic HRV values [rMSSD, high frequency (HF), SD1)], global power (STD RR, SD2), non-linear HRV indexes [detrended fluctuation analysis (DFA)alpha1, DFAalpha2, approximate entropy (ApEn)] and mean RR compared to UCG (p<0.05). Conversely, higher values of mean HR, low frequency (LF) (sympathetic activity) and the LF/HF (global sympatho-vagal balance) were found in the UCG. A short-term supervised physiotherapy exercise protocol during inpatient CR improves CAR at the time of discharge. Thus, exercise-based inpatient CR might be an effective non-pharmacological tool to improve autonomic cardiac tone in patient's post-CABG.
Ermolova, N.E.; Martinez, L.; Vetrone, S.A.; Jordan, M. C.; Roos, K. .P.; Sweeney, H.L.; Spencer, M.J.
2014-01-01
Duchenne muscular dystrophy (DMD) is a degenerative skeletal muscle disease caused by mutations in the gene encoding dystrophin (DYS). Tumor necrosis factor (TNF) has been implicated in the pathogenesis of DMD since short-term treatment of mdx mice with TNF blocking drugs proved beneficial; however, it is not clear whether long-term treatment will also improve long-term outcomes of fibrosis and cardiac health. In this investigation, short and long-term dosing studies were carried out using the TNF blocking drug Remicade and a variety of outcome measures were assessed. Here we show no demonstrable benefit to muscle strength or morphology with 10mg/kg or 20 mg/kg Remicade; however, 3mg/kg produced positive strength benefits. Remicade treatment correlated with reductions in myostatin mRNA in the heart, and concomitant reductions in cardiac and skeletal fibrosis. Surprisingly, although Remicade treated mdx hearts were less fibrotic, reductions in LV mass and ejection fraction were also observed, and these changes coincided with reductions in AKT phosphorylation on threonine 308. Thus, TNF blockade benefits mdx skeletal muscle strength and fibrosis, but negatively impacts AKT activation, leading to deleterious changes to dystrophic heart function. These studies uncover a previously unknown relationship between TNF blockade and alteration of muscle growth signaling pathways. PMID:24844454
Yang, Chang-Bin; Zhang, Shu; Zhang, Yu; Wang, Bing; Yao, Yong-Jie; Wang, Yong-Chun; Wu, Yan-Hong; Liang, Wen-Bin; Sun, Xi-Qing
2010-12-01
Musculoskeletal and cardiovascular deconditioning occurring in long-term spaceflight gives rise to the needs to develop new strategies to counteract these adverse effects. Short-arm centrifuge combined with ergometer has been proposed as a strategy to counteract adverse effects of microgravity. This study sought to investigate whether the combination of short-arm centrifuge and aerobic exercise training have advantages over short-arm centrifuge or aerobic exercise training alone. One week training was conducted by 24 healthy men. They were randomly divided into 3 groups: (1) short-arm centrifuge training, (2) aerobic exercise training, 40 W, and (3) combined short-arm centrifuge and aerobic exercise training. Before and after training, the cardiac pump function represented by stroke volume, cardiac output, left ventricular ejection time, and total peripheral resistance was evaluated. Variability of heart rate and systolic blood pressure were determined by spectral analysis. Physical working capacity was surveyed by near maximal physical working capacity test. The 1-week combined short-arm centrifuge and aerobic exercise training remarkably ameliorated the cardiac pump function and enhanced vasomotor sympathetic nerve modulation and improved physical working capacity by 10.9% (P<.05, n=8). In contrast, neither the short-arm centrifuge nor the aerobic exercise group showed improvements in these functions. These results demonstrate that combined short-arm centrifuge and aerobic exercise training has advantages over short-arm centrifuge or aerobic exercise training alone in influencing several physiologically important cardiovascular functions in humans. The combination of short-arm centrifuge and aerobic exercise offers a promising countermeasure to microgravity.
Stembridge, Mike; Ainslie, Philip N; Hughes, Michael G; Stöhr, Eric J; Cotter, James D; Nio, Amanda Q X; Shave, Rob
2014-08-01
Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function. Copyright © 2014 the American Physiological Society.
Ainslie, Philip N.; Hughes, Michael G.; Stöhr, Eric J.; Cotter, James D.; Nio, Amanda Q. X.; Shave, Rob
2014-01-01
Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function. PMID:24876358
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kurhanewicz, Nicole
Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once tomore » 3 ppm acrolein, 0.3 ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24 h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24 h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles. - Highlights: • Acute acrolein exposure causes autonomic imbalance and altered CV function in mice. • TRPA1 mediates acrolein-induced autonomic nervous system cardiac effects. • Sensory irritation contributes to acrolein-induced cardiac arrhythmia & dysfunction.« less
Gayda, Mathieu; Gremeaux, Vincent; Bherer, Louis; Juneau, Martin; Drigny, Joffrey; Dupuy, Olivier; Lapierre, Gabriel; Labelle, Véronique; Fortier, Annik; Nigam, Anil
2017-01-01
Chronic exercise has been shown to prevent or slow age-related decline in cognitive functions in otherwise healthy, asymptomatic individuals. We sought to assess cognitive function in a stable coronary heart disease (CHD) sample and its relationship to cerebral oxygenation-perfusion, cardiac hemodynamic responses, and [Formula: see text] peak compared to age-matched and young healthy control subjects. Twenty-two young healthy controls (YHC), 20 age-matched old healthy controls (OHC) and 25 patients with stable CHD were recruited. Cognitive function assessment included short term-working memory, perceptual abilities, processing speed, cognitive inhibition and flexibility and long-term verbal memory. Maximal cardiopulmonary function (gas exchange analysis), cardiac hemodynamic (impedance cardiography) and left frontal cerebral oxygenation-perfusion (near-infra red spectroscopy) were measured during and after a maximal incremental ergocycle test. Compared to OHC and CHD, YHC had higher [Formula: see text] peak, maximal cardiac index (CI max), cerebral oxygenation-perfusion (ΔO2 Hb, ΔtHb: exercise and recovery) and cognitive function (for all items) (P<0.05). Compared to OHC, CHD patients had lower [Formula: see text] peak, CI max, cerebral oxygenation-perfusion (during recovery) and short term-working memory, processing speed, cognitive inhibition and flexibility and long-term verbal memory (P<0.05). [Formula: see text] peak and CI max were related to exercise cerebral oxygenation-perfusion and cognitive function (P<0.005). Cerebral oxygenation-perfusion (exercise) was related to cognitive function (P<0.005). Stable CHD patients have a worse cognitive function, a similar cerebral oxygenation/perfusion during exercise but reduced one during recovery vs. their aged-matched healthy counterparts. In the all sample, cognitive functions correlated with [Formula: see text] peak, CI max and cerebral oxygenation-perfusion.
Patron, Elisabetta; Messerotti Benvenuti, Simone; Zanatta, Paolo; Polesel, Elvio; Palomba, Daniela
2013-01-01
To examine whether preoperative psychological dysfunctions rather than intraoperative factors may differentially predict short- and long-term postoperative cognitive decline (POCD) in patients after cardiac surgery. Forty-two patients completed a psychological evaluation, including the Trail Making Test Part A and B (TMT-A/B), the memory with 10/30-s interference, the phonemic verbal fluency and the Center for Epidemiological Studies of Depression (CES-D) scale for cognitive functions and depressive symptoms, respectively, before surgery, at discharge and at 18-month follow-up. Ten (24%) and 11 (26%) patients showed POCD at discharge and at 18-month follow-up, respectively. The duration of cardiopulmonary bypass significantly predicted short-term POCD [odds ratio (OR)=1.04, P<.05], whereas preoperative psychological factors were unrelated to cognitive decline at discharge. Conversely, long-term cognitive decline after cardiac surgery was significantly predicted by preoperative scores in the CES-D (OR=1.26, P<.03) but not by intraoperative variables (all Ps >.23). Our findings showed that preexisting depressive symptoms rather than perioperative risk factors are associated with cognitive decline 18 months after cardiac surgery. This study suggests that a preoperative psychological evaluation of depressive symptoms is essential to anticipate which patients are likely to show long-term cognitive decline after cardiac surgery. Copyright © 2013 Elsevier Inc. All rights reserved.
Cardioprotective Signature of Short-Term Caloric Restriction
Isserlin, Ruth; Arab, Sara; Momen, Abdul; Cheng, Henry S.; Wu, Jun; Afroze, Talat; Li, Ren-Ke; Fish, Jason E.; Bader, Gary D.; Husain, Mansoor
2015-01-01
Objective To understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR). Background Lifelong CR has been suggested to reduce the incidence of cardiovascular disease through a variety of mechanisms. However, prolonged adherence to a CR life-style is difficult. Here we reveal the pathways that are modulated by short-term CR, which are associated with protection of the mouse heart from ischemia. Methods Male 10-12 wk old C57bl/6 mice were randomly assigned to an ad libitum (AL) diet with free access to regular chow, or CR, receiving 30% less food for 7 days (d), prior to myocardial infarction (MI) via permanent coronary ligation. At d8, the left ventricles (LV) of AL and CR mice were collected for Western blot, mRNA and microRNA (miR) analyses to identify cardioprotective gene expression signatures. In separate groups, infarct size, cardiac hemodynamics and protein abundance of caspase 3 was measured at d2 post-MI. Results This short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01). mRNA and miR profiles pre-MI (N=5/group) identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM). Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1α, cytochrome C and cyclooxygenase (COX) IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38). CR regimen was also associated with reduced protein abundance of cleaved caspase 3 in the infarcted heart and improved cardiac function. PMID:26098549
Tuzovic, Mirela; Kobayashi, Yukari; Wheeler, Matthew; Barrett, Christopher; Liedtke, Michaela; Lafayette, Richard; Schrier, Stanley; Haddad, Francois; Witteles, Ronald
2017-10-15
Cardiac involvement is common in patients with light-chain (AL) amyloidosis and portends a poor prognosis, although little is known about the changes in cardiac mechanics after chemotherapy. We sought to explore the relation between amyloidosis staging and baseline cardiac mechanics and to investigate short-term changes in cardiac mechanics after chemotherapy. We identified 41 consecutive patients from the Stanford Amyloid Center who had echocardiograms and free light-chain values before and after chemotherapy, along with 40 age- and gender-matched controls. Echocardiographic assessment included left ventricular global longitudinal strain, E/e' ratio, and left atrial (LA) stiffness. Hematologic response to chemotherapy was defined as ≥50% reduction in the difference between the involved and the uninvolved free light chain (dFLC). The mean age was 66.9 ± 8.4 years and 66% were men. Before chemotherapy, global longitudinal strain, E/e' ratio, and LA stiffness were impaired in patients with amyloidosis compared with controls, and the severity of impairment worsened with advanced staging. After chemotherapy, hematologic response was observed in 30 (73%) patients. There was a significant association between the change in dFLC and cardiac function (E/e' ratio: r = -0.43, p = 0.01; LA stiffness: r = -0.35, p = 0.05). There was no significant improvement in cardiac mechanics in patients without a hematologic response to chemotherapy. In conclusion, amyloidosis stage correlated with noninvasive measurements of cardiac mechanics, and improvement in dFLC correlated with cardiac improvement on short-term follow-up echocardiography. Copyright © 2017 Elsevier Inc. All rights reserved.
TRPA1 mediates changes in heart rate variability and cardiac ...
Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described; however, the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3ppm acrolein, 0.3ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to ac
Volkan-Salanci, Bilge; Aksoy, Hakan; Kiratli, Pınar Özgen; Tülümen, Erol; Güler, Nilüfer; Öksüzoglu, Berna; Tokgözoğlu, Lale; Erbaş, Belkıs; Alikaşifoğlu, Mehmet
2012-10-01
The aim of this prospective clinical study is to evaluate the relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 (CBR3p.V244M) and glutathione S transferase Pi (GSTP1p.I105V) polymorphisms. Seventy patients with normal cardiac function and no history of cardiac disease scheduled to undergo anthracycline chemotherapy were included in the study. The patients' cardiac function was evaluated by gated blood pool scintigraphy and echocardiography before and after chemotherapy, as well as 1 year following therapy. Gene polymorphisms were genotyped in 70 patients using TaqMan probes, validated by DNA sequencing. A deteriorating trend was observed in both systolic and diastolic parameters from GG to AA in CBR3p.V244M polymorphism. Patients with G-allele carriers of GSTP1p.I105V polymorphism were common (60%), with significantly decreased PFR compared to patiens with AA genotype. Variants of CBR3 and GSTP1 enzymes may be associated with changes in short-term functional cardiac parameters.
The Performance of Short-Term Heart Rate Variability in the Detection of Congestive Heart Failure
Barros, Allan Kardec; Ohnishi, Noboru
2016-01-01
Congestive heart failure (CHF) is a cardiac disease associated with the decreasing capacity of the cardiac output. It has been shown that the CHF is the main cause of the cardiac death around the world. Some works proposed to discriminate CHF subjects from healthy subjects using either electrocardiogram (ECG) or heart rate variability (HRV) from long-term recordings. In this work, we propose an alternative framework to discriminate CHF from healthy subjects by using HRV short-term intervals based on 256 RR continuous samples. Our framework uses a matching pursuit algorithm based on Gabor functions. From the selected Gabor functions, we derived a set of features that are inputted into a hybrid framework which uses a genetic algorithm and k-nearest neighbour classifier to select a subset of features that has the best classification performance. The performance of the framework is analyzed using both Fantasia and CHF database from Physionet archives which are, respectively, composed of 40 healthy volunteers and 29 subjects. From a set of nonstandard 16 features, the proposed framework reaches an overall accuracy of 100% with five features. Our results suggest that the application of hybrid frameworks whose classifier algorithms are based on genetic algorithms has outperformed well-known classifier methods. PMID:27891509
Germanakis, Ioannis; Tsarouhas, Konstantinos; Fragkiadaki, Persefoni; Tsitsimpikou, Christina; Goutzourelas, Nikolaos; Champsas, Maria Christakis; Stagos, Demetrios; Rentoukas, Elias; Tsatsakis, Aristidis M
2013-11-01
The present study focuses on the short term effects of repeated low level administration of turinabol and methanabol on cardiac function in young rabbits (4 months-old). The experimental scheme consisted of two oral administration periods, lasting 1 month each, interrupted by 1-month wash-out period. Serial echocardiographic evaluation at the end of all three experimental periods was performed in all animals. Oxidative stress markers have also been monitored at the end of each administration period. Treated animals originally showed significantly increased myocardial mass and systolic cardiac output, which normalized at the end of the wash out period. Re-administration led to increased cardiac output, at the cost though of a progressive myocardial mass reduction. A dose-dependent trend towards impaired longitudinal systolic, diastolic and global myocardial function was also observed. The adverse effects were more pronounced in the methanabol group. For both anabolic steroids studied, the low dose had no significant effects on oxidative stress markers monitored, while the high dose created a hostile oxidative environment. In conclusion, anabolic administration has been found to create a possible deleterious long term effect on the growth of the immature heart and should be strongly discouraged especially in young human subjects. Copyright © 2013 Elsevier Ltd. All rights reserved.
Wu, Yiming; Peng, Jun; Campbell, Kenneth B; Labeit, Siegfried; Granzier, Henk
2007-01-01
Because long-term hypothyroidism results in diastolic dysfunction, we investigated myocardial passive stiffness in hypothyroidism and focused on the possible role of titin, an important determinant of diastolic stiffness. A rat model of hypothyroidism was used, obtained by administering propylthiouracil (PTU) for times that varied from 1 month (short-term) to 4 months (long-term). Titin expression was determined by transcript analysis, gel electrophoresis and immunoelectron microscopy. Diastolic function was measured at the isolated heart, skinned muscle, and cardiac myocyte levels. We found that hypothyroidism resulted in expression of a large titin isoform, the abundance of which gradually increased with time to become the most dominant isoform in long-term hypothyroid rats. This isoform co-migrates on high-resolution gels with fetal cardiac titin. Transcript analysis on myocardium of long-term PTU rats, provided evidence for expression of additional PEVK and Ig domain exons, similar to what has been described in fetal myocardium. Consistent with the expression of a large titin isoform, titin-based restoring and passive forces were significantly reduced in single cardiac myocytes and muscle strips of long-term hypothyroid rats. Overall muscle stiffness and LV diastolic wall stiffness were increased, however, due to increased collagen-based stiffness. We conclude that long term hypothyroidism triggers expression of a large cardiac titin isoform and that the ensuing reduction in titin-based passive stiffness functions as a compensatory mechanism to reduce LV wall stiffness.
NASA Astrophysics Data System (ADS)
Laing, Kevin J. C.; Russamono, Thais
2013-02-01
The likelihood of trained astronauts developing a life threatening cardiac event during spaceflight is relatively rare, whilst the incidence in untrained individuals is unknown. Space tourists who live a sedentary lifestyle have reduced cardiovascular function, but the associated danger of sudden cardiac arrest (SCA) during a suborbital spaceflight (SOSF) is unclear. Risk during SOSF was examined by reviewing several microgravity studies and methods of determining poor cardiovascular condition. Accurately assessing cardiovascular function and improving baroreceptor sensitivity through exercise is suggested to reduce the incidence of SCA during future SOSFs. Future studies will benefit from past participants sharing medical history; allowing creation of risk profiles and suitable guidelines.
Rengo, Giuseppe; Lymperopoulos, Anastasios; Zincarelli, Carmela; Donniacuo, Maria; Soltys, Stephen; Rabinowitz, Joseph E.; Koch, Walter J.
2009-01-01
Background The upregulation of G protein–coupled receptor kinase 2 in failing myocardium appears to contribute to dysfunctional β-adrenergic receptor (βAR) signaling and cardiac function. The peptide βARKct, which can inhibit the activation of G protein–coupled receptor kinase 2 and improve βAR signaling, has been shown in transgenic models and short-term gene transfer experiments to rescue heart failure (HF). This study was designed to evaluate long-term βARKct expression in HF with the use of stable myocardial gene delivery with adeno-associated virus serotype 6 (AAV6). Methods and Results In HF rats, we delivered βARKct or green fluorescent protein as a control via AAV6-mediated direct intramyocardial injection. We also treated groups with concurrent administration of the β-blocker metoprolol. We found robust and long-term transgene expression in the left ventricle at least 12 weeks after delivery. βARKct significantly improved cardiac contractility and reversed left ventricular remodeling, which was accompanied by a normalization of the neurohormonal (catecholamines and aldosterone) status of the chronic HF animals, including normalization of cardiac βAR signaling. Addition of metoprolol neither enhanced nor decreased βARKct-mediated beneficial effects, although metoprolol alone, despite not improving contractility, prevented further deterioration of the left ventricle. Conclusions Long-term cardiac AAV6-βARKct gene therapy in HF results in sustained improvement of global cardiac function and reversal of remodeling at least in part as a result of a normalization of the neurohormonal signaling axis. In addition, βARKct alone improves outcomes more than a β-blocker alone, whereas both treatments are compatible. These findings show that βARKct gene therapy can be of long-term therapeutic value in HF. PMID:19103992
Garan, A Reshad; Eckhardt, Christina; Takeda, Koji; Topkara, Veli K; Clerkin, Kevin; Fried, Justin; Masoumi, Amirali; Demmer, Ryan T; Trinh, Pauline; Yuzefpolskaya, Melana; Naka, Yoshifumi; Burkhoff, Dan; Kirtane, Ajay; Colombo, Paolo C; Takayama, Hiroo
2017-11-01
Cardiogenic shock following acute myocardial infarction (AMI-CS) portends a poor prognosis. Short-term mechanical circulatory support devices (MCSDs) provide hemodynamic support for patients with cardiogenic shock but predictors of survival and the ability to wean from short-term MCSDs remain largely unknown. All patients > 18 years old treated at our institution with extra-corporeal membrane oxygenation or short-term surgical ventricular assist device for AMI-CS were studied. We collected acute myocardial infarction details with demographic and hemodynamic variables. Primary outcomes were survival to discharge and recovery from MCSD (i.e. survival without heart replacement therapy including durable ventricular assist device or heart transplant). One hundred and twenty-four patients received extra-corporeal membrane oxygenation or short-term surgical ventricular assist device following acute myocardial infarction from 2007 to 2016; 89 received extra-corporeal membrane oxygenation and 35 short-term ventricular assist device. Fifty-five (44.4%) died in the hospital and 69 (55.6%) survived to discharge. Twenty-six (37.7%) required heart replacement therapy (four transplant, 22 durable ventricular assist device) and 43 (62.3%) were discharged without heart replacement therapy. Age and cardiac index at MCSD implantation were predictors of survival to discharge; patients over 60 years with cardiac index <1.5 l/min per m 2 had a low likelihood of survival. The angiographic result after revascularization predicted recovery from MCSD (odds ratio 9.00, 95% confidence interval 2.45-32.99, p=0.001), but 50% of those optimally revascularized still required heart replacement therapy. Cardiac index predicted recovery from MCSD among this group (odds ratio 4.06, 95% confidence interval 1.45-11.55, p=0.009). Among AMI-CS patients requiring short-term MCSDs, age and cardiac index predict survival to discharge. Angiographic result and cardiac index predict ventricular recovery but 50% of those optimally revascularized still required heart replacement therapy.
Beetz, Nadine; Rommel, Carolin; Schnick, Tilman; Neumann, Elena; Lother, Achim; Monroy-Ordonez, Elsa Beatriz; Zeeb, Martin; Preissl, Sebastian; Gilsbach, Ralf; Melchior-Becker, Ariane; Rylski, Bartosz; Stoll, Monika; Schaefer, Liliana; Beyersdorf, Friedhelm; Stiller, Brigitte; Hein, Lutz
2016-12-01
Biglycan, a small leucine-rich proteoglycan, has been shown to play an important role in stabilizing fibrotic scars after experimental myocardial infarction. However, the role of biglycan in the development and regression of cardiomyocyte hypertrophy and fibrosis during cardiac pressure overload and unloading remains elusive. Thus, the aim of the present study was to assess the effect of biglycan on cardiac remodeling in a mouse model of left ventricular pressure overload and unloading. Left ventricular pressure overload induced by transverse aortic constriction (TAC) in mice resulted in left ventricular dysfunction, fibrosis and increased biglycan expression. Fluorescence- and magnetic-assisted sorting of cardiac cell types revealed upregulation of biglycan in the fibroblast population, but not in cardiomyocytes, endothelial cells or leukocytes after TAC. Removal of the aortic constriction (rTAC) after short-term pressure overload (3weeks) improved cardiac contractility and reversed ventricular hypertrophy but not fibrosis in wild-type (WT) mice. Biglycan ablation (KO) enhanced functional recovery but did not resolve cardiac fibrosis. After long-term TAC for 9weeks, ablation of biglycan attenuated the development of cardiac hypertrophy and fibrosis. In vitro, biglycan induced hypertrophy of neonatal rat cardiomyocytes and led to activation of a hypertrophic gene program. Putative downstream mediators of biglycan signaling include Rcan1, Abra and Tnfrsf12a. These genes were concordantly induced by TAC in WT but not in biglycan KO mice. Left ventricular pressure overload induces biglycan expression in cardiac fibroblasts. Ablation of biglycan improves cardiac function and attenuates left ventricular hypertrophy and fibrosis after long-term pressure overload. In vitro biglycan induces hypertrophy of cardiomyocytes, suggesting that biglycan may act as a signaling molecule between cell types to modulate cardiac remodeling. Copyright © 2016 Elsevier Ltd. All rights reserved.
Geri, Guillaume; Dumas, Florence; Bougouin, Wulfran; Varenne, Olivier; Daviaud, Fabrice; Pène, Frédéric; Lamhaut, Lionel; Chiche, Jean-Daniel; Spaulding, Christian; Mira, Jean-Paul; Empana, Jean-Philippe; Cariou, Alain
2015-10-01
Whether to perform or not an immediate percutaneous coronary intervention (PCI) after out-of-hospital cardiac arrest is still debated. We aimed to evaluate the impact of PCI on short- and long-term survival in out-of-hospital cardiac arrest patients admitted after successful resuscitation. Between 2000 and 2013, all nontrauma out-of-hospital cardiac arrest patients admitted in a Parisian cardiac arrest center after return of spontaneous circulation were prospectively included. The association between immediate PCI and short- and long-term mortality was analyzed using logistic regression and Cox multivariate analysis, respectively. Propensity score-matching method was used to assess the influence of PCI on short- and long-term survival. During the study period, 1722 patients (71.5% male, median age 60 [49.6, 72.2] years) were analyzed: 628 (35.6%) without coronary angiography, 615 (35.7%) with coronary angiography without PCI, and 479 (27.8%) with both. Among these groups, day 30 and year-10 survival rates were 21% and 11.9%, 35% and 29%, 43% and 38%, respectively (P<0.01 for each). PCI as compared with no coronary angiography was associated with a lower day-30 and long-term mortality (adjORcoro with PCI versus no coro 0.71, 95% confidence interval [0.54, 0.92]; P=0.02 and adjHRcoro with PCI versus no coro 0.44, 95% confidence interval [0.27, 0.71]; P<0.01, respectively). PCI remained associated with a lower risk of long-term mortality (adjHR 0.29; 95% confidence interval [0.14, 0.61]; P<0.01) in propensity score-matching analysis. Immediate PCI after out-of-hospital cardiac arrest was associated with significant reduced risk of short- and long-term mortality. These findings should suggest physicians to consider immediate coronary angiography and PCI if indicated in these patients. © 2015 American Heart Association, Inc.
Electrocardiography (ECG) is one of the standard technologies used to monitor and assess cardiac function, and provide insight into the mechanisms driving myocardial pathology. Increased understanding of the effects of cardiovascular disease on rat ECG may help make ECG assessmen...
Lunz, Wellington; Natali, Antônio José; Carneiro, Miguel Araújo; Dos Santos Aggum Capettini, Luciano; Baldo, Marcelo Perim; de Souza, Matheus Ornelas; Quintão, Judson Fonseca; Bozi, Luiz Henrique Marchesi; Lemos, Virginia Soares; Mill, José Geraldo
2011-04-01
The main purpose of this study was to investigate the effects of short-term L-NAME treatment on the contractile function of left ventricle (LV) myocytes and the expression of proteins related to Ca(2+) homeostasis. Data from Wistar rats treated with L-NAME (L group, n = 20; 0.7 g/L in drinking water; 7 days) were compared with results from untreated controls (C group, n = 20). Cardiomyocytes from the L group showed increased (p < 0.05) fractional shortening (23%) and maximum rate of shortening (20%) compared with the C group. LV from the L group also showed increased (p < 0.05) expression of the ryanodine receptor 2 and Na(+)/Ca(2+) exchanger proteins (76% and 83%, respectively; p < 0.05). However, the L and C groups showed similar in vivo hemodynamic parameters of cardiac function. In conclusion, short-term NOS inhibition determines an increased expression of Ca(2+) regulatory proteins, which contributes to improving cardiomyocyte contractile function, preserving left ventricular function.
Worster, Andrew; Devereaux, P J; Heels-Ansdell, Diane; Guyatt, Gordon H; Opie, John; Mookadam, Farouk; Hill, Stephen A
2005-06-21
Ischemia-modified albumin (IMA) has been suggested as a marker of cardiac ischemia. Little, however, is known about its capacity to predict short-term serious cardiac outcomes (death, myocardial infarction, congestive heart failure, serious arrhythmia, or refractory ischemic cardiac pain) in patients arriving at the emergency department with symptoms that may indicate cardiac ischemia. We screened 546 patients over a 4-week period, of whom 189 fulfilled our entry criteria by presenting to an emergency department with potential cardiac-ischemia symptoms within 6 hours after chest pain, seeing an emergency physician who chose to order a troponin I test, and having no serious cardiac outcome before the troponin result became available. We followed the study patients for 72 hours to determine if any experienced a serious cardiac outcome. We calculated the likelihood ratios (LRs) of IMA findings predicting serious cardiac outcomes that could not be diagnosed at presentation with current techniques. Of the 189 patients, 24 had a serious cardiac outcome within 72 hours after their arrival at the emergency department. The likelihood ratios for IMA measurement within 6 hours after chest pain predicting a serious cardiac outcome within the next 72 hours were 1.35 (95% confidence interval [CI] 0.315-5.79) for IMA < or = 80 U/mL and 0.98 (95% CI 0.86- 1.11) for IMA > 80 U/mL. These data suggest that in patients presenting with chest pain who have not yet experienced a serious cardiac event, IMA is a poor predictor of serious cardiac outcomes in the short term.
NASA Astrophysics Data System (ADS)
Zhang, Dongqing; Icke, Ilknur; Dogdas, Belma; Parimal, Sarayu; Sampath, Smita; Forbes, Joseph; Bagchi, Ansuman; Chin, Chih-Liang; Chen, Antong
2018-03-01
In the development of treatments for cardiovascular diseases, short axis cardiac cine MRI is important for the assessment of various structural and functional properties of the heart. In short axis cardiac cine MRI, Cardiac properties including the ventricle dimensions, stroke volume, and ejection fraction can be extracted based on accurate segmentation of the left ventricle (LV) myocardium. One of the most advanced segmentation methods is based on fully convolutional neural networks (FCN) and can be successfully used to do segmentation in cardiac cine MRI slices. However, the temporal dependency between slices acquired at neighboring time points is not used. Here, based on our previously proposed FCN structure, we proposed a new algorithm to segment LV myocardium in porcine short axis cardiac cine MRI by incorporating convolutional long short-term memory (Conv-LSTM) to leverage the temporal dependency. In this approach, instead of processing each slice independently in a conventional CNN-based approach, the Conv-LSTM architecture captures the dynamics of cardiac motion over time. In a leave-one-out experiment on 8 porcine specimens (3,600 slices), the proposed approach was shown to be promising by achieving average mean Dice similarity coefficient (DSC) of 0.84, Hausdorff distance (HD) of 6.35 mm, and average perpendicular distance (APD) of 1.09 mm when compared with manual segmentations, which improved the performance of our previous FCN-based approach (average mean DSC=0.84, HD=6.78 mm, and APD=1.11 mm). Qualitatively, our model showed robustness against low image quality and complications in the surrounding anatomy due to its ability to capture the dynamics of cardiac motion.
Impact of Milrinone Administration in Adult Cardiac Surgery Patients: Updated Meta-Analysis.
Ushio, Masahiro; Egi, Moritoki; Wakabayashi, Junji; Nishimura, Taichi; Miyatake, Yuji; Obata, Norihiko; Mizobuchi, Satoshi
2016-12-01
To determine the effects of milrinone on short-term mortality in cardiac surgery patients with focus on the presence or absence of heterogeneity of the effect. A systematic review and meta-analysis. Five hundred thirty-seven adult cardiac surgery patients from 12 RCTs. Milrinone administration. The authors conducted a systematic Medline and Pubmed search to assess the effect of milrinone on short-term mortality in adult cardiac surgery patients. Subanalysis was performed according to the timing for commencement of milrinone administration and the type of comparators. The primary outcome was any short-term mortality. Overall analysis showed no difference in mortality rates in patients who received milrinone and patients who received comparators (odds ratio = 1.25, 95% CI 0.45-3.51, p = 0.67). In subanalysis for the timing to commence milrinone administration and the type of comparators, odds ratio for mortality varied from 0.19 (placebo as control drug, start of administration after cardiopulmonary bypass) to 2.58 (levosimendan as control drug, start of administration after cardiopulmonary bypass). Among RCTs to assess the effect of milrinone administration in adult cardiac surgery patients, there are wide variations of the odds ratios of administration of milrinone for short-term mortality according to the comparators and the timing of administration. This fact may suggest that a simple pooling meta-analysis is not applicable for assessing the risk and benefit of milrinone administration in an adult cardiac surgery cohort. Copyright © 2016 Elsevier Inc. All rights reserved.
Dencker, D; Pedersen, F; Engstrøm, T; Schroeder, T V; Lönn, L; Johansson, P I; De Backer, O
2017-08-01
To study the effect of red blood cell (RBC) storage duration on long-term mortality in patients undergoing cardiac intervention. RBCs undergo numerous structural and functional changes during storage. Observational studies have assessed the association between RBC storage duration and patient outcomes with conflicting results. Between January 2006 and December 2014, 82 408 patients underwent coronary angiography. Of these, 1856 patients received one to four RBC units within 30 days after this procedure. Patients were allocated according to length of RBC storage duration: short-term (≤11 days), intermediate (IM)-term (12-23 days) and long-term (≥24 days). The study endpoints were 30-day and long-term all-cause mortality. A total of 4168 RBC units were given to 1856 patients. The mean RBC storage duration was 8.5 ± 2.1, 17.7 ± 3.4 and 29.9 ± 3.4 days in the short-term, IM-term and long-term storage groups, respectively. There was no difference in baseline characteristics between the groups. The long-term storage group received significantly more units (2.4 ± 1.0 units) as compared to the short-term (2.0 ± 1.0 units; P < 0.001) and IM-term storage group (2.2 ± 1.0 units; P < 0.01). In the survival analysis, there was no significant difference in all-cause mortality between the groups (log-rank: 0.509 for 30-days mortality; 0.493 for 5-year mortality). Additional stratified analysis demonstrated no association between RBC storage duration and long-term mortality. This study did not find an association between RBC storage duration and 30-days or long-term mortality in patients undergoing cardiac intervention. © 2017 British Blood Transfusion Society.
Suppression of class I and II histone deacetylases blunts pressure-overload cardiac hypertrophy.
Kong, Yongli; Tannous, Paul; Lu, Guangrong; Berenji, Kambeez; Rothermel, Beverly A; Olson, Eric N; Hill, Joseph A
2006-06-06
Recent work has demonstrated the importance of chromatin remodeling, especially histone acetylation, in the control of gene expression in the heart. In cell culture models of cardiac hypertrophy, pharmacological suppression of histone deacetylases (HDACs) can either blunt or amplify cell growth. Thus, HDAC inhibitors hold promise as potential therapeutic agents in hypertrophic heart disease. In the present investigation, we studied 2 broad-spectrum HDAC inhibitors in a physiologically relevant banding model of hypertrophy, observing dose-responsive suppression of ventricular growth that was well tolerated in terms of both clinical outcome and cardiac performance measures. In both short-term (3-week) and long-term (9-week) trials, cardiomyocyte growth was blocked by HDAC inhibition, with no evidence of cell death or apoptosis. Fibrotic change was diminished in hearts treated with HDAC inhibitors, and collagen synthesis in isolated cardiac fibroblasts was blocked. Preservation of systolic function in the setting of blunted hypertrophic growth was documented by echocardiography and by invasive pressure measurements. The hypertrophy-associated switch of adult and fetal isoforms of myosin heavy chain expression was attenuated, which likely contributed to the observed preservation of systolic function in HDAC inhibitor-treated hearts. Together, these data suggest that HDAC inhibition is a viable therapeutic strategy that holds promise in the treatment of load-induced heart disease.
Sun, Xiao-Juan; Pan, Shan-Shan
2014-07-01
To examine the role of calcitonin gene-related peptide (CGRP) in cardioprotection of short-term and long-term exercise preconditioning (EP). Male Sprague-Dawley rats were, respectively, subjected to continuous intermittent treadmill training 3 days or 3 weeks as short-term or long-term EP protocols. The myocardial injury induced by isoproterenol (ISO) was performed 24 hours after short-term and long-term EP. The myocardial injury was evaluated in terms of the serum cardiac troponin levels and the hematoxylin-basic fuchsin-picric acid staining. Additionally, serum CGRP levels, CGRP expression in the dorsal root ganglion (DRG), and heart were analyzed as possible mechanisms to explain short-term and long-term EP-induced cardioprotection. Both short-term and long-term EP markedly attenuated the isoproterenol-induced myocardial ischemia with lower serum cardiac troponin levels. Short-term EP does not alter serum CGRP levels and CGRP expression in the DRG and heart. Long-term EP significantly increases serum CGRP levels and CGRP expression in the DRG and heart. The results indicate that short-term EP does not increase the synthesis and release of CGRP. Therefore, the cardioprotective effect of short-term EP does not involve CGRP adaptation. Furthermore, long-term EP increases CGRP synthesis in the DRG and promotes CGRP release in the blood and heart. Hence, CGRP may play an important role in the cardioprotective effect of long-term EP.
Bish, Lawrence T; Sleeper, Meg M; Reynolds, Caryn; Gazzara, Jeffrey; Withnall, Elanor; Singletary, Gretchen E; Buchlis, George; Hui, Daniel; High, Katherine A; Gao, Guangping; Wilson, James M; Sweeney, H Lee
2011-08-01
Derangements in calcium cycling have been described in failing hearts, and preclinical studies have suggested that therapies aimed at correcting this defect can lead to improvements in cardiac function and survival. One strategy to improve calcium cycling would be to inhibit phospholamban (PLB), the negative regulator of SERCA2a that is upregulated in failing hearts. The goal of this study was to evaluate the safety and efficacy of using adeno-associated virus (AAV)-mediated cardiac gene transfer of short hairpin RNA (shRNA) to knock down expression of PLB. Six dogs were treated with self-complementary AAV serotype 6 (scAAV6) expressing shRNA against PLB. Three control dogs were treated with empty AAV6 capsid, and two control dogs were treated with scAAV6 expressing dominant negative PLB. Vector was delivered via a percutaneously inserted cardiac injection catheter. PLB mRNA and protein expression were analyzed in three of six shRNA dogs between days 16 and 26. The other three shRNA dogs and five control dogs were monitored long-term to assess cardiac safety. PLB mRNA was reduced 16-fold, and PLB protein was reduced 5-fold, with treatment. Serum troponin elevation and depressed cardiac function were observed in the shRNA group only at 4 weeks. An enzyme-linked immunospot assay failed to detect any T cells reactive to AAV6 capsid in peripheral blood mononuclear cells, heart, or spleen. Microarray analysis revealed alterations in cardiac expression of several microRNAs with shRNA treatment. AAV6-mediated cardiac gene transfer of shRNA effectively knocks down PLB expression but is associated with severe cardiac toxicity. Toxicity may result from dysregulation of endogenous microRNA pathways.
Sleeper, Meg M.; Reynolds, Caryn; Gazzara, Jeffrey; Withnall, Elanor; Singletary, Gretchen E.; Buchlis, George; Hui, Daniel; High, Katherine A.; Gao, Guangping; Wilson, James M.; Sweeney, H. Lee
2011-01-01
Abstract Derangements in calcium cycling have been described in failing hearts, and preclinical studies have suggested that therapies aimed at correcting this defect can lead to improvements in cardiac function and survival. One strategy to improve calcium cycling would be to inhibit phospholamban (PLB), the negative regulator of SERCA2a that is upregulated in failing hearts. The goal of this study was to evaluate the safety and efficacy of using adeno-associated virus (AAV)-mediated cardiac gene transfer of short hairpin RNA (shRNA) to knock down expression of PLB. Six dogs were treated with self-complementary AAV serotype 6 (scAAV6) expressing shRNA against PLB. Three control dogs were treated with empty AAV6 capsid, and two control dogs were treated with scAAV6 expressing dominant negative PLB. Vector was delivered via a percutaneously inserted cardiac injection catheter. PLB mRNA and protein expression were analyzed in three of six shRNA dogs between days 16 and 26. The other three shRNA dogs and five control dogs were monitored long-term to assess cardiac safety. PLB mRNA was reduced 16-fold, and PLB protein was reduced 5-fold, with treatment. Serum troponin elevation and depressed cardiac function were observed in the shRNA group only at 4 weeks. An enzyme-linked immunospot assay failed to detect any T cells reactive to AAV6 capsid in peripheral blood mononuclear cells, heart, or spleen. Microarray analysis revealed alterations in cardiac expression of several microRNAs with shRNA treatment. AAV6-mediated cardiac gene transfer of shRNA effectively knocks down PLB expression but is associated with severe cardiac toxicity. Toxicity may result from dysregulation of endogenous microRNA pathways. PMID:21542669
Spiroski, Dejan; Andjić, Mojsije; Stojanović, Olivera Ilić; Lazović, Milica; Dikić, Ana Djordjević; Ostojić, Miodrag; Beleslin, Branko; Kostić, Snežana; Zdravković, Marija; Lović, Dragan
2017-05-01
Exercise-based rehabilitation is an important part of treatment patients following coronary artery bypass graft (CABG) surgery. To evaluate effect of very short/short-term exercise training on cardiopulmonary exercise testing (CPET) parameters. We studied 54 consecutive patients with myocardial infarction (MI) treated with CABG surgery referred for rehabilitation. The study population consisted of 50 men and 4 women (age 57.72 ± 7.61 years, left ventricular ejection fraction 55% ± 5.81%), who participated in a 3-week clinical and 6-month outpatient cardiac rehabilitation program. The Inpatient program consisted of cycling 7 times/week and daily walking for 45 minutes. The outpatient program consisted mainly of walking 5 times/week for 45 minutes and cycling 3 times/week. All patients performed symptom-limited CPET on a bicycle ergometer with a ramp protocol of 10 W/minute at the start, for 3 weeks, and for 6 months. After 3 weeks of an exercise-based cardiac rehabilitation program, exercise tolerance improved as compared to baseline, as well as peak respiratory exchange ratio. Most importantly, peak VO 2 (16.35 ± 3.83 vs 17.88 ± 4.25 mL/kg/min, respectively, P < 0.05), peak VCO 2 (1.48 ± 0.40 vs 1.68 ± 0.43, respectively, P < 0.05), peak ventilatory exchange (44.52 ± 11.32 vs 52.56 ± 12.37 L/min, respectively, P < 0.05), and peak breathing reserve (52.00% ± 13.73% vs 45.75% ± 14.84%, respectively, P < 0.05) were also improved. The same improvement trend continued after 6 months (respectively, P < 0.001 and P < 0.0001). No major adverse cardiac events were noted during the rehabilitation program. Very short/short-term exercise training in patients with MI treated with CABG surgery is safe and improves functional capacity. © 2017 Wiley Periodicals, Inc.
Meyer, Mary C; Mooney, Robert P; Sekera, Anna K
2006-05-01
We evaluate the safety and feasibility of a critical care pathway protocol in which patients with acute chest pain who are low risk for coronary artery disease and short-term adverse cardiac outcomes receive outpatient stress testing within 72 hours of an emergency department (ED) visit. We performed an observational study of an ED-based chest pain critical pathway in an urban, community hospital in 979 consecutive patients. Patients enrolled in the protocol were observed in the ED before receiving 72-hour outpatient stress testing. The pathway was primarily analyzed for rates of death or myocardial infarction in the 6 months after ED discharge and outpatient stress testing. Secondary outcome measures included need for coronary intervention at initial stress testing and within 6 months after discharge, subsequent ED visits for chest pain, and subsequent hospitalization. Of 871 stress-tested patients aged 40 years or older, who had low risk for coronary artery disease and short-term adverse cardiac events, and had 6-month follow-up, 18 (2%) required coronary intervention, 1 (0.1%) had a myocardial infarction within 1 month, 2 (0.2%) had a myocardial infarction within 6 months, 6 (0.7%) had normal stress test results after discharge but required cardiac catheterization within 6 months, and 5 (0.6%) returned to the ED within 6 months for ongoing chest pain. Hospital admission rates decreased significantly from 31.2% to 26.1% after initiation of the protocol (P<.001). For patients with chest pain and low risk for short-term cardiac events, outpatient stress testing is feasible, safe, and associated with decreased hospital admission rates. With an evidence-based protocol, physicians efficiently identify patients at low risk for clinically significant coronary artery disease and short-term adverse cardiac outcomes.
Molecular Mechanisms Underlying Cardiac Adaptation to Exercise
Vega, Rick B.; Konhilas, John P.; Kelly, Daniel P.; Leinwand, Leslie A.
2017-01-01
Exercise elicits coordinated multi-organ responses including skeletal muscle, vasculature, heart and lung. In the short term, the output of the heart increases to meet the demand of strenuous exercise. Long term exercise instigates remodeling of the heart including growth and adaptive molecular and cellular re-programming. Signaling pathways such as the insulin-like growth factor 1/PI3K/Akt pathway mediate many of these responses. Exercise-induced, or physiologic, cardiac growth contrasts with growth elicited by pathological stimuli such as hypertension. Comparing the molecular and cellular underpinnings of physiologic and pathologic cardiac growth has unveiled phenotype-specific signaling pathways and transcriptional regulatory programs. Studies suggest that exercise pathways likely antagonize pathological pathways, and exercise training is often recommended for patients with chronic stable heart failure or following myocardial infarction. Herein, we summarize the current understanding of the structural and functional cardiac responses to exercise as well as signaling pathways and downstream effector molecules responsible for these adaptations. PMID:28467921
Li, Y; Yin, S; Fang, J; Hua, Y; Wang, C; Mu, D; Zhou, K
2015-06-01
No consensus has been reached regarding whether brain injury related to congenital heart disease (CHD) is caused by infant cardiac surgery and/or prenatal injury resulting from the CHD. We performed this meta-analysis to identify the likely cause of neurodevelopmental delay in CHD patients. We carried out a literature search without language restriction in December 2013, retrieving records from PubMed, EMBASE, the Cochrane Library and the World Health Organization trials center, to identify studies applying functional magnetic resonance imaging (fMRI) evaluation of brain function before surgery and, in some cases, after surgery (both immediate term and short term postoperatively). The preoperative and postoperative fMRI results were extracted, and meta-analysis was performed using Revman 5.1.1 and STATA 11.0, according to the guidelines from the Cochrane review and MOOSE groups. The electronic search yielded 937 citations. Full text was retrieved for 15 articles and eight articles (nine studies) were eligible for inclusion: six studies (n = 312 cases) with fMRI analysis before surgery and three (n = 36 cases) with complete perioperative fMRI analysis. The overall average diffusivity of CHD cases was significantly higher than that of controls, with a summarized standard (std) mean difference of 1.39 (95% CI, 0.70-2.08), and the fractional anisotropy was lower in CHD cases, with a summarized mean difference of -1.43 (95% CI, -1.95 to -0.91). N-acetylaspartate (NAA)/choline (Cho) for the whole brain was significantly lower in CHD cases compared with healthy ones, while lactate/Cho was significantly higher in CHD cases. Immediate term postoperatively, significant changes in NAA/creatine and NAA/Cho, relative to preoperative values, were found. However, the difference did not persist at the short-term follow-up. This meta-analysis suggests that the delay in neurological development in newborns with CHD is due mainly to prenatal injury, and cardiac surgery might lead to mild brain injuries postoperatively, but fMRI shows recovery within a short period. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
Strategies for regeneration of heart muscle.
Guyette, Jacques P; Cohen, Ira S; Gaudette, Glenn R
2010-01-01
Regenerative medicine has emerged to the forefront of cardiac research, marrying discoveries in both basic science and engineering to develop viable therapeutic approaches for treating the diseased heart. Signifi cant advancements in gene therapy, stem cell biology, and cardiomyoplasty provide new optimism for regenerating damaged myocardium. Exciting new strategies for endogenous and exogenous regeneration have been proposed. However, questions remain as to whether these approaches can provide enough new myocyte mass to sufficiently restore mechanical function to the heart. In this article, we consider the mechanisms of endogenous cardiomyocyte regeneration and exogenous cell differentiation (with respect to myoblasts, stem cells, and induced pluripotent cells being researched for cell therapies). We begin by reviewing some of the cues that are being harnessed in strategies of gene/cell therapy for regenerating myocardium. We also consider some of the technical challenges that remain in determining new myocyte generation, tracking delivered cells in vivo, and correlating new myocyte contractility with cardiac function. Strategies for regenerating the heart are being realized as both animal and clinical trials suggest that these new approaches provide short-term improvement of cardiac function. However, a more complete understanding of the underlying mechanisms and applications is necessary to sustain longer-term therapeutic success.
Suppression of Class I and II Histone Deacetylases Blunts Pressure-Overload Cardiac Hypertrophy
Kong, Yongli; Tannous, Paul; Lu, Guangrong; Berenji, Kambeez; Rothermel, Beverly A.; Olson, Eric N.; Hill, Joseph A.
2014-01-01
Background Recent work has demonstrated the importance of chromatin remodeling, especially histone acetylation, in the control of gene expression in the heart. In cell culture models of cardiac hypertrophy, pharmacological suppression of histone deacetylases (HDACs) can either blunt or amplify cell growth. Thus, HDAC inhibitors hold promise as potential therapeutic agents in hypertrophic heart disease. Methods and Results In the present investigation, we studied 2 broad-spectrum HDAC inhibitors in a physiologically relevant banding model of hypertrophy, observing dose-responsive suppression of ventricular growth that was well tolerated in terms of both clinical outcome and cardiac performance measures. In both short-term (3-week) and long-term (9-week) trials, cardiomyocyte growth was blocked by HDAC inhibition, with no evidence of cell death or apoptosis. Fibrotic change was diminished in hearts treated with HDAC inhibitors, and collagen synthesis in isolated cardiac fibroblasts was blocked. Preservation of systolic function in the setting of blunted hypertrophic growth was documented by echocardiography and by invasive pressure measurements. The hypertrophy-associated switch of adult and fetal isoforms of myosin heavy chain expression was attenuated, which likely contributed to the observed preservation of systolic function in HDAC inhibitor–treated hearts. Conclusions Together, these data suggest that HDAC inhibition is a viable therapeutic strategy that holds promise in the treatment of load-induced heart disease. PMID:16735673
Continuous internal counterpulsation as a bridge to recovery in acute and chronic heart failure
Kontogiannis, Christos D; Malliaras, Konstantinos; Kapelios, Chris J; Mason, Jay W; Nanas, John N
2016-01-01
Cardiac recovery from cardiogenic shock (CS) and end-stage chronic heart failure (HF) remains an often insurmountable therapeutic challenge. The counterpulsation technique exerts numerous beneficial effects on systemic hemodynamics and left ventricular mechanoenergetics, rendering it attractive for promoting myocardial recovery in both acute and chronic HF. Although a recent clinical trial has questioned the clinical effectiveness of short-term hemodynamic support with intra-aortic balloon pump (IABP, the main representative of the counterpulsation technique) in CS complicating myocardial infarction, the issue remains open to further investigation. Moreover, preliminary data suggest that long-term IABP support in patients with end-stage HF is safe and may mediate recovery of left- or/and right-sided cardiac function, facilitating long-term weaning from mechanical support or enabling the application of other permanent, life-saving solutions. The potential of long-term counterpulsation could possibly be enhanced by implementation of novel, fully implantable counterpulsation devices. PMID:27011909
McSweeney, Jean C; Cleves, Mario A; Fischer, Ellen P; Pettey, Christina M; Beasley, Brittany
Few instruments capture symptoms that predict cardiac events in the short-term. This study examines the ability of the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey to predict acute cardiac events within 3 months of administration and to identify the prodromal symptoms most associated with short-term risk in women without known coronary heart disease. The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey was administered to 1,097 women referred to a cardiologist for initial coronary heart disease evaluation. Logistic regression models were used to examine prodromal symptoms individually and in combination to identify the subset of symptoms most predictive of an event within 3 months. Fifty-one women had an early cardiac event. In bivariate analyses, 4 of 30 prodromal symptoms were significantly associated with event occurrence within 90 days. In adjusted analyses, women reporting arm pain or discomfort and unusual fatigue were more likely (OR, 4.67; 95% CI, 2.08-10.48) to have a cardiac event than women reporting neither. The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey may assist in predicting short-term coronary heart disease events in women without known coronary heart disease. Copyright © 2017 Jacobs Institute of Women's Health. All rights reserved.
Clinical experience with a high-performance ATM-connected DICOM archive for cardiology
NASA Astrophysics Data System (ADS)
Solomon, Harry P.
1997-05-01
A system to archive large image sets, such as cardiac cine runs, with near realtime response must address several functional and performance issues, including efficient use of a high performance network connection with standard protocols, an architecture which effectively integrates both short- and long-term mass storage devices, and a flexible data management policy which allows optimization of image distribution and retrieval strategies based on modality and site-specific operational use. Clinical experience with such as archive has allowed evaluation of these systems issues and refinement of a traffic model for cardiac angiography.
Short-term effects of cardiac steroids on intracellular membrane traffic in neuronal NT2 cells.
Rosen, H; Glukmann, V; Feldmann, T; Fridman, E; Lichtstein, D
2006-12-30
Cardiac steroids (CS) are specific inhibitors of Na+, K+-ATPase activity. Although the presence of CS-like compounds in animal tissues has been established, their physiological role is not clear. In a previous study we showed that in pulse-chase membrane-labeling experiments, long term (hours) interaction of CS at physiological concentrations (nM) with Na+, K+-ATPase, caused changes in endocytosed membrane traffic in human NT2 cells. This was associated with the accumulation of large vesicles adjacent to the nucleus. For this sequence of events to function in the physiological setting, however, CS would be expected to modify membrane traffic upon short term (min) exposure and membrane labeling. We now demonstrate that CS affects membrane traffic also following a short exposure. This was reflected by the CS-induced accumulation of FM1-43 and transferrin in the cells, as well as by changes in their colocalization with Na+, K+-ATPase. We also show that the CS-induced changes in membrane traffic following up to 2 hrs exposure are reversible, whereas longer treatment induces irreversible effects. Based on these observations, we propose that endogenous CS-like compounds are physiological regulators of the recycling of endocytosed membrane proteins and cargo in neuronal cells, and may affect basic mechanisms such as neurotransmitter release and reuptake.
Altavilla, Riccardo; Di Flaviani, Alessandra; Giordani, Ilaria; Malandrucco, Ilaria; Picconi, Fabiana; Passarelli, Francesco; Pasqualetti, Patrizio; Ercolani, Matilde; Vernieri, Fabrizio; Frontoni, Simona
2013-01-01
Objective Impaired cerebral vasomotor reactivity (VMR) and flow-mediated dilation (FMD) were found in selected subgroups of type 2 diabetes mellitus (T2DM) patients with long-term disease. Our study aimed to evaluate cerebral hemodynamics, systemic endothelial function and sympatho-vagal balance in a selected population of well-controlled T2DM patients with short-term disease and without cardiac autonomic neuropathy (CAN). Research Design and Methods Twenty-six T2DM patients with short-term (4.40±4.80 years) and well-controlled (HbA1C = 6.71±1.29%) disease, without any complications, treated with diet and/or metformin, were consecutively recruited. Eighteen controls, comparable by sex and age, were enrolled also. Results FMD and shear rate FMD were found to be reduced in T2DM subjects with short-term disease (8.5% SD 3.5 and 2.5 SD 1.3, respectively) compared to controls (15.4% SD 4.1 and 3.5 SD 1.4; p<.001 and p<.05). T2DM patients also displayed reduced VMR values than controls (39.4% SD 12.4 vs 51.7%, SD 15.5; p<.05). Sympatho-vagal balance was not different in T2DM patients compared to healthy subjects. FMD and shear rate FMD did not correlate with VMR in T2DM patients or in controls (p>.05). Conclusions In well-controlled T2DM patients with short-term disease cerebral hemodynamics and systemic endothelial function are altered while autonomic balance appeared to be preserved. PMID:24391751
Epinephrine in Out-of-hospital Cardiac Arrest: Helpful or Harmful?
Shao, Huan; Li, Chun-Sheng
2017-01-01
Objective: Epinephrine is the primary drug administered during cardiopulmonary resuscitation (CPR) to reverse cardiac arrest. The evidence for the use of adrenaline in out-of-hospital cardiac arrest (OHCA) and in-hospital resuscitation is inconclusive. We conducted a systematic review on the clinical efficacy of adrenaline in adult OHCA patients to evaluate whether epinephrine provides any overall benefit for patients. Data Sources: The EMBASE and PubMed databases were searched with the key words “epinephrine,” “cardiac arrest,” and variations of these terms. Study Selection: Data from clinical randomized trials, meta-analyses, guidelines, and recent reviews were selected for review. Results: Sudden cardiac arrest causes 544,000 deaths in China each year, with survival occurring in <1% of cases (compared with 12% in the United States). The American Heart Association recommends the use of epinephrine in patients with cardiac arrest, as part of advanced cardiac life support. There is a clear evidence of an association between epinephrine and increased return of spontaneous circulation (ROSC). However, there are conflicting results regarding long-term survival and functional recovery, particularly neurological outcome, after CPR. There is currently insufficient evidence to support or reject epinephrine administration during resuscitation. We believe that epinephrine may have a role in resuscitation, as administration of epinephrine during CPR increases the probability of restoring cardiac activity with pulses, which is an essential intermediate step toward long-term survival. Conclusions: The administration of adrenaline was associated with improved short-term survival (ROSC). However, it appears that the use of adrenaline is associated with no benefit on survival to hospital discharge or survival with favorable neurological outcome after OHCA, and it may have a harmful effect. Larger placebo-controlled, double-blind, randomized control trials are required to definitively establish the effect of epinephrine. PMID:28836556
Epinephrine in Out-of-hospital Cardiac Arrest: Helpful or Harmful?
Shao, Huan; Li, Chun-Sheng
2017-09-05
Epinephrine is the primary drug administered during cardiopulmonary resuscitation (CPR) to reverse cardiac arrest. The evidence for the use of adrenaline in out-of-hospital cardiac arrest (OHCA) and in-hospital resuscitation is inconclusive. We conducted a systematic review on the clinical efficacy of adrenaline in adult OHCA patients to evaluate whether epinephrine provides any overall benefit for patients. The EMBASE and PubMed databases were searched with the key words "epinephrine," "cardiac arrest," and variations of these terms. Data from clinical randomized trials, meta-analyses, guidelines, and recent reviews were selected for review. Sudden cardiac arrest causes 544,000 deaths in China each year, with survival occurring in <1% of cases (compared with 12% in the United States). The American Heart Association recommends the use of epinephrine in patients with cardiac arrest, as part of advanced cardiac life support. There is a clear evidence of an association between epinephrine and increased return of spontaneous circulation (ROSC). However, there are conflicting results regarding long-term survival and functional recovery, particularly neurological outcome, after CPR. There is currently insufficient evidence to support or reject epinephrine administration during resuscitation. We believe that epinephrine may have a role in resuscitation, as administration of epinephrine during CPR increases the probability of restoring cardiac activity with pulses, which is an essential intermediate step toward long-term survival. The administration of adrenaline was associated with improved short-term survival (ROSC). However, it appears that the use of adrenaline is associated with no benefit on survival to hospital discharge or survival with favorable neurological outcome after OHCA, and it may have a harmful effect. Larger placebo-controlled, double-blind, randomized control trials are required to definitively establish the effect of epinephrine.
Effects of High Dietary HEME Iron and Radiation on Cardiovascular Function
NASA Technical Reports Server (NTRS)
Westby, Christian M.; Brown, A. K.; Platts, S. H.
2012-01-01
The radiation related health risks to astronauts is of particular concern to NASA. Data support that exposure to radiation is associated with a number of disorders including a heightened risk for cardiovascular diseases. Independent of radiation, altered nutrient status (e.g. high dietary iron) also increases ones risk for cardiovascular disease. However, it is unknown whether exposure to radiation in combination with high dietary iron further increases ones cardiovascular risk. The intent of our proposal is to generate compulsory data examining the combined effect of radiation exposure and iron overload on sensitivity to radiation injury to address HRP risks: 1) Risk Factor of Inadequate Nutrition; 2) Risk of Cardiac Rhythm Problems; and 3) Risk of Degenerative Tissue or other Health Effects from Space Radiation. Towards our goal we propose two distinct pilot studies using the following specific aims: Vascular Aim 1: To determine the short-term consequences of the independent and combined effects of exposure to gamma radiation and elevated body iron stores on measures of endothelial function and cell viability and integrity. We hypothesize that animals that have high body iron stores and are exposed to gamma radiation will show a greater reduction in endothelial dependent nitric oxid production and larger pathological changes in endothelial integrity than animals that have only 1 of those treatments (either high iron stores or exposure to gamma radiation). Vascular Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with endothelial cell function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with endothelial cell function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment. Cardiac Aim 1: To determine the short-term consequences of the independent and combined effects of gamma radiation and elevated body iron stores on measures of cardiac structure. We hypothesize that modifications to cardiac structure and function will be greater in rats with high body iron stores and exposed to gamma radiation than in rats that have only 1 of those treatments. Cardiac Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with cardiac structure and function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with cardiac contractile function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment.
Johansen, Anne Katrine; Molenaar, Bas; Versteeg, Danielle; Leitoguinho, Ana Rita; Demkes, Charlotte; Spanjaard, Bastiaan; de Ruiter, Hesther; Akbari Moqadam, Farhad; Kooijman, Lieneke; Zentilin, Lorena; Giacca, Mauro; van Rooij, Eva
2017-10-27
CRISPR/Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9)-based DNA editing has rapidly evolved as an attractive tool to modify the genome. Although CRISPR/Cas9 has been extensively used to manipulate the germline in zygotes, its application in postnatal gene editing remains incompletely characterized. To evaluate the feasibility of CRISPR/Cas9-based cardiac genome editing in vivo in postnatal mice. We generated cardiomyocyte-specific Cas9 mice and demonstrated that Cas9 expression does not affect cardiac function or gene expression. As a proof-of-concept, we delivered short guide RNAs targeting 3 genes critical for cardiac physiology, Myh6 , Sav1 , and Tbx20 , using a cardiotropic adeno-associated viral vector 9. Despite a similar degree of DNA disruption and subsequent mRNA downregulation, only disruption of Myh6 was sufficient to induce a cardiac phenotype, irrespective of short guide RNA exposure or the level of Cas9 expression. DNA sequencing analysis revealed target-dependent mutations that were highly reproducible across mice resulting in differential rates of in- and out-of-frame mutations. Finally, we applied a dual short guide RNA approach to effectively delete an important coding region of Sav1 , which increased the editing efficiency. Our results indicate that the effect of postnatal CRISPR/Cas9-based cardiac gene editing using adeno-associated virus serotype 9 to deliver a single short guide RNA is target dependent. We demonstrate a mosaic pattern of gene disruption, which hinders the application of the technology to study gene function. Further studies are required to expand the versatility of CRISPR/Cas9 as a robust tool to study novel cardiac gene functions in vivo. © 2017 American Heart Association, Inc.
Effect of Actual and Simulated Microgravity on Cardiac Mass and Function in the Rat
NASA Technical Reports Server (NTRS)
Ray, Chester H.; Vasques, Marilyn; Miller, Todd H.; Wilkerson, M. Keith; Delp, Michael D.; Dalton, Bonnie (Technical Monitor)
2001-01-01
The purpose of this study was to test the hypothesis that exposure to actual or simulated microgravity induces cardiac atrophy in male Sprague-Dawley rats. For the microgravity study, rats were subdivided into four groups: Preflight (PF, n = 12); Flight (FL, n = 7); Flight Cage Simulation (SIM, n = 6), and Vivarium Control (VIV, n = 7). Animals in the FL group were exposed to 7 days of microgravity during the Spacelab 3 mission. Animals in the simulated microgravity study were subdivided into three groups: Control (CON, n = 20); 7 day hindlimb unloaded (7HU, n = 10); and 28 day unloaded (28HU, n = 19). In a subset of CON (n = 7) and 28HU (n = 6) rats, a catheter was advanced into the left ventricle to measure the rate of rise in ventricular pressure (+dP/dt) during standing as an estimate of cardiac contractility. After completion of their respective treatments, hearts were removed and weighed. Animals in the PF group were sacrificed 24 hr prior to launch while the FL group was sacrificed 11- 17 hr after landing. The SM and VIV groups were sacrificed 48 and 96 hr after the FL group, respectively. Heart mass was unchanged in adult animals exposed to 7 days of actual microgravity (PF 1.33 +/- .03 g; FL 1.32 +/- 0.02 g; SIM 1.28 +/- 0.04 g; VIV 1.35 +/- 0.04 g). Similarly, heart mass was unaltered with hinlimb unloading (CON 1.40 +/- 0.04 g; 7HU 1.35 +/- 0.06 g; 28HU 1.42 +/- 0.03 g). Hindlimb unloading also had no effect on myocardial contractility (CON 8055 +/- 385 mmHg/sec; 28HU 8545 +/- 755 mmHg/sec). These data suggest that cardiac atrophy does not occur following short-term exposure to microgravity, and that neither short- nor long-term simulated microgravity alter cardiac mass or function.
Vergeade, Aurélia; Mulder, Paul; Vendeville-Dehaudt, Cathy; Estour, François; Fortin, Dominique; Ventura-Clapier, Renée; Thuillez, Christian; Monteil, Christelle
2010-09-01
The goal of this study was to assess mitochondrial function and ROS production in an experimental model of cocaine-induced cardiac dysfunction. We hypothesized that cocaine abuse may lead to altered mitochondrial function that in turn may cause left ventricular dysfunction. Seven days of cocaine administration to rats led to an increased oxygen consumption detected in cardiac fibers, specifically through complex I and complex III. ROS levels were increased, specifically in interfibrillar mitochondria. In parallel there was a decrease in ATP synthesis, whereas no difference was observed in subsarcolemmal mitochondria. This uncoupling effect on oxidative phosphorylation was not detectable after short-term exposure to cocaine, suggesting that these mitochondrial abnormalities were a late rather than a primary event in the pathological response to cocaine. MitoQ, a mitochondrial-targeted antioxidant, was shown to completely prevent these mitochondrial abnormalities as well as cardiac dysfunction characterized here by a diastolic dysfunction studied with a conductance catheter to obtain pressure-volume data. Taken together, these results extend previous studies and demonstrate that cocaine-induced cardiac dysfunction may be due to a mitochondrial defect. Copyright 2010 Elsevier Inc. All rights reserved.
A Short History of Cardiac Inspection: A Quest "To See with a Better Eye".
Evans, William N
2015-08-01
Cardiac examination has evolved over centuries. The goal of cardiac evaluation, regardless the era, is to "see" inside the heart to diagnose congenital and acquired intra-cardiac structural and functional abnormalities. This article briefly reviews the history of cardiac examination and discusses contemporary best, evidence-based methods of cardiac inspection.
Trotier, Aurélien J; Castets, Charles R; Lefrançois, William; Ribot, Emeline J; Franconi, Jean-Michel; Thiaudière, Eric; Miraux, Sylvain
2016-08-01
To develop and assess a 3D-cine self-gated method for cardiac imaging of murine models. A 3D stack-of-stars (SOS) short echo time (STE) sequence with a navigator echo was performed at 7T on healthy mice (n = 4) and mice with acute myocardial infarction (MI) (n = 4) injected with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. In all, 402 spokes were acquired per stack with the incremental or the golden angle method using an angle increment of (360/402)° or 222.48°, respectively. A cylindrical k-space was filled and repeated with a maximum number of repetitions (NR) of 10. 3D cine cardiac images at 156 μm resolution were reconstructed retrospectively and compared for the two methods in terms of contrast-to-noise ratio (CNR). The golden angle images were also reconstructed with NR = 10, 6, and 3, to assess cardiac functional parameters (ejection fraction, EF) on both animal models. The combination of 3D SOS-STE and USPIO injection allowed us to optimize the identification of cardiac peaks on navigator signal and generate high CNR between blood and myocardium (15.3 ± 1.0). The golden angle method resulted in a more homogeneous distribution of the spokes inside a stack (P < 0.05), enabling reducing the acquisition time to 15 minutes. EF was significantly different between healthy and MI mice (P < 0.05). The method proposed here showed that 3D-cine images could be obtained without electrocardiogram or respiratory gating in mice. It allows precise measurement of cardiac functional parameters even on MI mice. J. Magn. Reson. Imaging 2016;44:355-365. © 2016 Wiley Periodicals, Inc.
Slovinec D'Angelo, Monika E; Pelletier, Luc G; Reid, Robert D; Huta, Veronika
2014-11-01
Poor adherence to regular exercise is a documented challenge among people with heart disease. Identifying key determinants of exercise adherence and distinguishing between the processes driving short- and long-term adherence to regular exercise is a valuable endeavor. The purpose of the present study was to test a model of exercise behavior change, which incorporates motivational orientations and self-efficacy for exercise behavior, in the prediction of short- and long-term exercise adherence. Male and female patients (N = 801) hospitalized for coronary heart disease were recruited from 3 tertiary care cardiac centers and followed for a period of 1 year after hospital discharge. A prospective, longitudinal design was used to examine the roles of motivation and self-efficacy (measured at recruitment and at 2 and 6 months after discharge) in the prediction of exercise behavior at 6 and 12 months. Baseline measures of exercise and clinical and demographic covariates were included in the analyses. Structural equation modeling showed that both autonomous motivation and self-efficacy were important determinants of short-term (6-month) exercise behavior regulation, but that only autonomous motivation remained a significant predictor of long-term (12-month) exercise behavior. Self-efficacy partially mediated the relationship between motivation for exercise and 6-month exercise behavior. This research confirmed the roles of autonomous motivation and self-efficacy in the health behavior change process and emphasized the key function of autonomous motivation in exercise maintenance. Theoretical and cardiac rehabilitation program applications of this research are discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.
Bartko, Philipp E; Wiedemann, Dominik; Schrutka, Lore; Binder, Christina; Santos-Gallego, Carlos G; Zuckermann, Andreas; Steinlechner, Barbara; Koinig, Herbert; Heinz, Gottfried; Niessner, Alexander; Zimpfer, Daniel; Laufer, Günther; Lang, Irene M; Distelmaier, Klaus; Goliasch, Georg
2017-07-28
Extracorporeal membrane oxygenation following cardiac surgery safeguards end-organ oxygenation but unfavorably alters cardiac hemodynamics. Along with the detrimental effects of cardiac surgery to the right heart, this might impact outcome, particularly in patients with preexisting right ventricular (RV) dysfunction. We sought to determine the prognostic impact of RV function and to improve established risk-prediction models in this vulnerable patient cohort. Of 240 patients undergoing extracorporeal membrane oxygenation support following cardiac surgery, 111 had echocardiographic examinations at our institution before implantation of extracorporeal membrane oxygenation and were thus included. Median age was 67 years (interquartile range 60-74), and 74 patients were male. During a median follow-up of 27 months (interquartile range 16-63), 75 patients died. Fifty-one patients died within 30 days, 75 during long-term follow-up (median follow-up 27 months, minimum 5 months, maximum 125 months). Metrics of RV function were the strongest predictors of outcome, even stronger than left ventricular function ( P <0.001 for receiver operating characteristics comparisons). Specifically, RV free-wall strain was a powerful predictor univariately and after adjustment for clinical variables, Simplified Acute Physiology Score-3, tricuspid regurgitation, surgery type and duration with adjusted hazard ratios of 0.41 (95%CI 0.24-0.68; P =0.001) for 30-day mortality and 0.48 (95%CI 0.33-0.71; P <0.001) for long-term mortality for a 1-SD (SD=-6%) change in RV free-wall strain. Combined assessment of the additive EuroSCORE and RV free-wall strain improved risk classification by a net reclassification improvement of 57% for 30-day mortality ( P =0.01) and 56% for long-term mortality ( P =0.02) compared with the additive EuroSCORE alone. RV function is strongly linked to mortality, even after adjustment for baseline variables and clinical risk scores. RV performance improves established risk prediction models for short- and long-term mortality. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
BACKGROUND: Epidemiological studies have shown associations between air temperature and cardiovascular health outcomes. Metabolic dysregulation might also play a role in the development of cardiovascular disease.OBJECTIVES: To investigate short-term temperature effects on metabol...
Ward, Anthony R; Alarcón, Gabriela; Nigg, Joel T; Musser, Erica D
2015-11-01
Although attention deficit/hyperactivity disorder (ADHD) is associated with impairment in working memory and short-term memory, up to half of individual children with ADHD perform within a normative range. Heterogeneity in other ADHD-related mechanisms, which may compensate for or combine with cognitive weaknesses, is a likely explanation. One candidate is the robustness of parasympathetic regulation (as indexed by respiratory sinus arrhythmia; RSA). Theory and data suggest that a common neural network is likely tied to both heart-rate regulation and certain cognitive functions (including aspects of working and short-term memory). Cardiac-derived indices of parasympathetic reactivity were collected during short-term memory (STM) storage and rehearsal tasks from 243 children (116 ADHD, 127 controls). ADHD was associated with lower STM performance, replicating previous work. In addition, RSA reactivity moderated the association between STM and ADHD - both as a category and a dimension - independent of comorbidity. Specifically, conditional effects revealed that high levels of withdrawal interacted with weakened STM but high levels of augmentation moderated a positive association predicting ADHD. Thus, variations in parasympathetic reactivity may help explain neuropsychological heterogeneity in ADHD.
Elshama, Said Said; Osman, Hosam-Eldin Hussein; El-Kenawy, Ayman El-Meghawry; Youseef, Hamdi Mohamed
2016-02-17
Vitamin D3 has increased risk of toxicity due to its common use in multivitamin preparations. Vitamin K and vitamin A play an important role in vitamin D action. The goal of the current study was to compare the protective effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3 toxicity in rats by assessing serum calcium, renal function tests, cardiac enzymes, and related histopathological changes. Eighty adult albino rats were divided into four groups; each group consisted of 20 rats. The first group received water; the second received a toxic dose of vitamin D3; the third received a toxic dose of vitamin D3 with vitamin A; and the fourth received a toxic dose of vitamin D3 with vitamin K. Vitamin D3 toxicity led to significant abnormalities of cardiac enzymes, renal function tests, and serum calcium associated with histopathological changes in the kidney, heart, lung, adrenal gland, and aorta. Individual administration of vitamin A or vitamin K with a toxic dose of vitamin D improved the biochemical and histopathological abnormalities of hypervitaminosis D3. Vitamins A and K showed the same protective effects in the modulation of hypervitaminosis D3 short-term toxicity.
Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) may provoke cardiac events through defective co-ordination of the two main autonomic nervous system (ANS) branches. We exposed heart failure-prone rats once to DE (500 g/m3 ...
Background: Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) is an ubiquitous air pollutant believed to provoke cardiac events partly through imbalance of the sympathetic and parasympathetic branches of the autonomic nervo...
Frankenstein, Lutz; Nelles, Manfred; Slavutsky, Maxim; Schellberg, Dieter; Doesch, Andreas; Katus, Hugo; Remppis, Andrew; Zugck, Christian
2007-10-01
In chronic heart failure (CHF), the physiologic effects of natriuretic peptides and catecholamines are interdependent. Furthermore, reports state an agent-dependent effect of individual beta-blockers on biomarkers. Data on the short-term and long-term predictive power comparing these biomarkers as well as accounting for the influence of beta-blocker treatment both on the marker or the resultant prognostic information are scarce. We included 513 consecutive patients with systolic CHF, measured atrial natriuretic peptide (ANP), N-terminal prohormone brain natriuretic peptide (NTproBNP), noradrenaline, and adrenaline, and monitored them for 90 +/- 25 months. Death or the combination of death and cardiac transplantation at 1 year, 5 years, and overall follow-up were considered end points. Compared with patients not taking beta-blockers, patients taking beta-blockers had significantly lower levels of catecholamines but not natriuretic peptides. Only for adrenaline was the amount of this effect related to the specific beta-blocker chosen. Receiver operating characteristic curves demonstrated superior prognostic accuracy for NTproBNP both at the 1- and 5-year follow-up compared with ANP, noradrenaline, and adrenaline. In multivariate analysis including established risk markers (New York Heart Association functional class, left ventricular ejection fraction, peak oxygen uptake, and 6-minute walk test), of all neurohumoral parameters, only NTproBNP remained an independent predictor for both end points. Long-term beta-blocker therapy is associated with decreased levels of plasma catecholamines but not natriuretic peptides. This effect is independent from the actual beta-blocker chosen for natriuretic peptides and noradrenaline. In multivariate analysis, both for short-term and long-term prediction of mortality or the combined end point of death and cardiac transplantation, only NTproBNP remained independent from established clinical risk markers.
Hamon, David; Rajendran, Pradeep S; Chui, Ray W; Ajijola, Olujimi A; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S; Armour, J Andrew; Ardell, Jeffrey L; Shivkumar, Kalyanam
2017-04-01
Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system, a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on intrinsic cardiac nervous system function in generating cardiac neuronal and electric instability using a novel cardioneural mapping approach. In a porcine model (n=8), neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli ( P <0.001). Compared with fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response ( P <0.05 versus short CI), particularly on convergent neurons ( P <0.05), as well as neurons receiving sympathetic ( P <0.05) and parasympathetic input ( P <0.05). The greatest cardiac electric instability was also observed after variable (short) CI PVCs. Variable CI PVCs affect critical populations of intrinsic cardiac nervous system neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling, leading to cardiomyopathy. © 2017 American Heart Association, Inc.
Davarpasand, Tahereh; Hosseinsabet, Ali; Jalali, Arash
2015-09-01
It has been reported that the short-term mortality of concomitant aortic and mitral valve replacement (AVR and MVR) is considerable and concomitant coronary artery bypass graft (CABG) has adverse effects on the survival of patients with valve replacement surgery. We summarize the short- and mid-term outcome after concomitant CABG, AVR and MVR in our centre. Between 2003 and 2013, 103 patients (68 males, 35 females, age: 60.1 ± 10.1 years) underwent CABG, AVR and MVR for rheumatic heart disease (RHD) and coronary artery disease (CAD). The median follow-up was 47.6 months. Most of the patients were asymptomatic at rest. We analysed demographic, clinical and operative data of patients to define independent predictors of overall survival, cardiac event-free survival as well as cardiac death. The rate of 30-day survival was 93% (n = 96). The corresponding rates of overall survival and cardiac event-free survival and the cumulative incidence rate of cardiac death at 1 year were 80.2, 77.3 and 10.9%; the same at 4 years were 73.7, 64.6 and 15.8%. The corresponding freedom rates from anticoagulation-associated major haemorrhage; a composite of major bleeding events, thromboemboli and valvular thrombosis; cardiac rehospitalization; major adverse valve-associated events; and significant malfunction of the prosthetic valve were 96.2, 95.3, 94.7, 81.6 and 97.7% at 1 year. The corresponding freedom rates from anticoagulation-associated major haemorrhage; a composite of major bleeding events, thromboemboli and valvular thrombosis; cardiac rehospitalization; major adverse valve-associated events; and significant malfunction of the prosthetic valve were 93.5, 91.0, 91.4, 73.5 and 95.5% at 4 years. The independent predictors of overall survival were age, cigarette smoking, chronic kidney diseases and balloon pump insertion. The independent predictors of cardiac event-free survival were age and previous myocardial infarction, while age, cigarette smoking, history of cerebrovascular accident and balloon pump insertion were the independent predictors of cardiac death. Concomitant CABG, AVR and MVR for rheumatic heart disease accompanied by CAD appear to have acceptable short- and mid-term outcomes with symptomatic amelioration. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Effects of stress on heart rate complexity—A comparison between short-term and chronic stress
Schubert, C.; Lambertz, M.; Nelesen, R.A.; Bardwell, W.; Choi, J.-B.; Dimsdale, J.E.
2009-01-01
This study examined chronic and short-term stress effects on heart rate variability (HRV), comparing time, frequency and phase domain (complexity) measures in 50 healthy adults. The hassles frequency subscale of the combined hassles and uplifts scale (CHUS) was used to measure chronic stress. Short-term stressor reactivity was assessed with a speech task. HRV measures were determined via surface electrocardiogram (ECG). Because respiration rate decreased during the speech task (p < .001), this study assessed the influence of respiration rate changes on the effects of interest. A series of repeated-measures analyses of covariance (ANCOVA) with Bonferroni adjustment revealed that short-term stress decreased HR D2 (calculated via the pointwise correlation dimension PD2) (p < .001), but increased HR mean (p < .001), standard deviation of R–R (SDRR) intervals (p < .001), low (LF) (p < .001) and high frequency band power (HF) (p = .009). Respiratory sinus arrhythmia (RSA) and LF/HF ratio did not change under short-term stress. Partial correlation adjusting for respiration rate showed that HR D2 was associated with chronic stress (r = −.35, p = .019). Differential effects of chronic and short-term stress were observed on several HRV measures. HR D2 decreased under both stress conditions reflecting lowered functionality of the cardiac pacemaker. The results confirm the importance of complexity metrics in modern stress research on HRV. PMID:19100813
Effects of stress on heart rate complexity--a comparison between short-term and chronic stress.
Schubert, C; Lambertz, M; Nelesen, R A; Bardwell, W; Choi, J-B; Dimsdale, J E
2009-03-01
This study examined chronic and short-term stress effects on heart rate variability (HRV), comparing time, frequency and phase domain (complexity) measures in 50 healthy adults. The hassles frequency subscale of the combined hassles and uplifts scale (CHUS) was used to measure chronic stress. Short-term stressor reactivity was assessed with a speech task. HRV measures were determined via surface electrocardiogram (ECG). Because respiration rate decreased during the speech task (p<.001), this study assessed the influence of respiration rate changes on the effects of interest. A series of repeated-measures analyses of covariance (ANCOVA) with Bonferroni adjustment revealed that short-term stress decreased HR D2 (calculated via the pointwise correlation dimension PD2) (p<.001), but increased HR mean (p<.001), standard deviation of R-R (SDRR) intervals (p<.001), low (LF) (p<.001) and high frequency band power (HF) (p=.009). Respiratory sinus arrhythmia (RSA) and LF/HF ratio did not change under short-term stress. Partial correlation adjusting for respiration rate showed that HR D2 was associated with chronic stress (r=-.35, p=.019). Differential effects of chronic and short-term stress were observed on several HRV measures. HR D2 decreased under both stress conditions reflecting lowered functionality of the cardiac pacemaker. The results confirm the importance of complexity metrics in modern stress research on HRV.
Tan, Li Kuo; Liew, Yih Miin; Lim, Einly; McLaughlin, Robert A
2017-07-01
Automated left ventricular (LV) segmentation is crucial for efficient quantification of cardiac function and morphology to aid subsequent management of cardiac pathologies. In this paper, we parameterize the complete (all short axis slices and phases) LV segmentation task in terms of the radial distances between the LV centerpoint and the endo- and epicardial contours in polar space. We then utilize convolutional neural network regression to infer these parameters. Utilizing parameter regression, as opposed to conventional pixel classification, allows the network to inherently reflect domain-specific physical constraints. We have benchmarked our approach primarily against the publicly-available left ventricle segmentation challenge (LVSC) dataset, which consists of 100 training and 100 validation cardiac MRI cases representing a heterogeneous mix of cardiac pathologies and imaging parameters across multiple centers. Our approach attained a .77 Jaccard index, which is the highest published overall result in comparison to other automated algorithms. To test general applicability, we also evaluated against the Kaggle Second Annual Data Science Bowl, where the evaluation metric was the indirect clinical measures of LV volume rather than direct myocardial contours. Our approach attained a Continuous Ranked Probability Score (CRPS) of .0124, which would have ranked tenth in the original challenge. With this we demonstrate the effectiveness of convolutional neural network regression paired with domain-specific features in clinical segmentation. Copyright © 2017 Elsevier B.V. All rights reserved.
Gong, Haibin; Li, Yanfei; Wang, Lei; Lv, Qian; Wang, Xiuli
2016-09-01
The study was conducted to examine the effects of ICI 118,551 on the systolic function of cardiac muscle cells of rats in heart failure and determine the molecular mechanism of selective β2-adrenergic receptor (β2-AR) antagonist on these cells. The chronic heart failure model for rats was prepared through abdominal aortic constriction and separate cardiac muscle cells using the collagenase digestion method. The rats were then divided into Sham, HF and HF+ICI 50 nM goups and cultivated for 48 h. β2-AR, Gi/Gs and sarcoplasmic reticulum Ca 2+ -ATPase (SERCA2a) protein expression levels in the cardiac muscle cells were evaluated by western blotting and changes in the systolic function of cardiac muscle cells based on the boundary detection system of contraction dynamics for individual cells was measured. The results showed that compared with the Sham group, the survival rate, percentage of basic contraction and maximum contraction amplitude percentage of cardiac muscle cells with heart failure decreased, Gi protein expression increased while Gs and SERCA2a protein expression decreased. Compared with the HF group, the maximum contraction amplitude percentage of cardiac muscle cells in group HF+ICI 50 nM decreased, the Gi protein expression level increased while the SERCA2a protein expression level decreased. Following the stimulation of Ca 2+ and ISO, the maximum contraction amplitude percentage of cardiac muscle cells in the HF+ICI 50 nM group was lower than that in group HF. This indicated that ICI 118,551 has negative inotropic effects on cardiac muscle cells with heart failure, which may be related to Gi protein. Systolic function of cardiac muscle cells with heart failure can therefore be reduced by increasing Gi protein expression and lowering SERCA2a protein expression.
RATIONALE: Exposure to ambient particulate matter (PM) and ozone has been associated with cardiovascular disease (CVD). However, the mechanisms linking PM and ozone exposure to CVD remain poorly understood .OBJECTIVE: This study explored associations between short-term exposures ...
Naess, Halvor; Romi, Fredrik
2011-01-01
To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis.
Naess, Halvor; Romi, Fredrik
2011-01-01
Background: To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Methods: Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Results: Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Conclusion: Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis. PMID:21915166
Laher, Ismail; Beam, Julianne; Botta, Amy; Barendregt, Rebekah; Sulistyoningrum, Dian; Devlin, Angela; Rheault, Mark; Ghosh, Sanjoy
2013-01-01
Moderate exercise improves cardiac antioxidant status in young humans and animals with Type-2 diabetes (T2D). Given that both diabetes and advancing age synergistically decrease antioxidant expression in most tissues, it is unclear whether exercise can upregulate cardiac antioxidants in chronic animal models of T2D. To this end, 8-month-old T2D and normoglycemic mice were exercised for 3 weeks, and cardiac redox status was evaluated. As expected, moderate exercise increased cardiac antioxidants and attenuated oxidative damage in normoglycemic mice. In contrast, similar exercise protocol in 8-month-old db/db mice worsened cardiac oxidative damage, which was associated with a specific dysregulation of glutathione (GSH) homeostasis. Expression of enzymes for GSH biosynthesis [γ-glutamylcysteine synthase, glutathione reductase] as well as for GSH-mediated detoxification (glutathione peroxidase, glutathione-S-transferase) was lower, while toxic metabolites dependent on GSH for clearance (4-hydroxynonenal) were increased in exercised diabetic mice hearts. To validate GSH loss as an important factor for such aggravated damage, daily administration of GSH restored cardiac GSH levels in exercised diabetic mice. Such supplementation attenuated both oxidative damage and fibrotic changes in the myocardium. Expression of transforming growth factor beta (TGF-β) and its regulated genes which are responsible for such profibrotic changes were also attenuated with GSH supplementation. These novel findings in a long-term T2D animal model demonstrate that short-term exercise by itself can deplete cardiac GSH and aggravate cardiac oxidative stress. As GSH administration conferred protection in 8-month-old diabetic mice undergoing exercise, supplementation with GSH-enhancing agents may be beneficial in elderly diabetic patients undergoing exercise.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Blanck, Oliver, E-mail: oliver.blanck@uksh.de; CyberKnife Center Northern Germany, Guestrow; Bode, Frank
Purpose: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. Methods and Materials: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm{sup 3}). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. Results: Transmural scarringmore » of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. Conclusions: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.« less
Influenza epidemics, seasonality, and the effects of cold weather on cardiac mortality
2012-01-01
Background More people die in the winter from cardiac disease, and there are competing hypotheses to explain this. The authors conducted a study in 48 US cities to determine how much of the seasonal pattern in cardiac deaths could be explained by influenza epidemics, whether that allowed a more parsimonious control for season than traditional spline models, and whether such control changed the short term association with temperature. Methods The authors obtained counts of daily cardiac deaths and of emergency hospital admissions of the elderly for influenza during 1992–2000. Quasi-Poisson regression models were conducted estimating the association between daily cardiac mortality, and temperature. Results Controlling for influenza admissions provided a more parsimonious model with better Generalized Cross-Validation, lower residual serial correlation, and better captured Winter peaks. The temperature-response function was not greatly affected by adjusting for influenza. The pooled estimated increase in risk for a temperature decrease from 0 to −5°C was 1.6% (95% confidence interval (CI) 1.1-2.1%). Influenza accounted for 2.3% of cardiac deaths over this period. Conclusions The results suggest that including epidemic data explained most of the irregular seasonal pattern (about 18% of the total seasonal variation), allowing more parsimonious models than when adjusting for seasonality only with smooth functions of time. The effect of cold temperature is not confounded by epidemics. PMID:23025494
NASA Technical Reports Server (NTRS)
Huikuri, H. V.; Makikallio, T. H.; Peng, C. K.; Goldberger, A. L.; Hintze, U.; Moller, M.
2000-01-01
BACKGROUND: Preliminary data suggest that the analysis of R-R interval variability by fractal analysis methods may provide clinically useful information on patients with heart failure. The purpose of this study was to compare the prognostic power of new fractal and traditional measures of R-R interval variability as predictors of death after acute myocardial infarction. METHODS AND RESULTS: Time and frequency domain heart rate (HR) variability measures, along with short- and long-term correlation (fractal) properties of R-R intervals (exponents alpha(1) and alpha(2)) and power-law scaling of the power spectra (exponent beta), were assessed from 24-hour Holter recordings in 446 survivors of acute myocardial infarction with a depressed left ventricular function (ejection fraction =35%). During a mean+/-SD follow-up period of 685+/-360 days, 114 patients died (25.6%), with 75 deaths classified as arrhythmic (17.0%) and 28 as nonarrhythmic (6.3%) cardiac deaths. Several traditional and fractal measures of R-R interval variability were significant univariate predictors of all-cause mortality. Reduced short-term scaling exponent alpha(1) was the most powerful R-R interval variability measure as a predictor of all-cause mortality (alpha(1) <0.75, relative risk 3.0, 95% confidence interval 2.5 to 4.2, P<0.001). It remained an independent predictor of death (P<0.001) after adjustment for other postinfarction risk markers, such as age, ejection fraction, NYHA class, and medication. Reduced alpha(1) predicted both arrhythmic death (P<0.001) and nonarrhythmic cardiac death (P<0.001). CONCLUSIONS: Analysis of the fractal characteristics of short-term R-R interval dynamics yields more powerful prognostic information than the traditional measures of HR variability among patients with depressed left ventricular function after an acute myocardial infarction.
Parrinello, Gaspare; Paterna, Salvatore; Torres, Daniele; Di Pasquale, Pietro; Mezzero, Manuela; La Rocca, Gabriella; Cardillo, Mauro; Trapanese, Caterina; Caradonna, Mario; Licata, Giuseppe
2009-01-01
Hypertension is a significant cause of chronic renal injury and its effective treatment is capable of reducing the rate of renal failure. beta-Adrenoceptor antagonists (beta-blockers) have been reported to induce a deterioration in renal function, while several data have indicated a renoprotective effect of treatment with the angiotensin II type 1 receptor antagonist losartan. Previous studies of the interaction between the selective beta(1)-blocker bisoprolol and kidney function were performed only for short- and medium-term periods. The aim of this study was to compare the antihypertensive efficacy and renal and cardiac haemodynamic effects of bisoprolol with those of losartan over a 1-year time period in patients with essential hypertension. Seventy-two patients (40 males) with recently diagnosed uncomplicated (European Society of Hypertension [ESH] criteria stage 1-2) hypertension (mean +/- SD age 52 +/- 12 years) were enrolled in the study. After a run-in period of 14 days on placebo, the patients were randomized in a double-blind, prospective study to receive either bisoprolol 5 mg or losartan 50 mg, administered once daily for 1 year. At recruitment and 12 months after treatment, cardiac output and renal haemodynamics and function were evaluated by echocardiography and radionuclide studies, respectively. There were no significant differences in baseline clinical data, including glomerular filtration rate and blood pressure, between the two treatment groups. At 1 year, blood pressure had decreased significantly (p < 0.001) with both treatments, and heart rate was reduced only in the group taking bisoprolol. The long-term effects on renal haemodynamics and cardiac function were similar with both drugs, the only change being a significant reduction in the filtration fraction for each group. These data suggest that both bisoprolol and losartan are effective agents for the treatment of patients with recently diagnosed ESH stage 1-2 hypertension. Over a 1-year period, both agents maintained good renal and cardiac performance and haemodynamics.
Effect of HeartMate left ventricular assist device on cardiac autonomic nervous activity.
Kim, S Y; Montoya, A; Zbilut, J P; Mawulawde, K; Sullivan, H J; Lonchyna, V A; Terrell, M R; Pifarré, R
1996-02-01
Clinical performance of a left ventricular assist device is assessed via hemodynamic parameters and end-organ function. This study examined effect of a left ventricular assist device on human neurophysiology. This study evaluated the time course change of cardiac autonomic activity of 3 patients during support with a left ventricular assist device before cardiac transplantation. Cardiac autonomic activity was determined by power spectral analysis of short-term heart rate variability. The heart rate variability before cardiac transplantation was compared with that on the day before left ventricular assist device implantation. The standard deviation of the mean of the R-R intervals of the electrocardiogram, an index of vagal activity, increased to 27 +/- 7 ms from 8 +/- 0.6 ms. The modulus of power spectral components increased. Low frequency (sympathetic activity) and high frequency power (vagal activity) increased by a mean of 9 and 22 times of each baseline value (low frequency power, 5.2 +/- 3.0 ms2; high frequency power, 2.1 +/- 0.7 ms2). The low over high frequency power ratio decreased substantially, indicating an improvement of cardiac sympatho-vagal balance. The study results suggest that left ventricular assist device support before cardiac transplantation may exert a favorable effect on cardiac autonomic control in patients with severe heart failure.
Datta, Kaberi; Basak, Trayambak; Varshney, Swati; Sengupta, Shantanu; Sarkar, Sagartirtha
2017-01-30
Myocardial infarction is one of the leading causes of cardiac dysfunction, failure and sudden death. Post infarction cardiac remodeling presents a poor prognosis, with 30%-45% of patients developing heart failure, in a period of 5-25years. Oxidative stress has been labelled as the primary causative factor for cardiac damage during infarction, however, the impact it may have during the process of post infarction remodeling has not been well probed. In this study, we have implemented iTRAQ proteomics to catalogue proteins and functional processes, participating both temporally (early and late phases) and spatially (infarct and remote zones), during post myocardial infarction remodeling of the heart as functions of the differential oxidative stress manifest during the remodeling process. Cardiac metabolism was the dominant network to be affected during infarction and the remodeling time points considered in this study. A distinctive expression pattern of cytoskeletal proteins was also observed with increased remodeling time points. Further, it was found that the cytoskeletal protein Desmin, aggregated in the infarct zone during the remodeling process, mediated by the protease Calpain1. Taken together, all of these data in conjunction may lay the foundation to understand the effects of oxidative stress on the remodeling process and elaborate the mechanism behind the compromised cardiac function observed during post myocardial infarction remodeling. Oxidative stress is the major driving force for cardiac damage during myocardial infarction. However, the impact of oxidative stress on the process of post MI remodeling in conducting the heart towards functional failure has not been well explored. In this study, a spatial and temporal approach was taken to elaborate the major proteins and cellular processes involved in post MI remodeling. Based on level/ intensity of ROS, spatially, infarct and noninfarct zones were chosen for analysis while on the temporal scale, early (30days) and late time points (120days) post MI were included in the study. This design enabled us to delineate the differential protein expression on a spectrum of maximum oxidative stress at infarct zone during MI to minimum oxidative stress at noninfarct zone during late time point post MI. The proteome profiles for each of the study groups when comparatively analysed gave a holistic idea about the dominant cellular processes involved in post MI remodeling such as cardiac metabolism, both for short term and long term remodeling as well as unique processes such as Desmin mediated cytoskeletal remodeling of the infarcted myocardium that are involved in the compromise of cardiac function. Copyright © 2016 Elsevier B.V. All rights reserved.
Long-Term Heart Transplant Survival by Targeting the Ionotropic Purinergic Receptor P2X7
Vergani, Andrea; Tezza, Sara; D’Addio, Francesca; Fotino, Carmen; Liu, Kaifeng; Niewczas, Monika; Bassi, Roberto; Molano, R. Damaris; Kleffel, Sonja; Petrelli, Alessandra; Soleti, Antonio; Ammirati, Enrico; Frigerio, Maria; Visner, Gary; Grassi, Fabio; Ferrero, Maria E.; Corradi, Domenico; Abdi, Reza; Ricordi, Camillo; Sayegh, Mohamed H.; Pileggi, Antonello; Fiorina, Paolo
2013-01-01
Background Heart transplantation is a lifesaving procedure for patients with end-stage heart failure. Despite much effort and advances in the field, current immunosuppressive regimens are still associated with poor long-term cardiac allograft outcomes as well as with the development of complications including infections and malignancies. The development of a novel, short-term and effective immunomodulatory protocol will thus be an important achievement. The purine adenosine 5′-triphosphate (ATP), released during cell damage/activation, is sensed by the ionotropic purinergic receptor P2X7 (P2X7R) on lymphocytes and regulates T cell activation. Novel clinical-grade P2X7R inhibitors are available, rendering the targeting of P2X7R a potential therapy in cardiac transplantation. Methods and Results We analyzed P2X7R expression in patients and mice and P2X7R targeting in murine recipients in the context of cardiac transplantation. Our data demonstrate that P2X7R is specifically upregulated in graft-infiltrating lymphocytes in cardiac-transplanted humans and mice. Short-term P2X7R targeting with periodate-oxidized ATP (oATP) promotes long-term cardiac transplant survival in 80% of murine recipients of a fully mismatched allograft. Long-term survival of cardiac transplants was associated with reduced T cell activation, Th1/Th17 differentiation and inhibition of STAT3 phosphorylation in T cells, thus leading to a reduced transplant infiltrate and coronaropathy. In vitro genetic upregulation of the P2X7R pathway was also shown to stimulate Th1/Th17 cell generation. Finally, P2X7R targeting halted the progression of coronaropathy in a murine model of chronic rejection as well. Conclusions P2X7R targeting is a novel clinically relevant strategy to prolong cardiac transplant survival. PMID:23250993
Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing.
Kuo, Anderson H; Li, Cun; Li, Jinqi; Huber, Hillary F; Nathanielsz, Peter W; Clarke, Geoffrey D
2017-02-15
Rodent models of intrauterine growth restriction (IUGR) successfully identify mechanisms that can lead to short-term and long-term detrimental cardiomyopathies but differences between rodent and human cardiac physiology and placental-fetal development indicate a need for models in precocial species for translation to human development. We developed a baboon model for IUGR studies using a moderate 30% global calorie restriction of pregnant mothers and used cardiac magnetic resonance imaging to evaluate offspring heart function in early adulthood. Impaired diastolic and systolic cardiac function was observed in IUGR offspring with differences between male and female subjects, compared to their respective controls. Aspects of cardiac impairment found in the IUGR offspring were similar to those found in normal controls in a geriatric cohort. Understanding early cardiac biomarkers of IUGR using non-invasive imaging in this susceptible population, especially taking into account sexual dimorphisms, will aid recognition of the clinical presentation, development of biomarkers suitable for use in humans and management of treatment strategies. Extensive rodent studies have shown that reduced perinatal nutrition programmes chronic cardiovascular disease. To enable translation to humans, we developed baboon offspring cohorts from mothers fed ad libitum (control) or 70% of the control ad libitum diet in pregnancy and lactation, which were growth restricted at birth. We hypothesized that intrauterine growth restriction (IUGR) offspring hearts would show impaired function and a premature ageing phenotype. We studied IUGR baboons (8 male, 8 female, 5.7 years), control offspring (8 male, 8 female, 5.6 years - human equivalent approximately 25 years), and normal elderly (OLD) baboons (6 male, 6 female, mean 15.9 years). Left ventricular (LV) morphology and systolic and diastolic function were evaluated with cardiac MRI and normalized to body surface area. Two-way ANOVA by group and sex (with P < 0.05) indicated ejection fraction, 3D sphericity indices, cardiac index, normalized systolic volume, normalized LV wall thickness, and average filling rate differed by group. Group and sex differences were found for normalized LV wall thickening and normalized myocardial mass, without interactions. Normalized peak LV filling rate and diastolic sphericity index were not correlated in control but strongly correlated in OLD and IUGR baboons. IUGR programming in baboons produces myocardial remodelling, reduces systolic and diastolic function, and results in the emergence of a premature ageing phenotype in the heart. To our knowledge, this is the first demonstration of the specific characteristics of cardiac programming and early life functional decline with ageing in an IUGR non-human primate model. Further studies across the life span will determine progression of cardiac dysfunction. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
Hamon, David; Rajendran, Pradeep S.; Chui, Ray W.; Ajijola, Olujimi A.; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S.; Armour, J. Andrew; Ardell, Jeffrey L.; Shivkumar, Kalyanam
2017-01-01
Background Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system (ICNS), a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on ICNS function in generating cardiac neuronal and electrical instability using a novel cardio-neural mapping approach. Methods and Results In a porcine model (n=8) neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli (P<0.001). Compared to fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response (P<0.05 versus short CI), particularly on convergent neurons (P<0.05), as well as neurons receiving sympathetic (P<0.05) and parasympathetic input (P<0.05). The greatest cardiac electrical instability was also observed following variable (short) CI PVCs. Conclusions Variable CI PVCs affect critical populations of ICNS neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling leading to cardiomyopathy. PMID:28408652
Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong
2006-10-03
We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.
Katano, Satoshi; Hashimoto, Akiyoshi; Ohori, Katsuhiko; Watanabe, Ayako; Honma, Remi; Yanase, Rimi; Ishigo, Tomoyuki; Fujito, Takefumi; Ohnishi, Hirofumi; Tsuchihashi, Kazufumi; Ishiai, Sumio; Miura, Tetsuji
2018-05-25
Whether the short-term effect of cardiac rehabilitation (CR) in elderly patients with heart failure (HF) is influenced by nutritional status is uncertain, so the present study investigated the effect of nutritional status on functional recovery after CR in elderly HF inpatients.Methods and Results:We enrolled 145 patients admitted for treatment of HF who were aged ≥65 years and had a low functional status defined as a Barthel index (BI) score ≤85 points at the commencement of CR. Nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF) and total energy intake per day. The primary endpoint was functional status determined by the BI score at discharge. The median CR period was 20 days (interquartile range: 14-34 days), and 87 patients (60%) were functionally dependent (BI score ≤85) at discharge. Multivariate logistic regression analysis showed that MNA-SF score (odds ratio [OR]: 0.76, P=0.02) and total energy intake at the commencement of CR (OR: 0.91, P=0.02) were independent predictors of functional dependence after CR. MNA-SF score ≤7 and total energy intake ≤24.5 kcal/kg/day predicted functional dependence at discharge with moderate sensitivity and specificity. MNA-SF score and total energy intake at the commencement of CR are novel predictors of the extent of functional recovery of elderly HF inpatients after in-hospital CR.
FINE PARTICLE EXPOSURE IS ASSOCIATED WITH ALTERED VENTRICULAR REPOLARIZATION
Exposure to fine airborne particulate matter (PM2.5) has previously been associated with cardiac events, especially in older people with cardiovascular disease and in diabetics. This study examined the cardiac effects of short-term exposures to ambient PM2.5 in a prospective pane...
Early detection of acute kidney injury after pediatric cardiac surgery
Jefferies, John Lynn; Devarajan, Prasad
2016-01-01
Acute kidney injury (AKI) is increasingly recognized as a common problem in children undergoing cardiac surgery, with well documented increases in morbidity and mortality in both the short and the long term. Traditional approaches to the identification of AKI such as changes in serum creatinine have revealed a large incidence in this population with significant negative impact on clinical outcomes. However, the traditional diagnostic approaches to AKI diagnosis have inherent limitations that may lead to under-diagnosis of this pathologic process. There is a dearth of randomized controlled trials for the prevention and treatment of AKI associated with cardiac surgery, at least in part due to the paucity of early predictive biomarkers. Novel non-invasive biomarkers have ushered in a new era that allows for earlier detection of AKI. With these new diagnostic tools, a more consistent approach can be employed across centers that may facilitate a more accurate representation of the actual prevalence of AKI and more importantly, clinical investigation that may minimize the occurrence of AKI following pediatric cardiac surgery. A thoughtful management approach is necessary to mitigate the effects of AKI after cardiac surgery, which is best accomplished in close collaboration with pediatric nephrologists. Long-term surveillance for improvement in kidney function and potential development of chronic kidney disease should also be a part of the comprehensive management strategy. PMID:27429538
Kwun, Jean; Farris, Alton B; Song, Hyunjin; Mahle, William T; Burlingham, William J; Knechtle, Stuart J
2015-12-01
Blocking leukocyte function-associated antigen (LFA)-1 in organ transplant recipients prolongs allograft survival. However, the precise mechanisms underlying the therapeutic potential of LFA-1 blockade in preventing chronic rejection are not fully elucidated. Cardiac allograft vasculopathy (CAV) is the preeminent cause of late cardiac allograft failure characterized histologically by concentric intimal hyperplasia. Anti-LFA-1 monoclonal antibody was used in a multiple minor antigen-mismatched, BALB.B (H-2B) to C57BL/6 (H-2B), cardiac allograft model. Endogenous donor-specific CD8 T cells were tracked down using major histocompatibility complex multimers against the immunodominant H4, H7, H13, H28, and H60 minor Ags. The LFA-1 blockade prevented acute rejection and preserved palpable beating quality with reduced CD8 T-cell graft infiltration. Interestingly, less CD8 T cell infiltration was secondary to reduction of T-cell expansion rather than less trafficking. The LFA-1 blockade significantly suppressed the clonal expansion of minor histocompatibility antigen-specific CD8 T cells during the expansion and contraction phase. The CAV development was evaluated with morphometric analysis at postoperation day 100. The LFA-1 blockade profoundly attenuated neointimal hyperplasia (61.6 vs 23.8%; P < 0.05), CAV-affected vessel number (55.3 vs 15.9%; P < 0.05), and myocardial fibrosis (grade 3.29 vs 1.8; P < 0.05). Finally, short-term LFA-1 blockade promoted long-term donor-specific regulation, which resulted in attenuated transplant arteriosclerosis. Taken together, LFA-1 blockade inhibits initial endogenous alloreactive T-cell expansion and induces more regulation. Such a mechanism supports a pulse tolerance induction strategy with anti-LFA-1 rather than long-term treatment.
Bellomo, Rinaldo; Suzuki, Satoshi; Marino, Bruno; Starkey, Graeme K; Chambers, Brenton; Fink, Michael A; Wang, Bao Zhong; Houston, Shane; Eastwood, Glenn; Calzavacca, Paolo; Glassford, Neil; Skene, Alison; Jones, Daryl A; Jones, Robert
2012-09-01
Liver transplantation is a major life-saving procedure, and donation after cardiac death (DCD) has increased the pool of potential liver donors. However, DCD livers are at increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to protect, evaluate and, in future, transplant DCD livers. We conducted proof-of-concept experiments using a DCD model in the pig to assess the short-term (4 hours) feasibility and functional efficacy of NELP. Using extracorporeal membrane oxygenation, parenteral nutrition, separate hepatic artery and portal vein perfusion, and physiological perfusion pressures, we achieved NELP and evidence of function (bile production, paracetamol removal, maintenance of normal ammonia and lactate levels) for 4 hours in pig livers subjected to 15 and 30 minutes of cardiac arrest before explantation. Our experiments justify further investigations of the feasibility and efficacy of human DCD liver preservation by ex-vivo perfusion.
Ribeiro, Paula A B; Boidin, Maxime; Juneau, Martin; Nigam, Anil; Gayda, Mathieu
2017-01-01
Recently, high-intensity interval training (HIIT) has emerged as an alternative and/or complementary exercise modality to continuous aerobic exercise training (CAET) in CHD patients. However, the literature contains descriptions of many HIIT protocols with different stage durations, nature of recovery and intensities. In this review, we discuss the most recent forms of validated HIIT protocols in patients with coronary heart disease (CHD) and how to prescribe and use them during short- and long-term (phase II and III) cardiac rehabilitation programs. We also compare the superior and/or equivalent short- and long-term effects of HIIT versus CAET on aerobic fitness, cardiovascular function, and quality of life; their efficiency, safety, and tolerance; and exercise adherence. Short interval HIIT was found beneficial for CHD patients with lower aerobic fitness and would ideally be used in initiation and improvement stages. Medium and/or long interval HIIT protocols may be beneficial for CHD patients with higher aerobic fitness, and would be ideally used in the improvement and maintenance stages because of their high physiological stimulus. Finally, we propose progressive individualized models of HIIT programs (phase II to III) for patients with CHD and how to ideally use them according to the clinical status of patients and phase of the cardiac rehabilitation program. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Acute pulmonary effects of nitrogen dioxide exposure during exercise in competitive athletes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, S.U.; Koenig, J.Q.; Pierson, W.E.
The acute pulmonary responses of athletes after short-term exposure to ambient concentrations of NO{sub 2} during heavy exercise have been examined. Intercollegiate male athletes were screened for history of cardiac disease, respiratory disease, allergic conditions and extensive exposure to pollutants. After completion of serum IgE level determination, exercise tolerance test and methacholine challenge test with normal results, nine healthy subjects 18 to 23 years of age were exposed to filtered air and to 0.18 and 0.30 ppm NO{sub 2} for 30 min on different days while exercising on a treadmill. Pulmonary function parameters were measured before and after each exposure.more » In this study, no statistically significant changes were observed in FEV1, RT PEFR, and Vmax50% after exposure to 0.18 and 0.30 ppm NO{sub 2}. For these selected healthy athletes, short-term exposure to ambient NO{sub 2} levels during heavy exercise does not affect adversely the pulmonary function.« less
Mavinkurve-Groothuis, Annelies M C; Marcus, Karen A; Pourier, Milanthy; Loonen, Jacqueline; Feuth, Ton; Hoogerbrugge, Peter M; de Korte, Chris L; Kapusta, Livia
2013-06-01
The aim of this study was to investigate myocardial 2D strain echocardiography and cardiac biomarkers in the assessment of cardiac function in children with acute lymphoblastic leukaemia (ALL) during and shortly after treatment with anthracyclines. Cardiac function of 60 children with ALL was prospectively studied with measurements of cardiac troponin T (cTnT) and N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) and conventional and myocardial 2D strain echocardiography before start (T = 0), after 3 months (T = 1), and after 1 year (T = 2), and were compared with 60 healthy age-matched controls. None of the patients showed clinical signs of cardiac failure or abnormal fractional shortening. Cardiac function decreased significantly during treatment and was significantly decreased compared with normal controls. Cardiac troponin T levels were abnormal in 11% of the patients at T = 1 and were significantly related to increased time to global peak systolic longitudinal strain at T = 2 (P = 0.003). N-terminal-pro-brain natriuretic peptide levels were abnormal in 13% of patients at T = 1 and in 20% at T = 2, absolute values increased throughout treatment in 59%. Predictors for abnormal NT-pro-BNP at T = 2 were abnormal NT-pro-BNP at T = 0 and T = 1, for abnormal myocardial 2D strain parameters at T = 2 cumulative anthracycline dose and z-score of the diastolic left ventricular internal diameter at baseline. Children with newly diagnosed ALL showed decline of systolic and diastolic function during treatment with anthracyclines using cardiac biomarkers and myocardial 2D strain echocardiography. N-terminal-pro-brain natriuretic peptide levels were not related to echocardiographic strain parameters and cTnT was not a predictor for abnormal strain at T = 2.Therefore, the combination of cardiac biomarkers and myocardial 2D strain echocardiography is important in the assessment of cardiac function of children with ALL treated with anthracyclines.
Rubio-Muñoz, J J; Pérez-Redondo, M; Alcántara-Carmona, S; Lipperheide-Vallhonrat, I; Fernández-Simón, I; Valdivia-de la Fuente, M; Villanueva-Fernández, H; Balandín-Moreno, B; Ortega-López, A; Romera-Ortega, M A; Galdos-Anuncibay, P
2014-03-01
To present our experience with the implementation of a donation protocol following controlled cardiac death (Maastricht type III donation). A retrospective descriptive and observational study was made. Intensive Care Unit of a third-level university hospital. Eight patients in an irreversible state, in which withdrawal of all life support had been agreed, were evaluated as potential donors. Application of the adopted protocol. Clinical data of donors, evaluation of a donation protocol following cardiac death, warm ischemia times, and short-term outcome of the recipients. Eight patients were evaluated. In one case donation was not possible because no cardiac arrest developed in the 120 minutes after extubation. The 7 remaining patients were effective kidney donors. Warm ischemia times were less than 23 minutes in all cases. Although 7 of the 14 recipients suffered delayed graft function, all of them achieved good renal function. Donation after cardiac death in patients in an overwhelming and irreversible state represents a potential source of donors not previously considered in this country. The prior development of a consensus-based protocol can help increase the number of organs in combination with those obtained after brain death. In our experience, the results of kidney transplants obtained from donors after cardiac death are good, and the success of these types of protocols could be extended to other organs such as the liver and lungs. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.
Iliescu, Radu
2012-01-01
Device-based therapy for resistant hypertension by electrical activation of the carotid baroreflex is currently undergoing active clinical investigation, and initial findings from clinical trials have been published. The purpose of this mini-review is to summarize the experimental studies that have provided a conceptual understanding of the mechanisms that account for the long-term lowering of arterial pressure with baroreflex activation. The well established mechanisms mediating the role of the baroreflex in short-term regulation of arterial pressure by rapid changes in peripheral resistance and cardiac function are often extended to long-term pressure control, and the more sluggish actions of the baroreflex on renal excretory function are often not taken into consideration. However, because clinical, experimental, and theoretical evidence indicates that the kidneys play a dominant role in long-term control of arterial pressure, this review focuses on the mechanisms that link baroreflex-mediated reductions in central sympathetic outflow with increases in renal excretory function that lead to sustained reductions in arterial pressure. PMID:22797307
The Short-Term Effects of Ketogenic Diet on Cardiac Ventricular Functions in Epileptic Children.
Doksöz, Önder; Çeleğen, Kübra; Güzel, Orkide; Yılmaz, Ünsal; Uysal, Utku; İşgüder, Rana; Çeleğen, Mehmet; Meşe, Timur
2015-09-01
Our primary aim was to determine the short-term effects of a ketogenic diet on cardiac ventricular function in patients with refractory epilepsy. Thirty-eight drug-resistant epileptic patients who were treated with a ketogenic diet were enrolled in this prospective study. Echocardiography was performed on all patients before beginning the ketogenic diet and after the sixth month of therapy. Two-dimensional, M-mode, color flow, spectral Doppler, and pulsed-wave tissue Doppler imaging measurements were performed on all patients. The median age of the 32 patients was 45.5 months, and 22 (57.8%) of them were male. Body weight, height, and body mass index increased significantly at the sixth month of therapy when compared with baseline values (P < 0.05). Baseline variables assessed by conventional M-mode echocardiography showed no significant difference at month 6 (P > 0.05). Doppler flow indices of mitral annulus and tricuspid annulus velocity of patients at baseline and month 6 showed no significant differences (P > 0.05). Tricuspid annular E/A ratio was lower at month 6 (P < 0.05). Although mitral annulus tissue Doppler imaging studies showed no significant difference (P > 0.05), there was a decrease in Ea velocity and Ea/Aa ratio gathered from tricuspid annulus at month 6 compared with baseline (P < 0.05). A 6-month duration ketogenic diet does not impair left ventricular functions in children with refractory epilepsy; however, it may be associated with a right ventricular diastolic dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.
From door to recovery: a collaborative approach to the development of a post-cardiac arrest center.
Williams, Donna; Calder, Shelley; Cocchi, Michael N; Donnino, Michael W
2013-10-01
Out-of-hospital cardiac arrest remains common and, despite advances in resuscitation practices, continues to carry a high mortality that may be influenced by several factors, including where a patient is cared for after the cardiac arrest. Implementing a post-cardiac arrest care guideline for survivors of out-of-hospital and in-hospital cardiac arrest involves a multidisciplinary approach with short-term and long-term strategies. Physician and nursing leaders must work in synergy to guide the implementation of an evidence-based plan of care. A collaborative approach was used at a hospital to develop processes, build consensus for protocols, and provide support to staff and teams. A joint approach has allowed the hospital to move from traditional silos of individual departmental care to a continuum of patient-focused management after cardiac arrest. This care coordination is initiated in the emergency department and follows the patient through to discharge.
Richer, Stuart; Patel, Shana; Sockanathan, Shivani; Ulanski, Lawrence J.; Miller, Luke; Podella, Carla
2014-01-01
Background: Longevinex® (L/RV) is a low dose hormetic over-the-counter (OTC) oral resveratrol (RV) based matrix of red wine solids, vitamin D3 and inositol hexaphosphate (IP6) with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD) patients. Today we report long term (two to three year) clinical efficacy. Methods: We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease). We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging) and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus). Results: We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient’s pathophysiology. No side effects were observed. Conclusions: These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities. PMID:25329968
Richer, Stuart; Patel, Shana; Sockanathan, Shivani; Ulanski, Lawrence J; Miller, Luke; Podella, Carla
2014-10-17
Longevinex® (L/RV) is a low dose hormetic over-the-counter (OTC) oral resveratrol (RV) based matrix of red wine solids, vitamin D3 and inositol hexaphosphate (IP6) with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD) patients. Today we report long term (two to three year) clinical efficacy. We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease). We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging) and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus). We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient's pathophysiology. No side effects were observed. These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities.
NASA Astrophysics Data System (ADS)
Wendell, David C.; Dholakia, Ronak J.; Larsen, Paul M.; Menon, Arjun; LaDisa, John F., Jr.
2010-03-01
Coarctation of the aorta (CoA) is associated with reduced life expectancy despite successful surgical treatment. Interestingly, much of the related long-term morbidity can be explained by abnormal hemodynamics, vascular biomechanics and cardiac function. MRI has played an important role in assessing coarctation severity, but the heterogeneity and small number of patients at each center presents an obstacle for determining causality. This work describes optimized imaging parameters to create computational fluid dynamics (CFD) models revealing changes in hemodynamics and vascular biomechanics from a rabbit model. CoA was induced surgically at 10 weeks using silk or dissolvable ligatures to replicate native and end-to-end treatment cases, respectively. Cardiac function was evaluated at 32 weeks using a fastcard SPGR sequence in 6-8 two-chamber short-axis views. Left ventricular (LV) volume, ejection fraction, and mass were quantified and compared to control rabbits. Phase contrast (PC) and angiographic MRI were used to create CFD models. Ascending aortic PCMRI data were mapped to the model inflow and outflow boundary conditions replicated measured pressure (BP) and flow. CFD simulations were performed using a stabilized finite element method to calculate indices including velocity, BP and wall shear stress (WSS). CoA models displayed higher velocity through the coarctation region and decreased velocity elsewhere, leading to decreased WSS above and below the stenosis. Pronounced wall displacement was associated with CoA-induced changes in BP. CoA caused reversible LV hypertrophy. Cardiac function was maintained, but caused a persistent hyperdynamic state. This model may now be used to investigate potential mechanisms of long-term morbidity.
Jin, Li; Lin, Ming Quan; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Ryu, Yuhee; Sun, Simei; Kee, Hae Jin; Jeong, Myung Ho
2017-07-01
Gallic acid, a natural chemical found in plants, has been reported to show antioxidant, anticancer, and anti-inflammatory effects. We investigated the efficacy of a short-term or long-term treatment with gallic acid in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive mice and the underlying regulatory mechanism. Hypertension was sufficiently induced after 2 weeks of L-NAME administration. Cardiac remodeling was assessed by echocardiography. Hypertrophic markers, transcription factors, and fibrosis-related gene expression were evaluated by quantitative real-time polymerase chain reaction and western blotting. Gallic acid effectively lowered SBP, regardless of the administration route (intraperitoneal or oral). L-NAME increased the left ventricular (LV) thickness without an increase in the total heart weight. Weekly echocardiography demonstrated that gallic acid significantly reduced LV posterior wall and septum thickness in chronic L-NAME mice from 3 to 7 weeks. The administration of gallic acid to mice showed a dual preventive and therapeutic effect on the L-NAME-induced LV remodeling. The effect was associated with the suppression of the gene expression of hypertrophy markers and the GATA-binding factor 6 (GATA6) transcription factor. Short-term or long-term treatment with gallic acid attenuated cardiac fibrosis and reduced the expression of histone deacetylase 1 and 2 in H9c2 cells and in rat primary cardiac fibroblasts, as well as in vivo. Small interfering RNA knockdown confirmed the association of these enzymes with L-NAME-induced cardiac remodeling and fibrosis. These results suggested that gallic acid may be a potential therapeutic agent for the treatment of cardiovascular diseases with hypertension and cardiac fibrosis.
Impact of elevated cardiac biomarkers on mortality after vascular surgery procedures.
Buckley, Ryan; Stevens, Scott L
2014-12-01
Concurrent cardiac disease is an important cause of morbidity and mortality in vascular surgical patients. Increasingly, cardiac biomarkers are used to identify cardiac injury in these high-risk patients. This review provides data demonstrating that perioperative troponin elevation correlates with poor short- and long-term outcomes for vascular surgical patients. In addition, the data demonstrate that patients with high circulating troponin levels fair worse than those with lower levels. Early identification of patients with cardiac injury using biomarkers allows timely diagnosis, risk stratification, and aggressive medical therapy for vascular surgical patients. Copyright © 2014 Elsevier Inc. All rights reserved.
Joint multi-object registration and segmentation of left and right cardiac ventricles in 4D cine MRI
NASA Astrophysics Data System (ADS)
Ehrhardt, Jan; Kepp, Timo; Schmidt-Richberg, Alexander; Handels, Heinz
2014-03-01
The diagnosis of cardiac function based on cine MRI requires the segmentation of cardiac structures in the images, but the problem of automatic cardiac segmentation is still open, due to the imaging characteristics of cardiac MR images and the anatomical variability of the heart. In this paper, we present a variational framework for joint segmentation and registration of multiple structures of the heart. To enable the simultaneous segmentation and registration of multiple objects, a shape prior term is introduced into a region competition approach for multi-object level set segmentation. The proposed algorithm is applied for simultaneous segmentation of the myocardium as well as the left and right ventricular blood pool in short axis cine MRI images. Two experiments are performed: first, intra-patient 4D segmentation with a given initial segmentation for one time-point in a 4D sequence, and second, a multi-atlas segmentation strategy is applied to unseen patient data. Evaluation of segmentation accuracy is done by overlap coefficients and surface distances. An evaluation based on clinical 4D cine MRI images of 25 patients shows the benefit of the combined approach compared to sole registration and sole segmentation.
Suckau, Lennart; Fechner, Henry; Chemaly, Elie; Krohn, Stefanie; Hadri, Lahouaria; Kockskämper, Jens; Westermann, Dirk; Bisping, Egbert; Ly, Hung; Wang, Xiaomin; Kawase, Yoshiaki; Chen, Jiqiu; Liang, Lifan; Sipo, Isaac; Vetter, Roland; Weger, Stefan; Kurreck, Jens; Erdmann, Volker; Tschope, Carsten; Pieske, Burkert; Lebeche, Djamel; Schultheiss, Heinz-Peter; Hajjar, Roger J.; Poller, Wolfgang Ch.
2009-01-01
Background RNA interference (RNAi) has the potential to be a novel therapeutic strategy in diverse areas of medicine. We report on targeted RNAi for the treatment of heart failure (HF), an important disorder in humans resulting from multiple etiologies. Successful treatment of HF is demonstrated in a rat model of transaortic banding by RNAi targeting of phospholamban (PLB), a key regulator of cardiac Ca2+ homeostasis. Whereas gene therapy rests on recombinant protein expression as its basic principle, RNAi therapy employs regulatory RNAs to achieve its effect. Methods and Results We describe structural requirements to obtain high RNAi activity from adenoviral (AdV) and adeno-associated virus (AAV9) vectors and show that an AdV short hairpin RNA vector (AdV-shRNA) silenced PLB in cardiomyocytes (NRCMs) and improved hemodynamics in HF rats 1 month after aortic root injection. For simplified long-term therapy we developed a dimeric cardiotropic AAV vector (rAAV9-shPLB) delivering RNAi activity to the heart via intravenous injection. Cardiac PLB protein was reduced to 25% and SERCA2a suppression in the HF groups was rescued. In contrast to traditional vectors rAAV9 shows high affinity for myocardium, but low affinity for liver and other organs. rAAV9-shPLB therapy restored diastolic (LVEDP, dp/dtmin, Tau) and systolic (fractional shortening) functional parameters to normal range. The massive cardiac dilation was normalized and the cardiac hypertrophy, cardiomyocyte diameter and cardiac fibrosis significantly reduced. Importantly, there was no evidence of microRNA deregulation or hepatotoxicity during these RNAi therapies. Conclusion Our data show, for the first time, high efficacy of an RNAi therapeutic strategy in a cardiac disease. PMID:19237664
NASA Technical Reports Server (NTRS)
Makikallio, T. H.; Hoiber, S.; Kober, L.; Torp-Pedersen, C.; Peng, C. K.; Goldberger, A. L.; Huikuri, H. V.
1999-01-01
A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR variability predict mortality in patients with depressed left ventricular (LV) function after acute myocardial infarction (AMI). Traditional time- and frequency-domain HR variability indexes along with short-term fractal-like correlation properties of RR intervals (exponent alpha) and power-law scaling (exponent beta) were studied in 159 patients with depressed LV function (ejection fraction <35%) after an AMI. By the end of 4-year follow-up, 72 patients (45%) had died and 87 (55%) were still alive. Short-term scaling exponent alpha (1.07 +/- 0.26 vs 0.90 +/- 0.26, p <0.001) and power-law slope beta (-1.35 +/- 0.23 vs -1.44 +/- 0.25, p <0.05) differed between survivors and those who died, but none of the traditional HR variability measures differed between these groups. Among all analyzed variables, reduced scaling exponent alpha (<0.85) was the best univariable predictor of mortality (relative risk 3.17, 95% confidence interval 1.96 to 5.15, p <0.0001), with positive and negative predictive accuracies of 65% and 86%, respectively. In the multivariable Cox proportional hazards analysis, mortality was independently predicted by the reduced exponent alpha (p <0.001) after adjustment for several clinical variables and LV function. A short-term fractal-like scaling exponent was the most powerful HR variability index in predicting mortality in patients with depressed LV function. Reduction in fractal correlation properties implies more random short-term HR dynamics in patients with increased risk of death after AMI.
Comparison of Echocardiographic Measurements Before and After Short and Long Duration Spaceflight
NASA Technical Reports Server (NTRS)
Fritsch-Yelle, Janice M.; South, Donna A.; Wood, Margie L.; Bungo, Michael W.
2000-01-01
Previous echocardiography studies in astronauts before and after short duration (4 - 17 days) missions have demonstrated a decrease in resting left ventricular (LV) stroke volume (SV), but maintained ejection fraction (EF) and cardiac output. Similar studies before and after long duration (129 - 144 days) spaceflight have been rare and their overall results equivocal. The purpose of this work was to compare the echocardiographic measurements (M-mode, 2-D and Doppler) from short duration (n = 13) and long duration (n = 4) crewmembers. Compared to short duration astronauts, long duration crewmembers had a significantly greater percent decrease in EF (+6+/-0.02 vs.-10.5+/-0.03, p = 0.005) and percent fractional shortening (+7+/-0.03 vs. -11+/-0.07, p = 0.0 15), and an increase in LV end systolic volume (-12+/-0.06 vs. +39+/-0.24, p = 0.011). These data suggest a reduction in cardiac function that relates to mission duration. As the changes in blood pressure and circulating blood volume (9% - 12%) are reported to be similar after short and long duration flights, the drop in EF after longer spaceflights is likely due to a decrease in cardiac function rather than altered blood volume.
Kruppel-like factor 15 is required for the cardiac adaptive response to fasting.
Sugi, Keiki; Hsieh, Paishiun N; Ilkayeva, Olga; Shelkay, Shamanthika; Moroney, Bridget; Baadh, Palvir; Haynes, Browning; Pophal, Megan; Fan, Liyan; Newgard, Christopher B; Prosdocimo, Domenick A; Jain, Mukesh K
2018-01-01
Cardiac metabolism is highly adaptive in response to changes in substrate availability, as occur during fasting. This metabolic flexibility is essential to the maintenance of contractile function and is under the control of a group of select transcriptional regulators, notably the nuclear receptor family of factors member PPARα. However, the diversity of physiologic and pathologic states through which the heart must sustain function suggests the possible existence of additional transcriptional regulators that play a role in matching cardiac metabolism to energetic demand. Here we show that cardiac KLF15 is required for the normal cardiac response to fasting. Specifically, we find that cardiac function is impaired upon fasting in systemic and cardiac specific Klf15-null mice. Further, cardiac specific Klf15-null mice display a fasting-dependent accumulation of long chain acylcarnitine species along with a decrease in expression of the carnitine translocase Slc25a20. Treatment with a diet high in short chain fatty acids relieves the KLF15-dependent long chain acylcarnitine accumulation and impaired cardiac function in response to fasting. Our observations establish KLF15 as a critical mediator of the cardiac adaptive response to fasting through its regulation of myocardial lipid utilization.
Ågren, Susanna; Berg, Sören; Svedjeholm, Rolf; Strömberg, Anna
2015-02-01
Postoperative heart failure is a serious complication that changes the lives of both the person who is critically ill and family in many ways. The purpose of this study was to evaluate the effects of an intervention in postoperative heart failure patient-partner dyads regarding health, symptoms of depression and perceived control. Pilot study with a randomised controlled design evaluating psychosocial support and education from an interdisciplinary team. Patients with postoperative heart failure and their partners. SF-36, Beck Depression Inventory, Perceived Control at baseline, 3 and 12 months. A total of 42 patient-partner completed baseline assessment. Partners in the intervention group increased health in the role emotional and mental health dimensions and patients increased health in vitality, social function and mental health dimensions compared with the control group. Patients' perceived control improved significantly in the intervention group over time. Psychoeducational support to post cardiac surgery heart failure dyads improved health in both patients and partners at short term follow-up and improved patients' perceived control at both short and long-term follow-up. Psychoeducational support appears to be a promising intervention but the results need to be confirmed in larger studies. Copyright © 2014 Elsevier Ltd. All rights reserved.
Hagen, M D; Eckman, M H; Pauker, S G
1989-01-01
A previous decision analysis examined a patient with severe CAD, diminished ventricular function, and an abdominal aortic aneurysm and also concluded that CABG followed by aneurysm repair was optimal. This patient, who had well-preserved cardiac function but severely compromised pulmonary status, stood to gain less from CABG than would a patient with more severe coronary disease, thus accounting for the "close-call" between the CABG-AAA and AAA only strategies. Nevertheless, the analysis did emphasize the benefit of aneurysm repair, whether done alone or after CABG. The analysis also highlighted the significant risk of aneurysm rupture the patient is exposed to while recovering from CABG surgery. The operative mortality risks of the two procedures are similar; thus, the patient's total operative risk is approximately doubled if he undergoes both procedures rather than aneurysm repair alone. The key question raised by the analysis is whether this double jeopardy is more than compensated by the degree to which prior CABG reduces both short-term cardiac risk at subsequent aneurysm repair and long-term cardiac mortality. For this patient, who had good cardiac function, the gains appeared sufficient to offset the interval risk of aneurysm rupture and the additional risk associated with a surgical procedures. THE REAL WORLD The patient indeed underwent and tolerated CABG, although he had a stormy prolonged postoperative course due to pulmonary failure. After discharge from the hospital, he declined readmission for repair of the aneurysm. We did not model that possibility, clearly an inadequacy in our tree. Some six months later, the patient was still alive and was, reluctantly, readmitted for aneurysmorrhaphy. At that time, however, his pulmonary function had deteriorated and both the anesthesiologist and the pulmonary consultant stated unequivocally that further surgery was now impossible. In retrospect, the expected utility of CABG without aneurysm repair (thus providing only a decrease in the long-term mortality risk from his CAD) would have been 1.95 (DEALE) or 2.06 (Markov) years. Sensitivity analysis revealed that, even if long-term cardiac risk were completely eliminated by CABG, immediate aneurysm repair would have been a better approach had the patient's physicians known he would be likely to refuse or not be a candidate for the second operation. In summary, although the patient's comorbidities did indeed place him at significant operative risk for either aneurysmorrhaphy alone or two sequential procedures, the benefits to be gained were shown to far outweigh the risks when compared with expectant observation.(ABSTRACT TRUNCATED AT 400 WORDS)
Multi-purpose ECG telemetry system.
Marouf, Mohamed; Vukomanovic, Goran; Saranovac, Lazar; Bozic, Miroslav
2017-06-19
The Electrocardiogram ECG is one of the most important non-invasive tools for cardiac diseases diagnosis. Taking advantage of the developed telecommunication infrastructure, several approaches that address the development of telemetry cardiac devices were introduced recently. Telemetry ECG devices allow easy and fast ECG monitoring of patients with suspected cardiac issues. Choosing the right device with the desired working mode, signal quality, and the device cost are still the main obstacles to massive usage of these devices. In this paper, we introduce design, implementation, and validation of a multi-purpose telemetry system for recording, transmission, and interpretation of ECG signals in different recording modes. The system consists of an ECG device, a cloud-based analysis pipeline, and accompanied mobile applications for physicians and patients. The proposed ECG device's mechanical design allows laypersons to easily record post-event short-term ECG signals, using dry electrodes without any preparation. Moreover, patients can use the device to record long-term signals in loop and holter modes, using wet electrodes. In order to overcome the problem of signal quality fluctuation due to using different electrodes types and different placements on subject's chest, customized ECG signal processing and interpretation pipeline is presented for each working mode. We present the evaluation of the novel short-term recorder design. Recording of an ECG signal was performed for 391 patients using a standard 12-leads golden standard ECG and the proposed patient-activated short-term post-event recorder. In the validation phase, a sample of validation signals followed peer review process wherein two experts annotated the signals in terms of signal acceptability for diagnosis.We found that 96% of signals allow detecting arrhythmia and other signal's abnormal changes. Additionally, we compared and presented the correlation coefficient and the automatic QRS delineation results of both short-term post-event recorder and 12-leads golden standard ECG recorder. The proposed multi-purpose ECG device allows physicians to choose the working mode of the same device according to the patient status. The proposed device was designed to allow patients to manage the technical requirements of both working modes. Post-event short-term ECG recording using the proposed design provide physicians reliable three ECG leads with direct symptom-rhythm correlation.
Buchanan, Charlotte; Mohammed, Azharuddin; Cox, Eleanor; Köhler, Katrin; Canaud, Bernard; Taal, Maarten W.; Selby, Nicholas M.; Francis, Susan
2017-01-01
Hemodynamic stress during hemodialysis (HD) results in recurrent segmental ischemic injury (myocardial stunning) that drives cumulative cardiac damage. We performed a fully comprehensive study of the cardiovascular effect of dialysis sessions using intradialytic cardiac magnetic resonance imaging (MRI) to examine the comparative acute effects of standard HD versus hemodiafiltration (HDF) in stable patients. We randomly allocated 12 patients on HD (ages 32–72 years old) to either HD or HDF. Patients were stabilized on a modality for 2 weeks before undergoing serial cardiac MRI assessment during dialysis. Patients then crossed over to the other modality and were rescanned after 2 weeks. Cardiac MRI measurements included cardiac index, stroke volume index, global and regional contractile function (myocardial strain), coronary artery flow, and myocardial perfusion. Patients had mean±SEM ultrafiltration rates of 3.8±2.9 ml/kg per hour during HD and 4.4±2.5 ml/kg per hour during HDF (P=0.29), and both modalities provided a similar degree of cooling. All measures of systolic contractile function fell during HD and HDF, with partial recovery after dialysis. All patients experienced some degree of segmental left ventricular dysfunction, with severity proportional to ultrafiltration rate and BP reduction. Myocardial perfusion decreased significantly during HD and HDF. Treatment modality did not influence any of the cardiovascular responses to dialysis. In conclusion, in this randomized, crossover study, there was no significant difference in the cardiovascular response to HDF or HD with cooled dialysate as assessed with intradialytic MRI. PMID:28122851
Reeh, Matthias; Metze, Johannes; Uzunoglu, Faik G; Nentwich, Michael; Ghadban, Tarik; Wellner, Ullrich; Bockhorn, Maximilian; Kluge, Stefan; Izbicki, Jakob R; Vashist, Yogesh K
2016-02-01
Esophageal resection in patients with esophageal cancer (EC) is still associated with high mortality and morbidity rates. We aimed to develop a simple preoperative risk score for the prediction of short-term and long-term outcomes for patients with EC treated by esophageal resection. In total, 498 patients suffering from esophageal carcinoma, who underwent esophageal resection, were included in this retrospective cohort study. Three preoperative esophagectomy risk (PER) groups were defined based on preoperative functional evaluation of different organ systems by validated tools (revised cardiac risk index, model for end-stage liver disease score, and pulmonary function test). Clinicopathological parameters, morbidity, and mortality as well as disease-free survival (DFS) and overall survival (OS) were correlated to the PER score. The PER score significantly predicted the short-term outcome of patients with EC who underwent esophageal resection. PER 2 and PER 3 patients had at least double the risk of morbidity and mortality compared to PER 1 patients. Furthermore, a higher PER score was associated with shorter DFS (P < 0.001) and OS (P < 0.001). The PER score was identified as an independent predictor of tumor recurrence (hazard ratio [HR] 2.1; P < 0.001) and OS (HR 2.2; P < 0.001). The PER score allows preoperative objective allocation of patients with EC into different risk categories for morbidity, mortality, and long-term outcomes. Thus, multicenter studies are needed for independent validation of the PER score.
Goto, Seiko; Park, Bum-Jin; Tsunetsugu, Yuko; Herrup, Karl; Miyazaki, Yoshifumi
2013-01-01
The objective of this study is to trace short-term changes in mood and heart function in elderly individuals in response to exposure to different landscaped spaces. Nineteen elderly but cognitively intact residents of an assisted living facility participated in the study. They were exposed to three landscaped spaces: a Japanese style garden, an herb garden, and a simple landscaped area planted with a single tree. To assess the effect of different landscaped spaces on older adults, individuals were monitored for mood and cardiac function in response to short exposures to spaces. Mood state was assessed using Profile of Mood States (POMS) before and after viewing the spaces. Cardiac output was assessed using a portable electrocardiograph monitor before and during the viewing. We found that the structured gardens evoked greater responses in all outcome measures. Scores on the POMS improved after observation of the two organized gardens compared to responses to the simple landscaped space with a single tree. During the observation period, heart rate was significantly lower in the Japanese garden than in the other environments, and sympathetic function was significantly lower as well. We conclude that exposure to organized gardens can affect both the mood and cardiac physiology of elderly individuals. Our data further suggest that these effects can differ depending on the types of landscape to which an individual is exposed. Elderly, Japanese garden, herb garden, heart rate, mood, healing environmentPreferred Citation: Goto, S., Park, B-J., Tsunetsugu, Y., Herrup, K., & Miyazaki, Y. (2013). The effect of garden designs on mood and heart output in older adults residing in an assisted living facility. Health Environments Research & Design Journal 6(2), pp 27-42.
Souto Bayarri, M; Masip Capdevila, L; Remuiñan Pereira, C; Suárez-Cuenca, J J; Martínez Monzonís, A; Couto Pérez, M I; Carreira Villamor, J M
2015-01-01
To compare the methods of right ventricle segmentation in the short-axis and 4-chamber planes in cardiac magnetic resonance imaging and to correlate the findings with those of the tricuspid annular plane systolic excursion (TAPSE) method in echocardiography. We used a 1.5T MRI scanner to study 26 patients with diverse cardiovascular diseases. In all MRI studies, we obtained cine-mode images from the base to the apex in both the short-axis and 4-chamber planes using steady-state free precession sequences and 6mm thick slices. In all patients, we quantified the end-diastolic volume, end-systolic volume, and the ejection fraction of the right ventricle. On the same day as the cardiac magnetic resonance imaging study, 14 patients also underwent echocardiography with TAPSE calculation of right ventricular function. No statistically significant differences were found in the volumes and function of the right ventricle calculated using the 2 segmentation methods. The correlation between the volume estimations by the two segmentation methods was excellent (r=0,95); the correlation for the ejection fraction was slightly lower (r=0,8). The correlation between the cardiac magnetic resonance imaging estimate of right ventricular ejection fraction and TAPSE was very low (r=0,2, P<.01). Both ventricular segmentation methods quantify right ventricular function adequately. The correlation with the echocardiographic method is low. Copyright © 2012 SERAM. Published by Elsevier España, S.L.U. All rights reserved.
Circuit weight training and cardiac morphology: a trial with magnetic resonance imaging.
Camargo, M D; Stein, R; Ribeiro, J P; Schvartzman, P R; Rizzatti, M O; Schaan, B D
2008-02-01
Aerobic training (AT) and circuit weight training (CWT) improve peak oxygen uptake (VO(2)peak). During CWT the circulatory system is exposed to higher pressure, which could induce left ventricle morphological adaptations, possibly distinct from those derived from aerobic training. To compare the effects of aerobic training and CWT upon morphological and functional cardiac adaptations detected by magnetic resonance imaging. Twenty healthy sedentary individuals were randomly assigned to participate in a 12-week programme of aerobic training (n = 6), CWR (n = 7) or no intervention (n = 7, controls). Training programmes consisted of 36 sessions, 35 min each, 3 times per week, at 70% of maximal heart rate, and CWT included series of resistance exercises performed at 60% of 1 maximal repetition. Cardiopulmonary exercise testing and cardiac magnetic resonance imaging were performed before and after the intervention. There was a similar improvement in VO(2)peak following aerobic training (mean (SD) increment: 12 (4)%) and CWT (12 (4)%), while there was no change in the control group. Aerobic training (12 (6)%) and CWT (16 (5)%) improved strength in the lower limbs, and only CWT resulted in improvement of 13 (4)% in the strength of the upper limbs. However, there were no detectable changes in left ventricular mass, end-diastolic volume, stroke volume or ejection fraction. In previously sedentary individuals, short-term CWT and aerobic training induce similar improvement in functional capacity without any adaptation in cardiac morphology detectable by cardiac magnetic resonance imaging.
Ultra-Short-Term Heart Rate Variability is Sensitive to Training Effects in Team Sports Players.
Nakamura, Fabio Y; Flatt, Andrew A; Pereira, Lucas A; Ramirez-Campillo, Rodrigo; Loturco, Irineu; Esco, Michael R
2015-09-01
The aim of this study was to test the possibility of the ultra-short-term lnRMSSD (measured in 1-min post-1-min stabilization period) to detect training induced adaptations in futsal players. Twenty-four elite futsal players underwent HRV assessments pre- and post-three or four weeks preseason training. From the 10-min HRV recording period, lnRMSSD was analyzed in the following time segments: 1) from 0-5 min (i.e., stabilization period); 2) from 0-1 min; 1-2 min; 2-3 min; 3-4 min; 4-5 min and; 3) from 5-10 min (i.e., criterion period). The lnRMSSD was almost certainly higher (100/00/00) using the magnitude-based inference in all periods at the post- moment. The correlation between changes in ultra-short-term lnRMSSD (i.e., 0-1 min; 1-2 min; 2-3 min; 3-4 min; 4-5 min) and lnRMSSDCriterion ranged between 0.45-0.75, with the highest value (p = 0.75; 90% CI: 0.55 - 0.85) found between ultra-short-term lnRMDSSD at 1-2 min and lnRMSSDCriterion. In conclusion, lnRMSSD determined in a short period of 1-min is sensitive to training induced changes in futsal players (based on the very large correlation to the criterion measure), and can be used to track cardiac autonomic adaptations. Key pointsThe ultra-short-term (1 min) natural log of the root-mean-square difference of successive normal RR intervals (lnRMSSD) is sensitive to training effects in futsal playersThe ultra-short-term lnRMSSD may simplify the assessment of the cardiac autonomic changes in the field compared to the traditional and lengthier (10 min duration) analysisCoaches are encouraged to implement the ultra-short-term heart rate variability in their routines to monitor team sports athletes.
Ultra-Short-Term Heart Rate Variability is Sensitive to Training Effects in Team Sports Players
Nakamura, Fabio Y.; Flatt, Andrew A.; Pereira, Lucas A.; Ramirez-Campillo, Rodrigo; Loturco, Irineu; Esco, Michael R.
2015-01-01
The aim of this study was to test the possibility of the ultra-short-term lnRMSSD (measured in 1-min post-1-min stabilization period) to detect training induced adaptations in futsal players. Twenty-four elite futsal players underwent HRV assessments pre- and post-three or four weeks preseason training. From the 10-min HRV recording period, lnRMSSD was analyzed in the following time segments: 1) from 0-5 min (i.e., stabilization period); 2) from 0-1 min; 1-2 min; 2-3 min; 3-4 min; 4-5 min and; 3) from 5-10 min (i.e., criterion period). The lnRMSSD was almost certainly higher (100/00/00) using the magnitude-based inference in all periods at the post- moment. The correlation between changes in ultra-short-term lnRMSSD (i.e., 0-1 min; 1-2 min; 2-3 min; 3-4 min; 4-5 min) and lnRMSSDCriterion ranged between 0.45-0.75, with the highest value (p = 0.75; 90% CI: 0.55 – 0.85) found between ultra-short-term lnRMDSSD at 1-2 min and lnRMSSDCriterion. In conclusion, lnRMSSD determined in a short period of 1-min is sensitive to training induced changes in futsal players (based on the very large correlation to the criterion measure), and can be used to track cardiac autonomic adaptations. Key points The ultra-short-term (1 min) natural log of the root-mean-square difference of successive normal RR intervals (lnRMSSD) is sensitive to training effects in futsal players The ultra-short-term lnRMSSD may simplify the assessment of the cardiac autonomic changes in the field compared to the traditional and lengthier (10 min duration) analysis Coaches are encouraged to implement the ultra-short-term heart rate variability in their routines to monitor team sports athletes PMID:26336347
Hall, Allison B; Ziadi, Maria C; Leech, Judith A; Chen, Shin-Yee; Burwash, Ian G; Renaud, Jennifer; deKemp, Robert A; Haddad, Haissam; Mielniczuk, Lisa M; Yoshinaga, Keiichiro; Guo, Ann; Chen, Li; Walter, Olga; Garrard, Linda; DaSilva, Jean N; Floras, John S; Beanlands, Rob S B
2014-09-09
Heart failure with reduced ejection fraction and obstructive sleep apnea (OSA), 2 states of increased metabolic demand and sympathetic nervous system activation, often coexist. Continuous positive airway pressure (CPAP), which alleviates OSA, can improve ventricular function. It is unknown whether this is due to altered oxidative metabolism or presynaptic sympathetic nerve function. We hypothesized that short-term (6-8 weeks) CPAP in patients with OSA and heart failure with reduced ejection fraction would improve myocardial sympathetic nerve function and energetics. Forty-five patients with OSA and heart failure with reduced ejection fraction (left ventricular ejection fraction 35.8±9.7% [mean±SD]) were evaluated with the use of echocardiography and 11C-acetate and 11C-hydroxyephedrine positron emission tomography before and ≈6 to 8 weeks after randomization to receive short-term CPAP (n=22) or no CPAP (n=23). Work metabolic index, an estimate of myocardial efficiency, was calculated as follows: (stroke volume index×heart rate×systolic blood pressure÷Kmono), where Kmono is the monoexponential function fit to the myocardial 11C-acetate time-activity data, reflecting oxidative metabolism. Presynaptic sympathetic nerve function was measured with the use of the 11C-hydroxyephedrine retention index. CPAP significantly increased hydroxyephedrine retention versus no CPAP (Δretention: +0.012 [0.002, 0.021] versus -0.006 [-0.013, 0.005] min(-1); P=0.003). There was no significant change in work metabolic index between groups. However, in those with more severe OSA (apnea-hypopnea index>20 events per hour), CPAP significantly increased both work metabolic index and systolic blood pressure (P<0.05). In patients with heart failure with reduced ejection fraction and OSA, short-term CPAP increased hydroxyephedrine retention, indicating improved myocardial sympathetic nerve function, but overall did not affect energetics. In those with more severe OSA, CPAP may improve cardiac efficiency. Further outcome-based investigation of the consequences of CPAP is warranted. http://www.clinicaltrials.gov. Unique identifier: NCT00756366. © 2014 American Heart Association, Inc.
Hemodynamic directed CPR improves short-term survival from asphyxia-associated cardiac arrest.
Sutton, Robert M; Friess, Stuart H; Bhalala, Utpal; Maltese, Matthew R; Naim, Maryam Y; Bratinov, George; Niles, Dana; Nadkarni, Vinay M; Becker, Lance B; Berg, Robert A
2013-05-01
Adequate coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR) is essential for establishing return of spontaneous circulation. The objective of this study was to compare short-term survival using a hemodynamic directed resuscitation strategy versus an absolute depth-guided approach in a porcine model of asphyxia-associated cardiac arrest. We hypothesized that a hemodynamic directed approach would improve short-term survival compared to depth-guided care. After 7 min of asphyxia, followed by induction of ventricular fibrillation, 19 female 3-month old swine (31±0.4 kg) were randomized to receive one of three resuscitation strategies: (1) hemodynamic directed care (CPP-20): chest compressions (CCs) with depth titrated to a target systolic blood pressure of 100 mmHg and titration of vasopressors to maintain CPP>20 mmHg; (2) depth 33 mm (D33): target CC depth of 33 mm with standard American Heart Association (AHA) epinephrine dosing; or (3) depth 51 mm (D51): target CC depth of 51 mm with standard AHA epinephrine dosing. All animals received manual CPR guided by audiovisual feedback for 10 min before first shock. 45-Min survival was higher in the CPP-20 group (6/6) compared to D33 (1/7) or D51 (1/6) groups; p=0.002. Coronary perfusion pressures were higher in the CPP-20 group compared to D33 (p=0.011) and D51 (p=0.04), and in survivors compared to non-survivors (p<0.01). Total number of vasopressor doses administered and defibrillation attempts were not different. Hemodynamic directed care targeting CPPs>20 mmHg improves short-term survival in an intensive care unit porcine model of asphyxia-associated cardiac arrest. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Clinical cardiac regenerative studies in children.
Pavo, Imre J; Michel-Behnke, Ina
2017-02-26
Although the incidence of pediatric heart failure is low, the mortality is relatively high, with severe clinical symptoms requiring repeated hospitalization or intensive care treatment in the surviving patients. Cardiac biopsy specimens have revealed a higher number of resident human cardiac progenitor cells, with greater proliferation and differentiation capacity, in the neonatal period as compared with adults, demonstrating the regeneration potential of the young heart, with rising interest in cardiac regeneration therapy in critically ill pediatric patients. We review here the available literature data, searching the MEDLINE, Google Scholar and EMBASE database for completed, and www.clinicaltrials.gov homepage for ongoing studies involving pediatric cardiac regeneration reports. Because of difficulties conducting randomized blinded clinical trials in pediatric patients, mostly case reports or cohort studies with a limited number of individuals have been published in the field of pediatric regenerative cardiology. The majority of pediatric autologous cell transplantations into the cardiac tissue have been performed in critically ill children with severe or terminal heart failure. Congenital heart disease, myocarditis, and idiopathic hypertrophic or dilated cardiomyopathy leading to congestive heart failure are some possible areas of interest for pediatric cardiac regeneration therapy. Autologous bone marrow mononuclear cells, progenitor cells, or cardiospheres have been applied either intracoronary or percutaneously intramyocardially in severely ill children, leading to a reported clinical benefit of cell-based cardiac therapies. In conclusion, compassionate use of autologous stem cell administration has led to at least short-term improvement in heart function and clinical stability in the majority of the critically ill pediatric patients.
Li, Guo-Hua; Luo, Bin; Lv, Yan-Xia; Zheng, Fei; Wang, Lu; Wei, Meng-Xi; Li, Xian-Yu; Zhang, Lei; Wang, Jia-Ning; Chen, Shi-You; Tang, Jun-Ming; He, Xiaohua
2016-05-04
To investigate whether vascular endothelial growth factor B (VEGF-B) improves myocardial survival and cardiac stem cell (CSC) function in the ischemia-reperfusion (I/R) heart and promotes CSC mobilization and angiogenesis. One hour after myocardial ischemia and infarction, rats were treated with recombinant human VEGF-B protein following 24 h or 7 days of myocardial reperfusion. Twenty-four hours after myocardial I/R, VEGF-B increased pAkt and Bcl-2 levels, reduced p-p38MAPK, LC3-II/I, beclin-1, CK, CK-MB and cTnt levels, triggered cardiomyocyte protection against I/R-induced autophagy and apoptosis, and contributed to the decrease of infarction size and the improvement of heart function during I/R. Simultaneously, an in vitro hypoxia-reoxygenation (H/R)-induced H9c2 cardiomyocyte injury model was used to mimic I/R injury model in vivo; in this model, VEGF-B decreased LDH release, blocked H/R-induced apoptosis by inhibiting cell autophagy, and these special effects could be abolished by the autophagy inducer, rapamycin. Mechanistically, VEGF-B markedly activated the Akt signaling pathway while slightly inhibiting p38MAPK, leading to the blockade of cell autophagy and thus protecting cardiomyocyte from H/R-induced activation of the intrinsic apoptotic pathway. Seven days after I/R, VEGF-B induced the expression of SDF-1α and HGF, resulting in the massive mobilization and homing of c-Kit positive cells, triggering further angiogenesis and vasculogenesis in the infracted heart and contributing to the improvement of I/R heart function. VEGF-B could contribute to a favorable short- and long-term prognosis for I/R via the dual manipulation of cardiomyocytes and CSCs.
Cardiac Electrophysiology: Normal and Ischemic Ionic Currents and the ECG
ERIC Educational Resources Information Center
Klabunde, Richard E.
2017-01-01
Basic cardiac electrophysiology is foundational to understanding normal cardiac function in terms of rate and rhythm and initiation of cardiac muscle contraction. The primary clinical tool for assessing cardiac electrical events is the electrocardiogram (ECG), which provides global and regional information on rate, rhythm, and electrical…
Andrew, Emily; Mercier, Eric; Nehme, Ziad; Bernard, Stephen; Smith, Karen
2018-05-01
Understanding the prognosis of elderly out-of-hospital cardiac arrest (OHCA) patients is vital to informing resuscitation and advanced care planning decisions. However, short-term outcomes such as survival to hospital discharge do not account for post-arrest quality of life. We describe the 12-month functional recovery and health-related quality of life (HR-QOL) of elderly OHCA survivors, including those arresting in aged care facilities. We conducted a retrospective analysis of Victorian Ambulance Cardiac Arrest Registry data for all OHCA survivors to hospital discharge aged ≥65 years between 1 January 2010 and 30 June 2016. The influence of age on functional recovery and independent living was assessed using multivariable logistic regression. During the study period, 20,103 elderly OHCAs were attended, 9016 (44.9%) of whom received a resuscitation attempt. In total, 876 (9.7%) patients survived to hospital discharge and 777 were alive 12 months post-arrest. Of these, 651 participated in 12-month follow-up (response rate 83.8%). Most (60.6%) resided at home without additional care and 66.6% reported a good functional recovery, however both measures decreased with increasing age (p < 0.001). Mental HR-QOL increased with increasing age and was significantly better than the age- and sex-matched Australian population. Each 10-year increase in age was associated with a 40.8% (95%CI 25.6-53.0%) reduction in the odds of good functional recovery, and a 65.8% (95%CI 55.8-73.5%) reduction in the odds of living independently. Of the 2575 OHCAs in an aged care facility, 2.2% survived to hospital discharge, however no patient reported a good 12-month functional recovery. Most elderly OHCA survivors resided independently with good functionality 12 months post-arrest. However, increasing age was associated with less favourable outcomes. New strategies are needed with regard to resuscitation in aged care facilities. Copyright © 2018 Elsevier B.V. All rights reserved.
Serpooshan, Vahid; Sivanesan, Senthilkumar; Huang, Xiaoran; Mahmoudi, Morteza; Malkovskiy, Andrey V.; Zhao, Mingming; Inayathullah, Mohammed; Wagh, Dhananjay; Zhang, Xuexiang J.; Metzler, Scott; Bernstein, Daniel; Wu, Joseph C.; Ruiz-Lozano, Pilar; Rajadas, Jayakumar
2017-01-01
Nanoparticle-mediated sustained delivery of therapeutics is one of the highly effective and increasingly utilized applications of nanomedicine. Here, we report the development and application of a drug delivery system consisting of polyethylene glycol (PEG)-conjugated liposomal nanoparticles as an efficient in vivo delivery approach for [Pyr1]-apelin-13 polypeptide. Apelin is an adipokine that regulates a variety of biological functions including cardiac hypertrophy and hypertrophy-induced heart failure. The clinical use of apelin has been greatly impaired by its remarkably short half-life in circulation. Here, we investigate whether [Pyr1]-apelin-13 encapsulation in liposome nanocarriers, conjugated with PEG polymer on their surface, can prolong apelin stability in the blood stream and potentiate apelin beneficial effects in cardiac function. Atomic force microscopy and dynamic light scattering were used to assess the structure and size distribution of drug-laden nanoparticles. [Pyr1]-apelin-13 encapsulation in PEGylated liposomal nanocarriers resulted in sustained and extended drug release both in vitro and in vivo. Moreover, intraperitoneal injection of [Pyr1]-apelin-13 nanocarriers in a mouse model of pressure-overload induced heart failure demonstrated a sustainable long-term effect of [Pyr1]-apelin-13 in preventing cardiac dysfunction. We concluded that this engineered nanocarrier system can serve as a delivery platform for treating heart injuries through sustained bioavailability of cardioprotective therapeutics. PMID:25443792
Hansen, Laura S; Sloth, Erik; Hjortdal, Vibeke E; Jakobsen, Carl-Johan
2015-08-01
Short-term (30 days) mortality frequently is used as an outcome measure after cardiac surgery, although it has been proposed that the follow-up period should be extended to 120 days to allow for more accurate benchmarking. The authors aimed to evaluate whether mortality rates 120 days after surgery were comparable to general mortality and to compare causes of death between the cohort and the general population. A multicenter descriptive cohort study using prospectively entered registry data. University hospital. The cohort was obtained from the Western Denmark Heart Registry and matched to the Danish National Hospital Register as well as the Danish Register of Causes of Death. A weighted, age-matched general population consisting of all Danish patients who died within the study period was identified through the central authority on Danish statistics. A total of 11,988 patients (>15 years) who underwent cardiac-surgery at Aarhus, Aalborg and Odense University Hospitals from April 1, 2006 to December 31, 2012 were included. Coronary artery bypass grafting, valve surgery and combinations. Mortality after cardiac surgery matches with mortality in the general population after 140 days. Mortality curves run almost parallel from this point onwards, regardless of The European system for cardiac operative risk evaluation (EuroSCORE) and intervention. The causes of death in the cohort differed statistically significantly from the background population (p<0.0001; one-sample t-test) throughout the first postoperative year. The leading cause of death in the cohort was cardiac (38%); 53% of which was categorized as heart failure. A total of 54% of these patients were assessed preoperatively as having normal or mildly impaired heart function (EuroSCORE). This study supported an extended follow-up period after cardiac surgery when benchmarking cardiac surgery centers. Regardless of preoperative heart function, heart failure was the consistent leading cause of death. Copyright © 2015 Elsevier Inc. All rights reserved.
Jennings, Eric; Cuadrado, Angel; Maher, Kevin O; Kogon, Brian; Kirshbom, Paul M; Simsic, Janet M
2012-02-01
Prematurity is a recognized risk factor for morbidity and mortality following cardiac surgery. The purpose of this study was to examine short-term outcomes following cardiac surgery in premature neonates adhering to our institutional philosophy of supportive care allowing for weight gain and organ maturation. Retrospective review of all neonates undergoing cardiac surgery from January 2002 to May 2008. A total of 810 neonates (<30 days of age) were identified. Prematurity defined as less than 36 weeks of gestation. Neonates undergoing ductus arteriosus ligation alone were excluded. In all, 63 neonates comprised the premature group. Term group comprised 244 randomly selected term neonates in a 1:4 ratio. Outcome variables were compared between the 2 groups. Median gestation 34 weeks, range 24 to 35 weeks. Defects: 2 ventricle, normal arch (41% premature vs 44% term; P = .7), 2 ventricle, abnormal arch (24% vs 22%; P = .8), single ventricle, normal arch (21% vs 15%; P = .2), single ventricle, abnormal arch (14% vs 19%; P = .4). Premature neonates were older and smaller at surgery. Cardiopulmonary bypass procedures were performed less frequently in premature neonates (49% vs 69%; P = .004). Length of mechanical ventilation at our institution (6 days [0.5-54) vs 4 days [0.5-49); P = .06); postoperative hospital stay at our institution (17 days [1-161) vs 15 days [0-153); P = .06); and mortality (16% vs 11%; P = .2) was not different between the 2 groups. Early outcome seems independent of weight, prematurity, cardiopulmonary bypass, and type of first intervention. Importantly, there was no statistical difference in mortality between the 2 groups, regardless of how they were treated. Further long-term follow-up is needed in this patient population.
Reddy, Yogesh N V; Obokata, Masaru; Dean, Patrick G; Melenovsky, Vojtech; Nath, Karl A; Borlaug, Barry A
2017-06-21
Short-term studies have reported left ventricular (LV) dilatation following surgical creation of arteriovenous fistulas (AVF) or arteriovenous grafts (AVGs), but chronic cardiac structural and functional changes have not been examined or related to clinical outcomes following AVF/AVG. We sought to characterize the long-term changes in cardiac structure and function in patients undergoing shunt creation for haemodialysis. A retrospective analysis was performed of patients undergoing echocardiography before and after surgical AVF/AVG creation for the initiation of haemodialysis. 137 patients underwent echocardiographic examinations prior to AVF and 2.6 years (median) after AVF creation. Following AVF and dialysis initiation, there were reductions in blood pressure, body weight and estimated plasma volume coupled with modest reverse LV remodelling. In contrast, AVF/AVG creation was associated with significant right ventricular (RV) dilatation and deterioration in RV function. Incident heart failure (HF) developed in 43% of patients in tandem with greater RV remodeling. The development of RV dilation following surgical AVF/AVG was independently associated with increased risk of death [HR 3.9, 95% CI (1.7-9.2), P = 0.001]. In long-term follow-up, RV remodelling and dysfunction develop following AVF/AVG creation and dialysis initiation, despite improved control of LV pressure load through dialysis. Deleterious effects on right heart structure and function are coupled with development of incident HF and increased risk of death. Further study is required to identify patients at greatest risk for detrimental AVF/AVG changes who may benefit from alternate forms of dialysis or potentially ligation of existing AVF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.
Changes in skeletal and cardiac muscle enzymes during the Scottish Coast to Coast Triathlon.
Denvir, M A; Galloway, P J; Meighan, A S; Blyth, M; Alexander, C; Fleming, C; Frame, F
1999-04-01
While skeletal muscle injury is common after prolonged exercise, evidence in the literature supporting cardiac muscle injury is conflicting. Creatine kinase and cardiac troponin-I were measured, in 31 amateur athletes (25 male) before, and 12-24 hours after, a 300 km cycling/running/canoe triathlon event. A short questionnaire was used to assess level of fitness, training and previous experience. Creatine kinase levels were greater after the 45 km cross-country run compared with after a 155 km road cycle (60.5 +/- 62.8 iu/L/kg vs 19.3 +/- 9.6 iu/kg, P = 0.03). Individuals performing running and cycling events consecutively had creatine kinase similar to those observed after running alone (50.2 +/- 53.8 iu/L/kg vs 60.5 +/- 62.8 iu/L/kg, P = 0.55). Cardiac troponin-I was elevated above the normal range (0.1 ng/L) in six athletes (four in running and cycling events, one in the running and one in the cycling event). We conclude that running produces significantly more skeletal muscle injury than cycling and that strenuous endurance exercise involving running and cycling in amateur trained athletes is associated with release of cardiac specific enzymes. The functional and longer term consequences of this require further study.
Burzyńska, Małgorzata; Uryga, Agnieszka; Kasprowicz, Magdalena; Kędziora, Jarosław; Szewczyk, Ewa; Woźniak, Jowita; Jarmundowicz, Włodzimierz; Kübler, Andrzej
2017-12-01
Cardiopulmonary abnormalities are common after aneurysmal subarachnoid haemorrhage (aSAH). However, the relationship between short- and long-term outcome is poorly understood. In this paper, we present how cardiac troponine elevations (cTnI) and pulmonary disorders are associated with short- and long-term outcomes assessed by the Glasgow Outcome Scale (GOS) and Extended Glasgow Outcome Scale (GOSE). A total of 104 patients diagnosed with aSAH were analysed in the study. The non-parametric U Mann-Whitney test was used to evaluate the difference between good (GOS IV-V, GOSE V-VIII) and poor (GOS I-III, GOSE I-IV) outcomes in relation to cTnI elevation and pulmonary disorders. Outcome was assessed at discharge from the hospital, and then followed up 6 and 12 months later. Pulmonary disorders were determined by the PaO 2 /FiO 2 ratio and radiography. The areas under the ROC curves (AUCs) were used to determine the predictive power of these factors. In the group with good short-term outcomes cTnI elevation on the second day after aSAH was significantly lower (p = .00007) than in patients with poor short-term outcomes. The same trend was observed after 6 months, although there were different results 12 months from the onset (p = .024 and n.s., respectively). A higher peak of cTnI was observed in the group with a pathological X-ray (p = .008) and pathological PaO 2 /FiO 2 ratio (p ≪ .001). cTnI was an accurate predictor of short-term outcomes (AUC = 0.741, p ≪ .001) and the outcome after 6 months (AUC = 0.688, p = .015). The results showed that cardiopulmonary abnormalities perform well as predictive factors for short- and long-term outcomes after aSAH.
NASA Astrophysics Data System (ADS)
Irshad, Mehreen; Muhammad, Nazeer; Sharif, Muhammad; Yasmeen, Mussarat
2018-04-01
Conventionally, cardiac MR image analysis is done manually. Automatic examination for analyzing images can replace the monotonous tasks of massive amounts of data to analyze the global and regional functions of the cardiac left ventricle (LV). This task is performed using MR images to calculate the analytic cardiac parameter like end-systolic volume, end-diastolic volume, ejection fraction, and myocardial mass, respectively. These analytic parameters depend upon genuine delineation of epicardial, endocardial, papillary muscle, and trabeculations contours. In this paper, we propose an automatic segmentation method using the sum of absolute differences technique to localize the left ventricle. Blind morphological operations are proposed to segment and detect the LV contours of the epicardium and endocardium, automatically. We test the benchmark Sunny Brook dataset for evaluation of the proposed work. Contours of epicardium and endocardium are compared quantitatively to determine contour's accuracy and observe high matching values. Similarity or overlapping of an automatic examination to the given ground truth analysis by an expert are observed with high accuracy as with an index value of 91.30% . The proposed method for automatic segmentation gives better performance relative to existing techniques in terms of accuracy.
Effect of Frequent or Extended Hemodialysis on Cardiovascular Parameters: A Meta-analysis
Susantitaphong, Paweena; Koulouridis, Ioannis; Balk, Ethan M.; Madias, Nicolaos E.; Jaber, Bertrand L.
2012-01-01
Background Increased left ventricular (LV) mass is a risk factor for cardiovascular mortality in patients with chronic kidney failure. More frequent or extended hemodialysis (HD) has been hypothesized to have a beneficial effect on LV mass. Study Design Meta-analysis. Setting & Population MEDLINE literature search (inception-April 2011), Cochrane Central Register of Controlled Trials and ClinicalTrials.gov using the search terms “short daily HD”, “daily HD”, “quotidian HD”, “frequent HD”, “intensive HD”, “nocturnal HD”, and “home HD”. Selection Criteria for Studies Single-arm cohort studies (with pre- and post-study evaluations) and randomized controlled trials examining the effect of frequent or extended HD on cardiac morphology and function, and blood pressure parameters. Studies of hemofiltration, hemodiafiltration and peritoneal dialysis were excluded. Intervention Frequent (2–8 hours,> thrice weekly) or extended (>4 hours, thrice weekly) HD as compared with conventional (≤ 4 hours, thrice weekly) HD. Outcomes Absolute changes in cardiac morphology and function, including LV mass index (LVMI) (primary), and blood pressure parameters (secondary). Results We identified 38 single-arm studies, 5 crossover trials and 3 randomized controlled trials. By meta-analysis of 23 study arms, frequent or extended HD significantly reduced LVMI from baseline (−31.2 g/m2, 95% CI, −39.8 to −22.5; P<0.001).The 3 randomized trials found a less pronounced net reduction in LVMI (−7.0 g/m2; 95% CI, −10.2 to −3.7; P<0.001). LV ejection fraction improved by 6.7% (95% CI, 1.6 to 11.9; P=0.01). Other cardiac morphological parameters displayed similar improvements. There were also significant decreases in systolic, diastolic, and mean blood pressure, and mean number of anti-hypertensive medications. Limitations Paucity of randomized controlled trials. Conclusions Conversion from conventional to frequent or extended HD is associated with an improvement in cardiac morphology and function, including LVMI and LV ejection fraction, respectively, and in several blood pressure parameters, which collectively might confer long-term cardiovascular benefit. Trials with long-term clinical outcomes are needed. PMID:22370022
Concrete induced cardiac contusion.
Curzen, N.; Brett, S.; Fox, K.
1997-01-01
A previously fit 22 year old man was struck in the chest by a concrete block dropped through the windscreen of his car while he was driving on the motorway. He suffered extensive chest wall trauma and lung contusion, which subsequently precipitated acute respiratory distress. On admission ECG showed right bundle branch block and left axis deviation. Three days later QRS duration was normal but there was anterior ST segment elevation and subsequent T wave change. There was a large rise in creatine kinase, and echocardiography revealed septal and apical hyokinesis as well as a mobile mass attached to the left side of the interventricular septum, which had the echogenic texture of myocardium. The patient had fixed perfusion defects in the areas of hypokinesis on thallium scanning but the coronary arteries were unobstructed at angiography. He was treated with warfarin in the short term and an angiotensin converting enzyme inhibitor in the longer term and has made an asymptomatic recovery. Outpatient echocardiography two months after the injury demonstrated some recovery in overall left ventricular systolic function and no evidence of the intracardiac mass. This case illustrates some of the typical features of non-fatal cardiac contusion associated with non-penetrating cardiac trauma, and was complicated by partial thickness avulsion of a strip of the myocardium in the interventricular septum. Images PMID:9391297
Wu, Chung-Kuan; Wu, Chia-Lin; Lin, Chia-Hsun; Leu, Jyh-Gang; Kor, Chew-Teng; Tarng, Der-Cherng
2017-09-24
To investigate the impact of vascular access flow (Qa) on vascular and all-cause mortality in chronic haemodialysis (HD) patients. Observational cohort study. Single centre. Adult chronic HD patients at the HD unit of Shin Kong Wu Ho-Su Memorial Hospital between 1 January 2003 and 31 December 2003 were recruited. Patients were excluded if they had arteriovenous fistula or arteriovenous graft failure within 3 months before the date of Qa measurement, were aged <18 years and had Qa levels of ≥2000mL/min. A total of 378 adult chronic HD patients were eventually enrolled for the study. The selected patients were evaluated with Qa and cardiac index (CI). They were divided into four groups according to three Qa cut-off points (500, 1000 and 1500 mL/min). Short-term and long-term vascular (cardiovascular or cerebrovascular) and all-cause mortality. Qa was positively correlated with CI ( r =0.48, p<0.001). A Qa level of <1000 mL/min was independently associated with 1-year all-cause mortality (adjusted OR, 6.04; 95% CI 1.64 to 22.16; p=0.007). Kaplan-Meier analysis revealed that the cumulative incidence rates of all-cause and vascular mortality were significantly higher in the patients with a Qa level of <1000 mL/min (log-rank test; all p<0.01). Furthermore, a Qa level of <1000 mL/min was independently associated with long-term all-cause mortality (adjusted HR, 1.62; 95% CI 1.11 to 2.37; p=0.013); however, the risk of vascular mortality did not significantly increase after adjustment for confounders. Qa is moderately correlated with cardiac function, and a Qa level of <1000 mL/min is an independent risk factor for both short-term and long-term all-cause mortality in chronic HD patients. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Cardiac Delayed Rectifier Potassium Channels in Health and Disease.
Chen, Lei; Sampson, Kevin J; Kass, Robert S
2016-06-01
Cardiac delayed rectifier potassium channels conduct outward potassium currents during the plateau phase of action potentials and play pivotal roles in cardiac repolarization. These include IKs, IKr and the atrial specific IKur channels. In this article, we will review their molecular identities and biophysical properties. Mutations in the genes encoding delayed rectifiers lead to loss- or gain-of-function phenotypes, disrupt normal cardiac repolarization and result in various cardiac rhythm disorders, including congenital Long QT Syndrome, Short QT Syndrome and familial atrial fibrillation. We will also discuss the prospect of using delayed rectifier channels as therapeutic targets to manage cardiac arrhythmia. Copyright © 2016 Elsevier Inc. All rights reserved.
Cardiac Delayed Rectifier Potassium Channels in Health and Disease
Chen, Lei; Sampson, Kevin J.; Kass, Robert S.
2016-01-01
Cardiac delayed rectifier potassium channels conduct outward potassium currents during the plateau phase of action potentials and play pivotal roles in cardiac repolarization. These include IKs, IKr and the atrial specific IKur channels. In this chapter, we will review the molecular identities and biophysical properties of these channels. Mutations in the genes encoding delayed rectifiers lead to loss- or gain-of-function phenotypes, disrupt normal cardiac repolarization and result in various cardiac rhythm disorders, including congenital Long QT Syndrome, Short QT Syndrome and familial atrial fibrillation. We will also discuss the possibility and prospect of using delayed rectifier channels as therapeutic targets to manage cardiac arrhythmia. PMID:27261823
Sonin, Dmitry L.; Wakatsuki, Tetsuro; Routhu, Kasi V.; Harmann, Leanne M.; Petersen, Matthew; Meyer, Jennifer; Strande, Jennifer L.
2013-01-01
Purpose Fibroblast activity promotes adverse left ventricular (LV) remodeling that underlies the development of ischemic cardiomyopathy. Transforming growth factor-β (TGF-β) is a potent stimulus for fibrosis, and the extracellular signal-regulated kinases(ERK) 1/2 pathway also contributes to the fibrotic response. The thrombin receptor, protease-activated receptor 1 (PAR1), has been shown to play an important role in the excessive fibrosis in different tissues. The aim of this study was to investigate the influence of a PAR1 inhibitor, SCH79797, on cardiac fibrosis, tissue stiffness and postinfarction remodeling, and effects of PAR1 inhibition on thrombin-induced TGF-β and (ERK) 1/2 activities in cardiac fibroblasts. Methods We used a rat model of myocardial ischemia–reperfusion injury, isolated cardiac fibroblasts, and 3-dimensional (3D) cardiac tissue models fabricated to ascertain the contribution of PAR1 activation on cardiac fibrosis and LV remodeling. Results The PAR1 inhibitor attenuated LV dilation and improved LV systolic function of the reperfused myocardium at 28 days. This improvement was associated with a nonsignificant decrease in scar size (%LV) from 23 ± % in the control group (n = 10) to 16% ± 5.5% in the treated group (n = 9; P = .052). In the short term, the PAR1 inhibitor did not rescue infarct size or LV systolic function after 3 days. The PAR1 inhibition abolished thrombin-mediated ERK1/2 phosphorylation, TGF-β and type I procollagen production, matrix metalloproteinase-2/9 activation, myofibroblasts transformation in vitro, and abrogated the remodeling of 3D tissues induced by chronic thrombin treatment. Conclusion These studies suggest PAR1 inhibition initiated after ischemic injury attenuates adverse LV remodeling through late-stage antifibrotic events. PMID:23598708
Hautvast, Gilion L T F; Salton, Carol J; Chuang, Michael L; Breeuwer, Marcel; O'Donnell, Christopher J; Manning, Warren J
2012-05-01
Quantitative analysis of short-axis functional cardiac magnetic resonance images can be performed using automatic contour detection methods. The resulting myocardial contours must be reviewed and possibly corrected, which can be time-consuming, particularly when performed across all cardiac phases. We quantified the impact of manual contour corrections on both analysis time and quantitative measurements obtained from left ventricular short-axis cine images acquired from 1555 participants of the Framingham Heart Study Offspring cohort using computer-aided contour detection methods. The total analysis time for a single case was 7.6 ± 1.7 min for an average of 221 ± 36 myocardial contours per participant. This included 4.8 ± 1.6 min for manual contour correction of 2% of all automatically detected endocardial contours and 8% of all automatically detected epicardial contours. However, the impact of these corrections on global left ventricular parameters was limited, introducing differences of 0.4 ± 4.1 mL for end-diastolic volume, -0.3 ± 2.9 mL for end-systolic volume, 0.7 ± 3.1 mL for stroke volume, and 0.3 ± 1.8% for ejection fraction. We conclude that left ventricular functional parameters can be obtained under 5 min from short-axis functional cardiac magnetic resonance images using automatic contour detection methods. Manual correction more than doubles analysis time, with minimal impact on left ventricular volumes and ejection fraction. Copyright © 2011 Wiley Periodicals, Inc.
Pecoraro, Michela; Rodríguez-Sinovas, Antonio; Marzocco, Stefania; Ciccarelli, Michele; Iaccarino, Guido; Pinto, Aldo; Popolo, Ada
2017-10-11
The use of Doxorubicin (DOXO), a potent antineoplastic agent, is limited by the development of cardiotoxicity. DOXO-induced cardiotoxicity is multifactorial, although alterations in calcium homeostasis, seem to be involved. Since even the Connexin43 (Cx43) plays a pivotal role in these two phenomena, in this study we have analyzed the effects of DOXO on Cx43 expression and localization. Damage caused by anthracyclines on cardiomyocytes is immediate after each injection, in the present study we used a short-term model of DOXO-induced cardiomyopathy. C57BL/6j female mice were randomly divided in groups and injected with DOXO (2 or 10 mg/kg i.p.) for 1-3 or 7 days once every other day. Cardiac function was assessed by Echocardiography. Sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCAII) and phospholamban (PLB) expression were assessed by Western blot analysis, intracellular [Ca 2+ ] were detected spectrofluorometrically by means of Fura-2 pentakis (acetoxymethyl) ester (FURA-2AM), and Cx43 and pCx43 expression and localization was analyzed by Western blot and confirmed by immunofluorescence analysis. DOXO induces impairment in Ca 2+ homeostasis, already evident after a single administration, and affects Cx43 expression and localization. Our data suggest that DOXO-induced alterations in Ca 2+ homeostasis causes in the cells the induction of compensatory mechanisms until a certain threshold, above which cardiac injury is triggered.
Reduced size liver transplantation from a donor supported by a Berlin Heart.
Misra, M V; Smithers, C J; Krawczuk, L E; Jenkins, R L; Linden, B C; Weldon, C B; Kim, H B
2009-11-01
Patients on cardiac assist devices are often considered to be high-risk solid organ donors. We report the first case of a reduced size liver transplant performed using the left lateral segment of a pediatric donor whose cardiac function was supported by a Berlin Heart. The recipient was a 22-day-old boy with neonatal hemochromatosis who developed fulminant liver failure shortly after birth. The transplant was complicated by mild delayed graft function, which required delayed biliary reconstruction and abdominal wall closure, as well as a bile leak. However, the graft function improved quickly over the first week and the patient was discharged home with normal liver function 8 weeks after transplant. The presence of a cardiac assist device should not be considered an absolute contraindication for abdominal organ donation. Normal organ procurement procedures may require alteration due to the unusual technical obstacles that are encountered when the donor has a cardiac assist device.
NASA Astrophysics Data System (ADS)
Jelinek, Herbert F.; Pham, Phuong; Struzik, Zbigniew R.; Spence, Ian
2007-07-01
Diabetes mellitus (DM) is a serious and increasing health problem worldwide. Compared to non-diabetics, patients experience an increased risk of all cardiovascular diseases, including dysfunctional neural control of the heart. Poor diagnoses of cardiac autonomic neuropathy (CAN) may result in increased incidence of silent myocardial infarction and ischaemia, which can lead to sudden death. Traditionally the Ewing battery of tests is used to identify CAN. The purpose of this study is to examine the usefulness of heart rate variability (HRV) analyses of short-term ECG recordings as a method for detecting CAN. HRV may be able to identify asymptomatic individuals, which the Ewing battery is not able to do. Several HRV parameters are assessed, including time and frequency domain, as well as nonlinear parameters. Eighteen out of thirty-eight individuals with diabetes were positive for two or more of the Ewing battery of tests indicating CAN. Approximate Entropy (ApEn), log normalized total power (LnTP) and log normalized high frequency (LnHF) power demonstrate a significant difference at p < 0.05 between CAN+ and CAN-. This indicates that nonlinear scaling parameters are able to identify people with cardiac autonomic neuropathy in short ECG recordings. Our study paves the way to assess the utility of nonlinear parameters in identifying asymptomatic CAN.
Kocur, Piotr; Deskur-Smielecka, Ewa; Wilk, Malgorzata; Dylewicz, Piotr
2009-11-01
To investigate the effects of Nordic Walking training supplemental to a standard, early rehabilitation programme on exercise capacity and physical fitness in men after an acute coronary syndrome. A controlled trial. Cardiac rehabilitation service of a provincial hospital. Eighty men 2-3 weeks after an acute coronary syndrome, with good exercise tolerance. Three-week, inpatient cardiac rehabilitation programme (control group) supplemented with Nordic Walking (Nordic Walking group), or with traditional walking training (walking training group). Exercise capacity was assessed as peak energy cost (in metabolic equivalents) in symptom-limited treadmill exercise test, and physical fitness with the Fullerton Functional Fitness Test. Exercise capacity after the rehabilitation programme was higher in the Nordic Walking group than in the control group (10.8 +/- 1.8 versus 9.2 +/- 2.2 metabolic equivalents, P =0.025). The improvement in exercise capacity in the Nordic Walking group was higher than in the control group (1.8 +/- 1.5 versus 0.7 +/- 1.4 metabolic equivalents, P =0.002). In contrast to the control group, the results of all components of the Fullerton test improved in the Nordic Walking and walking training groups. After the programme, lower body endurance, and dynamic balance were significantly better in the Nordic Walking group in comparison with the walking training and control groups, and upper body endurance was significantly better in the Nordic Walking and walking training groups than in the control group. Nordic Walking may improve exercise capacity, lower body endurance and coordination of movements in patients with good exercise tolerance participating in early, short-term rehabilitation after an acute coronary syndrome.
Pathological presentation of cardiac mitochondria in a rat model for chronic kidney disease.
Bigelman, Einat; Cohen, Lena; Aharon-Hananel, Genya; Levy, Ran; Rozenbaum, Zach; Saada, Ann; Keren, Gad; Entin-Meer, Michal
2018-01-01
Mitochondria hold crucial importance in organs with high energy demand especially the heart. We investigated whether chronic kidney disease (CKD), which eventually culminates in cardiorenal syndrome, could affect cardiac mitochondria and assessed the potential involvement of angiotensin II (AngII) in the process. Male Lewis rats underwent 5/6 nephrectomy allowing CKD development for eight months or for eleven weeks. Short-term CKD rats were administered with AngII receptor blocker (ARB). Cardiac function was assessed by echocardiography and cardiac sections were evaluated for interstitial fibrosis and cardiomyocytes' hypertrophy. Electron microscopy was used to explore the spatial organization of the cardiomyocytes. Expression levels of mitochondrial content and activity markers were tested in order to delineate the underlying mechanisms for mitochondrial pathology in the CKD setting with or without ARB administration. CKD per-se resulted in induced cardiac interstitial fibrosis and cardiomyocytes' hypertrophy combined with a marked disruption of the mitochondrial structure. Moreover, CKD led to enhanced cytochrome C leakage to the cytosol and to enhanced PARP-1 cleavage which are associated with cellular apoptosis. ARB treatment did not improve kidney function but markedly reduced left ventricular mass, cardiomyocytes' hypertrophy and interstitial fibrosis. Interestingly, ARB administration improved the spatial organization of cardiac mitochondria and reduced their increased volume compared to untreated CKD animals. Nevertheless, ARB did not improve mitochondrial content, mitochondrial biogenesis or the respiratory enzyme activity. ARB mildly upregulated protein levels of mitochondrial fusion-related proteins. CKD results in cardiac pathological changes combined with mitochondrial damage and elevated apoptotic markers. We anticipate that the increased mitochondrial volume mainly represents mitochondrial swelling that occurs during the pathological process of cardiac hypertrophy. Chronic administration of ARB may improve the pathological appearance of the heart. Further recognition of the molecular pathways leading to mitochondrial insult and appropriate intervention is of crucial importance.
Sacre, J W; Jellis, C L; Coombes, J S; Marwick, T H
2012-09-01
Poor prognosis associated with blunted post-exercise heart-rate recovery may reflect autonomic dysfunction. This study sought the accuracy of post-exercise heart-rate recovery in the diagnosis of cardiac autonomic neuropathy, which represents a serious, but often unrecognized complication of Type 2 diabetes. Clinical assessment of cardiac autonomic neuropathy and maximal treadmill exercise testing for heart-rate recovery were performed in 135 patients with Type 2 diabetes and negative exercise echocardiograms. Cardiac autonomic neuropathy was defined by abnormalities in ≥ 2 of 7 autonomic function markers, including four cardiac reflex tests and three indices of short-term (5-min) heart-rate variability. Heart-rate recovery was defined at 1-, 2- and 3-min post-exercise. Patients with cardiac autonomic neuropathy (n = 27; 20%) had lower heart-rate recovery at 1-, 2- and 3-min post-exercise (P < 0.01). Heart-rate recovery demonstrated univariate associations with autonomic function markers (r-values 0.20-0.46, P < 0.05). Area under the receiver-operating characteristic curve revealed good diagnostic performance of all heart-rate recovery parameters (range 0.80-0.83, P < 0.001). Optimal cut-offs for heart-rate recovery at 1-, 2- and 3-min post-exercise were ≤ 28 beats/min (sensitivity 93%, specificity 69%), ≤ 50 beats/min (sensitivity 96%, specificity 63%) and ≤ 52 beats/min (sensitivity 70%, specificity 84%), respectively. These criteria predicted cardiac autonomic neuropathy independently of relevant clinical and exercise test information (adjusted odds ratios 7-28, P < 0.05). Post-exercise heart-rate recovery provides an accurate diagnostic test for cardiac autonomic neuropathy in Type 2 diabetes. The high sensitivity and modest specificity suggests heart-rate recovery may be useful to screen for patients requiring clinical autonomic evaluation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.
El-sherbiny, Islam; Nabil, Baher; Saber, Tamer; Abdelgawad, Fathy Elsayed
2015-01-01
We aimed to assess the predictive value of admission HbA1c level in nondiabetic patients presented by acute STEMI, on outcome of PCI and short term outcome of adverse cardiac events. Methods. 60 nondiabetic patients were admitted to Cardiology Department, Zagazig University Hospital, with acute STMI: 27 patients with HbA1c levels of 4.5% to 6.4% (group 1), 17 patients with HbA1c levels of 6.5% to 8.5% (group 2), and 16 patients with HbA1c levels higher than 8.5% (group 3). Either invasive intervention was done at admission by (pPCI) or coronary angiography was done within month (3–28 days) from taking thrombolytic. Participants were followed up for 6 months. Results. There was significant difference among different groups of HbA1c as regards the number of diseased vessels, severity of CAD lesions (p value < 0.01), and TIMI flow grades (p value < 0.05). There was significant difference among different groups as regards the adverse cardiac events on short term follow-up period (p value < 0.05). Conclusion. The present study showed that admission higher HbA1c level in patients presented by acute STEMI is associated with more severe CAD, lower rate of complete revascularization, and higher incidence of adverse cardiac events. PMID:26697259
Tan, Li Kuo; Liew, Yih Miin; Lim, Einly; Abdul Aziz, Yang Faridah; Chee, Kok Han; McLaughlin, Robert A
2018-06-01
In this paper, we develop and validate an open source, fully automatic algorithm to localize the left ventricular (LV) blood pool centroid in short axis cardiac cine MR images, enabling follow-on automated LV segmentation algorithms. The algorithm comprises four steps: (i) quantify motion to determine an initial region of interest surrounding the heart, (ii) identify potential 2D objects of interest using an intensity-based segmentation, (iii) assess contraction/expansion, circularity, and proximity to lung tissue to score all objects of interest in terms of their likelihood of constituting part of the LV, and (iv) aggregate the objects into connected groups and construct the final LV blood pool volume and centroid. This algorithm was tested against 1140 datasets from the Kaggle Second Annual Data Science Bowl, as well as 45 datasets from the STACOM 2009 Cardiac MR Left Ventricle Segmentation Challenge. Correct LV localization was confirmed in 97.3% of the datasets. The mean absolute error between the gold standard and localization centroids was 2.8 to 4.7 mm, or 12 to 22% of the average endocardial radius. Graphical abstract Fully automated localization of the left ventricular blood pool in short axis cardiac cine MR images.
Cardiac surgery-associated acute kidney injury.
Vives, Marc; Wijeysundera, Duminda; Marczin, Nandor; Monedero, Pablo; Rao, Vivek
2014-05-01
Acute kidney injury develops in up to 30% of patients who undergo cardiac surgery, with up to 3% of patients requiring dialysis. The requirement for dialysis after cardiac surgery is associated with an increased risk of infection, prolonged stay in critical care units and long-term need for dialysis. The development of acute kidney injury is independently associated with substantial short- and long-term morbidity and mortality. Its pathogenesis involves multiple pathways. Haemodynamic, inflammatory, metabolic and nephrotoxic factors are involved and overlap each other leading to kidney injury. Clinical studies have identified predictors for cardiac surgery-associated acute kidney injury that can be used effectively to determine the risk for acute kidney injury in patients undergoing cardiac surgery. High-risk patients can be targeted for renal protective strategies. Nonetheless, there is little compelling evidence from randomized trials supporting specific interventions to protect or prevent acute kidney injury in cardiac surgery patients. Several strategies have shown some promise, including less invasive procedures in those at greatest risk, natriuretic peptide, fenoldopam, preoperative hydration, preoperative optimization of anaemia and postoperative early use of renal replacement therapy. The efficacy of larger-scale trials remains to be confirmed.
NASA Astrophysics Data System (ADS)
Atehortúa, Angélica; Zuluaga, Maria A.; Ourselin, Sébastien; Giraldo, Diana; Romero, Eduardo
2016-03-01
An accurate ventricular function quantification is important to support evaluation, diagnosis and prognosis of several cardiac pathologies. However, expert heart delineation, specifically for the right ventricle, is a time consuming task with high inter-and-intra observer variability. A fully automatic 3D+time heart segmentation framework is herein proposed for short-axis-cardiac MRI sequences. This approach estimates the heart using exclusively information from the sequence itself without tuning any parameters. The proposed framework uses a coarse-to-fine approach, which starts by localizing the heart via spatio-temporal analysis, followed by a segmentation of the basal heart that is then propagated to the apex by using a non-rigid-registration strategy. The obtained volume is then refined by estimating the ventricular muscle by locally searching a prior endocardium- pericardium intensity pattern. The proposed framework was applied to 48 patients datasets supplied by the organizers of the MICCAI 2012 Right Ventricle segmentation challenge. Results show the robustness, efficiency and competitiveness of the proposed method both in terms of accuracy and computational load.
Ganz, Patricia A; Romond, Edward H; Cecchini, Reena S; Rastogi, Priya; Geyer, Charles E; Swain, Sandra M; Jeong, Jong-Hyeon; Fehrenbacher, Louis; Gross, Howard M; Brufsky, Adam M; Flynn, Patrick J; Wahl, Tanya A; Seay, Thomas E; Wade, James L; Biggs, David D; Atkins, James N; Polikoff, Jonathan; Zapas, John L; Mamounas, Eleftherios P; Wolmark, Norman
2017-12-10
Purpose Early cardiac toxicity is a risk associated with adjuvant chemotherapy plus trastuzumab. However, objective measures of cardiac function and health-related quality of life are lacking in long-term follow-up of patients who remain cancer free after completion of adjuvant treatment. Patients and Methods Patients in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or without trastuzumab for adjuvant treatment of node-positive, human epidermal growth factor receptor 2-positive early-stage breast cancer. A long-term follow-up assessment was undertaken for patients who were alive and disease free, which included measurement of left ventricular ejection fraction by multigated acquisition scan along with patient-reported outcomes using the Duke Activity Status Index (DASI), the Medical Outcomes Study questionnaire, and a review of current medications and comorbid conditions. Results At a median follow-up of 8.8 years among eligible participants, five (4.5%) of 110 in the control group and 10 (3.4%) of 297 in the trastuzumab group had a > 10% decline in left ventricular ejection fraction from baseline to a value < 50%. Lower DASI scores correlated with age and use of medications for hypertension, cardiac conditions, diabetes, and hyperlipidemia, but not with whether patients had received trastuzumab. Conclusion In patients without underlying cardiac disease at baseline, the addition of trastuzumab to adjuvant anthracycline and taxane-based chemotherapy does not result in long-term worsening of cardiac function, cardiac symptoms, or health-related quality of life. The DASI questionnaire may provide a simple and useful tool for monitoring patient-reported changes that reflect cardiac function.
Viana-Tejedor, Ana; Domínguez, Francisco J; Moreno Yangüela, Mar; Moreno, Raúl; López de Sá, Esteban; Mesa, José M; López-Sendón, José
2008-10-04
Increasing life expectancy in Western countries in the last decades has resulted in a significant gradual increasing number of octogenarians referred for cardiac surgery. There is a need for a critical evaluation of the long-term surgical outcome and quality of life in the elderly. The aim of this study is to identify risk factors of mortality in octogenarians undergoing cardiac surgery and to assess the long term survival and quality of life. Data were reviewed on 150 patients aged over 80 years--mean age (standard deviation): 82.7 (2.5) years--who underwent cardiac surgery at our institution in the last 26 years. We analyzed clinical and epidemiological variables included in the European System for Cardiac Operative Risk Evaluation (euroSCORE), in-hospital morbidity and mortality, long term survival and quality of life after cardiac surgery. The 30-day mortality rate was 30.1%, with a mean hospital stay of 16.5 days (13-27). Emergent procedure, reparation of postinfarction ventricular ruptures, New York Heart Association functional class IV, chronic renal failure and previous myocardial infarction were independent predictors of in-hospital mortality. Mean follow up was 72.2 (9.9) months with survival rates of 87.3% and 57% at 1 and 5 years, respectively. Late postoperative quality of life in our 53 long-term survivors was significantly better than prior to surgery. New York Heart Association functional class improved from 2.52 to 1.48. Most survivors (97.7%) were satisfied with present quality of life Cardiac surgery in octogenarians is associated with increased in-hospital mortality rate and longer hospital stay. Our findings support that cardiac surgery can be performed in a selected elderly population with good long-term survival and quality of life.
Neves, Claodete Hasselstrom; Tibana, Ramires Alsamir; Prestes, Jonato; Voltarelli, Fabricio Azevedo; Aguiar, Andreo Fernando; Ferreira Mota, Gustavo Augusto; de Sousa, Sergio Luiz Borges; Leopoldo, Andre Soares; Leopoldo, Ana Paula Lima; Mueller, Andre; Aguiar, Danilo Henrique; Navalta, James Wilfred; Sugizaki, Mario Mateus
2017-04-01
Cardiotonic drugs and exercise training promote cardiac inotropic effects, which may affect training-induced cardiac adaptations. This study investigated the effects of long-term administration of digoxin on heart structure and function, and physical performance of rats submitted to high-intensity interval training (HIIT). Male Wistar rats, 60 days old, were divided into control (C), digoxin (DIGO), trained (T), and trained with digoxin (TDIGO). Digoxin was administered by gavage (30 µg/kg/day) for 75 days. The HIIT program consisted of treadmill running 60 min/day (8 min at 80% of the maximum speed (MS) and 2 min at 20% of the MS), 5 days per week during 60 days. The main cardiac parameters were evaluated by echocardiograph and cardiomyocyte area was determined by histology. There were no group x time effects of digoxin, HIIT or interactions (digoxin and HIIT) on functional echocardiographic parameters (heart rate; ejection fraction) or in the maximum exercise test. There was a group x time interaction, as evidenced by observed cardiac hypertrophy in the TDIGO group evaluated by ratio of left ventricle weight to body weight (p<0.002) and cardiomyocyte area (p<0.000002). Long-term administration of digoxin promoted cardiac hypertrophy without affecting cardiac function and physical performance in rats submitted to HIIT. © Georg Thieme Verlag KG Stuttgart · New York.
Lin, Lian-Yu; Chang, Chin-Hao; Chu, Fang-Ying; Lin, Yen-Hung; Wu, Cho-Kai; Lee, Jen-Kuang; Hwang, Juei-Jen; Lin, Jiunn-Lee; Chiang, Fu-Tien
2016-01-01
Background and Objectives Patients with severe kidney function impairment often have autonomic dysfunction, which could be evaluated noninvasively by heart rate variability (HRV) analysis. Nonlinear HRV parameters such as detrended fluctuation analysis (DFA) has been demonstrated to be an important outcome predictor in patients with cardiovascular diseases. Whether cardiac autonomic dysfunction measured by DFA is also a useful prognostic factor in patients with end-stage renal disease (ESRD) receiving peritoneal dialysis (PD) remains unclear. The purpose of the present study was designed to test the hypothesis. Materials and Methods Patients with ESRD receiving PD were included for the study. Twenty-four hour Holter monitor was obtained from each patient together with other important traditional prognostic makers such as underlying diseases, left ventricular ejection fraction (LVEF) and serum biochemistry profiles. Short-term (DFAα1) and long-term (DFAα2) DFA as well as other linear HRV parameters were calculated. Results A total of 132 patients (62 men, 72 women) with a mean age of 53.7±12.5 years were recruited from July 2007 to March 2009. During a median follow-up period of around 34 months, eight cardiac and six non-cardiac deaths were observed. Competing risk analysis demonstrated that decreased DFAα1 was a strong prognostic predictor for increased cardiac and total mortality. ROC analysis showed that the AUC of DFAα1 (<0.95) to predict mortality was 0.761 (95% confidence interval (CI). = 0.617–0.905). DFAα1≧ 0.95 was associated with lower cardiac mortality (Hazard ratio (HR) 0.062, 95% CI = 0.007–0.571, P = 0.014) and total mortality (HR = 0.109, 95% CI = 0.033–0.362, P = 0.0003). Conclusion Cardiac autonomic dysfunction evaluated by DFAα1 is an independent predictor for cardiac and total mortality in patients with ESRD receiving PD. PMID:26828209
James, Susan H; Wald, Rachel; Wintersperger, Bernd J; Jimenez-Juan, Laura; Deva, Djeven; Crean, Andrew M; Nguyen, Elsie; Paul, Narinder S; Ley, Sebastian
2013-08-01
The left ventricle (LV) is routinely assessed with cardiac magnetic resonance imaging (MRI) by using short-axis orientation; it remains unclear whether the right ventricle (RV) can also be adequately assessed in this orientation or whether dedicated axial orientation is required. We used phase-contrast (PC) flow measurements in the main pulmonary artery (MPA) and the ascending aorta (Aorta) as nonvolumetric standard of reference and compared RV and LV volumes in short-axis and axial orientations. A retrospective analysis identified 30 patients with cardiac MRI data sets. Patients underwent MRI (1.5 T or 3 T), with retrospectively gated cine steady-state free-precession in axial and short-axis orientations. PC flow analyses of MPA and Aorta were used as the reference measure of RV and LV output. There was a high linear correlation between MPA-PC flow and RV-stroke volume (SV) short axis (r = 0.9) and RV-SV axial (r = 0.9). Bland-Altman analysis revealed a mean offset of 1.4 mL for RV axial and -2.3 mL for RV-short-axis vs MPA-PC flow. There was a high linear correlation between Aorta-PC flow and LV-SV short-axis (r = 0.9) and LV-SV axial (r = 0.9). Bland-Altman analysis revealed a mean offset of 4.8 m for LV short axis and 7.0 mL for LV axial vs Aorta-PC flow. There was no significant difference (P = .6) between short-axis-LV SV and short-axis-RV SV. No significant impact of the slice acquisition orientation for determination of RV and LV stroke volumes was found. Therefore, cardiac magnetic resonance workflow does not need to be extended by an axial data set for patients without complex cardiac disease for assessment of biventricular function and volumes. Copyright © 2013 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.
Lithium-manganese dioxide cells for implantable defibrillator devices-Discharge voltage models
NASA Astrophysics Data System (ADS)
Root, Michael J.
The discharge potential behavior of lithium-manganese dioxide cells designed for implantable cardiac defibrillators was characterized as a function of extent of cell depletion for tests designed to discharge the cells for times between 1 and 7 years. The discharge potential curves may be separated into two segments from 0 ≤ x ≤ ∼0.51 and ∼0.51 ≤ x ≤ 1.00, where x is the dimensionless extent of discharge referenced to the rated cell capacity. The discharge potentials conform to Tafel kinetics in each segment. This behavior allows the discharge potential curves to be predicted for an arbitrary discharge load and long term discharge performance may be predicted from short term test results. The discharge potentials may subsequently be modeled by fitting the discharge curves to empirical functions like polynomials and Padé approximants. A function based on the Nernst equation that includes a term accounting for nonideal interactions between lithium ions and the cathode host material, such as the Redlich-Kister relationship, also may be used to predict discharge behavior.
Guppy-Coles, Kristyan B; Prasad, Sandhir B; Smith, Kym C; Hillier, Samuel; Lo, Ada; Atherton, John J
2015-06-01
We aimed to determine the feasibility of training cardiac nurses to evaluate left ventricular function utilising a semi-automated, workstation-based protocol on three dimensional echocardiography images. Assessment of left ventricular function by nurses is an attractive concept. Recent developments in three dimensional echocardiography coupled with border detection assistance have reduced inter- and intra-observer variability and analysis time. This could allow abbreviated training of nurses to assess cardiac function. A comparative, diagnostic accuracy study evaluating left ventricular ejection fraction assessment utilising a semi-automated, workstation-based protocol performed by echocardiography-naïve nurses on previously acquired three dimensional echocardiography images. Nine cardiac nurses underwent two brief lectures about cardiac anatomy, physiology and three dimensional left ventricular ejection fraction assessment, before a hands-on demonstration in 20 cases. We then selected 50 cases from our three dimensional echocardiography library based on optimal image quality with a broad range of left ventricular ejection fractions, which was quantified by two experienced sonographers and the average used as the comparator for the nurses. Nurses independently measured three dimensional left ventricular ejection fraction using the Auto lvq package with semi-automated border detection. The left ventricular ejection fraction range was 25-72% (70% with a left ventricular ejection fraction <55%). All nurses showed excellent agreement with the sonographers. Minimal intra-observer variability was noted on both short-term (same day) and long-term (>2 weeks later) retest. It is feasible to train nurses to measure left ventricular ejection fraction utilising a semi-automated, workstation-based protocol on previously acquired three dimensional echocardiography images. Further study is needed to determine the feasibility of training nurses to acquire three dimensional echocardiography images on real-world patients to measure left ventricular ejection fraction. Nurse-performed evaluation of left ventricular function could facilitate the broader application of echocardiography to allow cost-effective screening and monitoring for left ventricular dysfunction in high-risk populations. © 2014 John Wiley & Sons Ltd.
Continuous Intravenous Milrinone Therapy in Pediatric Outpatients.
Curley, Michelle; Liebers, Jill; Maynard, Roy
Milrinone is a phosphodiesterase 3 inhibitor with both positive inotropic and vasodilator properties. Administered as a continuous infusion, milrinone is indicated for the short-term treatment of patients with acute decompensated heart failure. Despite limited data supporting long-term milrinone therapy in adults with congestive heart failure, children managed as outpatients may benefit from continuous milrinone as a treatment for cardiac dysfunction, as a destination therapy for cardiac transplant, or as palliative therapy for cardiomyopathy. The aim of this article is to review the medical literature and describe a home infusion company's experience with pediatric outpatient milrinone therapy.
Continuous Intravenous Milrinone Therapy in Pediatric Outpatients
Curley, Michelle; Liebers, Jill
2017-01-01
Milrinone is a phosphodiesterase 3 inhibitor with both positive inotropic and vasodilator properties. Administered as a continuous infusion, milrinone is indicated for the short-term treatment of patients with acute decompensated heart failure. Despite limited data supporting long-term milrinone therapy in adults with congestive heart failure, children managed as outpatients may benefit from continuous milrinone as a treatment for cardiac dysfunction, as a destination therapy for cardiac transplant, or as palliative therapy for cardiomyopathy. The aim of this article is to review the medical literature and describe a home infusion company's experience with pediatric outpatient milrinone therapy. PMID:28248808
Al Tmimi, Layth; Van de Velde, Marc; Herijgers, Paul; Meyns, Bart; Meyfroidt, Geert; Milisen, Koen; Fieuws, Steffen; Coburn, Mark; Poesen, Koen; Rex, Steffen
2015-10-09
Postoperative delirium (POD) is a manifestation of acute postoperative brain dysfunction that is frequently observed after cardiac surgery. POD is associated with short-term complications such as an increase in mortality, morbidity, costs and length of stay, but can also have long-term sequelae, including persistent cognitive deficits, loss of independence, and increased mortality for up to 2 years. The noble gas xenon has been demonstrated in various models of neuronal injury to exhibit remarkable neuroprotective properties. We therefore hypothesize that xenon anesthesia reduces the incidence of POD in elderly patients undergoing cardiac surgery with the use of cardiopulmonary bypass. One hundred and ninety patients, older than 65 years, and scheduled for elective cardiac surgery, will be enrolled in this prospective, randomized, controlled trial. Patients will be randomized to receive general anesthesia with either xenon or sevoflurane. Primary outcome parameter will be the incidence of POD in the first 5 postoperative days. The occurrence of POD will be assessed by trained research personnel, blinded to study group, with the validated 3-minute Diagnostic Confusion Assessment Method (3D-CAM) (on the intensive care unit in its version specifically adapted for the ICU), in addition to chart review and the results of delirium screening tools that will be performed by the bedside nurses). Secondary outcome parameters include duration and severity of POD, and postoperative cognitive function as assessed with the Mini-Mental State Examination. Older patients undergoing cardiac surgery are at particular risk to develop POD. Xenon provides remarkable hemodynamic stability and has been suggested in preclinical studies to exhibit neuroprotective properties. The present trial will assess whether the promising profile of xenon can be translated into a better outcome in the geriatric population. EudraCT Identifier: 2014-005370-11 (13 May 2015).
Breitner, Susanne; Schneider, Alexandra; Devlin, Robert B; Ward-Caviness, Cavin K; Diaz-Sanchez, David; Neas, Lucas M; Cascio, Wayne E; Peters, Annette; Hauser, Elizabeth R; Shah, Svati H; Kraus, William E
2016-12-01
Exposure to ambient particulate matter (PM) and ozone has been associated with cardiovascular disease (CVD). However, the mechanisms linking PM and ozone exposure to CVD remain poorly understood. This study explored associations between short-term exposures to PM with a diameter <2.5μm (PM 2.5 ) and ozone with plasma metabolite concentrations. We used cross-sectional data from a cardiac catheterization cohort at Duke University, North Carolina (NC), USA, accumulated between 2001 and 2007. Amino acids, acylcarnitines, ketones and total non-esterified fatty acid plasma concentrations were determined in fasting samples. Daily concentrations of PM 2.5 and ozone were obtained from a Bayesian space-time hierarchical model, matched to each patient's residential address. Ten metabolites were selected for the analysis based on quality criteria and cluster analysis. Associations between metabolites and PM 2.5 or ozone were analyzed using linear regression models adjusting for long-term trend and seasonality, calendar effects, meteorological parameters, and participant characteristics. We found delayed associations between PM 2.5 or ozone and changes in metabolite levels of the glycine-ornithine-arginine metabolic axis and incomplete fatty acid oxidation associated with mitochondrial dysfunction. The strongest association was seen for an increase of 8.1μg/m 3 in PM 2.5 with a lag of one day and decreased mean glycine concentrations (-2.5% [95% confidence interval: -3.8%; -1.2%]). Short-term exposures to ambient PM 2.5 and ozone is associated with changes in plasma concentrations of metabolites in a cohort of cardiac catheterization patients. Our findings might help to understand the link between air pollution and cardiovascular disease. Copyright © 2016 Elsevier Ltd. All rights reserved.
Liu, Kuan-Liang; Lee, Hsin-Fu; Chou, Shing-Hsien; Lin, Yen-Chen; Lin, Chia-Pin; Wang, Chun-Li; Chang, Chi-Jen; Hsu, Lung-An
2014-01-01
Large epidemiologic studies have associated gouty arthritis with the risk of coronary heart disease. However, there has been a lack of information regarding the outcomes for patients who have gout attacks during hospitalization for acute myocardial infarction. We reviewed the data of 444 consecutive patients who were admitted to our hospital between 2005 and 2008 due to acute ST elevation myocardial infarction (STEMI). The clinical outcomes were compared between patients with gout attack and those without. Of the 444, 48 patients with acute STEMI developed acute gouty arthritis during hospitalization. The multivariate analysis identified prior history of gout and estimated glomerular filtration rate as independent risk factors of gout attack for patients with acute STEMI (odds ratio (OR) 21.02, 95 % CI 2.96-149.26, p = 0.002; OR 0.92, 95 % CI 0.86-0.99, p = 0.035, respectively). The in-hospital mortality and duration of hospital stay did not differ significantly between the gouty group and the non-gouty group (controls). During a mean follow-up of 49 ± 28 months, all-cause mortality and stroke were similar for both groups. Multivariate Cox regression showed that gout attack was independently associated with short- and long-term adverse non-fatal cardiac events (hazard ratio (HR) 1.88, 95 % CI 1.09-3.24, p = 0.024; HR 1.82, 95 % CI 1.09-3.03, p = 0.022, respectively). Gout attack among patients hospitalized due to acute STEMI was independently associated with short-term and long-term rates of adverse non-fatal cardiac events.
Morbidity, mortality and economic burden of renal impairment in cardiac intensive care.
Chew, D P; Astley, C; Molloy, D; Vaile, J; De Pasquale, C G; Aylward, P
2006-03-01
Moderate to severe impairment of renal function has emerged as a potent risk factor for adverse short- and long-term outcomes among patients presenting with cardiac disease. We sought to define the clinical, late mortality and economic burden of this risk factor among patients presenting to cardiac intensive care. A clinical audit of patients presenting to cardiac intensive care was undertaken between July 2002 and June 2003. All patients presenting with cardiac diagnoses were included in the study. Baseline creatinine levels were assessed in all patients. Late mortality was assessed by the interrogation of the National Death Register. Renal impairment was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2, as calculated by the Modified Diet in Renal Disease formula. In-hospital and late outcomes were compared by Cox proportional hazards modelling, adjusting for known confounders. A matched analysis and attributable risk calculation were undertaken to assess the proportion of late mortality accounted for by impairment of renal function and other known negative prognostic factors. The in-hospital total cost associated with renal impairment was assessed by linear regression. Glomerular filtration rate <60 mL/min per 1.73 m2 was evident in 33.0% of this population. Among these patients, in-hospital and late mortality were substantially increased: risk ratio 13.2; 95% CI 3.0-58.1; P < 0.001 and hazard ratio 6.2; 95% CI 3.6-10.7; P < 0.001, respectively. In matched analysis, renal impairment to this level was associated with 42.1% of all the late deaths observed. Paradoxically, patients with renal impairment were more conservatively managed, but their hospitalizations were associated with an excess adjusted in-hospital cost of $A1676. Impaired renal function is associated with a striking clinical and economic burden among patients presenting to cardiac intensive care. As a marker for future risk, renal function accounts for a substantial proportion of the burden of late mortality. The burden of risk suggests a greater potential opportunity for improvement of outcomes through optimisation of therapeutic strategies.
Mathison, Megumi; Singh, Vivek P; Chiuchiolo, Maria J; Sanagasetti, Deepthi; Mao, Yun; Patel, Vivekkumar B; Yang, Jianchang; Kaminsky, Stephen M; Crystal, Ronald G; Rosengart, Todd K
2017-02-01
The reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells improves ventricular function in myocardial infarction models. Only integrating persistent expression vectors have thus far been used to induce reprogramming, potentially limiting its clinical applicability. We therefore tested the reprogramming potential of nonintegrating, acute expression adenoviral (Ad) vectors. Ad or lentivirus vectors encoding Gata4 (G), Mef2c (M), and Tbx5 (T) were validated in vitro. Sprague-Dawley rats then underwent coronary ligation and Ad-mediated administration of vascular endothelial growth factor to generate infarct prevascularization. Three weeks later, animals received Ad or lentivirus encoding G, M, or T (AdGMT or LentiGMT) or an equivalent dose of a null vector (n = 11, 10, and 10, respectively). Outcomes were analyzed by echocardiography, magnetic resonance imaging, and histology. Ad and lentivirus vectors provided equivalent G, M, and T expression in vitro. AdGMT and LentiGMT both likewise induced expression of the cardiomyocyte marker cardiac troponin T in approximately 6% of cardiac fibroblasts versus <1% cardiac troponin T expression in AdNull (adenoviral vector that does not encode a transgene)-treated cells. Infarcted myocardium that had been treated with AdGMT likewise demonstrated greater density of cells expressing the cardiomyocyte marker beta myosin heavy chain 7 compared with AdNull-treated animals. Echocardiography demonstrated that AdGMT and LentiGMT both increased ejection fraction compared with AdNull (AdGMT: 21% ± 3%, LentiGMT: 14% ± 5%, AdNull: -0.4% ± 2%; P < .05). Ad vectors are at least as effective as lentiviral vectors in inducing cardiac fibroblast transdifferentiation into induced cardiomyocyte-like cells and improving cardiac function in postinfarct rat hearts. Short-term expression Ad vectors may represent an important means to induce cardiac cellular reprogramming in humans. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
23-year experience on diagnosis and surgical treatment of benign and malignant cardiac tumors.
Kośmider, Anna; Jaszewski, Ryszard; Marcinkiewicz, Anna; Bartczak, Karol; Knopik, Jerzy; Ostrowski, Stanisław
2013-10-31
Although myxoma is the most frequent cardiac tumor, other conditions should be taken into consideration in the differential diagnosis. Transthoracic echocardiography (TTE), followed by transesophageal echocardiography (TEE) remain the principal methods for cardiac tumor screening and visualizing. The aim of the study was to compare the diagnostics, surgical treatment and prognosis of malignant and benign cardiac tumors. From 1986 to 2009 there were 121 patients with cardiac tumors operated on in the Cardiac Surgery Clinic of the Medical University in Lodz. Patients were referred to surgery mainly on the basis of the TTE and TEE image. In 4 cases valvular prosthesis implantation or valve repair were carried out. Patients remained under long-term observation in the Cardiac Surgery Outpatient Clinic. Myxoma was diagnosed in 114 cases. Malignancies were discovered in 7 cases. The left atrium was the most frequent localization. The echocardiographic image differed significantly in benign and malignant tumors. The postoperative period was complicated by embolic events or myocardial infarctions. Only malignant tumors were associated with mortality due to cardiovascular events. The survival for malignant tumors was significantly shorter. Short and long-term results of operative treatment are very good for benign tumors in contrast to cardiac malignancies. The TTE and TEE image can be very significant in the final diagnosis.
Ekmekci, Ahmet; Uluganyan, Mahmut; Tufan, Fatif; Uyarel, Huseyin; Karaca, Gurkan; Kul, Seref; Gungor, Barış; Ertas, Gokhan; Erer, Betul; Sayar, Nurten; Gul, Mehmet; Eren, Mehmet
2013-01-01
Objective Admission hyperglycemia in acute myocardial infarction (MI) is related with increased in-hospital and long term mortality and major cardiac adverse events. We aimed to investigate how admission hyperglycemia affects the short and long term outcomes in elderly patients (> 65 years) after primary percutaneous coronary intervention for ST elevation myocardial infarction. Methods We retrospectively analyzed 677 consecutive elderly patients (mean age 72.2 ± 5.4). Patients were divided into two groups according to admission blood glucose levels. Group 1: low glucose group (LLG), glucose < 168 mg/dL; and Group 2: high glucose group (HGG), glucose > 168 mg/dL. Results In-hospital, long term mortality and in-hospital major adverse cardiac events were higher in the high admission blood glucose group (P < 0.001). Multivariate regression analysis showed: Killip > 1, post-thrombolysis in MI < 3 and admission blood glucose levels were independent predictors of in-hospital adverse cardiac events (P < 0.001). Conclusions Admission hyperglycemia in elderly patients presented with ST elevation myocardial infarction is an independent predictor of in-hospital major adverse cardiac events and is associated with in-hospital and long term mortality. PMID:24454322
Yamashita, Yugo; Shiomi, Hiroki; Morimoto, Takeshi; Yaku, Hidenori; Furukawa, Yutaka; Nakagawa, Yoshihisa; Ando, Kenji; Kadota, Kazushige; Abe, Mitsuru; Nagao, Kazuya; Shizuta, Satoshi; Ono, Koh; Kimura, Takeshi
2017-01-01
In patients with ST-segment-elevation acute myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention, long-term risks for cardiac and noncardiac death beyond acute phase of STEMI have not been thoroughly evaluated yet. We identified 3942 STEMI patients who had primary percutaneous coronary intervention within 24 hours after onset between January 2005 and December 2007 in the CREDO-Kyoto AMI registry (Coronary Revascularization Demonstrating Outcome study in Kyoto Acute Myocardial Infarction) and evaluated their short-term (within 6-month) and long-term (beyond 6-month) incidences and causes of deaths. The cumulative 5-year incidence of all-cause death in the current study population was 20.4% (cardiac death, 12.2% and noncardiac death, 9.4%, respectively). The vast majority of deaths were cardiac in origin within 6-month (cardiac death, 8.0% and noncardiac death, 0.9%), whereas noncardiac death accounted for nearly two thirds of all-cause death beyond 6-month (cardiac death, 4.6% and noncardiac death, 8.5%). In the stratified analysis according to age, the proportion of noncardiac death was similar regardless of age although the absolute mortality rate was higher with increasing age. By the multivariable Cox regression models, the independent risk factors of all-cause death were advanced age, cardiogenic shock, renal dysfunction, large infarct size, and anterior wall infarction within 6 months after STEMI, and advanced age, previous heart failure, renal dysfunction, and liver cirrhosis beyond 6 months after STEMI, respectively. In STEMI patients who underwent primary percutaneous coronary intervention, the long-term risk for cardiac death was relatively low compared with that for noncardiac death, which accounted for nearly two thirds of all-cause death beyond 6 months. © 2017 American Heart Association, Inc.
Hannan, Edward L; Cozzens, Kimberly; King, Spencer B; Walford, Gary; Shah, Nirav R
2012-06-19
In 1988, the New York State Health Commissioner was confronted with hospital-level data demonstrating very large, multiple-year, interhospital variations in short-term mortality and complications for cardiac surgery. The concern with the extent to which these differences were due to variations in patients' pre-surgical severity of illness versus hospitals' quality of care led to the development of clinical registries for cardiac surgery in 1989 and for percutaneous coronary interventions in 1992 in New York. In 1990, the Department of Health released hospitals' risk-adjusted cardiac surgery mortality rates for the first time, and shortly thereafter, similar data were released for hospitals and physicians for percutaneous coronary interventions, cardiac valve surgery, and pediatric cardiac surgery (only hospital data). This practice is still ongoing. The purpose of this communication is to relate the history of this initiative, including changes or purported changes that have occurred since the public release of cardiac data. These changes include decreases in risk-adjusted mortality, cessation of cardiac surgery in New York by low-volume and high-mortality surgeons, out-of-state referral or avoidance of cardiac surgery/angioplasty for high-risk patients, alteration of contracting choices by insurance companies, and modifications in market share of cardiac hospitals. Evidence related to these impacts is reviewed and critiqued. This communication also includes a summary of numerous studies that used New York's cardiac registries to examine a variety of policy issues regarding the choice and use of cardiac procedures, the comparative effectiveness of competing treatment options, and the examination of the relationship among processes, structures, and outcomes of cardiac care. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Micromolded gelatin hydrogels for extended culture of engineered cardiac tissues.
McCain, Megan L; Agarwal, Ashutosh; Nesmith, Haley W; Nesmith, Alexander P; Parker, Kevin Kit
2014-07-01
Defining the chronic cardiotoxic effects of drugs during preclinical screening is hindered by the relatively short lifetime of functional cardiac tissues in vitro, which are traditionally cultured on synthetic materials that do not recapitulate the cardiac microenvironment. Because collagen is the primary extracellular matrix protein in the heart, we hypothesized that micromolded gelatin hydrogel substrates tuned to mimic the elastic modulus of the heart would extend the lifetime of engineered cardiac tissues by better matching the native chemical and mechanical microenvironment. To measure tissue stress, we used tape casting, micromolding, and laser engraving to fabricate gelatin hydrogel muscular thin film cantilevers. Neonatal rat cardiac myocytes adhered to gelatin hydrogels and formed aligned tissues as defined by the microgrooves. Cardiac tissues could be cultured for over three weeks without declines in contractile stress. Myocytes on gelatin had higher spare respiratory capacity compared to those on fibronectin-coated PDMS, suggesting that improved metabolic function could be contributing to extended culture lifetime. Lastly, human induced pluripotent stem cell-derived cardiac myocytes adhered to micromolded gelatin surfaces and formed aligned tissues that remained functional for four weeks, highlighting their potential for human-relevant chronic studies. Copyright © 2014 Elsevier Ltd. All rights reserved.
Micromolded Gelatin Hydrogels for Extended Culture of Engineered Cardiac Tissues
McCain, Megan L.; Agarwal, Ashutosh; Nesmith, Haley W.; Nesmith, Alexander P.; Parker, Kevin Kit
2014-01-01
Defining the chronic cardiotoxic effects of drugs during preclinical screening is hindered by the relatively short lifetime of functional cardiac tissues in vitro, which are traditionally cultured on synthetic materials that do not recapitulate the cardiac microenvironment. Because collagen is the primary extracellular matrix protein in the heart, we hypothesized that micromolded gelatin hydrogel substrates tuned to mimic the elastic modulus of the heart would extend the lifetime of engineered cardiac tissues by better matching the native chemical and mechanical microenvironment. To measure tissue stress, we used tape casting, micromolding, and laser engraving to fabricate gelatin hydrogel muscular thin film cantilevers. Neonatal rat cardiac myocytes adhered to gelatin hydrogels and formed aligned tissues as defined by the microgrooves. Cardiac tissues could be cultured for over three weeks without declines in contractile stress. Myocytes on gelatin had higher spare respiratory capacity compared to those on fibronectin-coated PDMS, suggesting that improved metabolic function could be contributing to extended culture lifetime. Lastly, human induced pluripotent stem cell-derived cardiac myocytes adhered to micromolded gelatin surfaces and formed aligned tissues that remained functional for four weeks, highlighting their potential for human-relevant chronic studies. PMID:24731714
Pasala, Krishna K; Gujja, Karthik; Prabhu, Hejmadi; Vasavada, Balendu; Konka, Sudarsanam
2012-11-01
A 48-year-old man presented with complaints of shortness of breath and lower extremity swelling. His medical history was significant for hypertension on minoxidil and recent intracerebellar hemorrhage. Electrocardiography showed sinus tachycardia with left ventricular hypertrophy, and cardiomegaly was noted in the chest x-ray. The patient was hypertensive and tachypneic on admission. An echocardiogram taken immediately showed a large pericardial effusion with evidence of cardiac tamponade. He underwent immediate pericardiocentesis with drainage of 900 mL of pericardial fluid with significant improvement in the symptoms. Analysis of the pericardial fluid proved to be nondiagnostic. Infectious and rheumatologic causes were ruled out. After an extensive battery of tests, not yielding any diagnostic results, the pericardial effusion was attributed to minoxidil therapy. Closer monitoring is needed to prevent potentially fatal complications such as cardiac tamponade as in our patient.
Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation
Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; ...
2014-10-22
Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ( 1H; 0.5 Gy, 1 GeV) and iron ion ( 56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiatedmore » mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Finally, understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.« less
Lima-Leopoldo, Ana Paula; Leopoldo, André S; da Silva, Danielle C T; do Nascimento, André F; de Campos, Dijon H S; Luvizotto, Renata A M; de Deus, Adriana F; Freire, Paula P; Medeiros, Alessandra; Okoshi, Katashi; Cicogna, Antonio C
2014-09-15
Few studies have evaluated the relationship between the duration of obesity, cardiac function, and the proteins involved in myocardial calcium (Ca(2+)) handling. We hypothesized that long-term obesity promotes cardiac dysfunction due to a reduction of expression and/or phosphorylation of myocardial Ca(2+)-handling proteins. Thirty-day-old male Wistar rats were distributed into two groups (n = 10 each): control (C; standard diet) and obese (Ob; high-fat diet) for 30 wk. Morphological and histological analyses were assessed. Left ventricular cardiac function was assessed in vivo by echocardiographic evaluation and in vitro by papillary muscle. Cardiac protein expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a), calsequestrin, L-type Ca(2+) channel, and phospholamban (PLB), as well as PLB serine-16 phosphorylation (pPLB Ser(16)) and PLB threonine-17 phosphorylation (pPLB Thr(17)) were determined by Western blot. The adiposity index was higher (82%) in Ob rats than in C rats. Obesity promoted cardiac hypertrophy without alterations in interstitial collagen levels. Ob rats had increased endocardial and midwall fractional shortening, posterior wall shortening velocity, and A-wave compared with C rats. Cardiac index, early-to-late diastolic mitral inflow ratio, and isovolumetric relaxation time were lower in Ob than in C. The Ob muscles developed similar baseline data and myocardial responsiveness to increased extracellular Ca(2+). Obesity caused a reduction in cardiac pPLB Ser(16) and the pPLB Ser(16)/PLB ratio in Ob rats. Long-term obesity promotes alterations in diastolic function, most likely due to the reduction of pPLB Ser(16), but does not impair the myocardial Ca(2+) entry and recapture to SR. Copyright © 2014 the American Physiological Society.
Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah
Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ( 1H; 0.5 Gy, 1 GeV) and iron ion ( 56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiatedmore » mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Finally, understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.« less
Ge, Yi-Peng; Li, Cheng-Nan; Chen, Lei; Liu, Wei; Cheng, Li-Jian; Liu, Yong-Min; Zheng, Jun; Ma, Wei-Guo; Zhu, Jun-Ming; Sun, Li-Zhong
2015-11-01
The aim of this study was to evaluate if the previous cardiac surgery (PCS) is the risk factor for short- and mid-term mortality following total aortic arch replacement in patients with Stanford type A aortic dissection. Between February 2009 and February 2012, a total of 384 patients who suffered Stanford type A aortic dissection involving aortic arch underwent total aortic arch replacement with frozen elephant trunk. Of these patients, 36 patients had PCS. Logistic regression was used to identify if the previous cardiac surgery was the risk factor for in-hospital mortality. Propensity score-matching (1:1 match) was used to yield patients from the primary surgery group who matched PCS group with respect to pre-operative clinical characteristics and post-operative complications. Survival analysis and differences between the two groups were performed by the Kaplan-Meier estimate and the log-rank test. The overall in-hospital mortality was 8%. Logistic multiple regression identified that cardiopulmonary bypass time≥ 300minutes (OR=12.05, p<0.001) and surgical period from symptom onset shorter than one week (OR=2.43, p=0.04) were final risk factors for in-hospital mortality and PCS was not the final risk factor. Of 36 patients with PCS, three patients died in the hospital and 33 patients were discharged from the hospital. Of these 33 patients, 32 patients matched primary surgery group successfully. During the follow-up period, two patients died in PCS group, one patient died in primary surgery group. The mean follow-up time was 35.38±14.12 months. The five-year survival was 96% for the primary surgery group. Previous cardiac surgery group five-year survival was 73%. Five-year survival was not significantly different between the two groups (p=0.84 log-rank test). PCS is not the risk factor for short- and mid-term mortality following total aortic arch replacement in patients with Stanford type A aortic dissection. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
Cigarette smoking causes epigenetic changes associated with cardiorenal fibrosis
Haller, Steven T.; Fan, Xiaoming; Xie, Jeffrey X.; Kennedy, David J.; Liu, Jiang; Yan, Yanling; Hernandez, Dawn-Alita; Mathew, Denzil P.; Cooper, Christopher J.; Shapiro, Joseph I.; Tian, Jiang
2016-01-01
Clinical studies indicate that smoking combustible cigarettes promotes progression of renal and cardiac injury, leading to functional decline in the setting of chronic kidney disease (CKD). However, basic studies using in vivo small animal models that mimic clinical pathology of CKD are lacking. To address this issue, we evaluated renal and cardiac injury progression and functional changes induced by 4 wk of daily combustible cigarette smoke exposure in the 5/6th partial nephrectomy (PNx) CKD model. Molecular evaluations revealed that cigarette smoke significantly (P < 0.05) decreased renal and cardiac expression of the antifibrotic microRNA miR-29b-3 and increased expression of molecular fibrosis markers. In terms of cardiac and renal organ structure and function, exposure to cigarette smoke led to significantly increased systolic blood pressure, cardiac hypertrophy, cardiac and renal fibrosis, and decreased renal function. These data indicate that decreased expression of miR-29b-3p is a novel mechanism wherein cigarette smoke promotes accelerated cardiac and renal tissue injury in CKD. (155 words) PMID:27789733
Friess, Stuart H; Sutton, Robert M; Bhalala, Utpal; Maltese, Matthew R; Naim, Maryam Y; Bratinov, George; Weiland, Theodore R; Garuccio, Mia; Nadkarni, Vinay M; Becker, Lance B; Berg, Robert A
2013-12-01
During cardiopulmonary resuscitation, adequate coronary perfusion pressure is essential for establishing return of spontaneous circulation. Current American Heart Association guidelines recommend standardized interval administration of epinephrine for patients in cardiac arrest. The objective of this study was to compare short-term survival using a hemodynamic directed resuscitation strategy versus chest compression depth-directed cardiopulmonary resuscitation in a porcine model of cardiac arrest. Randomized interventional study. Preclinical animal laboratory. Twenty-four 3-month-old female swine. After 7 minutes of ventricular fibrillation, pigs were randomized to receive one of three resuscitation strategies: 1) Hemodynamic directed care (coronary perfusion pressure-20): chest compressions with depth titrated to a target systolic blood pressure of 100 mm Hg and titration of vasopressors to maintain coronary perfusion pressure greater than 20 mm Hg; 2) Depth 33 mm: target chest compression depth of 33 mm with standard American Heart Association epinephrine dosing; or 3) Depth 51 mm: target chest compression depth of 51 mm with standard American Heart Association epinephrine dosing. All animals received manual cardiopulmonary resuscitation guided by audiovisual feedback for 10 minutes before first shock. Forty-five-minute survival was higher in the coronary perfusion pressure-20 group (8 of 8) compared to depth 33 mm (1 of 8) or depth 51 mm (3 of 8) groups; p equals to 0.002. Coronary perfusion pressures were higher in the coronary perfusion pressure-20 group compared to depth 33 mm (p = 0.004) and depth 51 mm (p = 0.006) and in survivors compared to nonsurvivors (p < 0.01). Total epinephrine dosing and defibrillation attempts were not different. Hemodynamic directed resuscitation targeting coronary perfusion pressures greater than 20 mm Hg during 10 minutes of cardiopulmonary resuscitation for ventricular fibrillation cardiac arrest improves short-term survival, when compared to resuscitation with depth of compressions guided to 33 mm or 51 mm and standard American Heart Association vasopressor dosing.
Bosch-Morató, Mònica; Guivernau, Biuse; Albericio, Guillermo; Muñoz, Francisco J.; Pérez-Jurado, Luis A.
2018-01-01
Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a heterozygous deletion of 26–28 genes at chromosome band 7q11.23. The complete deletion (CD) mouse model mimics the most common deletion found in WBS patients and recapitulates most neurologic features of the disorder along with some cardiovascular manifestations leading to significant cardiac hypertrophy with increased cardiomyocytes’ size. Epigallocatechin-3-gallate (EGCG), the most abundant catechin found in green tea, has been associated with potential health benefits, both on cognition and cardiovascular phenotypes, through several mechanisms. We aimed to investigate the effects of green tea extracts on WBS-related phenotypes through a phase I clinical trial in mice. After feeding CD animals with green tea extracts dissolved in the drinking water, starting at three different time periods (prenatal, youth and adulthood), a set of behavioral tests and several anatomical, histological and molecular analyses were performed. Treatment resulted to be effective in the reduction of cardiac hypertrophy and was also able to ameliorate short-term memory deficits of CD mice. Taken together, these results suggest that EGCG might have a therapeutic and/or preventive role in the management of WBS. PMID:29554110
Fabregat-Andrés, Oscar; García-González, Pilar; Valle-Muñoz, Alfonso; Estornell-Erill, Jordi; Pérez-Boscá, Leandro; Palanca-Gil, Victor; Payá-Serrano, Rafael; Quesada-Dorador, Aurelio; Morell, Salvador; Ridocci-Soriano, Francisco
2014-02-01
Cardiac resynchronization therapy with a defibrillator prolongs survival and improves quality of life in advanced heart failure. Traditionally, patients with ejection fraction > 35 estimated by echocardiography have been excluded. We assessed the prognostic impact of this therapy in a group of patients with severely depressed systolic function as assessed by echocardiography but with an ejection fraction > 35% as assessed by cardiac magnetic resonance. We analyzed consecutive patients admitted for decompensated heart failure between 2004 and 2011. The patients were in functional class II-IV, with a QRS ≥ to 120 ms, ejection fraction ≤ 35% estimated by echocardiography, and a cardiac magnetic resonance study. We included all patients (n=103) who underwent device implantation for primary prevention. Ventricular arrhythmia, all-cause mortality and readmission for heart failure were considered major cardiac events. The patients were divided into 2 groups according to systolic function assessed by magnetic resonance. The 2 groups showed similar improvements in functional class and ejection fraction at 6 months. We found a nonsignificant trend toward a higher risk of all-cause mortality in patients with systolic function ≤ 35% at long-term follow-up. The presence of a pattern of necrosis identified patients with a worse prognosis for ventricular arrhythmias and mortality in both groups. We conclude that cardiac resynchronization therapy with a defibrillator leads to a similar clinical benefit in patients with an ejection fraction ≤ 35% or > 35% estimated by cardiac magnetic resonance. Analysis of the pattern of late gadolinium enhancement provides additional information on arrhythmic risk and long-term prognosis. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.
2013-01-01
Background Interoception refers to the conscious perception of body signals. Mindfulness is a meditation practice that encourages individuals to focus on their internal experiences such as bodily sensations, thoughts, and emotions. In this study, we selected a behavioral measure of interoceptive sensitivity (heartbeat detection task, HBD) to compare the effect of meditation practice on interoceptive sensitivity among long term practitioners (LTP), short term meditators (STM, subjects that completed a Mindfulness-Based Stress Reduction (MBSR) program) and controls (non-meditators). All participants were examined with a battery of different tasks including mood state, executive function and social cognition tests (emotion recognition, empathy and theory of mind). Findings Compared to controls, both meditators’ groups showed lower levels of anxiety and depression, but no improvement in executive function or social cognition performance was observed (except for lower scores compared to controls only in the personal distress dimension of empathy). More importantly, meditators’ performance did not differ from that of nonmeditators regarding cardiac interoceptive sensitivity. Conclusion Results suggest no influence of meditation practice in cardiac interoception and in most related social cognition measures. These negative results could be partially due to the fact that awareness of heartbeat sensations is not emphasized during mindfulness/vipassana meditation and may not be the best index of the awareness supported by the practice of meditation. PMID:24365106
Bish, Lawrence T; Yarchoan, Mark; Sleeper, Meg M; Gazzara, Jeffrey A; Morine, Kevin J; Acosta, Pedro; Barton, Elisabeth R; Sweeney, H Lee
2011-01-01
Duchenne muscular dystrophy (DMD) is a degenerative disorder affecting skeletal and cardiac muscle for which there is no effective therapy. Angiotension receptor blockade (ARB) has excellent therapeutic potential in DMD based on recent data demonstrating attenuation of skeletal muscle disease progression during 6-9 months of therapy in the mdx mouse model of DMD. Since cardiac-related death is major cause of mortality in DMD, it is important to evaluate the effect of any novel treatment on the heart. Therefore, we evaluated the long-term impact of ARB on both the skeletal muscle and cardiac phenotype of the mdx mouse. Mdx mice received either losartan (0.6 g/L) (n = 8) or standard drinking water (n = 9) for two years, after which echocardiography was performed to assess cardiac function. Skeletal muscle weight, morphology, and function were assessed. Fibrosis was evaluated in the diaphragm and heart by Trichrome stain and by determination of tissue hydroxyproline content. By the study endpoint, 88% of treated mice were alive compared to only 44% of untreated (p = 0.05). No difference in skeletal muscle morphology, function, or fibrosis was noted in losartan-treated animals. Cardiac function was significantly preserved with losartan treatment, with a trend towards reduction in cardiac fibrosis. We saw no impact on the skeletal muscle disease progression, suggesting that other pathways that trigger fibrosis dominate over angiotensin II in skeletal muscle long term, unlike the situation in the heart. Our study suggests that ARB may be an important prophylactic treatment for DMD-associated cardiomyopathy, but will not impact skeletal muscle disease.
Rengo, Giuseppe; Galasso, Gennaro; Femminella, Grazia D; Parisi, Valentina; Zincarelli, Carmela; Pagano, Gennaro; De Lucia, Claudio; Cannavo, Alessandro; Liccardo, Daniela; Marciano, Caterina; Vigorito, Carlo; Giallauria, Francesco; Ferrara, Nicola; Furgi, Giuseppe; Filardi, Pasquale Perrone; Koch, Walter J; Leosco, Dario
2014-01-01
Increased cardiac G protein-coupled receptor kinase-2 (GRK2) expression has a pivotal role at inducing heart failure (HF)-related β-adrenergic receptor (βAR) dysfunction. Importantly, abnormalities of βAR signalling in the failing heart, including GRK2 overexpression, are mirrored in circulating lymphocytes and correlate with HF severity. Exercise training has been shown to exert several beneficial effects on the failing heart, including normalization of cardiac βAR function and GRK2 protein levels. In the present study, we evaluated whether lymphocyte GRK2 levels and short-term changes of this kinase after an exercise training programme can predict long-term survival in HF patients. For this purpose, we prospectively studied 193 HF patients who underwent a 3-month exercise training programme. Lymphocyte GRK2 protein levels, plasma N-terminal pro-brain natriuretic peptide, and norepinephrine were measured at baseline and after training along with clinical and functional parameters (left ventricular ejection fraction, NYHA class, and peak-VO2). Cardiac-related mortality was evaluated during a mean follow-up period of 37 ± 20 months. Exercise was associated with a significant reduction of lymphocyte GRK2 protein levels (from 1.29 ± 0.52 to 1.16 ± 0.65 densitometric units, p < 0.0001). Importantly, exercise related changes of GRK2 (delta values) robustly predicted survival in our study population. Interestingly, HF patients who did not show reduced lymphocyte GRK2 protein levels after training presented the poorest outcome. Our data offer the first demonstration that changes of lymphocyte GRK2 after exercise training can strongly predict outcome in advanced HF.
Functional screening identifies miRNAs inducing cardiac regeneration.
Eulalio, Ana; Mano, Miguel; Dal Ferro, Matteo; Zentilin, Lorena; Sinagra, Gianfranco; Zacchigna, Serena; Giacca, Mauro
2012-12-20
In mammals, enlargement of the heart during embryonic development is primarily dependent on the increase in cardiomyocyte numbers. Shortly after birth, however, cardiomyocytes stop proliferating and further growth of the myocardium occurs through hypertrophic enlargement of the existing myocytes. As a consequence of the minimal renewal of cardiomyocytes during adult life, repair of cardiac damage through myocardial regeneration is very limited. Here we show that the exogenous administration of selected microRNAs (miRNAs) markedly stimulates cardiomyocyte proliferation and promotes cardiac repair. We performed a high-content microscopy, high-throughput functional screening for human miRNAs that promoted neonatal cardiomyocyte proliferation using a whole-genome miRNA library. Forty miRNAs strongly increased both DNA synthesis and cytokinesis in neonatal mouse and rat cardiomyocytes. Two of these miRNAs (hsa-miR-590 and hsa-miR-199a) were further selected for testing and were shown to promote cell cycle re-entry of adult cardiomyocytes ex vivo and to promote cardiomyocyte proliferation in both neonatal and adult animals. After myocardial infarction in mice, these miRNAs stimulated marked cardiac regeneration and almost complete recovery of cardiac functional parameters. The miRNAs identified hold great promise for the treatment of cardiac pathologies consequent to cardiomyocyte loss.
Schweitzer, P
2006-12-01
The management of ventricular tachyarrhythmias and prevention of sudden cardiac death after acute myocardial infarction (AMI) underwent important evolution. In the CAST study, encanaide and other antiarrhythmic drugs were not only ineffective but also increased mortality after myocardial infarction. Amiodarone had some beneficial effect on arrhythmic events without improving survival, and ICDs failed to improve outcome early after AMI. In comparison, short and long term survival benefits of beta blockers, angiotensine converting enzyme inhibitors and aldosterone antagonists after AMI is well established. This review discusses the role of non-arrhythmic therapy in the prevention of ventricular tachyarrhythmia's and sudden cardiac death after AMI.
23-year experience on diagnosis and surgical treatment of benign and malignant cardiac tumors
Jaszewski, Ryszard; Marcinkiewicz, Anna; Bartczak, Karol; Knopik, Jerzy; Ostrowski, Stanisław
2013-01-01
Introduction Although myxoma is the most frequent cardiac tumor, other conditions should be taken into consideration in the differential diagnosis. Transthoracic echocardiography (TTE), followed by transesophageal echocardiography (TEE) remain the principal methods for cardiac tumor screening and visualizing. The aim of the study was to compare the diagnostics, surgical treatment and prognosis of malignant and benign cardiac tumors. Material and methods From 1986 to 2009 there were 121 patients with cardiac tumors operated on in the Cardiac Surgery Clinic of the Medical University in Lodz. Patients were referred to surgery mainly on the basis of the TTE and TEE image. In 4 cases valvular prosthesis implantation or valve repair were carried out. Patients remained under long-term observation in the Cardiac Surgery Outpatient Clinic. Results Myxoma was diagnosed in 114 cases. Malignancies were discovered in 7 cases. The left atrium was the most frequent localization. The echocardiographic image differed significantly in benign and malignant tumors. The postoperative period was complicated by embolic events or myocardial infarctions. Only malignant tumors were associated with mortality due to cardiovascular events. The survival for malignant tumors was significantly shorter. Conclusions Short and long-term results of operative treatment are very good for benign tumors in contrast to cardiac malignancies. The TTE and TEE image can be very significant in the final diagnosis. PMID:24273564
Antunes, André; Prieto, David; Pinto, Carlos; Branco, Carlos; Correia, Pedro; Batista, Manuel; Antunes, Manuel
2017-01-01
Coronary allograft vasculopathy (CAV) is still a serious long-term complication after cardiac transplantation. To evaluate the prevalence of CAV in a single institution, its impact on survival and to explore associated risk factors. From November-2003 through June-2016, 316 patients were submitted to cardiac transplantation. After excluding those with paediatric age (n=8), those with previous renal or hepatic transplantation (n=2) and those who didn't survive the first year after cardiac transplantation (n=40), the study population resulted in 266 patients. Forty two patients (15.8%) with CAV, diagnosed by a new >50% coronary artery stenosis in any vessel during follow-up, were compared with a non-CAV group. Both groups share de same median age (54+10years). Recipient male sex predominated in the CAV group (93% vs. 74%), as did ischemic etiology (52% vs. 37%). Although not reaching statistical significance, CAV patients also had more dyslipidemia (60% vs. 50%), history of smoking (52% vs. 44%) and peripheral vascular disease (45% vs. 29%). The incidence of celular acute rejection 1R is more frequent in CAV group (69% vs. 60%) such as 2R or 3R (29% vs. 27%). Prolonged use of inotropic support and mechanical assistance after cardiac transplantation were comparable between both groups. The survival of this patients, who were submitted to cardiac transplantation and had lived at least 1 year, between CAV and non-CAV group was comparable at 5-year (91% vs. 85%), but tended to be lower for CAV patients in 10-year interval (52% vs. 73%). This data confirms CAV as a common long-term complication following cardiac transplantation. Although short to mid-term survival seems not to be affected by CAV, long-term survival appears lower, hence a longer follow-up is needed.
Jin, L X; Pitt, S C; Doyle, M B; Klein, C; Shenoy, S; Lowell, J A; Chapman, W C; Wellen, J R
2014-01-01
Morbid obesity (MO) has become an epidemic in the United Sates and is associated with adverse effects on health. The purpose of this study was to examine the effects of MO on the short-term outcomes of kidneys transplanted from donation after cardiac death (DCD) donors. Using a prospectively collected database, we reviewed 467 kidney transplantations performed at a single center between January 2008 and June 2011 to identify 67 recipients who received transplants from 40 DCD donors. The outcomes of 14 MO DCD donor kidneys were compared with 53 non-MO DCD grafts. MO was defined as a body mass index ≥ 35. Mean patient follow-up was 16 months. The MO and non-MO DCD donor groups were similar with respect to donor and recipient age, gender, race, cause of death and renal disease, time from withdrawal of life support to organ perfusion, mean human leukocyte antigen (HLA) mismatch, and overall recipient survival. Organs from MO DCD donors also had comparable rates of delayed graft function (21.4% vs 20.0%; P = not significant [NS]). At 1 year post-transplantation, a small but statistically insignificant difference was observed in the graft survival rates of MO and non-MO donors (87% vs. 96%; P = NS). One MO kidney had primary nonfunction. These data demonstrate that kidneys procured from MO DCD donors have equivalent short-term outcomes compared with non-MO grafts and should continue to be used. Further investigation is needed to examine the effect of MO on long-term renal allograft survival. Copyright © 2014 Elsevier Inc. All rights reserved.
Cardiac myosin binding protein C regulates postnatal myocyte cytokinesis
Jiang, Jianming; Burgon, Patrick G.; Wakimoto, Hiroko; Onoue, Kenji; Gorham, Joshua M.; O’Meara, Caitlin C.; Fomovsky, Gregory; McConnell, Bradley K.; Lee, Richard T.; Seidman, J. G.; Seidman, Christine E.
2015-01-01
Homozygous cardiac myosin binding protein C-deficient (Mybpct/t) mice develop dramatic cardiac dilation shortly after birth; heart size increases almost twofold. We have investigated the mechanism of cardiac enlargement in these hearts. Throughout embryogenesis myocytes undergo cell division while maintaining the capacity to pump blood by rapidly disassembling and reforming myofibrillar components of the sarcomere throughout cell cycle progression. Shortly after birth, myocyte cell division ceases. Cardiac MYBPC is a thick filament protein that regulates sarcomere organization and rigidity. We demonstrate that many Mybpct/t myocytes undergo an additional round of cell division within 10 d postbirth compared with their wild-type counterparts, leading to increased numbers of mononuclear myocytes. Short-hairpin RNA knockdown of Mybpc3 mRNA in wild-type mice similarly extended the postnatal window of myocyte proliferation. However, adult Mybpct/t myocytes are unable to fully regenerate the myocardium after injury. MYBPC has unexpected inhibitory functions during postnatal myocyte cytokinesis and cell cycle progression. We suggest that human patients with homozygous MYBPC3-null mutations develop dilated cardiomyopathy, coupled with myocyte hyperplasia (increased cell number), as observed in Mybpct/t mice. Human patients, with heterozygous truncating MYBPC3 mutations, like mice with similar mutations, have hypertrophic cardiomyopathy. However, the mechanism leading to hypertrophic cardiomyopathy in heterozygous MYBPC3+/− individuals is myocyte hypertrophy (increased cell size), whereas the mechanism leading to cardiac dilation in homozygous Mybpc3−/− mice is primarily myocyte hyperplasia. PMID:26153423
Park, Ji Yeon; Li, Wencheng; Zheng, Dinghai; Zhai, Peiyong; Zhao, Yun; Matsuda, Takahisa; Vatner, Stephen F.; Sadoshima, Junichi; Tian, Bin
2011-01-01
Cardiac hypertrophy is enlargement of the heart in response to physiological or pathological stimuli, chiefly involving growth of myocytes in size rather than in number. Previous studies have shown that the expression pattern of a group of genes in hypertrophied heart induced by pressure overload resembles that at the embryonic stage of heart development, a phenomenon known as activation of the “fetal gene program”. Here, using a genome-wide approach we systematically defined genes and pathways regulated in short- and long-term cardiac hypertrophy conditions using mice with transverse aortic constriction (TAC), and compared them with those regulated at different stages of embryonic and postnatal development. In addition, exon-level analysis revealed widespread mRNA isoform changes during cardiac hypertrophy resulting from alternative usage of terminal or internal exons, some of which are also developmentally regulated and may be attributable to decreased expression of Fox-1 protein in cardiac hypertrophy. Genes with functions in certain pathways, such as cell adhesion and cell morphology, are more likely to be regulated by alternative splicing. Moreover, we found 3′UTRs of mRNAs were generally shortened through alternative cleavage and polyadenylation in hypertrophy, and microRNA target genes were generally de-repressed, suggesting coordinated mechanisms to increase mRNA stability and protein production during hypertrophy. Taken together, our results comprehensively delineated gene and mRNA isoform regulation events in cardiac hypertrophy and revealed their relations to those in development, and suggested that modulation of mRNA isoform expression plays an importance role in heart remodeling under pressure overload. PMID:21799842
Iso, Yoshitaka; Spees, Jeffrey L.; Serrano, Claudia; Bakondi, Benjamin; Pochampally, Radhika; Song, Yao-Hua; Sobel, Burton E.; Delafontaine, Patrick; Prockop, Darwin J.
2007-01-01
The aim of this study was to determine whether intravenously-administered multipotent stromal cells from human bone marrow (hMSCs) can improve cardiac function after myocardial infarction (MI) without long-term engraftment and therefore whether transitory paracrine effects or secreted factors are responsible for the benefit conferred. hMSCs were injected systemically into immunodeficient mice with acute MI. Cardiac function and fibrosis after MI in the hMSC-treated group was significantly improved compared with that in controls. However, despite the cardiac improvement, there was no evident hMSC engraftment in the heart 3 weeks after MI. Microarray assays and ELISAs demonstrated that multiple protective factors were expressed and secreted from the hMSCs in culture. Factors secreted by hMSCs prevented cell death of cultured cardiomyocytes and endothelial cells under conditions that mimicked tissue ischemia. The favorable effects of hMSCs appear to reflect the impact of secreted factors rather than engraftment, differentiation, or cell fusion. PMID:17257581
NASA Astrophysics Data System (ADS)
Silva, Augusto F. d.; Costa, Carlos; Abrantes, Pedro; Gama, Vasco; Den Boer, Ad
1998-07-01
This paper describes an integrated system designed to provide efficient means for DICOM compliant cardiac imaging archival, transmission and visualization based on a communications backbone matching recent enabling telematic technologies like Asynchronous Transfer Mode (ATM) and switched Local Area Networks (LANs). Within a distributed client-server framework, the system was conceived on a modality based bottom-up approach, aiming ultrafast access to short term archives and seamless retrieval of cardiac video sequences throughout review stations located at the outpatient referral rooms, intensive and intermediate care units and operating theaters.
ERIC Educational Resources Information Center
Ai, A. L.; Ladd, K. L.; Peterson, C.; Cook, C. A.; Shearer, M.; Koenig, H. G.
2010-01-01
Purpose: Despite the growing evidence for effects of religious factors on cardiac health in general populations, findings are not always consistent in sicker and older populations. We previously demonstrated that short-term negative outcomes (depression and anxiety) among older adults following open heart surgery are partially alleviated when…
The role of sympathetic and vagal cardiac control on complexity of heart rate dynamics.
Silva, Luiz Eduardo Virgilio; Silva, Carlos Alberto Aguiar; Salgado, Helio Cesar; Fazan, Rubens
2017-03-01
Analysis of heart rate variability (HRV) by nonlinear approaches has been gaining interest due to their ability to extract additional information from heart rate (HR) dynamics that are not detectable by traditional approaches. Nevertheless, the physiological interpretation of nonlinear approaches remains unclear. Therefore, we propose long-term (60 min) protocols involving selective blockade of cardiac autonomic receptors to investigate the contribution of sympathetic and parasympathetic function upon nonlinear dynamics of HRV. Conscious male Wistar rats had their electrocardiogram (ECG) recorded under three distinct conditions: basal, selective (atenolol or atropine), or combined (atenolol plus atropine) pharmacological blockade of autonomic muscarinic or β 1 -adrenergic receptors. Time series of RR interval were assessed by multiscale entropy (MSE) and detrended fluctuation analysis (DFA). Entropy over short (1 to 5, MSE 1-5 ) and long (6 to 30, MSE 6-30 ) time scales was computed, as well as DFA scaling exponents at short (α short , 5 ≤ n ≤ 15), mid (α mid , 30 ≤ n ≤ 200), and long (α long , 200 ≤ n ≤ 1,700) window sizes. The results show that MSE 1-5 is reduced under atropine blockade and MSE 6-30 is reduced under atropine, atenolol, or combined blockade. In addition, while atropine expressed its maximal effect at scale six, the effect of atenolol on MSE increased with scale. For DFA, α short decreased during atenolol blockade, while the α mid increased under atropine blockade. Double blockade decreased α short and increased α long Results with surrogate data show that the dynamics during combined blockade is not random. In summary, sympathetic and vagal control differently affect entropy (MSE) and fractal properties (DFA) of HRV. These findings are important to guide future studies. NEW & NOTEWORTHY Although multiscale entropy (MSE) and detrended fluctuation analysis (DFA) are recognizably useful prognostic/diagnostic methods, their physiological interpretation remains unclear. The present study clarifies the effect of the cardiac autonomic control on MSE and DFA, assessed during long periods (1 h). These findings are important to help the interpretation of future studies. Copyright © 2017 the American Physiological Society.
Niu, Youguo; Herrera, Emilio A; Evans, Rhys D; Giussani, Dino A
2013-01-01
Glucocorticoids are widely used to treat chronic lung disease in premature infants but their longer-term adverse effects on the cardiovascular system raise concerns. We reported that neonatal dexamethasone treatment in rats induced in the short term molecular indices of cardiac oxidative stress and cardiovascular tissue remodelling at weaning, and that neonatal combined antioxidant and dexamethasone treatment was protective at this time. In this study, we investigated whether such effects of neonatal dexamethasone have adverse consequences for NO bioavailability and cardiovascular function at adulthood, and whether neonatal combined antioxidant and dexamethasone treatment is protective in the adult. Newborn rat pups received daily i.p. injections of a human-relevant tapering dose of dexamethasone (D; n= 8; 0.5, 0.3, 0.1 μg g−1) or D with vitamins C and E (DCE; n= 8; 200 and 100 mg kg−1, respectively) on postnatal days 1–3 (P1–3); vitamins were continued from P4 to P6. Controls received equal volumes of vehicle from P1 to P6 (C; n= 8). A fourth group received vitamins alone (CCE; n= 8). At P100, plasma NO metabolites (NOx) was measured and isolated hearts were assessed under both Working and Langendorff preparations. Relative to controls, neonatal dexamethasone therapy increased mortality by 18% (P < 0.05). Surviving D pups at adulthood had lower plasma NOx concentrations (10.6 ± 0.8 vs. 28.0 ± 1.5 μm), an increased relative left ventricular (LV) mass (70 ± 2 vs. 63 ± 1%), enhanced LV end-diastolic pressure (14 ± 2 vs. 8 ± 1 mmHg) and these hearts failed to adapt output with increased preload (Δcardiac output: 2.9 ± 2.0 vs. 10.6 ± 1.2 ml min−1) or afterload (Δcardiac output: −5.3 ± 2.0 vs.1.4 ± 1.2 ml min−1); all P < 0.05. Combined neonatal dexamethasone with antioxidant vitamins improved postnatal survival, restored plasma NOx and protected against cardiac dysfunction at adulthood. In conclusion, neonatal dexamethasone therapy promotes cardiac dysfunction at adulthood. Combined neonatal treatment with antioxidant vitamins is an effective intervention. PMID:23940378
NASA Astrophysics Data System (ADS)
Latka, Miroslaw; Glaubic-Latka, Marta; Latka, Dariusz; West, Bruce J.
2004-04-01
We study the middle cerebral artery blood flow velocity (MCAfv) in humans using transcranial Doppler ultrasonography (TCD). Scaling properties of time series of the axial flow velocity averaged over a cardiac beat interval may be characterized by two exponents. The short time scaling exponent (STSE) determines the statistical properties of fluctuations of blood flow velocities in short-time intervals while the Hurst exponent describes the long-term fractal properties. In many migraineurs the value of the STSE is significantly reduced and may approach that of the Hurst exponent. This change in dynamical properties reflects the significant loss of short-term adaptability and the overall hyperexcitability of the underlying cerebral blood flow control system. We call this effect fractal rigidity.
Ruiz-Hurtado, Gema; García-Prieto, Concha F.; Pulido-Olmo, Helena; Velasco-Martín, Juan P.; Villa-Valverde, Palmira; Fernández-Valle, María E.; Boscá, Lisardo; Fernández-Velasco, María; Regadera, Javier; Somoza, Beatriz; Fernández-Alfonso, María S.
2017-01-01
Caloric restriction (CR) ameliorates cardiac dysfunction associated with obesity. However, most of the studies have been performed under severe CR (30–65% caloric intake decrease) for several months or even years in aged animals. Here, we investigated whether mild (20% food intake reduction) and short-term (2-weeks) CR prevented the obese cardiomyopathy phenotype and improved the metabolic profile of young (14 weeks of age) genetically obese Zucker fa/fa rats. Heart weight (HW) and HW/tibia length ratio was significantly lower in fa/fa rats after 2 weeks of CR than in counterparts fed ad libitum. Invasive pressure measurements showed that systolic blood pressure, maximal rate of positive left ventricle (LV) pressure, LV systolic pressure and LV end-diastolic pressure were all significantly higher in obese fa/fa rats than in lean counterparts, which were prevented by CR. Magnetic resonance imaging revealed that the increase in LV end-systolic volume, stroke volume and LV wall thickness observed in fa/fa rats was significantly lower in animals on CR diet. Histological analysis also revealed that CR blocked the significant increase in cardiomyocyte diameter in obese fa/fa rats. High resolution magic angle spinning magnetic resonance spectroscopy analysis of the LV revealed a global decrease in metabolites such as taurine, creatine and phosphocreatine, glutamate, glutamine and glutathione, in obese fa/fa rats, whereas lactate concentration was increased. By contrast, fatty acid concentrations in LV tissue were significantly elevated in obese fa/fa rats. CR failed to restore the LV metabolomic profile of obese fa/fa rats. In conclusion, mild and short-term CR prevented an obesity-induced cardiomyopathy phenotype in young obese fa/fa rats independently of the cardiac metabolic profile. PMID:28203206
Carr, John Alfred; Buterakos, Roxanne; Bowling, William M; Janson, Lisa; Kralovich, Kurt A; Copeland, Craig; Link, Renee; Roiter, Cecilia; Casey, Gregory; Wagner, James W
2011-03-01
There is almost no data describing the long-term functional outcome of patients after penetrating cardiac injury. A retrospective study at a Level I trauma center from 2000 to 2009. Sixty-three patients had penetrating cardiac injuries from 28 stabbings and 35 gunshots. Men comprised 89% (56) of the patients. Overall, there were 21 survivors (33%) and 42 died in the emergency room or perioperative period. The mean age did not significantly differ between survivors (36 years ± 12 years) compared with those who died (30 years ± 11 years; p=0.07). There was an increased chance of survival after being stabbed compared with being shot (17 patients vs. 4 patients; odds ratio=12; p=0.002). Thirteen (62%) had injuries to the right ventricle only. Three patients died during follow-up: one from lung cancer and two other patients died from myocardial infarctions, one 9 years later at the age of 45 years and the other 8 years later at the age of 55 years. The survivors had functional follow-up evaluations from 2 months to 114 months (median, 71; interquartile range, 34-92 months) and echocardiographic follow-up from 2 months to 107 months (median, 64; interquartile range, 31-84 months) after their injuries. Functionally, all patients were in NYHA class 1 status, except one patient in class II who was 54 years old and had a mild exertional limitation. The previously injured area could only be identified by echocardiogram in one patient who had a patch repair of a ventricular septal defect (VSD). The mean ejection fraction improved over time from a mean of 51% ± 8% in the immediate postoperative period to 60% ± 9% after a mean follow-up of 59 months (p=0.01). After surgery, 43% of patients had a mild to moderate pericardial effusion; however, the long-term follow-up studies showed that all these had resolved. Wall motion abnormalities occurred in 33% of patients in the immediate postoperative period and, again, all these resolved during long-term follow-up. Patients who survive penetrating cardiac injuries, without coronary arterial or valvular disruption, have an excellent long-term functional outcome with minimal subsequent cardiac morbidity related to the injury. Full physiologic recovery and normal cardiac function can be expected if the patient survives. Copyright © 2011 by Lippincott Williams & Wilkins
Wilson, K S; Baily, J; Tucker, C S; Matrone, G; Vass, S; Moran, C; Chapman, K E; Mullins, J J; Kenyon, C; Hadoke, P W F; Denvir, M A
2015-10-15
Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/μm vs control 2.18 ± 0.13 cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 μg/mg vs controls 0.63 ± 0.06 μg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Wilson, K.S.; Baily, J.; Tucker, C.S.; Matrone, G.; Vass, S.; Moran, C.; Chapman, K.E.; Mullins, J.J.; Kenyon, C.; Hadoke, P.W.F.; Denvir, M.A.
2015-01-01
Background Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. Methods and results Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/μm vs control 2.18 ± 0.13 cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 μg/mg vs controls 0.63 ± 0.06 μg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. Conclusion Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart. PMID:26219824
NASA Astrophysics Data System (ADS)
Mantilla, Juan; Garreau, Mireille; Bellanger, Jean-Jacques; Paredes, José Luis
2013-11-01
Assessment of the cardiac Left Ventricle (LV) wall motion is generally based on visual inspection or quantitative analysis of 2D+t sequences acquired in short-axis cardiac cine-Magnetic Resonance Imaging (MRI). Most often, cardiac dynamic is globally analized from two particular phases of the cardiac cycle. In this paper, we propose an automated method to classify regional wall motion in LV function based on spatio-temporal pro les and Support Vector Machines (SVM). This approach allows to obtain a binary classi cation between normal and abnormal motion, without the need of pre-processing and by exploiting all the images of the cardiac cycle. In each short- axis MRI slice level (basal, median, and apical), the spatio-temporal pro les are extracted from the selection of a subset of diametrical lines crossing opposites LV segments. Initialized at end-diastole phase, the pro les are concatenated with their corresponding projections into the succesive temporal phases of the cardiac cycle. These pro les are associated to di erent types of information that derive from the image (gray levels), Fourier, Wavelet or Curvelet domains. The approach has been tested on a set of 14 abnormal and 6 healthy patients by using a leave-one-out cross validation and two kernel functions for SVM classi er. The best classi cation performance is yielded by using four-level db4 wavelet transform and SVM with a linear kernel. At each slice level the results provided a classi cation rate of 87.14% in apical level, 95.48% in median level and 93.65% in basal level.
Novelties in pharmacological management of cardiopulmonary resuscitation
Bartos, Jason A.; Yannopoulos, Demetris
2014-01-01
Purpose of review The ultimate goal of cardiopulmonary resuscitation is long-term neurologically intact survival. Despite numerous well designed studies, the medications currently used in advanced cardiac life support have not demonstrated success in this regard. This review describes the novel therapeutics under investigation to improve functional recovery and survival. Recent findings Whereas current medications focus on achieving return of spontaneous circulation and improved hemodynamics, novel therapies currently in development are focused on improving cellular survival and function by preventing metabolic derangement, protecting mitochondria, and preventing cell death caused by cardiac arrest. Improved cardiac and neurologic function and survival benefits have been observed using animal models of cardiopulmonary arrest. Summary Although substantial data have shown benefits using robust animal models, further human studies are necessary to investigate the potential long-term benefits of these therapies. PMID:23995130
Sleep Duration and Quality as Related to Left Ventricular Structure and Function.
Lee, Jae-Hon; Park, Sung Keun; Ryoo, Jae-Hong; Oh, Chang-Mo; Kang, Jeong Gyu; Mansur, Rodrigo B; Alfonsi, Jeffrey E; Lee, Yena; Shin, Sun-Han; McIntyre, Roger S; Jung, Ju Young
2018-01-01
Inadequate sleep is associated with increased risk of cardiovascular events; however, the associations between sleep duration or quality and cardiac function or structure are not well understood. This cross-sectional study was conducted to investigate to what extent sleep duration and quality are associated with left ventricular (LV) diastolic dysfunction or structural deterioration. A total of 31,598 healthy Korean adults who received echocardiography and completed the Pittsburg Sleep Quality Index were enrolled in this study. Participants were stratified into three groups by self-reported sleep duration (i.e., <7, 7-9, >9 hours) and into two groups by subjective sleep quality. Sleep duration was also assessed as a continuous variable. The odds ratios for impaired LV diastolic function, increased relative wall thickness, and LV hypertrophy (LVH) were compared between groups using multivariable logistic regression analyses. After adjustment for confounding variables (e.g., age, smoking, body mass index), there was a statistically significant association between short sleep duration (<7 hours) and greater LVH (fully adjusted odds ratio = 1.32 [95% confidence interval {CI} = 1.02-1.73]). Short sleep duration was also significantly associated with greater LVH (0.87 per hour [95% CI = 0.78-0.98]) and increased relative wall thickness (0.92 [95% CI = 0.86-0.99]), but there was no significant association between sleep and LV diastolic function. Among individuals with normal sleep duration, poor quality of sleep was not associated with adverse cardiac measures. These results indicate that short sleep duration (<7 hours) is associated with unfavorable LV structural characteristics. The association of insufficient sleep with adverse cardiovascular health outcomes may be mediated in part by adverse changes in cardiac structure and function.
Banerjee, Rupa; Pratap, Nitesh; Kalpala, Rakesh; Reddy, D Nageshwar
2014-03-01
Electrical stimulation therapy (EST) has been shown to increase lower esophageal sphincter (LES) pressure in animals; however, data on the effect of EST on LES pressure in patients with gastroesophageal reflux disease (GERD) are lacking. The aim of our study was to investigate the effect of EST on LES pressure and esophageal function in patients with GERD. Patients with a diagnosis of GERD responsive to proton pump inhibitors (PPIs), increased esophageal acid on 24-h pH monitoring off GERD medications, basal LES pressure >5 mmHg, hernia <2 cm and esophagitis
Sano, Toshikazu; Ousaka, Daiki; Goto, Takuya; Ishigami, Shuta; Hirai, Kenta; Kasahara, Shingo; Ohtsuki, Shinichi; Sano, Shunji; Oh, Hidemasa
2018-03-30
Intracoronary administration of cardiosphere-derived cells (CDCs) in patients with single ventricles resulted in a short-term improvement in cardiac function. To test the hypothesis that CDC infusion is associated with improved cardiac function and reduced mortality in patients with heart failure. We evaluated the effectiveness of CDCs using an integrated cohort study in 101 patients with single ventricles, including 41 patients who received CDC infusion and 60 controls treated with staged palliation alone. Heart failure with preserved ejection fraction (EF) or reduced EF was stratified by the cardiac function after surgical reconstruction. The main outcome measure was to evaluate the magnitude of improvement in cardiac function and all-cause mortality at 2 years. Animal studies were conducted to clarify the underlying mechanisms of heart failure with preserved EF and heart failure with reduced EF phenotypes. At 2 years, CDC infusion increased ventricular function (stage 2: +8.4±10.0% versus +1.6±6.4%, P =0.03; stage 3: +7.9±7.5% versus -1.1±5.5%, P <0.001) compared with controls. In all available follow-up data, survival did not differ between the 2 groups (log-rank P =0.225), whereas overall patients treated by CDCs had lower incidences of late failure ( P =0.022), adverse events ( P =0.013), and catheter intervention ( P =0.005) compared with controls. CDC infusion was associated with a lower risk of adverse events (hazard ratio, 0.411; 95% CI, 0.179-0.942; P =0.036). Notably, CDC infusion reduced mortality ( P =0.038) and late complications ( P <0.05) in patients with heart failure with reduced EF but not with heart failure with preserved EF. CDC-treated rats significantly reversed myocardial fibrosis with differential collagen deposition and inflammatory responses between the heart failure phenotypes. CDC administration in patients with single ventricles showed favorable effects on ventricular function and was associated with reduced late complications except for all-cause mortality after staged procedures. Patients with heart failure with reduced EF but not heart failure with preserved EF treated by CDCs resulted in significant improvement in clinical outcome. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01273857 and NCT01829750. © 2018 American Heart Association, Inc.
Effect of a puzzle on the process of students' learning about cardiac physiology.
Cardozo, Lais Tono; Miranda, Aline Soares; Moura, Maria José Costa Sampaio; Marcondes, Fernanda Klein
2016-09-01
The aim of the present study was to evaluate the effects of using a puzzle to learn about cardiac physiology. Students were divided into control and game groups. In class 1, the control group had a 2-h theoretical class about cardiac physiology, including a detailed description of the phases of the cardiac cycle, whereas the game group had a 50-min theoretical class without the description of the cardiac cycle. In class 2, the control group did an assessment exercise before an activity with the cardiac puzzle and the game group answered questions after the above-mentioned activity. While solving the puzzle, the students had to describe the cardiac cycle by relating the concepts of heart morphology and physiology. To evaluate short-term learning, the number of wrong answers and grades in the assessment exercise were compared between the control and game groups. To evaluate medium-term learning, we compared the grades obtained by students of the control and game groups in questions about cardiac physiology that formed part of the academic exam. In the assessment exercise, the game group presented a lower number of errors and higher score compared with the control group. In the academic exam, applied after both groups had used the puzzle, there was no difference in the scores obtained by the control and game groups in questions about cardiac physiology. These results showed a positive effect of the puzzle on students' learning about cardiac physiology compared with those not using the puzzle. Copyright © 2016 The American Physiological Society.
Functional 3-D cardiac co-culture model using bioactive chitosan nanofiber scaffolds.
Hussain, Ali; Collins, George; Yip, Derek; Cho, Cheul H
2013-02-01
The in vitro generation of a three-dimensional (3-D) myocardial tissue-like construct employing cells, biomaterials, and biomolecules is a promising strategy in cardiac tissue regeneration, drug testing, and tissue engineering applications. Despite significant progress in this field, current cardiac tissue models are not yet able to stably maintain functional characteristics of cardiomyocytes for long-term culture and therapeutic purposes. The objective of this study was to fabricate bioactive 3-D chitosan nanofiber scaffolds using an electrospinning technique and exploring its potential for long-term cardiac function in the 3-D co-culture model. Chitosan is a natural polysaccharide biomaterial that is biocompatible, biodegradable, non-toxic, and cost effective. Electrospun chitosan was utilized to provide structural scaffolding characterized by scale and architectural resemblance to the extracellular matrix (ECM) in vivo. The chitosan fibers were coated with fibronectin via adsorption in order to enhance cellular adhesion to the fibers and migration into the interfibrous milieu. Ventricular cardiomyocytes were harvested from neonatal rats and studied in various culture conditions (i.e., mono- and co-cultures) for their viability and function. Cellular morphology and functionality were examined using immunofluorescent staining for alpha-sarcomeric actin (SM-actin) and gap junction protein, Connexin-43 (Cx43). Scanning electron microscopy (SEM) and light microscopy were used to investigate cellular morphology, spatial organization, and contractions. Calcium indicator was used to monitor calcium ion flux of beating cardiomyocytes. The results demonstrate that the chitosan nanofibers retained their cylindrical morphology in long-term cell cultures and exhibited good cellular attachment and spreading in the presence of adhesion molecule, fibronectin. Cardiomyocyte mono-cultures resulted in loss of cardiomyocyte polarity and islands of non-coherent contractions. However, the cardiomyocyte-fibroblast co-cultures resulted in polarized cardiomyocyte morphology and retained their morphology and function for long-term culture. The Cx43 expression in the fibroblast co-culture was higher than the cardiomyocytes mono-culture and endothelial cells co-culture. In addition, fibroblast co-cultures demonstrated synchronized contractions involving large tissue-like cellular networks. To our knowledge, this is the first attempt to test chitosan nanofiber scaffolds as a 3-D cardiac co-culture model. Our results demonstrate that chitosan nanofibers can serve as a potential scaffold that can retain cardiac structure and function. These studies will provide useful information to develop a strategy that allows us to generate engineered 3-D cardiac tissue constructs using biocompatible and biodegradable chitosan nanofiber scaffolds for many tissue engineering applications. Copyright © 2012 Wiley Periodicals, Inc.
Direct Reprogramming—The Future of Cardiac Regeneration?
Doppler, Stefanie A.; Deutsch, Marcus-André; Lange, Rüdiger; Krane, Markus
2015-01-01
Today, the only available curative therapy for end stage congestive heart failure (CHF) is heart transplantation. This therapeutic option is strongly limited by declining numbers of available donor hearts and by restricted long-term performance of the transplanted graft. The disastrous prognosis for CHF with its restricted therapeutic options has led scientists to develop different concepts of alternative regenerative treatment strategies including stem cell transplantation or stimulating cell proliferation of different cardiac cell types in situ. However, first clinical trials with overall inconsistent results were not encouraging, particularly in terms of functional outcome. Among other approaches, very promising ongoing pre-clinical research focuses on direct lineage conversion of scar fibroblasts into functional myocardium, termed “direct reprogramming” or “transdifferentiation.” This review seeks to summarize strategies for direct cardiac reprogramming including the application of different sets of transcription factors, microRNAs, and small molecules for an efficient generation of cardiomyogenic cells for regenerative purposes. PMID:26230692
Hierarchical approaches for systems modeling in cardiac development.
Gould, Russell A; Aboulmouna, Lina M; Varner, Jeffrey D; Butcher, Jonathan T
2013-01-01
Ordered cardiac morphogenesis and function are essential for all vertebrate life. The heart begins as a simple contractile tube, but quickly grows and morphs into a multichambered pumping organ complete with valves, while maintaining regulation of blood flow and nutrient distribution. Though not identical, cardiac morphogenesis shares many molecular and morphological processes across vertebrate species. Quantitative data across multiple time and length scales have been gathered through decades of reductionist single variable analyses. These range from detailed molecular signaling pathways at the cellular levels to cardiac function at the tissue/organ levels. However, none of these components act in true isolation from others, and each, in turn, exhibits short- and long-range effects in both time and space. With the absence of a gene, entire signaling cascades and genetic profiles may be shifted, resulting in complex feedback mechanisms. Also taking into account local microenvironmental changes throughout development, it is apparent that a systems level approach is an essential resource to accelerate information generation concerning the functional relationships across multiple length scales (molecular data vs physiological function) and structural development. In this review, we discuss relevant in vivo and in vitro experimental approaches, compare different computational frameworks for systems modeling, and the latest information about systems modeling of cardiac development. Finally, we conclude with some important future directions for cardiac systems modeling. Copyright © 2013 Wiley Periodicals, Inc.
Westerdahl, Elisabeth; Urell, Charlotte; Jonsson, Marcus; Bryngelsson, Ing-Liss; Hedenström, Hans; Emtner, Margareta
2014-01-01
Postoperative breathing exercises are recommended to cardiac surgery patients. Instructions concerning how long patients should continue exercises after discharge vary, and the significance of treatment needs to be determined. Our aim was to assess the effects of home-based deep breathing exercises performed with a positive expiratory pressure device for 2 months following cardiac surgery. The study design was a prospective, single-blinded, parallel-group, randomized trial. Patients performing breathing exercises 2 months after cardiac surgery (n = 159) were compared with a control group (n = 154) performing no breathing exercises after discharge. The intervention consisted of 30 slow deep breaths performed with a positive expiratory pressure device (10-15 cm H2O), 5 times a day, during the first 2 months after surgery. The outcomes were lung function measurements, oxygen saturation, thoracic excursion mobility, subjective perception of breathing and pain, patient-perceived quality of recovery (40-Item Quality of Recovery score), health-related quality of life (36-Item Short Form Health Survey), and self-reported respiratory tract infection/pneumonia and antibiotic treatment. Two months postoperatively, the patients had significantly reduced lung function, with a mean decrease in forced expiratory volume in 1 second to 93 ± 12% (P< .001) of preoperative values. Oxygenation had returned to preoperative values, and 5 of 8 aspects in the 36-Item Short Form Health Survey were improved compared with preoperative values (P< .01). There were no significant differences between the groups in any of the measured outcomes. No significant differences in lung function, subjective perceptions, or quality of life were found between patients performing home-based deep breathing exercises and control patients 2 months after cardiac surgery.
Zeng, Xiaofang; Lincoff, A Michael; Schulz-Schüpke, Stefanie; Steg, Philippe Gabriel; Elbez, Yedid; Mehran, Roxana; Stone, Gregg W; McAndrew, Thomas; Lin, Jianhui; Zhang, Xindan; Shi, Wenhai; Lei, Han; Jing, Zhicheng; Huang, Wei
2018-05-01
Patients with chronic kidney disease (CKD) have elevated bleeding and ischemic outcomes. We aim to assess the short- and long-term efficacy and safety of bivalirudin compared to heparin plus glycoprotein IIb/IIIa inhibitors (GPIs) in coronary artery disease (CAD) patients with CKD. Randomized trials were searched in PubMed, Cochrane, and Embase databases up to January 2017. Among the trials retrieved, efficacy endpoints were defined as mortality, myocardial infarction (MI), repeat revascularization, stent thrombosis, and major adverse cardiac events (MACEs). Safety endpoints were reported as non-coronary artery bypass grafting (CABG) related major bleeding and thrombolysis in myocardial infarction (TIMI) major bleeding. Risk ratio (RR) and 95% confidence interval (CI) were calculated for each outcome using a fixed effect model. Five studies with a total of 3796 patients were included. In short-term follow up (30 days), bivalirudin significantly reduced non-CABG related major bleeding (p=0.0004) and TIMI major bleeding (p=0.007) compared to heparin plus GPIs. No significant differences were observed in rates of mortality, MI, repeat revascularization, stent thrombosis, and MACEs between the two groups in short- and long-term follow up (6 months to 3 years). In patients with ST elevated myocardial infarction (STEMI) with concurrent CKD, the decreased non-CABG related major bleeding (p=0.04) without increasing ischemic events was also observed after short-term follow up. (1) Bivalirudin is safer than and as effective as heparin plus GPIs in CAD patients with CKD. (2) Impaired renal function does not affect the safety benefits of bivalirudin. (3) Similar efficacy profiles were identified between the two groups after both short- and long-term follow up in the CAD patients with CKD. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Terho, Henri K; Tikkanen, Jani T; Kenttä, Tuomas V; Junttila, M Juhani; Aro, Aapo L; Anttonen, Olli; Kerola, Tuomas; Rissanen, Harri A; Knekt, Paul; Reunanen, Antti; Huikuri, Heikki V
2016-11-01
The long-term prognostic value of a standard 12-lead electrocardiogram (ECG) for predicting cardiac events in apparently healthy middle-aged subjects is not well defined. A total of 9511 middle-aged subjects (mean age 43 ± 8.2 years, 52% males) without a known cardiac disease and with a follow-up 40 years were included in the study. Fatal and non-fatal cardiac events were collected from the national registries. The predictive value of ECG was separately analyzed for 10 and 30 years. Major ECG abnormalities were classified according to the Minnesota code. Subjects with major ECG abnormalities (N = 1131) had an increased risk of cardiac death after 10-years (adjusted hazard ratio [HR] 1.7; 95% confidence interval [95% CI], 1.1-2.5, p = 0.009) and 30-years of follow-up (HR 1.3, 95% CI, 1.1-1.5, p < 0.001). Model discrimination measured with the C-index showed only a minor improvement with the inclusion of ECG abnormalities: 0.851 versus 0.853 and 0.742 versus 0.743 for 10- and 30-year follow-up, respectively. ECG did not predict non-fatal cardiac events after 10-years or 30-years of follow-up. Major ECG abnormalities are associated with an increased risk of short and long-term cardiac mortality in middle-aged subjects. However, the improvement in discrimination between subjects with and without fatal cardiac events was marginal with abnormal ECG. Abnormalities observed on 12-lead electrocardiogram are shown to have prognostic significance for cardiac events in elderly subjects without known cardiac disease. Our results suggest that ECG abnormalities increase the risk of fatal cardiac events also in middle-aged healthy subjects.
Lataro, Renata M; Silva, Carlos A A; Fazan, Rubens; Rossi, Marcos A; Prado, Cibele M; Godinho, Rosely O; Salgado, Helio C
2013-10-15
Heart failure (HF) is characterized by elevated sympathetic activity and reduced parasympathetic control of the heart. Experimental evidence suggests that the increase in parasympathetic function can be a therapeutic alternative to slow HF evolution. The parasympathetic neurotransmission can be improved by acetylcholinesterase inhibition. We investigated the long-term (4 wk) effects of the acetylcholinesterase inhibitor pyridostigmine on sympathovagal balance, cardiac remodeling, and cardiac function in the onset of HF following myocardial infarction. Myocardial infarction was elicited in adult male Wistar rats. After 4 wk of pyridostigmine administration, per os, methylatropine and propranolol were used to evaluate the cardiac sympathovagal balance. The tachycardic response caused by methylatropine was considered to be the vagal tone, whereas the bradycardic response caused by propranolol was considered to be the sympathetic tone. In conscious HF rats, pyridostigmine reduced the basal heart rate, increased vagal, and reduced sympathetic control of heart rate. Pyridostigmine reduced the myocyte diameter and collagen density of the surviving left ventricle. Pyridostigmine also increased vascular endothelial growth factor protein in the left ventricle, suggesting myocardial angiogenesis. Cardiac function was assessed by means of the pressure-volume conductance catheter system. HF rats treated with pyridostigmine exhibited a higher stroke volume, ejection fraction, cardiac output, and contractility of the left ventricle. It was demonstrated that the long-term administration of pyridostigmine started right after coronary artery ligation augmented cardiac vagal and reduced sympathetic tone, attenuating cardiac remodeling and left ventricular dysfunction during the progression of HF in rats.
Gómez-Mauricio, Guadalupe; Moscoso, Isabel; Martín-Cancho, María-Fernanda; Crisóstomo, Verónica; Prat-Vidal, Cristina; Báez-Díaz, Claudia; Sánchez-Margallo, Francisco M; Bernad, Antonio
2016-07-16
Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are among the most promising growth factors for promoting cardiorepair. Here, we evaluated the combination of cell- and gene-based therapy using mesenchymal stem cells (MSC) genetically modified to overexpress IGF-1 or HGF to treat acute myocardial infarction (AMI) in a porcine model. Pig MSC from adipose tissue (paMSC) were genetically modified for evaluation of different therapeutic strategies to improve AMI treatment. Three groups of infarcted Large White pigs were compared (I, control, non-transplanted; II, transplanted with paMSC-GFP (green fluorescent protein); III, transplanted with paMSC-IGF-1/HGF). Cardiac function was evaluated non-invasively using magnetic resonance imaging (MRI) for 1 month. After euthanasia and sampling of the animal, infarcted areas were studied by histology and immunohistochemistry. Intramyocardial transplant in a porcine infarct model demonstrated the safety of paMSC in short-term treatments. Treatment with paMSC-IGF-1/HGF (1:1) compared with the other groups showed a clear reduction in inflammation in some sections analyzed and promoted angiogenic processes in ischemic tissue. Although cardiac function parameters were not significantly improved, cell retention and IGF-1 overexpression was confirmed within the myocardium. The simultaneous administration of IGF-1- and HGF-overexpressing paMSC appears not to promote a synergistic effect or effective repair. The combined enhancement of neovascularization and fibrosis in paMSC-IGF-1/HGF-treated animals nonetheless suggests that sustained exposure to high IGF-1 + HGF levels promotes beneficial as well as deleterious effects that do not improve overall cardiac regeneration.
Lu, Yi; Zhao, Ming; Liu, Jin-Jun; He, Xi; Yu, Xiao-Jiang; Liu, Long-Zhu; Sun, Lei; Chen, Li-Na; Zang, Wei-Jin
2017-09-01
Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload-induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4 pathway and suppression of the interaction of Orai1/STIM1. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Background – Short-term exposure to air pollutants has been linked to acute cardiovascular morbidity and mortality. Even in the absence of overt symptoms, pollutants can cause subtle disruptions of internal regulatory mechanisms, which maintain homeostatic balance, thereby reduci...
CARDIOVASCULAR RESPONSES IN UNRESTRAINED WKY-RATS TO INHALED ULTRAFINE CARBON PARTICLES
Abstract
This study provides evidence for adverse cardiac effects of inhaled ultrafine particles (UFPs) in healthy WKY rats. Short term exposure (24 h) with carbon UFPs (180 ?g?m ?) induced a moderate but significant heart rate increase of 18 bpm (4.8 %) in association with a ...
Acute Peat Smoke Inhalation Increases Blood Pressure and Cardiac Arrhythmia Risk in Rats
Wildland fires are increasingly linked to adverse health impacts related to poor air quality. For instance, short-term exposure to smoldering peat (SP) air pollution in eastern North Carolina during separate burns in 2008 and 2011 led to increased cardiopulmonary emergency room v...
The data show that a single exposure to acrolein causes autonomic imbalance in mice through the TRPA1 sensor and subsequent cardiac dysfunction. Human and animal studies have shown that short-term air pollution exposure causes...
Epidemiologic studies strongly link short-term exposures to vehicular traffic and particulate matter (PM) air pollution with adverse cardiovascular events, especially in those with preexisting cardiovascular disease. Diesel engine exhaust (DE) is a key contributor to urban ambien...
Clinical review: Positive end-expiratory pressure and cardiac output
Luecke, Thomas; Pelosi, Paolo
2005-01-01
In patients with acute lung injury, high levels of positive end-expiratory pressure (PEEP) may be necessary to maintain or restore oxygenation, despite the fact that 'aggressive' mechanical ventilation can markedly affect cardiac function in a complex and often unpredictable fashion. As heart rate usually does not change with PEEP, the entire fall in cardiac output is a consequence of a reduction in left ventricular stroke volume (SV). PEEP-induced changes in cardiac output are analyzed, therefore, in terms of changes in SV and its determinants (preload, afterload, contractility and ventricular compliance). Mechanical ventilation with PEEP, like any other active or passive ventilatory maneuver, primarily affects cardiac function by changing lung volume and intrathoracic pressure. In order to describe the direct cardiocirculatory consequences of respiratory failure necessitating mechanical ventilation and PEEP, this review will focus on the effects of changes in lung volume, factors controlling venous return, the diastolic interactions between the ventricles and the effects of intrathoracic pressure on cardiac function, specifically left ventricular function. Finally, the hemodynamic consequences of PEEP in patients with heart failure, chronic obstructive pulmonary disease and acute respiratory distress syndrome are discussed. PMID:16356246
Determinants of Acute Kidney Injury Duration After Cardiac Surgery: An Externally Validated Tool
Brown, Jeremiah R.; Kramer, Robert S.; MacKenzie, Todd A.; Coca, Steven G.; Sint, Kyaw; Parikh, Chirag R.
2013-01-01
Background Acute kidney injury (AKI) duration following cardiac surgery is associated with poor survival in a dose-dependent manner. However, it is not known what peri-operative risk factors contribute to prolonged AKI and delayed recovery. We sought to identify peri-operative risk factors that predict duration of AKI, a complication that effects short and long term survival. Methods We studied 4,987 consecutive cardiac surgery patients from 2002 through 2007. AKI was defined as a ≥0.3 (mg/dL) or ≥50% increase in SCr from baseline. Duration of AKI was defined by the number of days AKI was present. Step-wise multivariable negative binomial regression analysis was conducted using peri-operative risk factors for AKI duration. C-index was estimated by Kendall’s tau. Results AKI developed in 39% of patients with a median duration of AKI at 3 days and ranged from 1 to 108 days. Patients without AKI had duration of zero days. Independent predictors of AKI duration included baseline patient and disease characteristics, operative and post-operative factors. Prediction for mean duration of AKI was developed using coefficients from the regression model and externally validated the model on 1,219 cardiac surgery patients in a separate cardiac surgery cohort (TRIBE-AKI). The C-index was 0.65 (p<0.001) for the derivation cohort and 0.62 (p<0.001) for the validation cohort. Conclusion We identified and externally validated peri-operative predictors of AKI duration. These risk-factors will be useful to evaluate a patient’s risk for the tempo of recovery from AKI after cardiac surgery and subsequent short and long term survival. The level of awareness created by working with these risk factors have implications regarding positive changes in processes of care that have the potential to decrease the incidence and mitigate AKI. PMID:22206952
Silva, Luiz Eduardo Virgilio; Lataro, Renata Maria; Castania, Jaci Airton; Silva, Carlos Alberto Aguiar; Salgado, Helio Cesar; Fazan, Rubens; Porta, Alberto
2017-08-01
Heart rate variability (HRV) has been extensively explored by traditional linear approaches (e.g., spectral analysis); however, several studies have pointed to the presence of nonlinear features in HRV, suggesting that linear tools might fail to account for the complexity of the HRV dynamics. Even though the prevalent notion is that HRV is nonlinear, the actual presence of nonlinear features is rarely verified. In this study, the presence of nonlinear dynamics was checked as a function of time scales in three experimental models of rats with different impairment of the cardiac control: namely, rats with heart failure (HF), spontaneously hypertensive rats (SHRs), and sinoaortic denervated (SAD) rats. Multiscale entropy (MSE) and refined MSE (RMSE) were chosen as the discriminating statistic for the surrogate test utilized to detect nonlinearity. Nonlinear dynamics is less present in HF animals at both short and long time scales compared with controls. A similar finding was found in SHR only at short time scales. SAD increased the presence of nonlinear dynamics exclusively at short time scales. Those findings suggest that a working baroreflex contributes to linearize HRV and to reduce the likelihood to observe nonlinear components of the cardiac control at short time scales. In addition, an increased sympathetic modulation seems to be a source of nonlinear dynamics at long time scales. Testing nonlinear dynamics as a function of the time scales can provide a characterization of the cardiac control complementary to more traditional markers in time, frequency, and information domains. NEW & NOTEWORTHY Although heart rate variability (HRV) dynamics is widely assumed to be nonlinear, nonlinearity tests are rarely used to check this hypothesis. By adopting multiscale entropy (MSE) and refined MSE (RMSE) as the discriminating statistic for the nonlinearity test, we show that nonlinear dynamics varies with time scale and the type of cardiac dysfunction. Moreover, as complexity metrics and nonlinearities provide complementary information, we strongly recommend using the test for nonlinearity as an additional index to characterize HRV. Copyright © 2017 the American Physiological Society.
Rocco, Isadora Salvador; Viceconte, Marcela; Pauletti, Hayanne Osiro; Matos-Garcia, Bruna Caroline; Marcondi, Natasha Oliveira; Bublitz, Caroline; Bolzan, Douglas William; Moreira, Rita Simone Lopes; Reis, Michel Silva; Hossne, Nelson Américo; Gomes, Walter José; Arena, Ross; Guizilini, Solange
2017-12-26
We aimed to investigate the ability of oxygen uptake kinetics to predict short-term outcomes after off-pump coronary artery bypass grafting. Fifty-two patients aged 60.9 ± 7.8 years waiting for off-pump coronary artery bypass surgery were evaluated. The 6-min walk test distance was performed pre-operatively, while simultaneously using a portable cardiopulmonary testing device. The transition of oxygen uptake kinetics from rest to exercise was recorded to calculate oxygen uptake kinetics fitting a monoexponential regression model. Oxygen uptake at steady state, constant time, and mean response time corrected by work rate were analysed. Short-term clinical outcomes were evaluated during the early post-operative of off-pump coronary artery bypass surgery. Multivariate analysis showed body mass index, surgery time, and mean response time corrected by work rate as independent predictors for short-term outcomes. The optimal mean response time corrected by work rate cut-off to estimate short-term clinical outcomes was 1.51 × 10 -3 min 2 /ml. Patients with slower mean response time corrected by work rate demonstrated higher rates of hypertension, diabetes, EuroSCOREII, left ventricular dysfunction, and impaired 6-min walk test parameters. The per cent-predicted distance threshold of 66% in the pre-operative was associated with delayed oxygen uptake kinetics. Pre-operative oxygen uptake kinetics during 6-min walk test predicts short-term clinical outcomes after off-pump coronary artery bypass surgery. From a clinically applicable perspective, a threshold of 66% of pre-operative predicted 6-min walk test distance indicated slower kinetics, which leads to longer intensive care unit and post-surgery hospital length of stay. Implications for rehabilitation Coronary artery bypass grafting is a treatment aimed to improve expectancy of life and prevent disability due to the disease progression; The use of pre-operative submaximal functional capacity test enabled the identification of patients with high risk of complications, where patients with delayed oxygen uptake kinetics exhibited worse short-term outcomes; Our findings suggest the importance of the rehabilitation in the pre-operative in order to "pre-habilitate" the patients to the surgical procedure; Faster oxygen uptake on-kinetics could be achieved by improving the oxidative capacity of muscles and cardiovascular conditioning through rehabilitation, adding better results following cardiac surgery.
Jiang, Can; Zheng, Dong; Feng, Yun-Lu; Guo, Jun; Li, Hai-Rui; Zhang, Ai-Dong
2016-09-20
Objective To investigate the short- and long-term therapeutic efficacies of intravenous trans- plantation of bone marrow stem cells (MSCs) in rats with experimental myocardial infarction by meta- analysis. Methods Randomized controlled trials were systematically searched from PubMed, Science Citation Index (SCI), Chinese journal full-text database (CJFD) up to December 2014. While the experimental groups (MSCs groups) were injected MSCs intravenously, the control groups were injected Delubecco's minimum essential medium (DMEM) or phosphate buffered saline (PBS). Subgroup analysis for each outcome measure was performed for the observing time point after the transplantation of MSCs. Weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated for outcome parameters including ejection fraction (EF) and fractional shortening (FS), which were measured by echocardiogram after intravenous injection and analyzed by RevMan 5.2 and STATA 12.0. Results Data from 9 studies (190 rats) were included in the meta-analysis. As compared to the control groups, the cardiac function of the experimental groups were not improved at day 7 (EF: WMD=0.08, 95%CI -1.32 to 1.16, P>0.01; FS: WMD=-0.12, 95%CI -0.90 to 0.65, P>0.01) until at day 14 after MSCs' transplantation (EF: WMD=10.79, 95%CI 9.16 to 12.42, P<0.01; FS: WMD=11.34, 95%CI 10.44 to 12.23, P<0.01), and it lasted 4 weeks or more after transplantation of MSCs (EF: WMD=13.94, 95%CI 12.24 to 15.64, P<0.01; FS: WMD=9.64, 95%CI 7.98 to 11.31, P<0.01). Conclusion The therapeutic efficacies of MSCs in rats with myocardid infarction become increasing apparent as time advances since 2 weeks after injection.
Randers, Morten Bredsgaard; Andersen, Lars Juel; Orntoft, Christina; Bendiksen, Mads; Johansen, Lars; Horton, Joshua; Hansen, Peter Riis; Krustrup, Peter
2013-01-01
This study examined the intermittent exercise performance and cardiovascular health profile in elite female football players in comparison to untrained young women, as well as a subgroup subjected to football training 2x1 h · week(-1) for 16 weeks. Twenty-seven Danish national team players (elite trained, ET) and 28 untrained women (UT) underwent dual-energy X-ray absorptiometry-scanning (DXA), comprehensive transthoracic echocardiography, treadmill and Yo-Yo Intermittent Endurance level 2 (IE2) testing. Eight women in UT were also tested after the football training period. Maximal oxygen uptake rate (VO2max), peak ventilation and peak lactate were 40, 18 and 51% higher (P< 0.01) in ET than UT, respectively. Cardiac dimensions and function were greater in ET than UT, with left ventricular diastolic diameter, right ventricular diastolic diameter, tricuspid annular plane systolic excursion (TAPSE) and peak transmitral flow in early diastole divided by peak transmitral flow velocity in late diastole during atrial contraction (E/A-ratio) being 13, 19, 27 and 41%, respectively, greater in ET than UT (P< 0.001 to< 0.05). Yo-Yo IE2 performance was 7-fold higher in ET than UT (1772 ± 508 vs. 234 ± 66 m, P< 0.001), fat mass was 51% lower (P< 0.001) and high density lipoprotein (HDL) cholesterol levels were 20% higher (P< 0.01). Sixteen weeks of football elevated VO2max and Yo-Yo IE2 performance by 16 and 40%, respectively, and lowered fat mass by 6%. Cardiac function was markedly improved by 16 weeks of football training with 26 and 46% increases in TAPSE and E/A ratio, respectively, reaching levels comparable to ET. In summary, elite female football players have a superior cardiovascular health profile and intermittent exercise performance compared to untrained controls, but short-term football training can markedly improve the cardiovascular health status.
Rodent Studies of Cardiovascular Deconditioning
NASA Technical Reports Server (NTRS)
Shoukas, Artin A.
1999-01-01
Changes in blood pressure can occur for two reasons: 1) A decrease in cardiac output resulting from the altered contractility of the heart or through changes in venous filling pressure via the Frank Starling mechanism or; 2) A change in systemic vascular resistance. The observed changes in cardiac output and blood pressure after long term space flight cannot be entirely explained through changes in contractility or heart rate alone. Therefore, alterations in filling pressure mediated through changes in systemic venous capacitance and arterial resistance function may be important determinants of cardiac output and blood pressure after long term space flight. Our laboratory and previous studies have shown the importance of veno-constriction mediated by the carotid sinus baroreceptor reflex system on overall circulatory homeostasis and in the regulation of cardiac output. Our proposed experiments test the overall hypothesis that alterations in venous capacitance function and arterial resistance by the carotid sinus baroreceptor reflex system are an important determinant of the cardiac output and blood pressure response seen in astronauts after returning to earth from long term exposure to microgravity. This hypothesis is important to our overall understanding of circulatory adjustments made during long term space flight. It also provides a framework for investigating counter measures to reduce the incidence of orthostatic hypotension caused by an attenuation of cardiac output. We continue to use hind limb unweighted (HLU) rat model to simulate the patho physiological effects as they relate to cardiovascular deconditioning in microgravity. We have used this model to address the hypothesis that microgravity induced cardiovascular deconditioning results in impaired vascular responses and that these impaired vascular responses result from abnormal alpha-1 AR signaling. The impaired vascular reactivity results in attenuated blood pressure and cardiac output responses to an orthostatic challenge. We have used in vitro vascular reactivity assays to explore abnormalities in vascular responses in vessels from HLU animals and, cardiac output (CO), blood pressure (BP) and heart rate (HR) measurements to characterize changes in hemodynamics following HLU.
Carter, Timothy; Bodzin, Adam S; Hirose, Hitoshi; West, Sharon; Hasz, Richard; Maley, Warren R; Cavarocchi, Nicholas C
2014-07-01
Extracorporeal membrane oxygenation has become rescue therapy for adults with overwhelming cardiac and/or respiratory failure. Not all patients are saved, creating a new cohort of potential organ donors. This study examines the outcomes of liver and kidney allografts procured from donors on extracorporeal membrane oxygenation (ECMO). A retrospective review was conducted through the local organ procurement organization. Donors on ECMO prior to notification were classified into donation after brain death (DBD) and donation after cardiac death (DCD). We compared short-term outcome data against published standards. Between 1995 and 2012, 97 organs were procured from 41 donors supported on ECMO. There were 68 kidneys donated, 51 were transplanted and 17 discarded. Excluding extended criteria donors, 29 DBD and 13 DCD kidneys were transplanted from donors supported on ECMO. Delayed graft function occurred in 34% of DBD kidneys and 38% of DCD kidneys. Kidney allograft survival at one yr was 93%. Twenty-four livers were procured, nine discarded, and 15 transplanted. Ninety-three percent of liver transplant recipients were alive with graft function at one yr. Donation after brain death kidneys procured from donors on ECMO perform similarly to non-ECMO organs with regard to delayed graft function (DGF), one-yr graft survival and function. Livers from ECMO donors have a higher discard rate than non-ECMO donors, but function similarly at six months and one yr. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Memory-induced nonlinear dynamics of excitation in cardiac diseases.
Landaw, Julian; Qu, Zhilin
2018-04-01
Excitable cells, such as cardiac myocytes, exhibit short-term memory, i.e., the state of the cell depends on its history of excitation. Memory can originate from slow recovery of membrane ion channels or from accumulation of intracellular ion concentrations, such as calcium ion or sodium ion concentration accumulation. Here we examine the effects of memory on excitation dynamics in cardiac myocytes under two diseased conditions, early repolarization and reduced repolarization reserve, each with memory from two different sources: slow recovery of a potassium ion channel and slow accumulation of the intracellular calcium ion concentration. We first carry out computer simulations of action potential models described by differential equations to demonstrate complex excitation dynamics, such as chaos. We then develop iterated map models that incorporate memory, which accurately capture the complex excitation dynamics and bifurcations of the action potential models. Finally, we carry out theoretical analyses of the iterated map models to reveal the underlying mechanisms of memory-induced nonlinear dynamics. Our study demonstrates that the memory effect can be unmasked or greatly exacerbated under certain diseased conditions, which promotes complex excitation dynamics, such as chaos. The iterated map models reveal that memory converts a monotonic iterated map function into a nonmonotonic one to promote the bifurcations leading to high periodicity and chaos.
Memory-induced nonlinear dynamics of excitation in cardiac diseases
NASA Astrophysics Data System (ADS)
Landaw, Julian; Qu, Zhilin
2018-04-01
Excitable cells, such as cardiac myocytes, exhibit short-term memory, i.e., the state of the cell depends on its history of excitation. Memory can originate from slow recovery of membrane ion channels or from accumulation of intracellular ion concentrations, such as calcium ion or sodium ion concentration accumulation. Here we examine the effects of memory on excitation dynamics in cardiac myocytes under two diseased conditions, early repolarization and reduced repolarization reserve, each with memory from two different sources: slow recovery of a potassium ion channel and slow accumulation of the intracellular calcium ion concentration. We first carry out computer simulations of action potential models described by differential equations to demonstrate complex excitation dynamics, such as chaos. We then develop iterated map models that incorporate memory, which accurately capture the complex excitation dynamics and bifurcations of the action potential models. Finally, we carry out theoretical analyses of the iterated map models to reveal the underlying mechanisms of memory-induced nonlinear dynamics. Our study demonstrates that the memory effect can be unmasked or greatly exacerbated under certain diseased conditions, which promotes complex excitation dynamics, such as chaos. The iterated map models reveal that memory converts a monotonic iterated map function into a nonmonotonic one to promote the bifurcations leading to high periodicity and chaos.
Chowdhury, Enayet K; Jennings, Garry L R; Dewar, Elizabeth; Wing, Lindon M H; Reid, Christopher M
2016-07-01
Hypertension leads to cardiac structural and functional changes, commonly assessed by echocardiography. In this study, we assessed the predictive performance of different echocardiographic parameters including left ventricular hypertrophy (LVH) on future cardiovascular outcomes in elderly hypertensive patients without heart failure. Data from LVH substudy of the Second Australian National Blood Pressure trial were used. Echocardiograms were performed at entry into the study. Cardiovascular outcomes were identified over short term (median 4.2 years) and long term (median 10.9 years). LVH was defined using threshold values of LV mass (LVM) indexed to either body surface area (BSA) or height(2.7): >115/95g/m(2) (LVH-BSA(115/95)) or ≥49/45g/m(2.7) (LVH-ht(49/45)) in males/females, respectively, and ≥125g/m(2) (LVH-BSA(125)) or ≥51g/m(2.7) (LVH-ht(51)) for both sexes. In the 666 participants aged ≥65 years in this analysis, LVH prevalence at baseline was 33%-70% depending on definition; and after adjusting for potential risk factors, only LVH-BSA(115/95) predicted both short- and long-term cardiovascular outcomes. Participants having LVH-BSA(115/95) (69%) at baseline had twice the risk of having any first cardiovascular event over the short term (hazard ratio, 95% confidence interval: 2.00, 1.12-3.57, P = 0.02) and any fatal cardiovascular events (2.11, 1.21-3.68, P = 0.01) over the longer term. Among other echocardiographic parameters, LVM and LVM indexed to either BSA or height(2.7) predicted cardiovascular events over both short and longer term. In elderly treated hypertensive patients without heart failure, determining LVH by echocardiography is highly dependent on the methodology adopted. LVH-BSA(115/95) is a reliable predictor of future cardiovascular outcomes in the elderly. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Behr, Luc; Chetboul, Valérie; Sampedrano, Carolina Carlos; Vassiliki, Gouni; Pouchelon, Jean-Louis; Laborde, François; Borenstein, Nicolas
2007-04-01
To describe an open, beating heart surgical technique and use of a bovine pericardial prosthetic valve for mitral valve replacement (MVR) in the dog. Clinical case report. Male Bull Terrier (17-month-old, 26 kg) with mitral valve dysplasia and severe regurgitation. A bovine pericardial bioprosthesis was used to replace the mitral valve using an open beating heart surgical technique and cardiopulmonary bypass. Successful MVR was achieved using a beating heart technique. Mitral regurgitation resolved and cardiac performances improved (left ventricular end-diastolic diameter decreased from 57.6 to 48.7 mm, and left atrium/aorta ratio returned to almost normal, from 1.62 to 1.19). Cardiopulmonary by-pass time and total surgical duration were decreased compared with standard cardioplegic techniques. Surgical recovery was uneventful and on echocardiography 6 months later valve function was excellent. Considering the technique advantages (no cardiac arrest, ischemic reperfusion injury, and hypothermia, or the need for aortic dissection and cannulation for administration of cardioplegic solution), short-term mortality and morbidity may be reduced compared with standard cardioplegic techniques. Based on experience in this dog, beating heart mitral valvular replacement is a seemingly safe and viable option for the dog and bovine pericardial prosthesis may provide better long-term survival than mechanical prostheses.
Acosta, Pedro; Sleeper, Meg M.; Barton, Elisabeth R.; Sweeney, H. Lee
2013-01-01
Dystrophin-deficient muscles suffer from free radical injury, mitochondrial dysfunction, apoptosis, and inflammation, among other pathologies that contribute to muscle fiber injury and loss, leading to wheelchair confinement and death in the patient. For some time, it has been appreciated that endurance training has the potential to counter many of these contributing factors. Correspondingly, numerous investigations have shown improvements in limb muscle function following endurance training in mdx mice. However, the effect of long-term volitional wheel running on diaphragm and cardiac function is largely unknown. Our purpose was to determine the extent to which long-term endurance exercise affected dystrophic limb, diaphragm, and cardiac function. Diaphragm specific tension was reduced by 60% (P < 0.05) in mice that performed 1 yr of volitional wheel running compared with sedentary mdx mice. Dorsiflexor mass (extensor digitorum longus and tibialis anterior) and function (extensor digitorum longus) were not altered by endurance training. In mice that performed 1 yr of volitional wheel running, plantarflexor mass (soleus and gastrocnemius) was increased and soleus tetanic force was increased 36%, while specific tension was similar in wheel-running and sedentary groups. Cardiac mass was increased 15%, left ventricle chamber size was increased 20% (diastole) and 18% (systole), and stroke volume was increased twofold in wheel-running compared with sedentary mdx mice. These data suggest that the dystrophic heart may undergo positive exercise-induced remodeling and that limb muscle function is largely unaffected. Most importantly, however, as the diaphragm most closely recapitulates the human disease, these data raise the possibility of exercise-mediated injury in dystrophic skeletal muscle. PMID:23823150
Ogawa, Masato; Izawa, Kazuhiro P; Satomi-Kobayashi, Seimi; Kitamura, Aki; Ono, Rei; Sakai, Yoshitada; Okita, Yutaka
2017-04-01
Preoperative nutritional status and physical function are important predictors of mortality and morbidity after cardiac surgery. However, the influence of nutritional status before cardiac surgery on physical function and the progress of postoperative rehabilitation requires clarification. To determine the effect of preoperative nutritional status on preoperative physical function and progress of rehabilitation after elective cardiac surgery. We enrolled 131 elderly patients with mean age of 73.7 ± 5.8 years undergoing cardiac surgery. We divided them into two groups by nutritional status as measured by the Geriatric Nutritional Risk Index (GNRI): high GNRI group (GNRI ≥ 92, n = 106) and low GNRI group (GNRI < 92, n = 25). Physical function was estimated by handgrip strength, knee extensor muscle strength (KEMS), the Short Physical Performance Battery (SPPB), and 6-minute walk test (6MWT). Progress of postoperative rehabilitation was evaluated by the number of days to independent walking after surgery, length of stay in the ICU, and length of hospital stay. After adjusting for potential confounding factors, preoperative handgrip strength (P = 0.034), KEMS (P = 0.009), SPPB (P < 0.0001), and 6MWT (P = 0.012) were all significantly better in the high GNRI group. Multiple regression analysis revealed that a low GNRI was an independent predictor of the retardation of postoperative rehabilitation. Preoperative nutritional status as assessed by the GNRI could reflect perioperative physical function. Preoperative poor nutritional status may be an independent predictor of the retardation of postoperative rehabilitation in patients undergoing elective cardiac surgery.
Short-Term Health Impact Assessment of Urban PM10 in Bejaia City (Algeria).
Benaissa, Fatima; Maesano, Cara Nichole; Alkama, Rezak; Annesi-Maesano, Isabella
2016-01-01
We used Health Impact Assessment (HIA) to analyze the impact on a given population's health outcomes in terms of all-causes mortality and respiratory and cardiovascular hospitalizations attributable to short-term exposure to particulate matter less than 10 μm diameter (PM10) in Bejaia city, for which health effects of air pollution have never been investigated. Two scenarios of PM10 reduction were considered: first, a scenario where the PM10 annual mean is decreased by 5 µg/m(3), and then a scenario where this PM10 mean is decreased to 20 µg/m(3) (World Health Organization annual air quality guideline (WHO-AQG)). Annual mean level of PM10 (81.7 µg/m(3)) was calculated from objective measurements assessed in situ. Each year, about 4 and 55 deaths could be postponed with the first and the second scenarios successfully. Furthermore, decreasing PM10 annual mean by 5 µg/m(3) would avoid 5 and 3 respiratory and cardiac hospitalizations, respectively, and not exceeding the PM10 WHO-AQG (20 µg/m(3)) would result in a potential gain of 36 and 23 per 100000 respiratory and cardiac hospitalizations, respectively. Lowering in current levels of PM10 has a nonnegligible impact in terms of public health that it is expected to be higher in the case of long-term effects.
2011-01-01
Background Progressive remodeling after myocardial infarction (MI) is a leading cause of morbidity and mortality. Recently, glucagon-like peptide (GLP)-1 was shown to have cardioprotective effects, but treatment with GLP-1 is limited by its short half-life. It is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4), an enzyme which inhibits GLP-1 activity. We hypothesized that the DPP-4 inhibitor vildagliptin will increase levels of GLP-1 and may exert protective effects on cardiac function after MI. Methods Sprague-Dawley rats were either subjected to coronary ligation to induce MI and left ventricular (LV) remodeling, or sham operation. Parts of the rats with an MI were pre-treated for 2 days with the DPP-4 inhibitor vildagliptin (MI-Vildagliptin immediate, MI-VI, 15 mg/kg/day). The remainder of the rats was, three weeks after coronary artery ligation, subjected to treatment with DPP-4 inhibitor vildagliptin (MI-Vildagliptin Late, MI-VL) or control (MI). At 12 weeks, echocardiography and invasive hemodynamics were measured and molecular analysis and immunohistochemistry were performed. Results Vildagliptin inhibited the DPP-4 enzymatic activity by almost 70% and increased active GLP-1 levels by about 3-fold in plasma in both treated groups (p < 0.05 vs. non-treated groups). Cardiac function (ejection fraction) was decreased in all 3 MI groups compared with Sham group (p < 0.05); treatment with vildagliptin, either early or late, did not reverse cardiac remodeling. ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide) mRNA levels were significantly increased in all 3 MI groups, but no significant reductions were observed in both vildagliptin groups. Vildagliptin also did not change cardiomyocyte size or capillary density after MI. No effects were detected on glucose level and body weight in the post-MI remodeling model. Conclusion Vildagliptin increases the active GLP-1 level via inhibition of DPP-4, but it has no substantial protective effects on cardiac function in this well established long-term post-MI cardiac remodeling model. PMID:21955567
Kageyama, T; Nishikido, N; Kobayashi, T; Kurokawa, Y; Kaneko, T; Kabuto, M
1998-07-01
To investigate the possible effects of long commuting time and extensive overtime on daytime cardiac autonomic activity, the short-term heart rate variability (HRV) both at supine rest and at standing rest of 223 male white-collar workers in the Tokyo Megalopolis was examined. Workers with a one-way commute of 90 min or more exhibited decreased vagal activity at supine rest and increased sympathetic activity regardless of posture, and those doing overtime of 60 h/month or more exhibited decreased vagal activity and increased sympathetic activity at standing rest. These findings suggest that chronic stress or fatigue resulting from long commuting time or extensive overtime caused these individuals to be in a sympathodominant state. Although these shifts in autonomic activities are not direct indicators of disease, it can be hypothesized that they can induce cardiovascular abnormalities or dysfunctions related to the onset of heart disease. Assessment of the daily and weekly variations in HRV as a function of daily life activities (such as working, commuting, sleeping, and exercising) among workers in Asia-Pacific urban areas might be one way of studying the possible effects of long commuting time, and extensive overtime, on health.
Schwaiger, Johannes P; Knight, Daniel S; Kaier, Thomas; Gallimore, Adele; Denton, Christopher P; Schreiber, Benjamin E; Handler, Clive; Coghlan, John G
2017-06-01
Data are scarce about short-term right ventricular changes in pulmonary hypertension. Two-dimensional knowledge-based reconstruction of the right ventricle with 2D echocardiography (2DKBR) has been shown to be a valid alternative to Cardiac MRI. In this longitudinal study 25 pulmonary hypertension patients underwent 2DKBR of the right ventricle, assessment of NT-proBNP levels and functional class at baseline and after a mean follow-up of 6.1 months. Patients were followed up clinically for a further mean of 8.2 months. The majority of patients had connective tissue disease (CTD) associated pulmonary arterial hypertension (n=15) or chronic thromboembolic pulmonary hypertension (CTEPH; n=6). A total of 15 patients underwent an intervention, either new targeted therapy, escalation of targeted therapy or pulmonary endarterectomy. A total of 10 clinically stable patients were routinely followed up without any change in therapy. There were significant improvements in the right ventricular end-diastolic volume index (111±29 mL/m² vs 100±36 mL/m²; P=.038), end-systolic volume index (72±23 mL/m² vs 61±25 mL/m²; P=.001), and ejection fraction (35±10% vs 40±9%; P=.030). Changes in NT-proBNP levels correlated strongest with changes in end-systolic volume index (r=-.77; P=<.0001). Four patients experienced clinical worsening during extended follow-up, dilatation of the right ventricle was associated with clinical worsening. In a CTD and CTEPH dominated patient population significant reverse remodeling and improvement of ejection fraction occurred despite a short follow-up and was paralleled by significant changes in NT-proBNP levels. Further right ventricular dilatation was associated with worse clinical outcome. 2DKBR is a feasible substitute for Cardiac MRI to follow-up right ventricular indices in pulmonary hypertension. © 2017, Wiley Periodicals, Inc.
Cardiac Ischemia/Reperfusion Injury: The Beneficial Effects of Exercise.
Borges, Juliana Pereira; da Silva Verdoorn, Karine
2017-01-01
Cardiac ischemia reperfusion injury (IRI) occurs when the myocardium is revascularized after an episode of limited or absent blood supply. Many changes, including free radical production, calcium overload, protease activation, altered membrane lipids and leukocyte activation, contribute to IRI-induced myocardium damage. Aerobic exercise is the only countermeasure against IRI that can be sustained on a regular basis in clinical practice. Interestingly, both short-term (3-5 days) and long-term (several weeks) exercise increase myocardial tolerance, reduce infarct size area and arrhythmias induced by IRI. Exercise protects the heart against IRI in a biphasic manner. The early phase of cardioprotection occurs between 30 min and 3 h following an acute exercise bout, whilst the late phase is achieved within 24 h after the exercise bout and persists for several days. As for the exercise intensity, although controversial data exists, it is feasible that the amount of cardioprotection is proportional to exercise intensity and only achieved above a critical threshold. It is known that aerobic exercise produces a cardioprotective phenotype, however the mechanisms responsible for this phenomenon remain unclear. Apparently, aerobic exercise-induced preconditioning is dependent on several factors that work together to protect the heart. Altered nitric oxide (NO) signaling, increased levels of heat shock proteins (HSPs), enhanced function of ATP-sensitive potassium channels, increased activation of opioids system, and enhanced antioxidant capacity may contribute to exercise-induced cardioprotection. Much has been discovered from animal models involving exercise-induced cardioprotection against cardiac IRI, however translating these findings to clinical practice still represents the major challenge in this field.
Ma, Fangfang; Takanari, Hiroki; Masuda, Kimiko; Morishima, Masaki; Ono, Katsushige
2016-07-01
Bepridil is an effective antiarrhythmic drug on supraventricular and ventricular arrhythmias, and inhibitor of calmodulin. Recent investigations have been elucidating that bepridil exerts antiarrhythmic effects through its acute and chronic application for patients. The aim of this study was to identify the efficacy and the potential mechanism of bepridil on the inward-rectifier potassium channel in neonatal rat cardiomyocytes in acute- and long-term conditions. Bepridil inhibited inward-rectifier potassium current (I K1) as a short-term effect with IC50 of 17 μM. Bepridil also reduced I K1 of neonatal cardiomyocytes when applied for 24 h in the culture medium with IC50 of 2.7 μM. Both a calmodulin inhibitor (W-7) and an inhibitor of calmodulin-kinase II (KN93) reduced I K1 when applied for 24 h as a long-term effect in the same fashion, suggesting that the long-term application of bepridil inhibits I K1 more potently than that of the short-term application through the inhibition of calmodulin kinase II pathway in cardiomyocytes.
2006-12-01
on specific short term problems. 1.1.1 Dynamic Physiological Modeling The oxygenation of the blood by the lung through respiration is a critical...tests as apnea , reduced arterial saturation, and may even be linked to long term CNS deficits. Inhalation of toxic gases can dramatically affect the...of TGAS model the respiration , circulation, and metabolic processes and include models of the ventilation and cardiac output control due to 3
This study shows that exposure to CAPs and acrolein causes an increase in HRV that is mediated by the parasympathetic nervous system. Numerous studies show that short-term air pollution exposure modulates heart rate variability (HRV), which is an indicator of autonomic influence...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Bartels, Emil D.; Nielsen, Jan M.; Hellgren, Lars I.; Ploug, Thorkil; Nielsen, Lars B.
2009-01-01
Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and β-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac triglycerides, induced cardiac expression of triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease. PMID:19390571
Air Pollution and Other Environmental Modulators of Cardiac Function.
Gorr, Matthew W; Falvo, Michael J; Wold, Loren E
2017-09-12
Cardiovascular disease (CVD) is the leading cause of death in developed regions and a worldwide health concern. Multiple external causes of CVD are well known, including obesity, diabetes, hyperlipidemia, age, and sedentary behavior. Air pollution has been linked with the development of CVD for decades, though the mechanistic characterization remains unknown. In this comprehensive review, we detail the background and epidemiology of the effects of air pollution and other environmental modulators on the heart, including both short- and long-term consequences. Then, we provide the experimental data and current hypotheses of how pollution is able to cause the CVD, and how exposure to pollutants is exacerbated in sensitive states. Published 2017. Compr Physiol 7:1479-1495, 2017. Copyright © 2017 John Wiley & Sons, Inc.
NASA Technical Reports Server (NTRS)
Chestukhin, V. V.; Katkov, V. Y.; Seid-Gusaynov, A. A.; Shalnev, B. I.; Georgiyevskiy, V. S.; Zybin, O. K.; Mikhaylov, V. M.; Utkin, V. N.
1981-01-01
A 15 minute orthostatic test was performed on healthy male volunteers under conditions of catheterization of the right ventricle of the heart and the radial (or brachial) artery before and after 5 day bedrest in an antiorthostatic position of the body (with the foot of the bed raised 4.5 degrees). The change to a vertical position after immobilization was attended by a more marked increase in the rate of cardiac contractions, an increase of max dp/dt pressure in the right ventricle, and a decrease of cardiac and stroke indices. The decrease of the cardiac index was compensated for, to a certain measure, by a further increase in the extraction and utilization of O2 by the tissues. The arterial blood pH did not change essentially, while the decrease in pCO2 and content of standard bicarbonate was more marked.
Mickelson, Alexis V; Chandra, Murali
2017-12-01
The central region of cardiac troponin T (TnT) is important for modulating the dynamics of muscle length-mediated cross-bridge recruitment. Therefore, hypertrophic cardiomyopathy mutations in the central region may affect cross-bridge recruitment dynamics to alter myofilament Ca 2+ sensitivity and length-dependent activation of cardiac myofilaments. Given the importance of the central region of TnT for cardiac contractile dynamics, we studied if hypertrophic cardiomyopathy-linked mutation (TnT R94H )-induced effects on contractile function would be differently modulated by sarcomere length (SL). Recombinant wild-type TnT (TnT WT ) and the guinea pig analog of the human R94H mutation (TnT R95H ) were reconstituted into detergent-skinned cardiac muscle fibers from guinea pigs. Steady-state and dynamic contractile measurements were made at short and long SLs (1.9 and 2.3 µm, respectively). Our results demonstrated that TnT R95H increased pCa 50 (-log of free Ca 2+ concentration) to a greater extent at short SL; TnT R95H increased pCa 50 by 0.11 pCa units at short SL and 0.07 pCa units at long SL. The increase in pCa 50 associated with an increase in SL from 1.9 to 2.3 µm (ΔpCa 50 ) was attenuated nearly twofold in TnT R95H fibers; ΔpCa 50 was 0.09 pCa units for TnT WT fibers but only 0.05 pCa units for TnT R95H fibers. The SL dependency of rate constants of cross-bridge distortion dynamics and tension redevelopment was also blunted by TnT R95H Collectively, our observations on the SL dependency of pCa 50 and rate constants of cross-bridge distortion dynamics and tension redevelopment suggest that mechanisms underlying the length-dependent activation cardiac myofilaments are attenuated by TnT R95H NEW & NOTEWORTHY Mutant cardiac troponin T (TnT R95H ) differently affects myofilament Ca 2+ sensitivity at short and long sarcomere length, indicating that mechanisms underlying length-dependent activation are altered by TnT R95H TnT R95H enhances myofilament Ca 2+ sensitivity to a greater extent at short sarcomere length, thus attenuating the length-dependent increase in myofilament Ca 2+ sensitivity. Copyright © 2017 the American Physiological Society.
Nagaraja, Pramod; Roberts, Gareth W; Stephens, Michael; Horvath, Szabolcs; Fialova, Jana; Chavez, Rafael; Asderakis, Argiris; Kaposztas, Zsolt
2012-12-27
Delayed graft function (DGF) and acute rejection (AR) exert an adverse impact on graft outcomes after kidney transplantation using organs from donation after brain-stem death (DBD) donors. Here, we examine the impact of DGF and AR on graft survival in kidney transplants using organs from donation after cardiac death (DCD) donors. We conducted a single-center retrospective study of DCD and DBD donor kidney transplants. We compared 1- and 4-year graft and patient survival rates, as well as death-censored graft survival (DCGS) rates, between the two groups using univariate analysis, and the impact of DGF and AR on graft function was compared using multivariate analysis. Eighty DCD and 206 DBD donor transplants were analyzed. Median follow-up was 4.5 years. The incidence of DGF was higher among DCD recipients (73% vs. 27%, P<0.001), and AR was higher among DBD recipients (23% vs. 9%, P<0.001). One-year and 4-year graft survival rates were similar (DCD 94% and 79% vs. DBD 90% and 82%). Among recipients with DGF, the 4-year DCGS rate was better for DCD recipients compared with DBD recipients (100% vs. 92%, P=0.04). Neither DGF nor AR affected the 1-year graft survival rate in DCD recipients, whereas in DBD recipients, the 1-year graft survival rate was worse in the presence of DGF (88% vs. 96%, P=0.04) and the 4-year DCGS rate was worse in the presence of AR (88% vs. 96%, P=0.04). Despite the high incidence of DGF, medium-term outcomes of DCD kidney transplants are comparable to those from DBD transplants. Short-term graft survival from DCD transplants is not adversely influenced by DGF and AR, unlike in DBD transplants.
The role of hemoglobin oxygen affinity in oxygen transport at high altitude.
Winslow, Robert M
2007-09-30
Hemoglobin is involved in the regulation of O(2) transport in two ways: a long-term adjustment in red cell mass is mediated by erythropoietin (EPO), a response to renal oxgyenation. Short-term, rapid-response adjustments are mediated by ventilation, cardiac output, hemoglobin oxygen affinity (P50), barriers to O(2) diffusion, and the control of local microvascular tissue perfusion. The distribution of O(2) between dissolved (PO2) and hemoglobin-bound (saturation) is the familiar oxygen equilibrium curve, whose position is noted as P50. Human hemoglobin is not genetically adapted for function at high altitude. However, more specialized species native to high altitudes (guinea pig and bar-headed goose, for example) seem to have a lower P50 than their sea level counterparts, an adaptation that presumably promotes O(2) uptake from a hypoxic environment. Humans, native to very high altitude either in the Andes or Himalayan mountains, also can increase O(2) affinity, not because of a fundamental difference in hemoglobin structure or function, but because of extreme hyperventilation and alkalosis.
Vogel, T; Leprêtre, P-M; Brechat, P-H; Lonsdorfer, E; Benetos, A; Kaltenbach, G; Lonsdorfer, J
2011-12-01
The aim of this study was to evaluate the efficiency of a short-term Intermittent Work Exercise Program (IWEP) among healthy elderly subjects. This longitudinal prospective study took place at the Strasbourg University Hospital geriatric department. One hundred and fifty older volunteers, previously determined as being free from cardiac and pulmonary disease, were separated into two age groups: the "young senior" (60.2 ± 3.1 yr) and the "older senior" groups (70.8 ± 5.2 yr). These groups were then subdivided by gender into the "young female senior", "young male senior" "older female senior" and "older male senior" groups. Before and after the IWEP, all subjects were asked to perform an incremental cycle exercise to obtain their first ventilatory threshold (VT1), maximal tolerated power (MTP), peak oxygen uptake (VO2peak) and maximal minute ventilation (MMV). The IWEP consisted of a 30-min cycling exercise which took place twice a week, and was divided into six 5-min stages consisting of 4 min at VT1 intensity and 1 min at 90% MTP. An assessment was made of the effects of the IWEP on maximal cardio-respiratory function (MTP, VO2peak, MMV) and endurance parameters (VT1, heart rate [HR] measured at pretraining VT1 and lactate concentrations at pre-training MTP). This short-term training program resulted in a significant increase of MTP (from 13.2% to 20.6%), VO2peak (from 8.9% to 16.6%) and MMV (from 11.1% to 21.8%) in all groups (p<0.05). VT1 improved from 21% at pretraining to 27%, while HR at pre-training VT1 as well as lactate concentrations at pre-training MTP decreased significantly in all groups (p<0.05). The post-training values for VO2peak and MMV of the "older seniors" were not significantly different (p>0.05) from the "young seniors" pre-training values for the same parameters. The most striking finding in this study is that after only 9 weeks, our short-term "individually-tailored" IWEP significantly improved both maximal cardio-respiratory function and endurance parameters in healthy, previously untrained seniors.
Inhomogeneous point-process entropy: An instantaneous measure of complexity in discrete systems
NASA Astrophysics Data System (ADS)
Valenza, Gaetano; Citi, Luca; Scilingo, Enzo Pasquale; Barbieri, Riccardo
2014-05-01
Measures of entropy have been widely used to characterize complexity, particularly in physiological dynamical systems modeled in discrete time. Current approaches associate these measures to finite single values within an observation window, thus not being able to characterize the system evolution at each moment in time. Here, we propose a new definition of approximate and sample entropy based on the inhomogeneous point-process theory. The discrete time series is modeled through probability density functions, which characterize and predict the time until the next event occurs as a function of the past history. Laguerre expansions of the Wiener-Volterra autoregressive terms account for the long-term nonlinear information. As the proposed measures of entropy are instantaneously defined through probability functions, the novel indices are able to provide instantaneous tracking of the system complexity. The new measures are tested on synthetic data, as well as on real data gathered from heartbeat dynamics of healthy subjects and patients with cardiac heart failure and gait recordings from short walks of young and elderly subjects. Results show that instantaneous complexity is able to effectively track the system dynamics and is not affected by statistical noise properties.
Design and formulation of functional pluripotent stem cell-derived cardiac microtissues
Thavandiran, Nimalan; Dubois, Nicole; Mikryukov, Alexander; Massé, Stéphane; Beca, Bogdan; Simmons, Craig A.; Deshpande, Vikram S.; McGarry, J. Patrick; Chen, Christopher S.; Nanthakumar, Kumaraswamy; Keller, Gordon M.; Radisic, Milica; Zandstra, Peter W.
2013-01-01
Access to robust and information-rich human cardiac tissue models would accelerate drug-based strategies for treating heart disease. Despite significant effort, the generation of high-fidelity adult-like human cardiac tissue analogs remains challenging. We used computational modeling of tissue contraction and assembly mechanics in conjunction with microfabricated constraints to guide the design of aligned and functional 3D human pluripotent stem cell (hPSC)-derived cardiac microtissues that we term cardiac microwires (CMWs). Miniaturization of the platform circumvented the need for tissue vascularization and enabled higher-throughput image-based analysis of CMW drug responsiveness. CMW tissue properties could be tuned using electromechanical stimuli and cell composition. Specifically, controlling self-assembly of 3D tissues in aligned collagen, and pacing with point stimulation electrodes, were found to promote cardiac maturation-associated gene expression and in vivo-like electrical signal propagation. Furthermore, screening a range of hPSC-derived cardiac cell ratios identified that 75% NKX2 Homeobox 5 (NKX2-5)+ cardiomyocytes and 25% Cluster of Differentiation 90 OR (CD90)+ nonmyocytes optimized tissue remodeling dynamics and yielded enhanced structural and functional properties. Finally, we demonstrate the utility of the optimized platform in a tachycardic model of arrhythmogenesis, an aspect of cardiac electrophysiology not previously recapitulated in 3D in vitro hPSC-derived cardiac microtissue models. The design criteria identified with our CMW platform should accelerate the development of predictive in vitro assays of human heart tissue function. PMID:24255110
Brugger, Daniel; Windisch, Wilhelm M
2017-04-01
Background: Subclinical zinc deficiency (SZD) represents the common zinc malnutrition phenotype. However, its association with oxidative stress is not well understood. The heart muscle may be a promising target for studying early changes in redox metabolism. Objective: We investigated the effects of short-term SZD on cardiac redox metabolism in weaned piglets. Methods: Forty-eight weaned German Large White × Landrace × Piétrain piglets (50% castrated males and 50% females; body weight of 8.5 kg) were fed diets with different zinc concentrations for 8 d. Measurements included cardiac parameters of antioxidative capacity, stress-associated gene expression, and tissue zinc status. Analyses comprised (linear, broken-line) regression models and Pearson correlation coefficients. Results: Glutathione and α-tocopherol concentrations as well as catalase, glutathione reductase, B-cell lymphoma 2-associated X protein, and caspase 9 gene expression plateaued in response to reduction in dietary zinc from 88.0 to 57.6, 36.0, 36.5, 41.3, 55.3, and 33.8 mg/kg, respectively ( P < 0.0001). Further reduction in dietary zinc promoted a linear decrease of glutathione and α-tocopherol (30 and 0.6 nmol/mg dietary Zn, respectively; P < 0.05) and a linear increase of gene expression [0.02, 0.01, 0.003, and 0.02 Log 10 (2 -ΔΔCt )/mg dietary Zn, respectively; P < 0.05)]. Tissue zinc declined linearly with reduction in dietary zinc (0.21 mg tissue Zn/mg dietary Zn; P = 0.004) from 88.0 to 42.7 mg/kg ( P < 0.0001), below which it linearly increased inversely to further reduction in dietary zinc (0.57 mg tissue Zn/mg dietary Zn; P = 0.006). H 2 O 2 -detoxification activity and metallothionein 1A gene expression decreased linearly with reduction in dietary zinc from 88.0 to 28.1 mg/kg [0.02 mU and 0.008 Log 10 (2 -ΔΔCt )/mg dietary Zn, respectively; P < 0.05]. Fas cell-surface death receptor, etoposide-induced 2.4 and cyclin-dependent kinase inhibitor 1A gene expression correlated positively to cardiac zinc in piglets fed ≤42.7 mg Zn/kg ( r ≥ 0.97; P < 0.05). Conclusions: Short-term SZD decreased cardiac antioxidative capacity of weaned piglets while simultaneously increasing stress-associated gene expression and zinc concentration. This is the first report to our knowledge on the effects of SZD on redox metabolism. © 2017 American Society for Nutrition.
Diagnostic approaches for diabetic cardiomyopathy and myocardial fibrosis
Maya, Lisandro; Villarreal, Francisco J.
2009-01-01
In diabetes mellitus, alterations in cardiac structure/function in the absence of ischemic heart disease, hypertension or other cardiac pathologies is termed diabetic cardiomyopathy. In the United States, the prevalence of diabetes mellitus continues to rise and the disease currently affects about 8% of the general population. Hence, it is imperative the use of appropriate diagnostic strategies for diabetic cardiomyopathy, which may help correctly identify the disease at early stages and implement suitable corrective therapies. Currently, there is no single diagnostic method for the identification of diabetic cardiomyopathy. Diabetic cardiomyopathy is known to induce changes in cardiac structure such as, myocardial hypertrophy, fibrosis and fat droplet deposition. Early changes in cardiac function are typically manifested as abnormal diastolic function that with time leads to loss of contractile function. Echocardiography based methods currently stands as the preferred diagnostic approach for diabetic cardiomyopathy, due to its wide availability and economical use. In addition to conventional techniques, magnetic resonance imaging and spectroscopy along with contrast agents are now leading new approaches in the diagnosis of myocardial fibrosis, and cardiac and hepatic metabolic changes. These strategies can be complemented with serum biomarkers so they can offer a clear picture as to diabetes-induced changes in cardiac structure/function even at very early stages of the disease. This review article intends to provide a summary of experimental and routine tools currently available to diagnose diabetic cardiomyopathy induced changes in cardiac structure/function. These tools can be reliably used in either experimental models of diabetes or for clinical applications. PMID:19595694
Yamakawa, Hiroyuki; Muraoka, Naoto; Miyamoto, Kazutaka; Sadahiro, Taketaro; Isomi, Mari; Haginiwa, Sho; Kojima, Hidenori; Umei, Tomohiko; Akiyama, Mizuha; Kuishi, Yuki; Kurokawa, Junko; Furukawa, Tetsushi; Fukuda, Keiichi; Ieda, Masaki
2015-01-01
Summary Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors, including Gata4, Mef2c, and Tbx5; however, this process is inefficient under serum-based culture conditions, in which conversion of partially reprogrammed cells into fully reprogrammed functional iCMs has been a major hurdle. Here, we report that a combination of fibroblast growth factor (FGF) 2, FGF10, and vascular endothelial growth factor (VEGF), termed FFV, promoted cardiac reprogramming under defined serum-free conditions, increasing spontaneously beating iCMs by 100-fold compared with those under conventional serum-based conditions. Mechanistically, FFV activated multiple cardiac transcriptional regulators and converted partially reprogrammed cells into functional iCMs through the p38 mitogen-activated protein kinase and phosphoinositol 3-kinase/AKT pathways. Moreover, FFV enabled cardiac reprogramming with only Mef2c and Tbx5 through the induction of cardiac reprogramming factors, including Gata4. Thus, defined culture conditions promoted the quality of cardiac reprogramming, and this finding provides new insight into the mechanism of cardiac reprogramming. PMID:26626177
Kapel, Gijsbert F L; Reichlin, Tobias; Wijnmaalen, Adrianus P; Piers, Sebastiaan R D; Holman, Eduard R; Tedrow, Usha B; Schalij, Martin J; Stevenson, William G; Zeppenfeld, Katja
2015-02-01
Ventricular tachycardia (VT) is an important cause of late morbidity and mortality in repaired congenital heart disease. The substrate often includes anatomic isthmuses that can be transected by radiofrequency catheter ablation similar to isthmus block for atrial flutter. This study evaluates the long-term efficacy of isthmus block for treatment of re-entry VT in adults with repaired congenital heart disease. Thirty-four patients (49±13 years; 74% male) with repaired congenital heart disease who underwent radiofrequency catheter ablation of VT in 2 centers were included. Twenty-two (65%) had a preserved left and right ventricular function. Patients were inducible for 1 (interquartile range, 1-2) VT, median cycle length: 295 ms (interquartile range, 242-346). Ablation aimed to transect anatomic isthmuses containing VT re-entry circuit isthmuses. Procedural success was defined as noninducibility of any VT and transection of the anatomic isthmus and was achieved in 25 (74%) patients. During long-term follow-up (46±29 months), all patients with procedural success (18/25 with internal cardiac defibrillators) were free of VT recurrence but 7 of 18 experienced internal cardiac defibrillator-related complications. One patient with procedural success and depressed cardiac function received an internal cardiac defibrillator shock for ventricular fibrillation. None of the 18 patients (12/18 with internal cardiac defibrillators) with complete success and preserved cardiac function experienced any ventricular arrhythmia. In contrast, VT recurred in 4 of 9 patients without procedural success. Four patients died from nonarrhythmic causes. In patients with repaired congenital heart disease with preserved ventricular function and isthmus-dependent re-entry, VT isthmus ablation can be curative. © 2014 American Heart Association, Inc.
Buscariollo, Daniela L; Fang, Xiefan; Greenwood, Victoria; Xue, Huiling; Rivkees, Scott A; Wendler, Christopher C
2014-01-01
Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs) mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg) or vehicle (0.09% NaCl) i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2-4 cups of coffee in humans. After dams gave birth, offspring were examined at 8-10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs) within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation.
Salis, Christos; Kelly, Helen; Code, Chris
2015-01-01
Aphasia following stroke refers to impairments that affect the comprehension and expression of spoken and/or written language, and co-occurring cognitive deficits are common. In this paper we focus on short-term and working memory impairments that impact on the ability to retain and manipulate auditory-verbal information. Evidence from diverse paradigms (large group studies, case studies) report close links between short-term/working memory and language functioning in aphasia. This evidence leads to the hypothesis that treating such memory impairments would improve language functioning. This link has only recently been acknowledged in aphasia treatment but has not been embraced widely by clinicians. To examine the association between language, and short-term and working memory impairments in aphasia. To describe practical ways of assessing short-term and working memory functioning that could be used in clinical practice. To discuss and critically appraise treatments of short-term and working memory reported in the literature. Taking a translational research approach, this paper provides clinicians with current evidence from the literature and practical information on how to assess and treat short-term and working memory impairments in people with aphasia. Published treatments of short-term and/or working memory in post-stroke aphasia are discussed through a narrative review. This paper provides the following. A theoretical rationale for adopting short-term and working memory treatments in aphasia. It highlights issues in differentially diagnosing between short-term, working memory disorders and other concomitant impairments, e.g. apraxia of speech. It describes short-term and working memory assessments with practical considerations for use with people with aphasia. It also offers a description of published treatments in terms of participants, treatments and outcomes. Finally, it critically appraises the current evidence base relating to the treatment of short-term and working memory treatments. The links between short-term/working memory functioning and language in aphasia are generally acknowledged. These strongly indicate the need to incorporate assessment of short-term/working memory functioning for people with aphasia. While the supportive evidence for treatment is growing and appears to highlight the benefits of including short-term/working memory in aphasia treatment, the quality of the evidence in its current state is poor. However, because of the clinical needs of people with aphasia and the prevalence of short-term/working memory impairments, incorporating related treatments through practice-based evidence is advocated. © 2015 Royal College of Speech and Language Therapists.
Selective Cerebro-Myocardial Perfusion in Complex Neonatal Aortic Arch Pathology: Midterm Results.
Hoxha, Stiljan; Abbasciano, Riccardo Giuseppe; Sandrini, Camilla; Rossetti, Lucia; Menon, Tiziano; Barozzi, Luca; Linardi, Daniele; Rungatscher, Alessio; Faggian, Giuseppe; Luciani, Giovanni Battista
2018-04-01
Aortic arch repair in newborns and infants has traditionally been accomplished using a period of deep hypothermic circulatory arrest. To reduce neurologic and cardiac dysfunction related to circulatory arrest and myocardial ischemia during complex aortic arch surgery, an alternative and novel strategy for cerebro-myocardial protection was recently developed, where regional low-flow perfusion is combined with controlled and independent coronary perfusion. The aim of the present retrospective study was to assess short-term and mid-term results of selective and independent cerebro-myocardial perfusion in neonatal aortic arch surgery. From April 2008 to August 2015, 28 consecutive neonates underwent aortic arch surgery under cerebro-myocardial perfusion. There were 17 male and 11 female, with median age of 15 days (3-30 days) and median body weight of 3 kg (1.6-4.2 kg), 9 (32%) of whom with low body weight (<2.5 kg). The spectrum of pathologies treated was heterogeneous and included 13 neonates having single-stage biventricular repair (46%), 7 staged biventricular repair (25%), and 8 single-ventricle repair (29%). All operations were performed under moderate hypothermia and with a "beating heart and brain." Average cardiopulmonary bypass time was 131 ± 64 min (42-310 min). A period of cardiac arrest to complete intra-cardiac repair was required in nine patients (32%), and circulatory arrest in 1 to repair total anomalous pulmonary venous connection. Average time of splanchnic ischemia during cerebro-myocardial perfusion was 30 ± 11 min (15-69 min). Renal dysfunction, requiring a period of peritoneal dialysis was observed in 10 (36%) patients, while liver dysfunction was noted only in 3 (11%). There were three (11%) early and two late deaths during a median follow-up of 2.9 years (range 6 months-7.7 years), with an actuarial survival of 82% at 7 years. At latest follow-up, no patient showed signs of cardiac or neurologic dysfunction. The present experience shows that a strategy of selective and independent cerebro-myocardial perfusion is safe, versatile, and feasible in high-risk neonates with complex congenital arch pathology. Encouraging outcomes were noted in terms of cardiac and neurological function, with limited end-organ morbidity. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
Aging Effects on Cardiac and Respiratory Dynamics in Healthy Subjects across Sleep Stages
Schumann, Aicko Y.; Bartsch, Ronny P.; Penzel, Thomas; Ivanov, Plamen Ch.; Kantelhardt, Jan W.
2010-01-01
Study Objectives: Respiratory and heart rate variability exhibit fractal scaling behavior on certain time scales. We studied the short-term and long-term correlation properties of heartbeat and breathing-interval data from disease-free subjects focusing on the age-dependent fractal organization. We also studied differences across sleep stages and night-time wake and investigated quasi-periodic variations associated with cardiac risk. Design: Full-night polysomnograms were recorded during 2 nights, including electrocardiogram and oronasal airflow. Setting: Data were collected in 7 laboratories in 5 European countries. Participants: 180 subjects without health complaints (85 males, 95 females) aged from 20 to 89 years. Interventions: None. Measurements and Results: Short-term correlations in heartbeat intervals measured by the detrended fluctuation analysis (DFA) exponent α1 show characteristic age dependence with a maximum around 50–60 years disregarding the dependence on sleep and wake states. Long-term correlations measured by α2 differ in NREM sleep when compared with REM sleep and wake, besides weak age dependence. Results for respiratory intervals are similar to those for α2 of heartbeat intervals. Deceleration capacity (DC) decreases with age; it is lower during REM and deep sleep (compared with light sleep and wake). Conclusion: The age dependence of α1 should be considered when using this value for diagnostic purposes in post-infarction patients. Pronounced long-term correlations (larger α2) for heartbeat and respiration during REM sleep and wake indicate an enhanced control of higher brain regions, which is absent during NREM sleep. Reduced DC possibly indicates an increased cardiovascular risk with aging and during REM and deep sleep. Citation: Schumann AY; Bartsch RP; Penzel T; Ivanov PC; Kantelhardt JW. Aging effects on cardiac and respiratory dynamics in healthy subjects across sleep stages. SLEEP 2010;33(7):943-955. PMID:20614854
Go, Alan S; Parikh, Chirag R; Ikizler, T Alp; Coca, Steven; Siew, Edward D; Chinchilli, Vernon M; Hsu, Chi-Yuan; Garg, Amit X; Zappitelli, Michael; Liu, Kathleen D; Reeves, W Brian; Ghahramani, Nasrollah; Devarajan, Prasad; Faulkner, Georgia Brown; Tan, Thida C; Kimmel, Paul L; Eggers, Paul; Stokes, John B
2010-08-27
The incidence of acute kidney injury (AKI) has been increasing over time and is associated with a high risk of short-term death. Previous studies on hospital-acquired AKI have important methodological limitations, especially their retrospective study designs and limited ability to control for potential confounding factors. The Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study was established to examine how a hospitalized episode of AKI independently affects the risk of chronic kidney disease development and progression, cardiovascular events, death, and other important patient-centered outcomes. This prospective study will enroll a cohort of 1100 adult participants with a broad range of AKI and matched hospitalized participants without AKI at three Clinical Research Centers, as well as 100 children undergoing cardiac surgery at three Clinical Research Centers. Participants will be followed for up to four years, and will undergo serial evaluation during the index hospitalization, at three months post-hospitalization, and at annual clinic visits, with telephone interviews occurring during the intervening six-month intervals. Biospecimens will be collected at each visit, along with information on lifestyle behaviors, quality of life and functional status, cognitive function, receipt of therapies, interim renal and cardiovascular events, electrocardiography and urinalysis. ASSESS-AKI will characterize the short-term and long-term natural history of AKI, evaluate the incremental utility of novel blood and urine biomarkers to refine the diagnosis and prognosis of AKI, and identify a subset of high-risk patients who could be targeted for future clinical trials to improve outcomes after AKI.
Mouquet, Frederic; Mostefa Kara, Meriem; Lamblin, Nicolas; Coulon, Capucine; Langlois, Stephane; Marquie, Christelle; de Groote, Pascal
2012-05-01
Aim Peripartum cardiomyopathy (PPCM) is a rare cause of dilated cardiomyopathy responsible for heart failure toward the end of pregnancy, which can lead to chronic heart failure in 50% of cases. In this short report, we assessed the benefit of cardiac resynchronization in patients with PPCM and chronic systolic dysfunction despite optimal medical treatment. For the last 10 years, we managed eight patients diagnosed with PPCM. Two of them presented severe systolic dysfunction, and medical treatment resulted in limited improvement from 10% to 25% and from 25% to 28% despite optimal treatment for 9 and 6 years, respectively. These two patients were porposed to receive an implantatable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT). Six months after ICD-CRT treatment, we observed a significant improvement in systolic function from 25% to 45% and 28% to 50%, respectively, and positive remodelling with reduction of left ventricular end-diastolic volume from 216 to 144 mL and from 354 to 105 mL, which represent a 34% and a 70% reduction, respectively. Physicians in charge of patients with PPCM should offer the opportunity of CRT for patients whose cardiac function has not significantly improved under standard medical treatment.
Genetically engineered SCN5A mutant pig hearts exhibit conduction defects and arrhythmias
Park, David S.; Cerrone, Marina; Morley, Gregory; Vasquez, Carolina; Fowler, Steven; Liu, Nian; Bernstein, Scott A.; Liu, Fang-Yu; Zhang, Jie; Rogers, Christopher S.; Priori, Silvia G.; Chinitz, Larry A.; Fishman, Glenn I.
2014-01-01
SCN5A encodes the α subunit of the major cardiac sodium channel NaV1.5. Mutations in SCN5A are associated with conduction disease and ventricular fibrillation (VF); however, the mechanisms that link loss of sodium channel function to arrhythmic instability remain unresolved. Here, we generated a large-animal model of a human cardiac sodium channelopathy in pigs, which have cardiac structure and function similar to humans, to better define the arrhythmic substrate. We introduced a nonsense mutation originally identified in a child with Brugada syndrome into the orthologous position (E558X) in the pig SCN5A gene. SCN5AE558X/+ pigs exhibited conduction abnormalities in the absence of cardiac structural defects. Sudden cardiac death was not observed in young pigs; however, Langendorff-perfused SCN5AE558X/+ hearts had an increased propensity for pacing-induced or spontaneous VF initiated by short-coupled ventricular premature beats. Optical mapping during VF showed that activity often began as an organized focal source or broad wavefront on the right ventricular (RV) free wall. Together, the results from this study demonstrate that the SCN5AE558X/+ pig model accurately phenocopies many aspects of human cardiac sodium channelopathy, including conduction slowing and increased susceptibility to ventricular arrhythmias. PMID:25500882
Higher sympathetic nerve activity during ventricular (VVI) than during dual-chamber (DDD) pacing
NASA Technical Reports Server (NTRS)
Taylor, J. A.; Morillo, C. A.; Eckberg, D. L.; Ellenbogen, K. A.
1996-01-01
OBJECTIVES: We determined the short-term effects of single-chamber ventricular pacing and dual-chamber atrioventricular (AV) pacing on directly measured sympathetic nerve activity. BACKGROUND: Dual-chamber AV cardiac pacing results in greater cardiac output and lower systemic vascular resistance than does single-chamber ventricular pacing. However, it is unclear whether these hemodynamic advantages result in less sympathetic nervous system outflow. METHODS: In 13 patients with a dual-chamber pacemaker, we recorded the electrocardiogram, noninvasive arterial pressure (Finapres), respiration and muscle sympathetic nerve activity (microneurography) during 3 min of underlying basal heart rate and 3 min of ventricular and AV pacing at rates of 60 and 100 beats/min. RESULTS: Arterial pressure was lowest and muscle sympathetic nerve activity was highest at the underlying basal heart rate. Arterial pressure increased with cardiac pacing and was greater with AV than with ventricular pacing (change in mean blood pressure +/- SE: 10 +/- 3 vs. 2 +/- 2 mm Hg at 60 beats/min; 21 +/- 5 vs. 14 +/- 2 mm Hg at 100 beats/min; p < 0.05). Sympathetic nerve activity decreased with cardiac pacing and the decline was greater with AV than with ventricular pacing (60 beats/min -40 +/- 11% vs. -17 +/- 7%; 100 beats/min -60 +/- 9% vs. -48 +/- 10%; p < 0.05). Although most patients showed a strong inverse relation between arterial pressure and muscle sympathetic nerve activity, three patients with severe left ventricular dysfunction (ejection fraction < or = 30%) showed no relation between arterial pressure and sympathetic activity. CONCLUSIONS: Short-term AV pacing results in lower sympathetic nerve activity and higher arterial pressure than does ventricular pacing, indicating that cardiac pacing mode may influence sympathetic outflow simply through arterial baroreflex mechanisms. We speculate that the greater incidence of adverse outcomes in patients treated with single-chamber ventricular rather than dual-chamber pacing may be due in part to increased sympathetic nervous outflow.
[Short and long term results of aortic valve replacement in patients 80 years of age and older].
Mortasawi, A; Gehle, S; Yaghmaie, M; Schröder, T; Ennker, I C; Rosendahl, U; Albert, A; Ennker, J
2001-03-01
Due to demographic changes in average life expectancy the age of patients undergoing cardiac surgery is increasing as well. We have reviewed the short- and long-term outcome in patients over 80 years of age after aortic valve replacement with or without concomitant coronary grafting. From 1.1.1995 until 31.12.1999, 126 patients (93 women, 33 men between 80 and 89 years, 82.8 +/- 2.4) underwent aortic valve replacement. 64 patients (group A) received isolated valve replacement, 62 (group B) underwent myocardial revascularization as well. The 30-day hospital mortality rate was 6.3% for group A and 14.5% for group B. The follow-up time ranged between 3 and 63 months (32 +/- 16). None of the patients had to be reoperated for prosthetic valve dysfunction or endocarditis. Bleeding complications due to anticoagulation therapy were observed by one patient from group A 3 years after the operation. Of the 15 deaths during the follow-up period seven (47%) were cardiac in nature and two (13%) related to stroke. Acturial survival rates for group A were 89%, 85% and 77% at 1, 2 and 3 years, and for group B 76%, 72% and 70%. Permanent nursing care was not required 1 year after the operation by 100% of patients in group A (2 years: 98%, 3 years 95%) and by 100% of patients in group B (2 years: 93%, 3 years: 90%). At an interval of 1 year after the operation 96% of patients in group A had not been hospitalized as a result of cardiac disorders (2 years: 96%, 3 years: 94%). The rates for group B were 88%, 81% and 75%. Compared with younger age groups, aortic valve replacement in patients 80 years of age and older is associated with a distinctly increased mortality and morbidity. However, our data suggest that considering the poor prognosis of conservative therapy of symptomatic aortic valve disease, functional status as well as life expectancy in this age group seem to be positively influenced by aortic valve replacement.
Steinbach, Daniel; Wilhelm, Bernhard; Kiermaier, Hans-Rudolf; Creutzig, Ursula; Schrappe, Martin; Zimmermann, Martin; Debatin, Klaus-Michael; Gruhn, Bernd; von Stackelberg, Arend; Jürgens, Heribert; Strahm, Brigitte; Reinhardt, Dirk; Möricke, Anja
2011-11-01
Previous reports have indicated that the short term prognosis for patients with malignant diseases and serious adverse events requiring mechanical ventilation (SAEV) is improving. The purpose of this study was to determine whether these patients can be cured of malignant disease or whether they survive SAEV only to subsequently relapse. The authors report the outcome of children with SAEV treated in the multicentre studies ALL-BFM 95 and AML-BFM 98. Data from 1182 patients with acute lymphoblastic leukaemia (ALL) and 334 patients with acute myeloid leukaemia (AML) were analysed. 88 patients (51 ALL and 37 AML) developed SAEV. The prognosis was almost identical in ALL and AML patients (survival of SAEV patients: 48%, 95% CI 38% to 58%; overall survival after 5 years: 31%, 95% CI 21% to 41%). Prognosis was independent of the time between leukaemia diagnosis and SAEV. Approximately 20% of children who required haemodialysis (n=14) or cardiac resuscitation (n=16) achieved long term survival, but no patient who fulfilled more than three of six identified risk factors (age ≥10 years, high risk leukaemia, C reactive protein ≥150 mg/l, administration of inotropic infusion, cardiac resuscitation and haemodialysis) survived (n=16; 0%, 95% CI 0% to 20%). Intensive care improves the short and long term survival of children with leukaemia. 64% (95% CI 50% to 78%) of children with acute leukaemia who survived SAEV achieved long term survival. Prognosis mainly depends on age and leukaemia risk group.
Cardiovascular Safety of Droxidopa in Patients With Symptomatic Neurogenic Orthostatic Hypotension.
White, William B; Hauser, Robert A; Rowse, Gerald J; Ziemann, Adam; Hewitt, L Arthur
2017-04-01
The norepinephrine prodrug droxidopa improves symptoms of neurogenic orthostatic hypotension, a condition that is associated with diseases of neurogenic autonomic failure (e.g., Parkinson disease, multiple system atrophy, pure autonomic failure). These conditions are more prevalent in older patients who also have cardiovascular co-morbidities. Hence, we evaluated the cardiovascular safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension who participated in randomized controlled studies (short-term studies of 1 to 2 weeks and an intermediate 8- to 10-week study) and long-term open-label studies. Rates of cardiovascular adverse events (AEs) for patients treated with droxidopa were 4.4% in the intermediate study and 10.8% in the long-term open-label studies. Adjusting for exposure time, cardiovascular AE rates were 0.30 events/patient-year in the short-term and intermediate studies and 0.15 events/patient-year in the long-term open-label studies. The incidence of treatment discontinuation due to blood pressure-related events was approximately 2.5%. Among patients with a history of cardiac disorders at baseline, the rates of cardiovascular-related and blood pressure-related AEs were nominally higher with droxidopa compared to placebo. Most of these events were minor atrial arrhythmias; none were major adverse cardiovascular events or deaths. In conclusion, small increases in cardiovascular AEs were observed with droxidopa compared to placebo; this was most evident in patients with preexisting cardiac disorders. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Pu, Jie-Lin,; Ye, Bin; Kroboth, Stacie L.; McNally, Elizabeth M.; Makielski, Jonathan C.; Shi, Nian-Qing
2008-01-01
The cardiac sarcolemmal ATP-sensitive potassium channel (KATP) consists of a Kir6.2 pore and a SUR2 regulatory subunit, which is an ATP-binding cassette (ABC) transporter. KATP channels have been proposed to play protective roles during ischemic preconditioning. A SUR2 mutant mouse was previously generated by disrupting the first nucleotide-binding domain (NBD1), where a glibenclamide action site was located. In the mutant ventricular myocytes, a non-conventional glibenclamide-insensitive (10 μM), ATP-sensitive current (IKATPn) was detected in 33% of single-channel recordings with an average amplitude of 12.3±5.4 pA per patch, an IC50 to ATP inhibition at 10 μM, and a mean burst duration at 20.6±1.8 ms. Newly designed SUR2-isoform or variant-specific antibodies identified novel SUR2 short forms in the sizes of 28 and 68 kDa in addition to a 150-kDa long form in the sarcolemmal membrane of wild-type (WT) heart. We hypothesized that channels constituted by these short forms that lack NBD1, confer IKATPn. The absence of the long form in the mutant corresponded to loss of the conventional glibenclamide-sensitive KATP currents (IKATP) in isolated cardiomyocytes and vascular smooth muscle cells but the SUR2 short forms remained intact. Nested exonic RT-PCR in the mutant indicated that the short forms lacked NBD1 but contained NBD2. The SUR2 short forms co-immunoprecipitated with Kir6.1 or Kir6.2 suggesting that the short forms may function as hemi-transporters reported in other eukaryotic ABC transporter subgroups. Our results indicate that different KATP compositions may co-exist in cardiac sarcolemmal membrane. PMID:18001767
Apaijai, Nattayaporn; Pintana, Hiranya; Chattipakorn, Siriporn C; Chattipakorn, Nipon
2013-01-01
Background and Purpose Long-term high-fat diet (HFD) consumption has been shown to cause insulin resistance, which is characterized by hyperinsulinaemia with metabolic inflexibility. Insulin resistance is associated with cardiac sympathovagal imbalance, cardiac dysfunction and cardiac mitochondrial dysfunction. Dipeptidyl peptidase-4 (DPP-4) inhibitors, vildagliptin and sitagliptin, are oral anti-diabetic drugs often prescribed in patients with cardiovascular disease. Therefore, in this study, we sought to determine the effects of vildagliptin and sitagliptin in a murine model of insulin resistance. Experimental Approach Male Wistar rats weighing 180–200 g, were fed either a normal diet (20% energy from fat) or a HFD (59% energy from fat) for 12 weeks. These rats were then divided into three subgroups to receive vildagliptin (3 mg·kg−1·day−1), sitagliptin (30 mg·kg−1·day−1) or vehicle for another 21 days. Metabolic parameters, oxidative stress, heart rate variability (HRV), cardiac function and cardiac mitochondrial function were determined. Key Results Rats that received HFD developed insulin resistance characterized by increased body weight, plasma insulin, total cholesterol and oxidative stress levels along with a decreased high-density lipoprotein (HDL) level. Moreover, cardiac dysfunction, depressed HRV, cardiac mitochondrial dysfunction and cardiac mitochondrial morphology changes were observed in HFD rats. Both vildagliptin and sitagliptin decreased plasma insulin, total cholesterol and oxidative stress as well as increased HDL level. Furthermore, vildagliptin and sitagliptin attenuated cardiac dysfunction, prevented cardiac mitochondrial dysfunction and completely restored HRV. Conclusions and Implications Both vildagliptin and sitagliptin share similar efficacy in cardioprotection in obese insulin-resistant rats. PMID:23488656
Medenwald, Daniel; Swenne, Cees A; Frantz, Stefan; Nuding, Sebastian; Kors, Jan A; Pietzner, Diana; Tiller, Daniel; Greiser, Karin H; Kluttig, Alexander; Haerting, Johannes
2017-12-01
To assess the value of cardiac structure/function in predicting heart rate variability (HRV) and the possibly predictive value of HRV on cardiac parameters. Baseline and 4-year follow-up data from the population-based CARLA cohort were used (790 men, 646 women, aged 45-83 years at baseline and 50-87 years at follow-up). Echocardiographic and HRV recordings were performed at baseline and at follow-up. Linear regression models with a quadratic term were used. Crude and covariate adjusted estimates were calculated. Missing values were imputed by means of multiple imputation. Heart rate variability measures taken into account consisted of linear time and frequency domain [standard deviation of normal-to-normal intervals (SDNN), high-frequency power (HF), low-frequency power (LF), LF/HF ratio] and non-linear measures [detrended fluctuation analysis (DFA1), SD1, SD2, SD1/SD2 ratio]. Echocardiographic parameters considered were ventricular mass index, diastolic interventricular septum thickness, left ventricular diastolic dimension, left atrial dimension systolic (LADS), and ejection fraction (Teichholz). A negative quadratic relation between baseline LADS and change in SDNN and HF was observed. The maximum HF and SDNN change (an increase of roughly 0.02%) was predicted at LADS of 3.72 and 3.57 cm, respectively, while the majority of subjects experienced a decrease in HRV. There was no association between further echocardiographic parameters and change in HRV, and there was no evidence of a predictive value of HRV in the prediction of changes in cardiac structure. In the general population, LADS predicts 4-year alteration in SDNN and HF non-linearly. Because of the novelty of the result, analyses should be replicated in other populations. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.
Long-term cardiac abnormalities after cranial radiotherapy in childhood cancer survivors.
Hummel, Yoran M; Hooimeijer, Hélène L; Zwart, Nynke; Tissing, Wim J E; Gietema, Jourik A; Voors, Adriaan A; van den Berg, Maarten P
2015-04-01
Cardiac morbidity is an important late effect in long-term childhood cancer survivors (CCS) treated with cardiotoxic agents or radiotherapy (RT) on the chest. However, there is limited data on the long-term cardiac sequelae in CCS who only received cranial RT. We hypothesized that cranial RT might negatively influence cardiac structure and function. We studied 13 CCS [mean age 30.8 (18.1-39.3) years, 7 males] who received RT only on the head for a cranial tumor and 36 age- and sex-matched healthy sibling controls. Echocardiographic follow-up was performed at median 21.7 (12.6-30.8) years after diagnosis. CCS had lower indexed diastolic LV volumes [56.0 (31.4-68.3) vs. 60.5 (41.9-94.3) mL/m(2), p = 0.024]. CCS also had reduced LV systolic and diastolic function, reflected by lower systolic LV myocardial velocities (5.3 ± 0.9 vs. 7.1 ± 1.7 cm/s, p = 0.001) and longitudinal deformation (- 17.3 ± 3.1 vs. - 20.7 ± 2.0%, p < 0.001), as well as lower diastolic LV myocardial velocities (- 10.7 ± 1.7 vs. - 12.2 ± 1.5 cm/s, p = 0.006) and deformation speed (1.1 ± 0.3 vs. 1.5 ± 0.2 1/s, p = 0.005). Additionally, in CCS insulin-like growth factor levels [15.4 (9.2-34.6) vs. 24.4 (14.8-55.5) nmol/L, p = 0.007] were lower. Cranial RT in CCS is associated with smaller cardiac volumes and reduced systolic and diastolic LV function. This off target effect of RT might be related to lower insulin-like growth factor levels.
Tang, Yao Liang; Qian, Keping; Zhang, Y Clare; Shen, Leping; Phillips, M Ian
2005-12-01
The effect of a cardiac specific, hypoxia-regulated, human heme oxygenase-1 (hHO-1) vector to provide cardioprotection from ischemia-reperfusion injury was assessed. When myocardial ischemia and reperfusion is asymptomatic, the damaging effects are cumulative and patients miss timely treatment. A gene therapy approach that expresses therapeutic genes only when ischemia is experienced is a desirable strategy. We have developed a cardiac-specific, hypoxia-regulated gene therapy "vigilant vector'' system that amplifies cardioprotective gene expression. Vigilant hHO-1 plasmids, LacZ plasmids, or saline (n = 40 per group) were injected into mouse heart 2 days in advance of ischemia-reperfusion injury. Animals were exposed to 60 minutes of ischemia followed by 24 hours of reperfusion. For that term (24 hours) effects, the protein levels of HO-1, inflammatory responses, apoptosis, and infarct size were determined. For long-term (3 week) effects, the left ventricular remodeling and recovery of cardiac function were assessed. Ischemia-reperfusion resulted in a timely overexpression of HO-1 protein. Infarct size at 24 hours after ischemia-reperfusion was significantly reduced in the HO-1-treated animals compared with the LacZ-treated group or saline-treated group (P < .001). The reduction of infarct size was accompanied by a decrease in lipid peroxidant activity, inflammatory cell infiltration, and proapoptotic protein level in ischemia-reperfusion-injured myocardium. The long-term study demonstrated that timely, hypoxia-induced HO-1 overexpression is beneficial in conserving cardiac function and attenuating left ventricle remodelling. The vigilant HO-1 vector provides a protective therapy in the heart for reducing cellular damage during ischemia-reperfusion injury and preserving heart function.
Badalzadeh, Reza; Shaghaghi, Mehrnoush; Mohammadi, Mustafa; Dehghan, Gholamreza; Mohammadi, Zeynab
2014-12-01
Regular training is suggested to offer a host of benefits especially on cardiovascular system. In addition, medicinal plants can attenuate oxidative stress-mediated damages induced by stressor insults. In this study, we investigated the concomitant effect of cinnamon extract and long-term aerobic training on cardiac function, biochemical alterations and lipid profile following exhaustive exercise. Male Wistar rats (250-300 g) were divided into five groups depending on receiving regular training, cinnamon bark extraction, none or both of them, and then encountered with an exhausted exercise in last session. An 8-week endurance training program was designed with a progressive increase in training speed and time. Myocardial hemodynamics was monitored using a balloon-tipped catheter inserted into left ventricles. Blood samples were collected for analyzing biochemical markers, lipid profiles and lipid-peroxidation marker, malondealdehyde (MDA). Trained animals showed an enhanced cardiac force and contractility similar to cinnamon-treated rats. Co-application of regular training and cinnamon had additive effect in cardiac hemodynamic (P<0.05). Both regular training and supplementation with cinnamon significantly decreased serum levels of total cholesterol, low-density lipoprotein (LDL), and increased high-density lipoprotein (HDL) level and HDL/LDL ratio as compared to control group (P<0.01). Furthermore, pre-treatment with cinnamon extract and/or regular training significantly reduced MDA level elevation induced by exhausted exercise (P<0.01). Long-term treatment of rats with cinnamon and regular training improved cardiac hemodynamic through an additive effect. The positive effects of cinnamon and regular training on cardiac function were associated with a reduced serum MDA level and an improved blood lipid profile.
Bobi, Joaquim; Solanes, Núria; Fernández-Jiménez, Rodrigo; Galán-Arriola, Carlos; Dantas, Ana Paula; Fernández-Friera, Leticia; Gálvez-Montón, Carolina; Rigol-Monzó, Elisabet; Agüero, Jaume; Ramírez, José; Roqué, Mercè; Bayés-Genís, Antoni; Sánchez-González, Javier; García-Álvarez, Ana; Sabaté, Manel; Roura, Santiago; Ibáñez, Borja; Rigol, Montserrat
2017-05-03
Autologous adipose tissue-derived mesenchymal stem cells (ATMSCs) therapy is a promising strategy to improve post-myocardial infarction outcomes. In a porcine model of acute myocardial infarction, we studied the long-term effects and the mechanisms involved in allogeneic ATMSCs administration on myocardial performance. Thirty-eight pigs underwent 50 minutes of coronary occlusion; the study was completed in 33 pigs. After reperfusion, allogeneic ATMSCs or culture medium (vehicle) were intracoronarily administered. Follow-ups were performed at short (2 days after acute myocardial infarction vehicle-treated, n=10; ATMSCs-treated, n=9) or long term (60 days after acute myocardial infarction vehicle-treated, n=7; ATMSCs-treated, n=7). At short term, infarcted myocardium analysis showed reduced apoptosis in the ATMSCs-treated animals (48.6±6% versus 55.9±5.7% in vehicle; P =0.017); enhancement of the reparative process with up-regulated vascular endothelial growth factor, granulocyte macrophage colony-stimulating factor, and stromal-derived factor-1α gene expression; and increased M2 macrophages (67.2±10% versus 54.7±10.2% in vehicle; P =0.016). In long-term groups, increase in myocardial perfusion at the anterior infarct border was observed both on day-7 and day-60 cardiac magnetic resonance studies in ATMSCs-treated animals, compared to vehicle (87.9±28.7 versus 57.4±17.7 mL/min per gram at 7 days; P =0.034 and 99±22.6 versus 43.3±14.7 22.6 mL/min per gram at 60 days; P =0.0001, respectively). At day 60, higher vascular density was detected at the border zone in the ATMSCs-treated animals (118±18 versus 92.4±24.3 vessels/mm 2 in vehicle; P =0.045). Cardiac magnetic resonance-measured left ventricular ejection fraction of left ventricular volumes was not different between groups at any time point. In this porcine acute myocardial infarction model, allogeneic ATMSCs-based therapy was associated with increased cardioprotective and reparative mechanisms and with better cardiac magnetic resonance-measured perfusion. No effect on left ventricular volumes or ejection fraction was observed. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Loma-Osorio, Pablo; Aboal, Jaime; Sanz, Maria; Caballero, Ángel; Vila, Montserrat; Lorente, Victoria; Sánchez-Salado, José Carlos; Sionis, Alessandro; Curós, Antoni; Lidón, Rosa-Maria
2013-08-01
Survivors of out-of-hospital cardiac arrest constitute an increasing patient population in cardiac intensive care units. Our aim was to characterize these patients and determine their vital and functional prognosis in accordance with the latest evidence. A multicenter, prospective register was constructed with information from patients admitted to 5 cardiac intensive care units from January 2010 through January 2012 with a diagnosis of resuscitated out-of-hospital cardiac arrest. The information included clinical status, cardiac arrest characteristics, in-hospital course, and vital and neurologic status at discharge and at 6 months. A total of 204 patients were included. In 64% of cases, a first shockable rhythm was identified. The time to return of spontaneous circulation was 29 (18) min. An etiologic diagnosis was made in 86% of patients; 44% were discharged with no neurologic sequelae; 40% died in the hospital. At 6 months, 79% of survivors at discharge were still alive and neurologically intact with minimal sequelae. Short resuscitation time, first recorded rhythm, pH on admission >7.1, absence of shock, and use of hypothermia were the independent variables associated with a good neurologic prognosis. Half the patients who recovered from out-of-hospital cardiac arrest had good neurologic prognosis at discharge, and 79% of survivors were alive and neurologically intact after 6 months of follow-up. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.
Two-Term Asymptotic Approximation of a Cardiac Restitution Curve*
Cain, John W.; Schaeffer, David G.
2007-01-01
If spatial extent is neglected, ionic models of cardiac cells consist of systems of ordinary differential equations (ODEs) which have the property of excitability, i.e., a brief stimulus produces a prolonged evolution (called an action potential in the cardiac context) before the eventual return to equilibrium. Under repeated stimulation, or pacing, cardiac tissue exhibits electrical restitution: the steady-state action potential duration (APD) at a given pacing period B shortens as B is decreased. Independent of ionic models, restitution is often modeled phenomenologically by a one-dimensional mapping of the form APDnext = f(B – APDprevious). Under some circumstances, a restitution function f can be derived as an asymptotic approximation to the behavior of an ionic model. In this paper, extending previous work, we derive the next term in such an asymptotic approximation for a particular ionic model consisting of two ODEs. The two-term approximation exhibits excellent quantitative agreement with the actual restitution curve, whereas the leading-order approximation significantly underestimates actual APD values. PMID:18080006
Short-term plasticity as a neural mechanism supporting memory and attentional functions.
Jääskeläinen, Iiro P; Ahveninen, Jyrki; Andermann, Mark L; Belliveau, John W; Raij, Tommi; Sams, Mikko
2011-11-08
Based on behavioral studies, several relatively distinct perceptual and cognitive functions have been defined in cognitive psychology such as sensory memory, short-term memory, and selective attention. Here, we review evidence suggesting that some of these functions may be supported by shared underlying neuronal mechanisms. Specifically, we present, based on an integrative review of the literature, a hypothetical model wherein short-term plasticity, in the form of transient center-excitatory and surround-inhibitory modulations, constitutes a generic processing principle that supports sensory memory, short-term memory, involuntary attention, selective attention, and perceptual learning. In our model, the size and complexity of receptive fields/level of abstraction of neural representations, as well as the length of temporal receptive windows, increases as one steps up the cortical hierarchy. Consequently, the type of input (bottom-up vs. top down) and the level of cortical hierarchy that the inputs target, determine whether short-term plasticity supports purely sensory vs. semantic short-term memory or attentional functions. Furthermore, we suggest that rather than discrete memory systems, there are continuums of memory representations from short-lived sensory ones to more abstract longer-duration representations, such as those tapped by behavioral studies of short-term memory. Copyright © 2011 Elsevier B.V. All rights reserved.
Arsenescu, Cătălina; Georgescu, G I M; Covic, A; Briotă, Laura
2002-01-01
Though sudden cardiac death accounts for as much as 15% of all cause mortality in uremia, reports concerning advanced A-V block, requiring permanent cardiac pacing in end-stage renal disease (ESRD) hemodialysed (HD) patients are very few. This is the first long term prospective study reporting on systematic permanent pacemaker implantation, in a cohort of ESRD patients from a single HD unit. Between 01/06/1997 and 30/12/2001, 396 pacemakers were inserted for advanced, symptomatic A-V block in our institution, including 5 in ESRD, HD patients (M/F--4/1, age 47-73, M +/- SD--61 +/- 12 years) from a single dialysis center, treating 137 patients during the study period. Thus, the incidence and prevalence of A-V defects treated by permanent pacing in uremic patients was 0.81% and 3.65% respectively. Conversely, the incidence and prevalence of ESRD treated by hemodialysis, among patients with advanced A-V conduction disturbances, requiring permanent pacing were 0.28% and 1.26%. Mitral valve calcifications were present in all patients; 3 subjects also had extensive aortic valve calcifications. Left ventricular hypertrophy (echocardiographic Framingham criteria) was present in 4 patients, but the systolic function (ejection fraction and fractional shortening index) was normal in all cases, although a clinical picture of chronic heart failure was seen in 3 subjects preoperatively. A-V conduction defects were attributed to extensive metastatic calcifications, involving the cardiac squeleton, consecutive to severe hyperparathyroidism and inadvertent use of calcitriol and calcium carbonate as phosphate binders. No technical difficulties, short or long-term complications related to pacemaker implantation (4 VVI and 1 VVD devices) were encountered. Acute threshold and sensing values were similar with those of non-uremic patients. During follow-up, one patients died from a non cardiac death. If optimal hemodialysis is provided, benefits of permanent pacing are equal in uremic or non uremic patients and pacemaker implantation should be instituted as a prompt life-saving method in all dialysis patients with chronic symptomatic advanced A-V blocks.
2018-01-01
Electrical restitution (ER) is a major determinant of repolarization stability and, under fast pacing rate, it reveals memory properties of the cardiac action potential (AP), whose dynamics have never been fully elucidated, nor their ionic mechanisms. Previous studies have looked at ER mainly in terms of changes in AP duration (APD) when the preceding diastolic interval (DI) changes and described dynamic conditions where this relationship shows hysteresis which, in turn, has been proposed as a marker of short-term AP memory and repolarization stability. By means of numerical simulations of a non-propagated human ventricular AP, we show here that measuring ER as APD versus the preceding cycle length (CL) provides additional information on repolarization dynamics which is not contained in the companion formulation. We focus particularly on fast pacing rate conditions with a beat-to-beat variable CL, where memory properties emerge from APD vs CL and not from APD vs DI and should thus be stored in APD and not in DI. We provide an ion-currents characterization of such conditions under periodic and random CL variability, and show that the memory stored in APD plays a stabilizing role on AP repolarization under pacing rate perturbations. The gating kinetics of L-type calcium current seems to be the main determinant of this safety mechanism. We also show that, at fast pacing rate and under otherwise identical pacing conditions, a periodically beat-to-beat changing CL is more effective than a random one in stabilizing repolarization. In summary, we propose a novel view of short-term AP memory, differentially stored between systole and diastole, which opens a number of methodological and theoretical implications for the understanding of arrhythmia development. PMID:29494628
Chen, David; Chang, Richard; Umakanthan, Branavan; Stoletniy, Liset N; Heywood, J Thomas
2007-09-01
In certain patients with left ventricular (LV) systolic dysfunction, improvements in cardiac function are seen after initiation of medical therapy; however, the long-term stability of ventricular function in such patients is not well described. We retrospectively analyzed 171 patients who had a baseline ejection fraction of 45% or less, a follow-up echocardiogram at 2 to 12 months after initiation of medical therapy, and a final echocardiogram. We found that 48.5% of the patients demonstrated initial improvements in LV function after initiation of medical therapy, and the improvements appear to be sustained (88% of patients) at 44 +/- 21 months follow-up. A nonischemic etiology and younger age were the only independent predictors of change of LV ejection fraction of 10 or more at a mean 8.4 +/- 3.4 months after optimal medical therapy. Our study revealed a trend toward improved long-term survival in individuals with an early improvement in LV ejection fraction with medical therapy, especially in those with sustained improvement.
Reda, Sherif M; Chandra, Murali
2018-05-18
Recent clinical studies have revealed a new hypertrophic cardiomyopathy-associated mutation (F87L) in the central region of human cardiac troponin T (TnT). However, despite its implication in several incidences of sudden cardiac death in young and old adults, whether F87L is associated with cardiac contractile dysfunction is unknown. Because the central region of TnT is important for modulating the muscle length-mediated recruitment of new force-bearing cross-bridges (XBs), we hypothesize that the F87L mutation causes molecular changes that are linked to the length-dependent activation of cardiac myofilaments. Length-dependent activation is important because it contributes significantly to the Frank-Starling mechanism, which enables the heart to vary stroke volume as a function of changes in venous return. We measured steady-state and dynamic contractile parameters in detergent-skinned guinea pig cardiac muscle fibers reconstituted with recombinant guinea pig wild-type TnT (TnT WT ) or the guinea pig analogue (TnT F88L ) of the human mutation at two different sarcomere lengths (SLs): short (1.9 µm) and long (2.3 µm). TnT F88L increases pCa 50 (-log [Ca 2+ ] free required for half-maximal activation) to a greater extent at short SL than at long SL; for example, pCa 50 increases by 0.25 pCa units at short SL and 0.17 pCa units at long SL. The greater increase in pCa 50 at short SL leads to the abolishment of the SL-dependent increase in myofilament Ca 2+ sensitivity (ΔpCa 50 ) in TnT F88L fibers, ΔpCa 50 being 0.10 units in TnT WT fibers but only 0.02 units in TnT F88L fibers. Furthermore, at short SL, TnT F88L attenuates the negative impact of strained XBs on force-bearing XBs and augments the magnitude of muscle length-mediated recruitment of new force-bearing XBs. Our findings suggest that the TnT F88L -mediated effects on cardiac thin filaments may lead to a negative impact on the Frank-Starling mechanism. © 2018 Reda and Chandra.
Manji, Rizwan A; Arora, Rakesh C; Singal, Rohit K; Hiebert, Brett; Moon, Michael C; Freed, Darren H; Menkis, Alan H
2016-01-01
There are minimal data on long-term functional survival (alive and not institutionalized) in patients undergoing cardiac operations who require a prolonged intensive care unit length of stay (prICULOS). We sought to describe 1- and 5-year functional survival in patients who had a prICULOS (ICULOS ≥ 5 days) and determine predictors of functional survival at 1 year. Data were obtained from linked clinical and administrative databases from January 1, 2000 to December 31, 2011 to conduct this retrospective single-region analysis. Logistic regression was used to develop a model predicting functional survival at 1 year for patients who had a prICULOS after cardiac operations. There were 9,545 admissions to the ICU after cardiac operations; of these patients, 728 (7.6%) experienced a prICULOS. There was an increasing trend in patients who had a prICULOS over this study period. The functional survival at 1 and 5 years from the surgical procedure for the non-prICULOS versus the prICULOS cohort was 1 year (94.9% versus 73.9%) and 5 years (84.9% versus 53.8%) (p < 0.001). Factors associated with lower rates of functional survival at 1 year were age 80 years or older, female sex, peripheral vascular disease, preoperative renal dysfunction, cerebrovascular disease, preoperative infection, need for extracorporeal membrane oxygenation/ventricular assist device (ECMO/VAD) after cardiotomy, number of days on mechanical ventilation, and number of days in the ICU beyond 5 days (area under the receiver operating characteristic [ROC] curve = 0.766). The majority of patients who had a prICULOS experienced successful functional survival up to 5 years after cardiac operations. Identification of risk factors for poor functional survival may be of assistance to clinicians, patients, and families for prognostication and decision making. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
The two-minute walk test as a measure of functional capacity in cardiac surgery patients.
Brooks, Dina; Parsons, Janet; Tran, Diem; Jeng, Bonnie; Gorczyca, Barbara; Newton, Janet; Lo, Vincent; Dear, Cheryl; Silaj, Ellen; Hawn, Therese
2004-09-01
To examine construct validity and sensitivity of the two-minute walk test (2MWT) in cardiac surgery patients. Measurements were made in patients preoperatively, during the postoperative in-hospital stay, and 6 to 8 weeks after discharge from hospital. Ambulatory and hospitalized care. Patients (N=122; mean age +/- standard deviation, 63+/-9 y) undergoing coronary artery bypass grafting. Not applicable. The 2MWT, New York Heart Association (NYHA) functional classification for cardiac disease, the Nottingham Extended Activities of Daily Living scale, and the Medical Outcomes Survey 36-Item Short-Form Health Questionnaire (SF-36). Distance walked in 2 minutes decreased significantly postoperatively (from 138+/-26 m to 84+/-33 m, P<.001), but increased again at follow-up (151+/-31 m, P<.0001). Distance walked on the 2MWT correlated significantly to SF-36 (physical function subscale) preoperatively (r=.44) and at follow-up (r=.48) (P<.001). There was a significant difference in distance walked between those with NYHA class I and II compared with those classified as III or IV (P=.04). However, there was no significant difference in distance walked in 2 minutes between those who developed cardiac or pulmonary complications postoperatively (P> or =0.2). The 2MWT was sensitive to change after cardiac surgery and showed moderate correlation with measures of physical functioning in this population. However, the 2MWT could not identify those who developed complications in the postoperative period.
Cardiovascular dynamics of Canadian Indigenous peoples.
Foulds, Heather J A; Bredin, Shannon S D; Warburton, Darren E R
2018-12-01
Limited understanding of Indigenous adults' cardiovascular structure and function exists despite high rates of cardiovascular disease. This investigation characterised cardiovascular structure and function among young Indigenous adults and compared to age- and sex-matched European descendants. Echocardiographic assessments included apical two- and four-chamber images, parasternal short-axis images and Doppler. Analyses included cardiac volumes, dimensions, velocities and strains. Cardiovascular structure and function were similar between Indigenous (n=10, 25 ± 3 years, 4 women) and European-descendant (n=10, 24 ± 4 years, 4 women,) adults, though European descendants demonstrated greater systemic vascular resistance (18.19 ± 3.94 mmHg∙min -1 ∙L -1 vs. 15.36 ± 2.97 mmHg∙min -1 ∙L -1 , p=0.03). Among Indigenous adults, women demonstrated greater arterial elastance (0.80 ± 0.15 mmHg·mL -1 ·m -2 vs. 0.55 ± 0.17 mmHg·mL -1 ·m -2 , p=0.02) and possibly greater systemic vascular resistance (17.51 ± 2.20 mmHg∙min -1 ∙L -1 vs. 13.93 ± 2.61 mmHg∙min -1 ∙L -1 , p=0.07). Indigenous men had greater cardiac size, dimensions and output, though body size differences accounted for cardiac size differences. Similar cardiac rotation and strains were observed across sexes. Arterial elastance and cardiac size were different between Indigenous men and women while cardiovascular structure and function may be similar between Indigenous and European descendants.
Beauchamp, Brittany; Thrush, A Brianne; Quizi, Jessica; Antoun, Ghadi; McIntosh, Nathan; Al-Dirbashi, Osama Y; Patti, Mary-Elizabeth; Harper, Mary-Ellen
2015-04-10
Intrauterine growth restriction (IUGR) is associated with an increased risk of developing obesity, insulin resistance and cardiovascular disease. However, its effect on energetics in heart remains unknown. In the present study, we examined respiration in cardiac muscle and liver from adult mice that were undernourished in utero. We report that in utero undernutrition is associated with impaired cardiac muscle energetics, including decreased fatty acid oxidative capacity, decreased maximum oxidative phosphorylation rate and decreased proton leak respiration. No differences in oxidative characteristics were detected in liver. We also measured plasma acylcarnitine levels and found that short-chain acylcarnitines are increased with in utero undernutrition. Results reveal the negative impact of suboptimal maternal nutrition on adult offspring cardiac energy metabolism, which may have life-long implications for cardiovascular function and disease risk. © 2015 Authors.
Chengyang, Li; Daqing, Huang; Jianlin, Qi; Haisheng, Chang; Qingqing, Meng; Jin, Wang; Jiajia, Liu; Enmao, Ye; Yongcong, Shao; Xi, Zhang
2017-08-01
Acute sleep restriction heavily influences cognitive function, affecting executive processes such as attention, response inhibition, and memory. Previous neuroimaging studies have suggested a link between hippocampal activity and short-term memory function. However, the specific contribution of the hippocampus to the decline of short-term memory following sleep restriction has yet to be established. In the current study, we utilized resting-state functional magnetic resonance imaging (fMRI) to examine the association between hippocampal functional connectivity (FC) and the decline of short-term memory following total sleep deprivation (TSD). Twenty healthy adult males aged 20.9 ± 2.3 years (age range, 18-24 years) were enrolled in a within-subject crossover study. Short-term memory and FC were assessed using a Delay-matching short-term memory test and a resting-state fMRI scan before and after TSD. Seed-based correlation analysis was performed using fMRI data for the left and right hippocampus to identify differences in hippocampal FC following TSD. Subjects demonstrated reduced alertness and a decline in short-term memory performance following TSD. Moreover, fMRI analysis identified reduced hippocampal FC with the superior frontal gyrus (SFG), temporal regions, and supplementary motor area. In addition, an increase in FC between the hippocampus and bilateral thalamus was observed, the extent of which correlated with short-term memory performance following TSD. Our findings indicate that the disruption of hippocampal-cortical connectivity is linked to the decline in short-term memory observed after acute sleep restriction. Such results provide further evidence that support the cognitive impairment model of sleep deprivation.
Intelligence as a predictor of outcome in short- and long-term psychotherapy.
Knekt, Paul; Saari, Taru; Lindfors, Olavi
2014-12-30
Intelligence has been suggested as a suitability factor for short-term therapy whereas its possible effect on short-term versus long-term therapy still is unknown. The aim of this study was to compare the prediction of intelligence on the level of psychiatric symptoms and psychosocial functioning in psychotherapies of different lengths. A total of 251 outpatients from the Helsinki Psychotherapy Study, aged 20–46 years, and suffering from mood or anxiety disorders were allocated to two long-term and two short-term therapies. Intelligence was assessed at baseline with the Wechsler Adult Intelligence Scale (WAIS-R). Psychiatric symptoms and psychosocial functioning were assessed 5–10 times during a 5-year follow-up using two primary symptom measures (HDRS and HARS) and one primary measure of psychosocial functioning (GAF). Short-term therapy was more effective than long-term therapy during the first year of follow-up. During the second to fourth follow-up year no differences between short- and long-term therapies or the intelligence groups were found. At the fifth follow-up year, however, long-term psychotherapy showed a statistically significantly larger change in all three primary measures compared to short-term therapy among those with higher intelligence. No differences between therapy groups were noted in those with lower intelligence. People with higher intelligence may benefit more from long-term than from short-term psychotherapy. These findings should be confirmed.
Israel, Benjamin; Buysse, Daniel J; Krafty, Robert T; Begley, Amy; Miewald, Jean; Hall, Martica
2012-09-01
Quantify the short-term stability of multiple indices of sleep and nocturnal physiology in good sleeper controls and primary insomnia patients. Intra-class correlation coefficients (ICC) were used to quantify the short-term stability of study outcomes. Sleep laboratory. Fifty-four adults with primary insomnia (PI) and 22 good sleeper controls (GSC). Visually scored sleep outcomes included indices of sleep duration, continuity, and architecture. Quantitative EEG outcomes included power in the delta, theta, alpha, sigma, and beta bands during NREM sleep. Power spectral analysis was used to estimate high-frequency heart rate variability (HRV) and the ratio of low- to high-frequency HRV power during NREM and REM sleep. With the exception of percent stage 3+4 sleep; visually scored sleep outcomes did not exhibit short-term stability across study nights. Most QEEG outcomes demonstrated short-term stability in both groups. Although power in the beta band was stable in the PI group (ICC = 0.75), it tended to be less stable in GSCs (ICC = 0.55). Both measures of cardiac autonomic tone exhibited short-term stability in GSCs and PIs during NREM and REM sleep. Most QEEG bandwidths and HRV during sleep show high short-term stability in good sleepers and patients with insomnia alike. One night of data is, thus, sufficient to derive reliable estimates of these outcomes in studies focused on group differences or correlates of QEEG and/or HRV. In contrast, one night of data is unlikely to generate reliable estimates of PSG-assessed sleep duration, continuity or architecture, with the exception of slow wave sleep.
Zhu, D; McCague, K; Lin, W; Rong, R; Xu, M; Chan, L; Zhu, T
2018-06-01
Kidney transplantation is limited by the shortage of donor kidneys. Donation after cardiac death (DCD) has been explored to alleviate this problem. To better understand the outcome of DCD kidney transplantation, we reanalyzed the Mycophenolic Renal Transplant (MORE) Registry. We compared delayed graft function (DGF), biopsy-proved acute rejection (BPAR), graft loss, and patient death between DCD and donation after brain death (DBD) kidney transplantations. Recipients were further stratified into depleting and nondepleting induction groups for exploratory analysis. There were 548 patients who received kidney transplants from deceased donor in the MORE Registry. Among them, 133 received grafts from DCD donors and 415 received from DBD donors. The incidence of DGF was 29.4% and 23.5% in the DCD group and the DBD group, respectively (P = .1812), and the incidence of BPAR at 12 months was 9.0% and 9.9% respectively (P = .7713). The 1-year graft loss rate in the DCD group was higher than that in the DBD group (7.5% vs 3.1%, P = .0283), and the 4-year graft loss rate and patient death rate were not significantly different between the 2 groups. The DCD kidney transplant group had acceptable short-term outcomes and good long-term outcomes as compared with the DBD kidney transplant group. Copyright © 2018 Elsevier Inc. All rights reserved.
Elaffandi, Ahmed H; Bonney, Glenn K; Gunson, Bridget; Scalera, Irene; Mergental, Hynek; Isaac, John R; Bramhall, Simon R; Mirza, Darius F; Perera, M Thamara P R; Muiesan, Paolo
2014-01-01
Donor warm ischemia has implications for outcomes after liver transplantation (LT) using organs from donation after circulatory death (DCD) donors. Prehospital cardiac arrest (PHCA) before donation may generate a further ischemic insult. The aim of this single-center study of 108 consecutive DCD LT procedures was to compare the outcomes of PHCA and non-PHCA cohorts. A review of a prospectively collected database of all DCD grafts transplanted between January 2007 and October 2011 was undertaken to identify donors who had sustained PHCA. The unit policy was to consider such donors when transaminase levels were ≤4 times the normal range and had an improving trend. Twenty-six of the 108 DCD transplants were from DCD donors with PHCA, and 82 were in the non-PHCA cohort. A comparative analysis of the PHCA and non-PHCA cohorts showed better short-term results (a low incidence of acute kidney injury) for the PHCA group but satisfactory long-term results for both groups with no significant differences in graft or patient survival between them. In conclusion, a careful donor selection policy for including PHCA DCD donors with normalized liver function tests or transaminase levels ≤ 4 times the norm resulted in successful transplantation and could boost the donor pool with no adverse outcomes. © 2013 American Association for the Study of Liver Diseases.
A single-bout of one-hour spinning exercise increases troponin T in healthy subjects.
Duttaroy, Smita; Thorell, Daniel; Karlsson, Lena; Börjesson, Mats
2012-02-01
While long-term endurance exercise is known to increase cardiac biomarkers, only a few studies on short-term exercise and these markers have been reported. The aim of this study was to investigate the acute effects of a one-hour bicycle spinning on cardiac biomarkers in healthy individuals. Serum levels of high-sensitive troponin T (TnT), creatinine kinase MB fraction (CK-MB), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatinine kinase (CK) and myoglobin were measured at baseline, 1 and 24 hour after one hour of spinning exercise in ten healthy and fit (age 31.0 ± 6.6 years) individuals. TnT doubled one hour post-exercise (All values ≤ 5 - 9.7 ± 6.0 ng/L, p < 0.001). Two individuals had TnT levels above upper reference limit, URL (20.7 and 20.2 ng/L, URL = 12 ng/L). Myoglobin levels increased 72% one hour post-exercise (38 ± 20 - 66 ± 41 mg/L, p < 0.02). TnT and myoglobin levels returned to baseline 24 hour post-exercise. Serum levels of CK-MB, NT-proBNP and CK were not significantly changed. A single-bout of one-hour bicycle spinning transiently increases TnT and myoglobin in healthy subjects. Some subjects even have TnT release above URL. Thus, recently performed exercise also of short duration should be taken into consideration in the evaluation of acute chest pain with release of cardiac TnT.
Compare, Angelo; Kouloulias, Vassilis; Apostolos, Vontas; Peña, Wendy Moreno; Molinari, Enrico; Grossi, Enzo; Efstathios, Efstathopoulos; Carenini, Michele
2012-09-03
There is compelling evidence that psychological factors may have the same or even greater impact on the possibility of adverse events on cardiac diseases (CD) than other traditional clinical risk factors. Anxiety and depression are predictors of short- and long-term adverse outcomes, increased risk for higher rates of in-hospital complications, re-infarction, malignant arrhythmias, and mortality in CD patients. Despite researchers finding that cognitive behavior therapy (CBT) reduced depressive and anxiety symptoms, the fact that such results are maintained only in the short term and the lack of maintenance of the long-term affects the absence of changes in lifestyles, preventing the possibility of a wide generalization of results. Recently wellbeing therapy (WBT) has been proposed as a useful approach to improve healthy lifestyle behaviors and reduce psychological distress. The present randomized controlled study will test WBT, in comparison with CBT, as far as the reduction of symptoms of depression, anxiety and psychological distress, and the improvement of lifestyle behaviors and quality of life in cardiac patients are concerned. Moreover, innovations in communication technologies allow patients to be constantly followed in real life. Therefore WBT based on personalized mobile technology will allow the testing of its effectiveness in comparison with usual WBT. The present study is a large outpatient study on the treatment of co-morbid depression, anxiety, and psychological distress in cardiac patients. The most important issues of this study are its randomized design, the focus on promotion of health-related behaviors, and the use of innovative technologies supporting patients' wellbeing in real life and in a continuous way. First results are expected in 2012. ClinicalTrials.gov Identifier: NCT01543815.
Perlman, Gidon Y; Loncar, Sasa; Pollak, Arthur; Gilon, Dan; Alcalai, Ronny; Planer, David; Lotan, Chaim; Danenberg, Haim D
2013-05-01
This study sought to investigate the blood pressure (BP) response after transcatheter aortic valve implantation (TAVI) and its correlation with short- and mid-term clinical outcomes. TAVI is an emerging therapy for aortic stenosis patients at high surgical risk. The acute hemodynamic sequelae of this procedure and their clinical relevance are yet unclear. Consecutive patients who underwent TAVI in a single center were prospectively monitored for BP response during 5 post-procedural days. Clinical parameters, adverse events, and medical treatment were recorded during hospitalization, at 30 days, and at 12 months after the procedure. Patients were divided according to their post-procedural BP response into 2 groups: increased BP and stable BP. One hundred and five patients were analyzed. Overall, systolic BP increased immediately after TAVI in the entire cohort by an average of 15 ± 31 mm Hg. This rise was sustained and led to intensification of antihypertensive treatment in 53 patients (51%); these patients were designated as the increased BP group. The increase in systolic BP after TAVI was associated with an increase in stroke volume and cardiac output and was not related to age, baseline cardiac function, or procedural outcomes. Patients with increased BP after TAVI had a significantly better prognosis with fewer adverse events in the hospital (21% vs. 62%, p < 0.01), after 30 days (30% vs. 71%, p < 0.01), and after 12 months (53% vs. 83%, p < 0.01) as compared with patients with stable BP. After TAVI, a substantial number of patients have a significant rise in systolic BP necessitating long-term treatment. This increase in BP is associated with an increase in cardiac output and predicts a better clinical outcome. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Matsuo, Tomoaki; Seino, Satoshi; Ohkawara, Kazunori; Tanaka, Kiyoji; Yamada, Shin; Ohshima, Hiroshi; Mukai, Chiaki
In a microgravity environment, the volume load on the left ventricle is reduced and the cardiac function deteriorates.Consequently, maximal oxygen consumption (VO2max) decreases during spaceflight. Reduced cardiac function can lead to serious health problems such as cardiac atrophy, diastolic dysfunction, and orthostatic hypotension. An exercise using a bicycle ergometer during spaceflight may help to increase the volume load on the left ventricle. On the other hand, many astronauts also experience weight loss during spaceflight because energy imbalances can occur. Some researchers indicate that excessive exercise may promote the energy deficit and have a negative impact on long-term spaceflight. Therefore, we have been devising an original bicyle erogometer protocol better suited to astronauts experiencing long-term spaceflight.One of our candidate protocols is the 3 × 3 protocol named J-HIAT, i.e., three times 3-min intervals with a 2-min active recovery period between intervals. In response to our preliminary experiments, we concluded that J-HIAT would be a potential protocol to control the increase of energy consumption and to have a significant impact on VO2max and the cardiac function. To further verify this method, we are working on full-scale experiments. In future, we will show the results of these experiments.
Electromechanical heterogeneity in the heart : A key to long QT syndrome?
Dressler, F F; Brado, J; Odening, K E
2018-03-01
In the healthy heart, physiological heterogeneities in structure and in electrical and mechanical activity are crucial for normal, efficient excitation and pumping. Alterations of heterogeneity have been linked to arrhythmogenesis in various cardiac disorders such as long QT syndrome (LQTS). This inherited arrhythmia disorder is caused by mutations in different ion channel genes and is characterized by (heterogeneously) prolonged cardiac repolarization and increased risk for ventricular tachycardia, syncope and sudden cardiac death. Cardiac electrical and mechanical function are not independent of each other but interact in a bidirectional manner by electromechanical and mechano-electrical coupling. Therefore, changes in either process will affect the other. Recent experimental and clinical evidence suggests that LQTS, which is primarily considered an "electrical" disorder, also exhibits features of disturbed mechanical function and heterogeneity, which in turn appears to correlate with the risk of arrhythmia in the individual patient. In this review, we give a short overview of the current knowledge about physiological and pathological, long QT-related electrical and mechanical heterogeneity in the heart. Also, their respective roles for future risk prediction approaches in LQTS are discussed.
Imbriaco, M; Pisani, A; Spinelli, L; Cuocolo, A; Messalli, G; Capuano, E; Marmo, M; Liuzzi, R; Visciano, B; Cianciaruso, B; Salvatore, M
2009-07-01
Anderson-Fabry disease is a multisystem X linked disorder of lipid metabolism frequently associated with cardiac symptoms, including left ventricular (LV) hypertrophy gradually impairing cardiac function. Evidence showing that enzyme-replacement therapy (ERT) can be effective in reducing LV hypertrophy and improving myocardial function in the long term is limited. This study aimed to assess the long-term effects of ERT with recombinant alpha-galactosidase A (agalsidase beta, Fabrazyme) on LV function and myocardial signal intensity in 11 patients with Anderson-Fabry disease. Eleven patients (eight males, three females) with varying stages of genetically confirmed Anderson-Fabry disease were examined by means of physical examination and magnetic resonance imaging before ERT with agalsidase beta at 1 mg/kg every other week (study 1) and after a mean treatment duration of 45 months (study 2). At 45 months of treatment, LV mass and LV wall thickness had significantly reduced: 188 (SD 60) g versus 153 (47) g, and 16 (4) mm versus 14 (4) mm, respectively. Furthermore, a significant reduction in myocardial T2 relaxation times was noted in all myocardial regions, that is, interventricular septum 80 (5) ms versus 66 (8) ms, apex 79 (10) ms versus 64 (10) ms, and lateral wall 80 (8) ms versus 65 (16) ms. Changes in LV ejection fraction were not significant. Amelioration of clinical symptoms was observed in all patients. Long-term therapy with agalsidase beta at 1 mg/kg every 2 weeks was effective in significantly reducing LV hypertrophy, improving overall cardiac performance and ameliorating clinical symptoms in patients with Anderson-Fabry disease.
Mlakar, Polona; Salobir, Barbara; Cobo, Nusret; Prezelj, Marija; Terčelj, Marjeta; Sabovič, Mišo
2013-01-01
Oxidative stress is an important nonclassical risk factor for myocardial infarction (MI), and thus, it seems extremely important to recognize factors that effectively reduce it. The aim of our study was to explore possible influences of short-term cardiac rehabilitation (CR) of only 2 weeks in duration on oxidative stress in men after MI. Male patients (N = 21; aged 41-88 years, median 56 years), 6 to 8 weeks after acute MI, were included in our observational study using a pretest/posttest design. We investigated markers of oxidative stress and antioxidant enzymes before and after CR of only 2 weeks in duration and influence of smoking status on these differences. We found significant decrease in isoprostanes in urine in nonsmokers (n = 9) (P = .036) but not in smokers (n = 12) (not significant) during CR. After CR, nonsmokers had lower isoprostanes in urine (P = .039), lower non-transferrin-bound iron (P = .020), and higher erythrocyte catalase (P = .023) than smokers. Of classical risk factors, only low-density lipoprotein cholesterol was lower in nonsmokers before (P = .041) and after CR (P = .015) than in smokers. No other significant differences were seen at the beginning or at the end of CR. To our knowledge, the results of our study indicate for the first time that short-term CR of only 2 weeks in duration already has a positive effect on reduction of oxidative stress in the body. However, this positive effect is seen only in nonsmokers and not in smokers.
Wang, Ting; Miller, Kenneth E.
2016-01-01
The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside intrinsic cardiac ganglia. In the present study, rat intrinsic cardiac ganglia neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) intrinsic cardiac ganglia contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial intrinsic cardiac ganglia contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT. (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG neurons could help in better understanding the function of the intrinsic cardiac nervous system. PMID:27167082
Manchini, Martha T; Antônio, Ednei L; Silva Junior, José Antônio; de Carvalho, Paulo de Tarso C; Albertini, Regiane; Pereira, Fernando C; Feliciano, Regiane; Montemor, Jairo; Vieira, Stella S; Grandinetti, Vanessa; Yoshizaki, Amanda; Chaves, Marcio; da Silva, Móises P; de Lima, Rafael do Nascimento; Bocalini, Danilo S; de Melo, Bruno L; Tucci, Paulo J F; Serra, Andrey J
2017-01-01
Low-level laser therapy (LLLT) has been targeted as a promising approach that can mitigate post-infarction cardiac remodeling. There is some interesting evidence showing that the beneficial role of the LLLT could persist long-term even after the end of the application, but it remains to be systematically evaluated. Therefore, the present study aimed to test the hypothesis that LLLT beneficial effects in the early post-infarction cardiac remodeling could remain in overt heart failure even with the disruption of irradiations. Female Wistar rats were subjected to the coronary occlusion to induce myocardial infarction or Sham operation. A single LLLT application was carried out after 60 s and 3 days post-coronary occlusion, respectively. Echocardiography was performed 3 days and at the end of the experiment (5 weeks) to evaluate cardiac function. After the last echocardiographic examination, LV hemodynamic evaluation was performed at baseline and on sudden afterload increases. Compared with the Sham group, infarcted rats showed increased systolic and diastolic internal diameter as well as a depressed shortening fraction of LV. The only benefit of the LLLT was a higher shortening fraction after 3 days of infarction. However, treated-LLLT rats show a lower shortening fraction in the 5th week of study when compared with Sham and non-irradiated rats. A worsening of cardiac function was confirmed in the hemodynamic analysis as evidenced by the higher LV end-diastolic pressure and lower +dP/dt and -dP/dt with five weeks of study. Cardiac functional reserve was also impaired by infarction as evidenced by an attenuated response of stroke work index and cardiac output to a sudden afterload stress, without LLLT repercussions. No significant differences were found in the myocardial expression of Akt 1 /VEGF pathway. Collectively, these findings illustrate that LLLT improves LV systolic function in the early post-infarction cardiac remodeling. However, this beneficial effect may be dependent on the maintenance of phototherapy. Long-term studies with LLLT application are needed to establish whether these effects ultimately translate into improved cardiac remodeling.
Fukazawa, Kyota; Nishida, Seigo; Hibi, Taizo; Pretto, Ernesto A
2013-01-01
During liver transplant (LT), the release of vasoactive substances into the systemic circulation is associated with severe hemodynamic instability that is injurious to the recipient and/or the post-ischemic graft. Crystalloid flush with backward unclamping (CB) and portal blood flush with forward unclamping (PF) are two reperfusion methods to reduce reperfusion-related cardiovascular perturbations in our center. The primary aim of this study was to compare these two methods. After institutional review board (IRB) approval, cadaveric whole LT cases performed between 2003 and 2008 were reviewed. Patients were divided into two groups based on reperfusion methods: CB or PF. After background matching with propensity score, the effect of each method on post-operative graft function was assessed in detail. In our cohort of 478 patients, CB was used in 313 grafts and PF in 165. Thirty-day graft survival was lower, and risk of retransplantation was higher in PF. Multivariable model showed that CB is an independent factor to reduce primary non-function, cardiac arrest and improve 30-d graft survival. Also, the incidence of ischemic-type biliary lesions was significantly higher in the PF group. Reperfusion methods affect intraoperative hemodynamics and post-transplant outcome. CB allows for control over temperature and composition of the perfusate, perfusion pressure, and the rate of infusion. © 2013 John Wiley & Sons A/S.
Yamakawa, Hiroyuki; Muraoka, Naoto; Miyamoto, Kazutaka; Sadahiro, Taketaro; Isomi, Mari; Haginiwa, Sho; Kojima, Hidenori; Umei, Tomohiko; Akiyama, Mizuha; Kuishi, Yuki; Kurokawa, Junko; Furukawa, Tetsushi; Fukuda, Keiichi; Ieda, Masaki
2015-12-08
Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors, including Gata4, Mef2c, and Tbx5; however, this process is inefficient under serum-based culture conditions, in which conversion of partially reprogrammed cells into fully reprogrammed functional iCMs has been a major hurdle. Here, we report that a combination of fibroblast growth factor (FGF) 2, FGF10, and vascular endothelial growth factor (VEGF), termed FFV, promoted cardiac reprogramming under defined serum-free conditions, increasing spontaneously beating iCMs by 100-fold compared with those under conventional serum-based conditions. Mechanistically, FFV activated multiple cardiac transcriptional regulators and converted partially reprogrammed cells into functional iCMs through the p38 mitogen-activated protein kinase and phosphoinositol 3-kinase/AKT pathways. Moreover, FFV enabled cardiac reprogramming with only Mef2c and Tbx5 through the induction of cardiac reprogramming factors, including Gata4. Thus, defined culture conditions promoted the quality of cardiac reprogramming, and this finding provides new insight into the mechanism of cardiac reprogramming. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Cardiac rehabilitation and mid-term follow-up after transcatheter aortic valve implantation
Zanettini, Renzo; Gatto, Gemma; Mori, Ileana; Pozzoni, Maria Beatrice; Pelenghi, Stefano; Martinelli, Luigi; Klugmann, Silvio
2014-01-01
Background Evaluation of patient outcomes following transcatheter aortic valve implantation (TAVI) has usually been based on survival and clinical improvement. Studies on quality of life are limited, and data from comprehensive assessments after the procedure are lacking. Methods Sixty patients referred for cardiac rehabilitation after TAVI underwent in-hospital and after-discharge multidimensional assessments to evaluate clinical, functional, and nutritional statuses, degree of autonomy, cognitive impairment, depression and quality of life. Results On admission to rehabilitation, approximately half of the patients had severe functional impairment and dependence for basic activities of daily living. During their hospital stay, one-third of the patients suffered significant clinical complications and two had to be transferred to the implantation center. Despite this, the overall outcome was very good. All of the remaining patients were clinically stable at discharge and functional status, autonomy and quality of life were improved in most. During a mean follow-up of 540 days (range: 192–738 days), five patients died from noncardiac causes, three were hospitalized for cardiac events, and nine for non cardiac reasons. Functional status and autonomy remained satisfactory in the majority of patients and most continued to live independently. Conclusions Patients referred for rehabilitation after TAVI are often very frail, with a high grade of functional impairment, dependence on others and high risk of clinical complications. During a rehabilitation programme, based on a multidimensional assessment and intervention, most patients showed significant improvement in functional status, quality of life, and autonomy, which remained stable in the majority of subjects during mid-term follow-up. PMID:25593575
NASA Astrophysics Data System (ADS)
McConnell, Gail; Riis, Erling
2004-10-01
We report on a novel and compact reliable laser source capable of short-wavelength two-photon laser scanning fluorescence microscopy based on soliton self-frequency shift effects in photonic crystal fibre. We demonstrate the function of the system by performing two-photon microscopy of smooth muscle cells and cardiac myocytes from the rat pulmonary vein and Chinese hamster ovary cells loaded with the fluorescent calcium indicator fura-2/AM.
Three nights leg thermal therapy could improve sleep quality in patients with chronic heart failure.
Sawatari, Hiroyuki; Nishizaka, Mari K; Miyazono, Mami; Ando, Shin-Ichi; Inoue, Shujiro; Takemoto, Masao; Sakamoto, Takafumi; Goto, Daisuke; Furumoto, Tomoo; Kinugawa, Shintaro; Hashiguchi, Nobuko; Rahmawati, Anita; Chishaki, Hiroaki; Ohkusa, Tomoko; Magota, Chie; Tsutsui, Hiroyuki; Chishaki, Akiko
2018-02-01
Sleep quality is often impaired in patients with chronic heart failure (HF), which may worsen their quality of life and even prognosis. Leg thermal therapy (LTT), topical leg warming, has been shown to improve endothelial function, oxidative stress, and cardiac function in patients with HF. However, its short-term influence to sleep quality has not been evaluated in HF patients. Eighteen of 23 patients with stable HF received LTT (15 min of warming at 45 °C and 30 min of insulation) at bedtime for 3 consecutive nights and 5 patients served as control. Subjective sleep quality was evaluated by St. Mary's Hospital Sleep Questionnaire, Oguri-Shirakawa-Azumi Sleep Inventory, and Epworth sleepiness scale, and also objectively evaluated by polysomnography. LTT significantly improved subjective sleep quality indicated by depth of sleep (p < 0.01), sleep duration (p < 0.05), number of awaking (p < 0.01), nap duration (p < 0.01), sleep quality (p < 0.05), and sleep satisfaction (p < 0.05). It was also objectively affirmed by a slight but significant decrease of sleep stage N1 (p < 0.01), and increase in sleep stage N2 (p < 0.05). No significant changes occurred in the controls. Hence, the short-term LTT could improve subjective and objective sleep quality in patients with HF. LTT can be a complimentary therapy to improve sleep quality in these patients.
Effect of first myocardial ischemic event on renal function.
Eijkelkamp, Wouter B A; de Graeff, Pieter A; van Veldhuisen, Dirk J; van Dokkum, Richard P E; Gansevoort, Ronald T; de Jong, Paul E; de Zeeuw, Dick; Hillege, Hans L
2007-07-01
Effects of cardiovascular dysfunction on renal function have been poorly characterized. Therefore, we investigated the relation between a first ischemic cardiac event and long-term renal function changes in the general population from the PREVEND study. We studied 6,360 subjects with a total follow-up duration of 27.017 subject-years. The estimated mean proportional increase in serum creatinine after a first ischemic cardiac event was 3.1% compared with 0.4% per year of follow-up in subjects without such an event (p = 0.005). This represented a significantly larger decrease in estimated glomerular filtration rate after the event in subjects with an event versus the decrease in subjects without a first ischemic cardiac event (2.2 vs 0.5 ml/min/1.73 m(2)/year of follow-up, p = 0.006). In multivariate analysis with adjustment for renal risk factors, this event showed an independent association with serum creatinine change. In conclusion, a first ischemic cardiac event appears to enhance the natural decrease in renal function. Because even mild renal dysfunction should be considered a major cardiovascular risk factor after myocardial infarction, increased renal function loss after an ischemic cardiac event could add to the risk for subsequent cardiovascular morbidity, thus closing a vicious circle.
Neonatal autonomic function after pregnancy complications and early cardiovascular development.
Aye, Christina Y L; Lewandowski, Adam James; Oster, Julien; Upton, Ross; Davis, Esther; Kenworthy, Yvonne; Boardman, Henry; Yu, Grace Z; Siepmann, Timo; Adwani, Satish; McCormick, Kenny; Sverrisdottir, Yrsa B; Leeson, Paul
2018-05-23
Heart rate variability (HRV) has emerged as a predictor of later cardiac risk. This study tested whether pregnancy complications that may have long-term offspring cardiac sequelae are associated with differences in HRV at birth, and whether these HRV differences identify abnormal cardiovascular development in the postnatal period. Ninety-eight sleeping neonates had 5-min electrocardiogram recordings at birth. Standard time and frequency domain parameters were calculated and related to cardiovascular measures at birth and 3 months of age. Increasing prematurity, but not maternal hypertension or growth restriction, was associated with decreased HRV at birth, as demonstrated by a lower root mean square of the difference between adjacent NN intervals (rMSSD) and low (LF) and high-frequency power (HF), with decreasing gestational age (p < 0.001, p = 0.009 and p = 0.007, respectively). We also demonstrated a relative imbalance between sympathetic and parasympathetic tone, compared to the term infants. However, differences in autonomic function did not predict cardiovascular measures at either time point. Altered cardiac autonomic function at birth relates to prematurity rather than other pregnancy complications and does not predict cardiovascular developmental patterns during the first 3 months post birth. Long-term studies will be needed to understand the relevance to cardiovascular risk.
Franklin, Rodney C G; Béland, Marie J; Colan, Steven D; Walters, Henry L; Aiello, Vera D; Anderson, Robert H; Bailliard, Frédérique; Boris, Jeffrey R; Cohen, Meryl S; Gaynor, J William; Guleserian, Kristine J; Houyel, Lucile; Jacobs, Marshall L; Juraszek, Amy L; Krogmann, Otto N; Kurosawa, Hiromi; Lopez, Leo; Maruszewski, Bohdan J; St Louis, James D; Seslar, Stephen P; Srivastava, Shubhika; Stellin, Giovanni; Tchervenkov, Christo I; Weinberg, Paul M; Jacobs, Jeffrey P
2017-12-01
An internationally approved and globally used classification scheme for the diagnosis of CHD has long been sought. The International Paediatric and Congenital Cardiac Code (IPCCC), which was produced and has been maintained by the International Society for Nomenclature of Paediatric and Congenital Heart Disease (the International Nomenclature Society), is used widely, but has spawned many "short list" versions that differ in content depending on the user. Thus, efforts to have a uniform identification of patients with CHD using a single up-to-date and coordinated nomenclature system continue to be thwarted, even if a common nomenclature has been used as a basis for composing various "short lists". In an attempt to solve this problem, the International Nomenclature Society has linked its efforts with those of the World Health Organization to obtain a globally accepted nomenclature tree for CHD within the 11th iteration of the International Classification of Diseases (ICD-11). The International Nomenclature Society has submitted a hierarchical nomenclature tree for CHD to the World Health Organization that is expected to serve increasingly as the "short list" for all communities interested in coding for congenital cardiology. This article reviews the history of the International Classification of Diseases and of the IPCCC, and outlines the process used in developing the ICD-11 congenital cardiac disease diagnostic list and the definitions for each term on the list. An overview of the content of the congenital heart anomaly section of the Foundation Component of ICD-11, published herein in its entirety, is also included. Future plans for the International Nomenclature Society include linking again with the World Health Organization to tackle procedural nomenclature as it relates to cardiac malformations. By doing so, the Society will continue its role in standardising nomenclature for CHD across the globe, thereby promoting research and better outcomes for fetuses, children, and adults with congenital heart anomalies.
Mechanisms of impaired exercise capacity in short duration experimental hyperthyroidism.
Martin, W H; Spina, R J; Korte, E; Yarasheski, K E; Angelopoulos, T J; Nemeth, P M; Saffitz, J E
1991-01-01
To investigate the mechanism of reduced exercise tolerance in hyperthyroidism, we characterized cardiovascular function and determinants of skeletal muscle metabolism in 18 healthy subjects aged 26 +/- 1 yr (mean +/- SE) before and after 2 wk of daily ingestion of 100 micrograms of triiodothyronine (T3). Resting oxygen uptake, heart rate, and cardiac output increased and heart rate and cardiac output at the same submaximal exercise intensity were higher in the hyperthyroid state (P less than 0.05). However, maximal oxygen uptake decreased after T3 administration (3.08 +/- 0.17 vs. 2.94 +/- 0.19 l/min; P less than 0.001) despite increased heart rate and cardiac output at maximal exercise (P less than 0.05). Plasma lactic acid concentration at an equivalent submaximal exercise intensity was elevated 25% (P less than 0.01) and the arteriovenous oxygen difference at maximal effort was reduced (P less than 0.05) in the hyperthyroid state. These effects were associated with a 21-37% decline in activities of oxidative (P less than 0.001) and glycolytic (P less than 0.05) enzymes in skeletal muscle and a 15% decrease in type IIA muscle fiber cross-sectional area (P less than 0.05). Lean body mass was reduced (P less than 0.001) and the rates of whole body leucine oxidation and protein breakdown were enhanced (P less than 0.05). Thus, exercise tolerance is impaired in short duration hyperthyroidism because of decreased skeletal muscle mass and oxidative capacity related to accelerated protein catabolism but cardiac pump function is not reduced. PMID:1752962
Qualitative similarities in the visual short-term memory of pigeons and people.
Gibson, Brett; Wasserman, Edward; Luck, Steven J
2011-10-01
Visual short-term memory plays a key role in guiding behavior, and individual differences in visual short-term memory capacity are strongly predictive of higher cognitive abilities. To provide a broader evolutionary context for understanding this memory system, we directly compared the behavior of pigeons and humans on a change detection task. Although pigeons had a lower storage capacity and a higher lapse rate than humans, both species stored multiple items in short-term memory and conformed to the same basic performance model. Thus, despite their very different evolutionary histories and neural architectures, pigeons and humans have functionally similar visual short-term memory systems, suggesting that the functional properties of visual short-term memory are subject to similar selective pressures across these distant species.
Ravingerová, T; Bernátová, I; Matejíková, J; Ledvényiová, V; Nemčeková, M; Pecháňová, O; Tribulová, N; Slezák, J
2011-01-01
Chronic hypertension may have a negative impact on the myocardial response to ischemia. On the other hand, intrinsic ischemic tolerance may persist even in the pathologically altered hearts of hypertensive animals, and may be modified by short- or long-term adaptation to different stressful conditions. The effects of long-term limitation of living space (ie, crowding stress [CS]) and brief ischemia-induced stress on cardiac response to ischemia/reperfusion (I/R) injury are not yet fully characterized in hypertensive subjects. The present study was designed to test the influence of chronic and acute stress on the myocardial response to I/R in spontaneously hypertensive rats (SHR) compared with their effects in normotensive counterparts. In both groups, chronic, eight-week CS was induced by caging five rats per cage in cages designed for two rats (200 cm(2)/rat), while controls (C) were housed four to a cage in cages designed for six animals (480 cm(2)/rat). Acute stress was evoked by one cycle of I/R (5 min each, ischemic preconditioning) before sustained I/R in isolated Langendorff-perfused hearts of normotensive and SHR rats. At baseline conditions, the effects of CS were manifested only as a further increase in blood pressure in SHR, and by marked limitation of coronary perfusion in normotensive animals, while no changes in heart mechanical function were observed in any of the groups. Postischemic recovery of contractile function, severity of ventricular arrhythmias and lethal injury (infarction size) were worsened in the hypertrophied hearts of C-SHR compared with normotensive C. However, myo-cardial stunning and reperfusion-induced ventricular arrhythmias were attenuated by CS in SHR, which was different from deterioration of I/R injury in the hearts of normotensive animals. In contrast, ischemic preconditioning conferred an effective protection against I/R in both groups, although the extent of anti-infarct and anti-arrhythmic effects was lower in SHR. Both forms of stress may improve the altered response to ischemia in hypertensive subjects. In contrast to short-term preconditioning stress, chronic psychosocial stress was associated with a higher risk of lethal arrhythmias and contractile failure in normotensive animals exposed to an acute ischemic challenge.
Zhang, Ming; Wang, Ximin; Xie, Xinxing; Wang, Zhongsu; Liu, Xiaoyan; Guan, Juan; Wang, Weizong; Li, Zhan; Wang, Jiangrong; Gao, Mei; Hou, Yinglong
2015-10-01
Long-term effects of ganglionated plexi (GP) ablation on sinoatrial node (SAN) and atrioventricular node (AVN) remain unclear. This study is to investigate the long-term effects of ablation of cardiac anterior right GP (ARGP) and inferior right GP (IRGP) on function and structure of SAN and AVN in canine. Thirty-two dogs were randomly divided into an operated group (n = 24) and sham-operated group (n = 8). ARGP and IRGP were ablated in operated group which was randomly divided into three subgroups according to the period of evaluation after operation (1 month, 6 months, 12 months). The functional and histological characteristics of SAN and AVN, as well as the expression of connexin (Cx) 43 and Cx 45 in SAN and AVN, were evaluated before and after ablation. Resting heart rate was increased and AVN effective refractory period was prolonged and sinus node recovery time (SNRT) and corrected SNRT were shortened immediately after ablation. These changes were reverted to preablation level after 1 month. At 1 month, ventricular rate during atrial fibrillation was slowed, atria-His intervals were prolonged, and Cx43 and Cx45 expression in SAN and AVN were downregulated. At 6 months, all changes were reverted to preablation level. The histological characteristics of SAN and AVN did not change. Ablation of ARGP and IRGP has short-term effects on function and structure of SAN and AVN rather than long-term effects, which suggests that ablation of ARGP and IRGP is safe. Atrioventricular conduction dysfunction after ablation may be related to downregulated Cx43 and Cx45 expression in AVN. © 2015 Wiley Periodicals, Inc.
[Image processing applying in analysis of motion features of cultured cardiac myocyte in rat].
Teng, Qizhi; He, Xiaohai; Luo, Daisheng; Wang, Zhengrong; Zhou, Beiyi; Yuan, Zhirun; Tao, Dachang
2007-02-01
Study of mechanism of medicine actions, by quantitative analysis of cultured cardiac myocyte, is one of the cutting edge researches in myocyte dynamics and molecular biology. The characteristics of cardiac myocyte auto-beating without external stimulation make the research sense. Research of the morphology and cardiac myocyte motion using image analysis can reveal the fundamental mechanism of medical actions, increase the accuracy of medicine filtering, and design the optimal formula of medicine for best medical treatments. A system of hardware and software has been built with complete sets of functions including living cardiac myocyte image acquisition, image processing, motion image analysis, and image recognition. In this paper, theories and approaches are introduced for analysis of living cardiac myocyte motion images and implementing quantitative analysis of cardiac myocyte features. A motion estimation algorithm is used for motion vector detection of particular points and amplitude and frequency detection of a cardiac myocyte. Beatings of cardiac myocytes are sometimes very small. In such case, it is difficult to detect the motion vectors from the particular points in a time sequence of images. For this reason, an image correlation theory is employed to detect the beating frequencies. Active contour algorithm in terms of energy function is proposed to approximate the boundary and detect the changes of edge of myocyte.
Andres, Axel; Kin, Tatsuya; O'Gorman, Doug; Livingstone, Scott; Bigam, David; Kneteman, Norman; Senior, Peter; Shapiro, A M James
2016-01-01
In islet transplantation, deceased cardiac death (DCD) donation has been identified as a potential extended source. There are currently no studies comparing outcomes between these categories, and our goal was to compare islet isolation success rates and transplantation outcomes between DCD and neurological determination of death (NDD) donors. Islet isolations from 15 DCD and 418 NDD were performed in our centre between September 2008 and September 2014. Donor variables, islet yields, metabolic function of isolated isled and insulin requirements at 1-month post-transplant were compared. Compared to NDD, pancreata from DCD were more often procured locally and donors required less vasopressive support (P < 0.001 and P = 0.023, respectively), but the other variables were similar between groups. Pre- and postpurification islet yields were similar between NDD and DCD (576 vs. 608 × 10(3) islet equivalent, P = 0.628 and 386 vs. 379, P = 0.881, respectively). The metabolic function was similar between NDD and DCD, as well as the mean decrease in insulin requirement at 1-month post-transplantation (NDD: 64.82%; DCD: 60.17% reduction, P = 0.517). These results support the broader use of DCD pancreata for islet isolation. A much larger DCD islet experience will be required to truly determine noninferiority of both short- and long-term outcomes. © 2015 Steunstichting ESOT.
Abdulrahman, Randa M; Delgado, Victoria; Hoftijzer, Hendrieke C; Ng, Arnold C T; Ewe, See Hooi; Marsan, Nina Ajmone; Holman, Eduard R; Hovens, Guido C; Corssmit, Eleonora P; Romijn, Johannes A; Bax, Jeroen J; Smit, Johannes W A
2011-05-01
The cardiovascular effects of transitions from exogenous subclinical hyperthyroidism to short-term overt hypothyroidism in patients treated for differentiated thyroid carcinoma remain unclear. The present study aims at evaluating the changes in multidirectional myocardial strain using two-dimensional (2D) speckle tracking during this controlled transition from exogenous subclinical hyperthyroidism to overt hypothyroidism. The study included 14 patients with differentiated thyroid carcinoma on thyrotropin suppressive thyroxine substitution who were subsequently withdrawn from thyroxine for 4 weeks. Cardiac function was assessed by 2D speckle tracking echocardiography before and 1 and 4 weeks after withdrawal and compared with values obtained in a control group of 24 individuals. At baseline, the left ventricular dimensions were significantly higher in patients as compared with controls. Using 2D speckle tracking imaging, the patients had significantly impaired baseline myocardial systolic function in the circumferential (-16.0% ± 2.1% vs. -19.2% ± 3.0%, p = 0.001) and longitudinal (-17.1% ± 2.5% vs. -19.7% ± 3.0%, p = 0.001) directions as compared with controls. Withdrawal of thyroid hormone did not induce significant changes in left ventricular dimensions or systolic function. During the transition from exogenous subclinical hyperthyroidism to overt hypothyroidism, a significant improvement in circumferential and longitudinal systolic shortening was observed and returned to abnormal values when the patients were overt hypothyroid (circumferential strain: from -16.0% ± 2.1% to -18.6% ± 1.9% and -14.7% ± 2.8%, p < 0.005; longitudinal strain: from -17.1% ± 2.5% to -18.8% ± 1.4% and -16.3% ± 1.3%, p < 0.005). A U-shaped relationship between a range of thyroid hormone levels (from hyper- to hypothyroid concentrations) and myocardial strains was observed. The clinical consequences of these findings remain to be determined but may point out an increased myocardial vulnerability even in states of moderate subclinical hyperthyroidism and short-term hypothyroidism.
Krustrup, P; Hansen, P R; Nielsen, C M; Larsen, M N; Randers, M B; Manniche, V; Hansen, L; Dvorak, J; Bangsbo, J
2014-08-01
The present study investigated the cardiac effects of a 10-week football training intervention for school children aged 9-10 years using comprehensive transthoracic echocardiography as a part of a larger ongoing study. A total of 97 pupils from four school classes were cluster-randomized into a control group that maintained their usual activities (CON; two classes, n = 51, 21 boys and 30 girls) and a football training group that performed an additional 3 × 40 min of small-sided football training per week (FT; two classes, n = 46, 23 boys and 23 girls). No baseline differences were observed in age, body composition, or echocardiographic variables between FT and CON. After the 10-week intervention, left ventricular posterior wall diameter was increased in FT compared with CON [0.4 ± 0.7 vs -0.1 ± 0.6 (± SD) mm; P < 0.01] as was the interventricular septum thickness (0.2 ± 0.7 vs -0.2 ± 0.8 mm; P < 0.001). Global isovolumetric relaxation time increased more in FT than in CON (3.8 ± 10.4 vs -0.9 ± 6.6 ms, P < 0.05) while the change in ventricular systolic ejection fraction tended to be higher (1.4 ± 8.0 vs -1.1 ± 5.5%; P = 0.08). No changes were observed in resting heart rate or blood pressure. In conclusion, a short-term, school-based intervention comprising small-sided football sessions resulted in significant structural and functional cardiac adaptations in pre-adolescent children. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Regulation of human cardiac potassium channels by full-length KCNE3 and KCNE4.
Abbott, Geoffrey W
2016-12-06
Voltage-gated potassium (Kv) channels comprise pore-forming α subunits and a multiplicity of regulatory proteins, including the cardiac-expressed and cardiac arrhythmia-linked transmembrane KCNE subunits. After recently uncovering novel, N-terminally extended (L) KCNE3 and KCNE4 isoforms and detecting their transcripts in human atrium, reported here are their functional effects on human cardiac Kv channel α subunits expressed in Xenopus laevis oocytes. As previously reported for short isoforms KCNE3S and KCNE4S, KCNE3L inhibited hERG; KCNE4L inhibited Kv1.1; neither form regulated the HCN1 pacemaker channel. Unlike KCNE4S, KCNE4L was a potent inhibitor of Kv4.2 and Kv4.3; co-expression of cytosolic β subunit KChIP2, which regulates Kv4 channels in cardiac myocytes, partially relieved Kv4.3 but not Kv4.2 inhibition. Inhibition of Kv4.2 and Kv4.3 by KCNE3L was weaker, and its inhibition of Kv4.2 abolished by KChIP2. KCNE3L and KCNE4L also exhibited subunit-specific effects on Kv4 channel complex inactivation kinetics, voltage dependence and recovery. Further supporting the potential physiological significance of the robust functional effects of KCNE4L on Kv4 channels, KCNE4L protein was detected in human atrium, where it co-localized with Kv4.3. The findings establish functional effects of novel human cardiac-expressed KCNE isoforms and further contribute to our understanding of the potential mechanisms influencing cardiomyocyte repolarization.
Is smog innocuous? Air pollution and cardiovascular disease.
Mishra, Sundeep
Air pollution is a significant environmental and health hazard. Earlier studies had examined the adverse health effects associated with short- and long-term exposure to particulate matter on respiratory disease. However, later studies demonstrated that was actually cardiovascular disease that accounted for majority of mortality. Furthermore, it was not gaseous pollutants like oxides of nitrate, sulfur, carbon mono-oxide or ozone but the particulate matter or PM, of fine or coarse size (PM 2.5 and PM 10 ) which was linearly associated with mortality; PM 2.5 with long term and PM 10 with short term. Several cardiovascular diseases are associated with pollution; acute myocardial infarction, heart failure, cardiac arrhythmias, atherosclerosis and cardiac arrest. The ideal way to address this problem is by adhering to stringent environmental standards of pollutants but some individual steps like choosing to stay indoors (on high pollution days), reducing outdoor air permeation to inside, purifying indoor air using air filters, and also limiting outdoor physical activity near source of air pollution can help. Nutritional anti-oxidants like statins or Mediterranean diet, and aspirin have not been associated with reduced risk but specific nutritional agents like broccoli, cabbage, cauliflower or brussels sprouts, fish oil supplement may help. Use of face-mask has been controversial but may be useful if particulate matter load is higher. Copyright © 2017. Published by Elsevier B.V.
Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse.
Baudouy, Delphine; Michiels, Jean-François; Vukolic, Ana; Wagner, Kay-Dietrich; Wagner, Nicole
2017-10-26
An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed in mice is high. Phenotypic characterization of these mouse models also requires the examination of cardiac function and morphology. Echocardiography and magnetic resonance imaging (MRI) are commonly used approaches to characterize cardiac function and morphology in mice. Echocardiographic and MRI equipment specialized for use in small rodents is expensive and requires a dedicated space. This protocol describes cardiac measurements in mice using a clinical echocardiographic system with a 15 MHz human vascular probe. Measurements are performed on anesthetized adult mice. At least three image sequences are recorded and analyzed for each animal in M-mode in the parasternal short-axis view. Afterwards, cardiac histological examination is performed, and cardiomyocyte diameters are determined on hematoxylin-eosin- or wheat germ agglutinin (WGA)-stained paraffin sections. Vessel density is determined morphometrically after Pecam-1 immunostaining. The protocol has been applied successfully to pharmacological studies and different genetic animal models under baseline conditions, as well as after experimental myocardial infarction by the permanent ligation of the left anterior descending coronary artery (LAD). In our experience, echocardiographic investigation is limited to anesthetized animals and is feasible in adult mice weighing at least 25 g.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yan, Lifeng; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029; Zhou, Yong
Genomic damage may devastate the potential of progenitor cells and consequently impair early organogenesis. We found that ogg1, a key enzyme initiating the base-excision repair, was enriched in the embryonic heart in zebrafish. So far, little is known about DNA repair in cardiogenesis. Here, we addressed the critical role of ogg1 in cardiogenesis for the first time. ogg1 mainly expressed in the anterior lateral plate mesoderm (ALPM), the primary heart tube, and subsequently the embryonic myocardium by in situ hybridisation. Loss of ogg1 resulted in severe cardiac morphogenesis and functional abnormalities, including the short heart length, arrhythmia, decreased cardiomyocytes andmore » nkx2.5{sup +} cardiac progenitor cells. Moreover, the increased apoptosis and repressed proliferation of progenitor cells caused by ogg1 deficiency might contribute to the heart phenotype. The microarray analysis showed that the expression of genes involved in embryonic heart tube morphogenesis and heart structure were significantly changed due to the lack of ogg1. Among those, foxh1 is an important partner of ogg1 in the cardiac development in response to DNA damage. Our work demonstrates the requirement of ogg1 in cardiac progenitors and heart development in zebrafish. These findings may be helpful for understanding the aetiology of congenital cardiac deficits. - Highlights: • A key DNA repair enzyme ogg1 is expressed in the embryonic heart in zebrafish. • We found that ogg1 is essential for normal cardiac morphogenesis in zebrafish. • The production of embryonic cardiomyocytes requires appropriate ogg1 expression. • Ogg1 critically regulated proliferation of cardiac progenitor cells in zebrafish. • foxh1 is a partner of ogg1 in the cardiac development in response to DNA damage.« less
Meck, J V; Reyes, C J; Perez, S A; Goldberger, A L; Ziegler, M G
2001-01-01
The incidence of postflight orthostatic intolerance after short-duration spaceflight is about 20%. However, the incidence after long-duration spaceflight was unknown. The purpose of this study was to test the hypothesis that orthostatic intolerance is more severe after long-duration than after short-duration flight. We performed tilt tests on six astronauts before and after long-duration (129-190 days) spaceflights and compared these data with data obtained during stand tests before and after previous short-duration missions. Five of the six astronauts studied became presyncopal during tilt testing after long-duration flights. Only one had become presyncopal during stand testing after short-duration flights. We also compared the long-duration flight tilt test data to tilt test data from 20 different astronauts who flew on the short-duration Shuttle missions that delivered and recovered the astronauts to and from the Mir Space Station. Five of these 20 astronauts became presyncopal on landing day. Heart rate responses to tilt were no different between astronauts on long-duration flights and astronauts on short-duration flights, but long-duration subjects had lower stroke volumes and cardiac outputs than short-duration presyncopal subjects, suggesting a possible decrease in cardiac contractile function. One subject had subnormal norepinephrine release with upright posture after the long flight but not after the short flight. Plasma volume losses were not greater after long flights. Long-duration spaceflight markedly increases orthostatic intolerance, probably with multiple contributing factors.
Ezerarslan, Hande; Beriat, Güçlü Kaan; Nurhat, Raziye Handan; Kazancı, Burak; Çelikkan, Ferda Topal; Sabuncuoğlu, Bizden; Sabuncuoğlu, Hakan
2016-08-01
We aimed to find out the effects of short term and long term hydrocephalus and intracranial ventricular volume changes on cochlear functions by using distortion product otoacoustic emission (DPOAE) in experimental hydrocephalus rat models for the first time in literature. This study was performed with 48 healthy, adult (8 weeks old), Sprague-Dawley rats which weighed between 200 and 240g. Six groups were formed in this study: short term control, short term sham, short term hydrocephalus, long term control, long term sham and long term hydrocephalus groups. Each group contained eight rats. Short term period was 4 weeks and long term period was 8 weeks after the study started. At the end of these periods, DPOAE measurements were performed and then rats were sacrificed to determine ventricular volumes. DPOAE values at all frequencies were significantly decreased in the short term hydrocephalus group when compared to the short term control and short term sham groups. DPOAE values at all frequencies were significantly decreased in the long term hydrocephalus group when compared to the long term control and long term sham groups. Besides, long term sham group which had higher ventricular volumes than long term control group also had lower DPOAE measurements. Significant associations were present between DPOAE measurements and ventricular volumes in hydrocephalus models. The functional disturbances in cochlear functions due to hydrocephalus have been demonstrated with DPOAE measurements in this study. DPOAE measurements may be thought as an easily applicable non-invasive method in detection and follow-up of patients with hydrocephalus. Our findings should be supported with clinical studies in humans. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Chiusolo, Monica; Cadum, Ennio; Stafoggia, Massimo; Galassi, Claudia; Faustini, Annunziata; Bisanti, Luigi; Vigotti, Maria Angela; Dessì, Maria Patrizia; Cernigliaro, Achille; Mallone, Sandra; Pacelli, Barbara; Minerba, Sante; Simonato, Lorenzo; Forastiere, Francesco
2011-01-01
Background: Several studies have shown an association between nitrogen dioxide (NO2) and mortality. In Italy, the EpiAir multicentric study, “Air Pollution and Health: Epidemiological Surveillance and Primary Prevention,” investigated short-term health effects of air pollution, including NO2. Objectives: To study the individual susceptibility, we evaluated the association between NO2 and cause-specific mortality, investigating individual sociodemographic features and chronic/acute medical conditions as potential effect modifiers. Methods: We considered 276,205 natural deaths of persons > 35 years of age, resident in 10 Italian cities, and deceased between 2001 and 2005. We chose a time-stratified case-crossover analysis to evaluate the short-term effects of NO2 on natural, cardiac, cerebrovascular, and respiratory mortality. For each subject, we collected information on sociodemographic features and hospital admissions in the previous 2 years. Fixed monitors provided daily concentrations of NO2, particulate matter ≤ 10 μm in aerodynamic diameter (PM10) and ozone (O3). Results: We found statistically significant associations with a 10-μg/m3 increase of NO2 for natural mortality [2.09% for lag 0–5; 95% confidence interval (CI), 0.96–3.24], for cardiac mortality (2.63% for lag 0–5; 95% CI, 1.53–3.75), and for respiratory mortality (3.48% for lag 1–5; 95% CI, 0.75–6.29). These associations were independent from those of PM10 and O3. Stronger associations were estimated for subjects with at least one hospital admission in the 2 previous years and for subjects with three or more specific chronic conditions. Some cardiovascular conditions (i.e., ischemic heart disease, pulmonary circulation impairment, heart conduction disorders, heart failure) and diabetes appeared to confer a strong susceptibility to air pollution. Conclusions: Our results suggest significant and likely independent effects of NO2 on natural, cardiac, and respiratory mortality, particularly among subjects with specific cardiovascular preexisting chronic conditions and diabetes. PMID:21586369
Yu, Tao; Yang, Zhengfei; Li, Heng; Ding, Youde; Huang, Zitong
2015-01-01
Objective. In this study, our aim was to investigate the effects of combined hypothermia with short duration maintenance on the resuscitation outcomes in a porcine model of ventricular fibrillation (VF). Methods. Fourteen porcine models were electrically induced with VF and untreated for 11 mins. All animals were successfully resuscitated manually and then randomized into two groups: combined mild hypothermia (CH group) and normothermia group (NT group). A combined hypothermia of ice cold saline infusion and surface cooling was implemented in the animals of the CH group and maintained for 4 hours. The survival outcomes and neurological function were evaluated every 24 hours until a maximum of 96 hours. Neuron apoptosis in hippocampus was analyzed. Results. There were no significant differences in baseline physiologies and primary resuscitation outcomes between both groups. Obvious improvements of cardiac output were observed in the CH group at 120, 180, and 240 mins following resuscitation. The animals demonstrated better survival at 96 hours in the CH group when compared to the NT group. In comparison with the NT group, favorable neurological functions were observed in the CH group. Conclusion. Short duration combined cooling initiated after resuscitation improves survival and neurological outcomes in a porcine model of prolonged VF. PMID:26558261
Jackson, Robyn; Tilokee, Everad L; Latham, Nicholas; Mount, Seth; Rafatian, Ghazaleh; Strydhorst, Jared; Ye, Bin; Boodhwani, Munir; Chan, Vincent; Ruel, Marc; Ruddy, Terrence D; Suuronen, Erik J; Stewart, Duncan J; Davis, Darryl R
2015-09-11
Insulin-like growth factor 1 (IGF-1) activates prosurvival pathways and improves postischemic cardiac function, but this key cytokine is not robustly expressed by cultured human cardiac stem cells. We explored the influence of an enhanced IGF-1 paracrine signature on explant-derived cardiac stem cell-mediated cardiac repair. Receptor profiling demonstrated that IGF-1 receptor expression was increased in the infarct border zones of experimentally infarcted mice by 1 week after myocardial infarction. Human explant-derived cells underwent somatic gene transfer to overexpress human IGF-1 or the green fluorescent protein reporter alone. After culture in hypoxic reduced-serum media, overexpression of IGF-1 enhanced proliferation and expression of prosurvival transcripts and prosurvival proteins and decreased expression of apoptotic markers in both explant-derived cells and cocultured neonatal rat ventricular cardiomyocytes. Transplant of explant-derived cells genetically engineered to overexpress IGF-1 into immunodeficient mice 1 week after infarction boosted IGF-1 content within infarcted tissue and long-term engraftment of transplanted cells while reducing apoptosis and long-term myocardial scarring. Paracrine engineering of explant-derived cells to overexpress IGF-1 provided a targeted means of improving cardiac stem cell-mediated repair by enhancing the long-term survival of transplanted cells and surrounding myocardium. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
Spaceflight alters autonomic regulation of arterial pressure in humans
NASA Technical Reports Server (NTRS)
Fritsch-Yelle, Janice M.; Charles, John B.; Jones, Michele M.; Beightol, Larry A.; Eckberg, Dwain L.
1994-01-01
Spaceflight is associated with decreased orthostatic tolerance after landing. Short-duration spaceflight (4 - 5 days) impairs one neutral mechanism: the carotid baroreceptor-cardiac reflex. To understand the effects of longer-duration spaceflight on baroreflex function, we measured R-R interval power spectra, antecubital vein plasma catecholamine levels, carotid baroreceptor-cardiac reflex responses, responses to Valsalva maneuvers, and orthostatic tolerance in 16 astronauts before and after shuttle missions lasting 8 - 14 days. We found the following changes between preflight and landing day: (1) orthostatic tolerance decreased; (2) R-R interval spectral power in the 0.05- to 0.15-Hz band increased; (3) plasma norepinephrine and epinephrine levels increased; (4) the slope, range, and operational point of the carotid baroreceptor cardiac reflex response decreased; and (5) blood pressure and heart rate responses to Valsalva maneuvers were altered. Autonomic changes persisted for several days after landing. These results provide further evidence of functionally relevent reductions in parasympathetic and increases in sympathetic influences on arterial pressure control after spaceflight.
Jonsson, Marcus; Urell, Charlotte; Emtner, Margareta; Westerdahl, Elisabeth
2014-03-28
Physical activity has well-established positive health-related effects. Sedentary behaviour has been associated with postoperative complications and mortality after cardiac surgery. Patients undergoing cardiac surgery often suffer from impaired lung function postoperatively. The association between physical activity and lung function in cardiac surgery patients has not previously been reported. Patients undergoing cardiac surgery were followed up two months postoperatively. Physical activity was assessed on a four-category scale (sedentary, moderate activity, moderate regular exercise, and regular activity and exercise), modified from the Swedish National Institute of Public Health's national survey. Formal lung function testing was performed preoperatively and two months postoperatively. The sample included 283 patients (82% male). Two months after surgery, the level of physical activity had increased (p < 0.001) in the whole sample. Patients who remained active or increased their level of physical activity had significantly better recovery of lung function than patients who remained sedentary or had decreased their level of activity postoperatively in terms of vital capacity (94 ± 11% of preoperative value vs. 91 ± 9%; p = 0.03), inspiratory capacity (94 ± 14% vs. 88 ± 19%; p = 0.008), and total lung capacity (96 ± 11% vs. 90 ± 11%; p = 0.01). An increased level of physical activity, compared to preoperative level, was reported as early as two months after surgery. Our data shows that there could be a significant association between physical activity and recovery of lung function after cardiac surgery. The relationship between objectively measured physical activity and postoperative pulmonary recovery needs to be further examined to verify these results.
[Primary prevention of sudden cardiac death through a wearable cardioverter-defibrillator].
Gabrielli, Domenico; Benvenuto, Manuela; Baroni, Matteo; Oliva, Fabrizio; Capucci, Alessandro
2015-01-01
Nowadays, the implantable cardioverter-defibrillator is the gold standard for the prevention of sudden cardiac death due to tachyarrhythmias. However, its use is not free from short and long-term risks. In the last years, the wearable cardioverter-defibrillator (WCD) has become a widespread option for patients who need a safe and reversible protection against ventricular tachyarrhythmias. Notwithstanding this, its everyday application is restricted by several limitations, including the risk of inappropriate shocks, the device size and the need for strict compliance of both patients and caregivers. In this review, we report the most relevant literature data on WCD usage along with the main fields of applications and future perspectives.
How to Practice Sports Cardiology: A Cardiology Perspective.
Lawless, Christine E
2015-07-01
The rigorous cardiovascular (CV) demands of sport, combined with training-related cardiac adaptations, render the athlete a truly unique CV patient and sports cardiology a truly unique discipline. Cardiologists are advised to adopt a systematic approach to the CV evaluation of athletes, taking into consideration the individual sports culture, sports-specific CV demands, CV adaptations and their appearance on cardiac testing, any existing or potential interaction of the heart with the internal and external sports environment, short- and long-term CV risks, and potential effect of performance-enhancing agents and antidoping regulations. This article outlines the systematic approach, provides a detailed example, and outlines contemporary sports cardiology core competencies. Copyright © 2015 Elsevier Inc. All rights reserved.
Synaptic plasticity functions in an organic electrochemical transistor
NASA Astrophysics Data System (ADS)
Gkoupidenis, Paschalis; Schaefer, Nathan; Strakosas, Xenofon; Fairfield, Jessamyn A.; Malliaras, George G.
2015-12-01
Synaptic plasticity functions play a crucial role in the transmission of neural signals in the brain. Short-term plasticity is required for the transmission, encoding, and filtering of the neural signal, whereas long-term plasticity establishes more permanent changes in neural microcircuitry and thus underlies memory and learning. The realization of bioinspired circuits that can actually mimic signal processing in the brain demands the reproduction of both short- and long-term aspects of synaptic plasticity in a single device. Here, we demonstrate the implementation of neuromorphic functions similar to biological memory, such as short- to long-term memory transition, in non-volatile organic electrochemical transistors (OECTs). Depending on the training of the OECT, the device displays either short- or long-term plasticity, therefore, exhibiting non von Neumann characteristics with merged processing and storing functionalities. These results are a first step towards the implementation of organic-based neuromorphic circuits.
AKI Associated with Cardiac Surgery
Thiele, Robert H.; Isbell, James M.
2015-01-01
Approximately 18% of patients undergoing cardiac surgery experience AKI (on the basis of modern standardized definitions of AKI), and approximately 2%–6% will require hemodialysis. The development of AKI after cardiac surgery portends poor short- and long-term prognoses, with those developing RIFLE failure or AKI Network stage III having an almost 2-fold increase in the risk of death. AKI is caused by a variety of factors, including nephrotoxins, hypoxia, mechanical trauma, inflammation, cardiopulmonary bypass, and hemodynamic instability, and it may be affected by the clinician’s choice of fluids and vasoactive agents as well as the transfusion strategy used. The risk of AKI may be ameliorated by avoidance of nephrotoxins, achievement of adequate glucose control preoperatively, and use of goal-directed therapy hemodynamic strategies. Remote ischemic preconditioning is an exciting future strategy, but more work is needed before widespread implementation. Unfortunately, there are no pharmacologic agents known to reduce the risk of AKI or treat established AKI. PMID:25376763
Positive inotropes in heart failure: a review article
Amin, Ahmad; Maleki, Majid
2012-01-01
Increasing myocardial contractility has long been considered a big help for patients with systolic heart failure, conferring an augmented haemodynamic profile in terms of higher cardiac output, lower cardiac filling pressure and better organ perfusion. Though concerns have been raised over the safety issues regarding the clinical trials of different inotropes in hearts with systolic dysfunction, they still stand as a main therapeutic strategy in many centres dealing with such patients. They must be used as short in duration, low in dose and stopped as early as possible. Evidence-based guidelines have provided clinicians with valuable data for better applying inotropes in heart failure patients. In this paper, the authors address clinical trials with different agents used for increasing cardiac contractility in heart failure patients. Furthermore, the authors focus on recent guidelines on making the most out of inotropes in heart failure patients. PMID:27326019
Kurfirst, Vojtech; Mokrácek, Aleš; Canádyová, Júlia; Frána, Radim; Zeman, Petr
2017-07-01
Occlusion of the left atrial appendage (LAA) has become an integral and important part of the surgical treatment of atrial fibrillation. Different methods of surgical occlusion of the LAA have been associated with varying levels of short- and long-term success for closure. The purpose of this study was to evaluate long-term results of epicardial placement and endocardial occlusion in patients undergoing cardiac operative procedures. A total of 101 patients (average age 65.7 years) undergoing cardiac operative procedures with the epicardial AtriClip Exclusion System of the LAA were enrolled in the study. The AtriClip was placed via a sternotomy or a thoracotomy or from a thoracoscopic approach. Postoperative variables, such as thromboembolic events, clip stability and endocardial leakage around the device, were examined by transoesophageal echocardiography (TEE) and/or computed tomography. Perioperative clip implantation was achieved in 98% of patients. TEE and/or computed tomography conducted during the follow-up period, comprising 1873 patient-months with a mean duration of 18 ± 11 months, revealed no clip migration, no leakage around the device and no clot formation near the remnant cul-de-sac. During the follow-up period, 4 of the cardiac patients experienced transitory ischaemic attacks, whereas no patient experienced a cerebrovascular attack. The Epicardial AtriClip Exclusion System of the LAA appears to be a feasable and safe operative method with a high success rate. Long-term follow-up confirmed clip stability, complete occlussion of the LAA and absence of any atrial fibrilation-related thromboembolic events. These results need to be confirmed by a larger, multicentre study. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Ozdemir, Rahmi; Kucuk, Mehmet; Guzel, Orkide; Karadeniz, Cem; Yilmaz, Unsal; Mese, Timur
2016-10-01
The ketogenic diet (KD) has been referred to as an "effective therapy with side effects" for children with intractable epilepsy. Among the most recognized adverse effects, there are cardiac conduction abnormalities, vascular and myocardial dysfunction. However, very limited and controversial data are available regarding the effects of the KD on cardiac functions. We sought to analyze the mid-term effect of ketogenic diet on cardiac functions in patients with intractable epilepsy who received a ketogenic diet for at least 12months using conventional and relatively new imaging techniques. This prospective study included 61 patients with intractable epilepsy who received ketogenic diet for at least 12months. Clinical examinations, serum carnitine and selenium levels as well as electrocardiographic and echocardiographic examinations were scheduled prior to the procedure and at 1, 3, 6 and 12months. We utilized two-dimensional, M-mode, colored Doppler, spectral Doppler and pulsed wave tissue Doppler imaging techniques to investigate ventricular systolic and diastolic functions of this subgroup of patients. In our study, there was no significant difference after 1year of KD therapy compared to baseline values-except a significantly decreased A wave velocity-in terms of pulse wave Doppler echocardiographic measurements of the diastolic function. The tissue Doppler measurements obtained from the lateral wall of tricuspide and mitral annuli were not different at baseline and at month 12 of the treatment, as well. The ketogenic diet appears to have no disturbing effect on ventricular functions in epileptic children in the midterm. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Long-lasting functional disabilities in patients who recover from coma after cardiac operations.
Rodriguez, Rosendo A; Nair, Shona; Bussière, Miguel; Nathan, Howard J
2013-03-01
Uncertainty regarding the long-term functional outcome of patients who awaken from coma after cardiac operations is difficult for families and physicians and may delay rehabilitation. We studied the long-term functional status of these patients to determine if duration of coma predicted outcome. We followed 71 patients who underwent cardiac operations; recovered their ability to respond to verbal commands after coma associated with postoperative stroke, encephalopathy, and/or seizures; and were discharged from the hospital. The Glasgow Outcome Scale Extended (GOSE) was used to assess functional disability 2 to 4 years after discharge. Outcomes were classified as favorable (GOSE scores 7 and 8) and unfavorable (GOSE scores 1-6). Of 71 patients identified, 39 were interviewed, 15 died, 1 refused to be interviewed, and 16 were lost to follow-up. Of the 54 patients with completed GOSE evaluations, only 15 (28%) had favorable outcomes. Among patients with unfavorable outcomes, 15 (28%) died, 14 (26%) survived with moderate disabilities, and 10 (18%) had severe disabilities. Factors associated with unfavorable outcomes were increases in duration of coma (p = 0.007), time in intensive care (p = 0.006), length of hospitalization (p = 0.004), and postoperative serum creatine kinase levels (p = 0.006). Only duration of coma was an independent predictor of unfavorable outcome (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.008-1.537; p = 0.042). Patients with durations of coma greater than 4 days were more likely to have unfavorable outcomes (OR, 5.1; 95% CI, 1.3-21.3; p = 0.02). Two thirds of comatose patients who survived to discharge after cardiac operations had unfavorable long-term functional outcomes. A longer duration of unconsciousness is a predictor of unfavorable outcome. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Xu, Ke; Butlin, Mark; Avolio, Alberto P
2012-01-01
Timing of biventricular pacing devices employed in cardiac resynchronization therapy (CRT) is a critical determinant of efficacy of the procedure. Optimization is done by maximizing function in terms of arterial pressure (BP) or cardiac output (CO). However, BP and CO are also determined by the hemodynamic load of the pulmonary and systemic vasculature. This study aims to use a lumped parameter circulatory model to assess the influence of the arterial load on the atrio-ventricular (AV) and inter-ventricular (VV) delay for optimal CRT performance.
From hemodynamic towards cardiomechanic sensors in implantable devices
NASA Astrophysics Data System (ADS)
Ferek-Petric, Bozidar
2013-06-01
Sensor could significantly improve the cardiac electrotherapy. It has to provide long-term stabile signal not impeding the device longevity and lead reliability. It may not introduce special implantation and adjustment procedures. Hemodynamic sensors based on the blood flow velocity and cardiomechanic sensors based on the lead bending measurement are disclosed. These sensors have a broad clinical utility. Triboelectric and high-frequency lead bending sensors yield accurate and stable signals whereby functioning with every cardiac lead. Moreover, high frequency measurement avoids use of any kind of special hardware mounted on the cardiac lead.
Carlton, Matthew; Campbell, John
2013-11-01
Membrane oxygenator heat exchanger (HE) device failure is reported to be very low for both short- and long-term extracorporeal devices. All oxygenator manufacturers provide instructions for leak testing of their HE devices prior to patient use. In addition to these recommendations, since 2006 at Nottingham University Hospitals (NUH) we have also additionally pressure tested HE devices prior to use. We conducted a national survey of cardiac centers in Great Britain and Ireland to determine the methods undertaken in individual centers for validation of the integrity of HE devices. Furthermore, we also collected information on the routine maintenance techniques utilized within these centers to inhibit microbial growth in the water used in the heater-cooler units (HCUs). In total, 34 responses were collected from the 57 centers performing cardiac surgery, producing a response rate of 60%. Of the responding centers, 71% are adhering to manufacturer's recommended guidelines of circulating the water through the device for 5 minutes. Of these centers, 17% reported detecting a leak between the HE and membrane compartment of the oxygenator. In responding centers, 29% reported using the pressure test technique. In the centers utilizing pressure testing, 60% reported detecting a leak. This survey reports an association of a greater HE leak detection rate using the pressure test technique compared to using water testing in isolation (p = 0.034). We believe the pressure testing method provides the perfusionist with confidence in the integrity of the HE for short- and long-term circulatory support devices prior to use in both elective and emergency situations.
Epinephrine and the metabolic syndrome.
Ziegler, Michael G; Elayan, Hamzeh; Milic, Milos; Sun, Ping; Gharaibeh, Munir
2012-02-01
Epinephrine is the prototypical stress hormone. Its stimulation of all α and β adrenergic receptors elicits short-term systolic hypertension, hyperglycemia, and other aspects of the metabolic syndrome. Acute epinephrine infusion increases cardiac output and induces insulin resistance, but removal of the adrenal medulla has no consistent effect on blood pressure. Epinephrine is the most effective endogenous agonist at the β2 receptor. Transgenic mice that cannot make epinephrine and mice that lack the β2 receptor become hypertensive during exercise, presumably owing to the absence of β2-mediated vasodilatation. Epinephrine-deficient mice also have cardiac remodeling and poor cardiac responses to stress, but do not develop resting hypertension. Mice that cannot make epinephrine have a normal metabolism on a regular 14% fat diet but become hyperglycemic and insulin resistant when they eat a high fat diet. Vigorous exercise prevents diabetes in young mice and humans that overeat. However, exercise is a less effective treatment in older type 2 human diabetics and had no effect on glucose or insulin responses in older, diabetic mice. Sensitivity of the β2 receptor falls sharply with advancing age, and adrenal epinephrine release also decreases. However, treatment of older diabetic mice with a β2 adrenergic agonist improved insulin sensitivity, indicating that β2 subsensitivity can be overcome pharmacologically. Recent studies show that over the long term, epinephrine prevents hypertension during stress and improves glucose tolerance. The hyperglycemic influence of epinephrine is short-lived. Chronic administration of epinephrine and other β2 agonists improves cellular glucose uptake and metabolism. Overall, epinephrine counteracts the metabolic syndrome.
Cardoso, Bárbara; Laranjo, Sérgio; Gomes, Inês; Freitas, Isabel; Trigo, Conceição; Fragata, Isabel; Fragata, José; Pinto, Fátima
2016-02-01
To characterize the epidemiology and risk factors for acute kidney injury (AKI) after pediatric cardiac surgery in our center, to determine its association with poor short-term outcomes, and to develop a logistic regression model that will predict the risk of AKI for the study population. This single-center, retrospective study included consecutive pediatric patients with congenital heart disease who underwent cardiac surgery between January 2010 and December 2012. Exclusion criteria were a history of renal disease, dialysis or renal transplantation. Of the 325 patients included, median age three years (1 day-18 years), AKI occurred in 40 (12.3%) on the first postoperative day. Overall mortality was 13 (4%), nine of whom were in the AKI group. AKI was significantly associated with length of intensive care unit stay, length of mechanical ventilation and in-hospital death (p<0.01). Patients' age and postoperative serum creatinine, blood urea nitrogen and lactate levels were included in the logistic regression model as predictor variables. The model accurately predicted AKI in this population, with a maximum combined sensitivity of 82.1% and specificity of 75.4%. AKI is common and is associated with poor short-term outcomes in this setting. Younger age and higher postoperative serum creatinine, blood urea nitrogen and lactate levels were powerful predictors of renal injury in this population. The proposed model could be a useful tool for risk stratification of these patients. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.
Kidney Outcomes 5 Years After Pediatric Cardiac Surgery
Greenberg, Jason H.; Zappitelli, Michael; Devarajan, Prasad; Thiessen-Philbrook, Heather R.; Krawczeski, Catherine; Li, Simon; Garg, Amit X.; Coca, Steve; Parikh, Chirag R.
2017-01-01
IMPORTANCE Acute kidney injury (AKI) after pediatric cardiac surgery is associated with high short-term morbidity and mortality; however, the long-term kidney outcomes are unclear. OBJECTIVE To assess long-term kidney outcomes after pediatric cardiac surgery and to determine if perioperative AKI is associated with worse long-term kidney outcomes. DESIGN, SETTING, AND PARTICIPANTS This prospective multicenter cohort study recruited children between ages 1 month to 18 years who underwent cardiopulmonary bypass for cardiac surgery and survived hospitalization from 3 North American pediatric centers between July 2007 and December 2009. Children were followed up with telephone calls and an in-person visit at 5 years after their surgery. EXPOSURES Acute kidney injury defined as a postoperative serum creatinine rise from preoperative baseline by 50% or 0.3 mg/dL or more during hospitalization for cardiac surgery. MAIN OUTCOMES AND MEASURES Hypertension (blood pressure ≥95th percentile for height, age, sex, or self-reported hypertension), microalbuminuria (urine albumin to creatinine ratio >30 mg/g), and chronic kidney disease (serum creatinine estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m2 or microalbuminuria). RESULTS Overall, 131 children (median [interquartile range] age, 7.7 [5.9–9.9] years) participated in the 5-year in-person follow-up visit; 68 children (52%) were male. Fifty-seven of 131 children (44%) had postoperative AKI. At follow-up, 22 children (17%) had hypertension (10 times higher than the published general pediatric population prevalence), while 9 (8%), 13 (13%), and 1 (1%) had microalbuminuria, an eGFR less than 90 mL/min/1.73 m2, and an eGFR less than 60 mL/min/1.73 m2, respectively. Twenty-one children (18%) had chronic kidney disease. Only 5 children (4%) had been seen by a nephrologist during follow-up. There was no significant difference in renal outcomes between children with and without postoperative AKI. CONCLUSIONS AND RELEVANCE Chronic kidney disease and hypertension are common 5 years after pediatric cardiac surgery. Perioperative AKI is not associated with these complications. Longer follow-up is needed to ascertain resolution or worsening of chronic kidney disease and hypertension. PMID:27618162
Lunde, Ida G; Herum, Kate M; Carlson, Cathrine C; Christensen, Geir
2016-09-01
Heart disease is a deadly syndrome affecting millions worldwide. It reflects an unmet clinical need, and the disease mechanisms are poorly understood. Cardiac fibrosis is central to heart disease. The four-membered family of transmembrane proteoglycans, syndecan-1 to -4, is believed to regulate fibrosis. We review the current literature concerning syndecans in cardiac fibrosis. Syndecan expression is up-regulated in response to pro-inflammatory stimuli in various forms of heart disease with fibrosis. Mice lacking syndecan-1 and -4 show reduced activation of pro-fibrotic signaling and increased cardiac rupture upon infarction indicating an important role for these molecules. Whereas the short cytoplasmic tail of syndecans regulates signaling, their extracellular part, substituted with heparan sulfate glycosaminoglycan chains, binds a plethora of extracellular matrix (ECM) molecules involved in fibrosis, e.g., collagens, growth factors, cytokines, and immune cell adhesion proteins. Full-length syndecans induce pro-fibrotic signaling, increasing the expression of collagens, myofibroblast differentiation factors, ECM enzymes, growth factors, and immune cell adhesion molecules, thereby also increasing cardiac stiffness and preventing cardiac rupture. Upon pro-inflammatory stimuli, syndecan ectodomains are enzymatically released from heart cells (syndecan shedding). Shed ectodomains affect the expression of ECM molecules, promoting ECM degradation and cardiac rupture upon myocardial infarction. Blood levels of shed syndecan-1 and -4 ectodomains are associated with hospitalization, mortality, and heart remodeling in patients with heart failure. Improved understanding of syndecans and their modifying enzymes in cardiac fibrosis might contribute to the development of compounds with therapeutic potential, and enzymatically shed syndecan ectodomains might constitute a future prognostic tool for heart diseases with fibrosis. Graphical Abstract Graphical abstract summarizing the contents of the current review on syndecans in cardiac fibrosis. The heart is subjected to various forms of pathological stimuli, e.g., myocardial infarction, hypertension, valvular stenosis, infection, or an inherited genetic mutation, triggering responses in cells resident in the heart. Here, we focus on the responses of cardiac fibroblasts directing changes in the extracellular matrix resulting in cardiac fibrosis. A family of four transmembrane proteoglycans, syndecan-1 to -4, is expressed in the cell membrane of cardiac fibroblasts and is generally up-regulated in response to the above-mentioned pathological stimuli. Syndecans carry glycosaminoglycan chains on their extracellular domain, binding a plethora of molecules involved in fibrosis, e.g., growth factors, cytokines, immune cell adhesion proteins, and pathogens. Syndecans have a short cytoplasmic tail involved in pro-fibrotic signaling. The signaling and cellular processes governed by syndecans in the heart in response to pathological stimuli regulate important aspects of extracellular matrix remodeling and fibrosis and have mainly been studied in cardiac remodeling in response to cardiac infarction and pressure overload. In general, adequate timing and the quantity and quality of fibrosis are absolutely crucial for heart function and survival, determining cardiac stiffness, contractility, compliance, probability of rupture, dilation, and diastolic and systolic function. Syndecan-1 and -4 have mainly been studied in the heart and are discussed in this review (LV left ventricle).
Zhang, W; Kong, C W; Tong, M H; Chooi, W H; Huang, N; Li, R A; Chan, B P
2017-02-01
Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are regarded as a promising source for regenerative medicine, drug testing and disease modeling. Nevertheless, cardiomyocytes are immature in terms of their contractile structure, metabolism and electrophysiological properties. Here, we fabricate cardiac muscle strips by encapsulating hESC-CMs in collagen-based biomaterials. Supplementation of niche cells at 3% to the number of hESC-CMs enhance the maturation of the hESC-CMs in 3D tissue matrix. The benefits of adding mesenchymal stem cells (MSCs) are comparable to that of adding fibroblasts. These two cell types demonstrate similar effects in promoting the compaction and cell spreading, as well as expression of maturation markers at both gene and protein levels. Mechanical loading, particularly cyclic stretch, produces engineered cardiac tissues with higher maturity in terms of twitch force, elastic modulus, sarcomere length and molecular signature, when comparing to static stretch or non-stretched controls. The current study demonstrates that the application of niche cells and mechanical stretch both stimulate the maturation of hESC-CMs in 3D architecture. Our results therefore suggest that this 3D model can be used for in vitro cardiac maturation study. Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are regarded as being a promising source of cells for regenerative medicine, drug testing and disease modeling. Nevertheless, cardiomyocytes are immature in terms of their contractile structure, metabolism and electrophysiological properties. In the current study, we have fabricated cardiac muscle strips by encapsulating hESC-CMs in collagen-based biomaterials and demonstrated that supplementation of mesenchymal niche cells as well as provision of mechanical loading particularly stretching have significantly promoted the maturation of the cardiomyocytes and hence improved the mechanical functional characteristics of the tissue strips. Specifically, with 3% niche cells including both fibroblasts and mesenchymal stem cells, a more mature hESC-CMs derived cardiac strip was resulted, in terms of compaction and spreading of cells, and upregulation of molecular signature in both gene and protein expression of maturation. Mechanical loading, particularly cyclic stretch, produces engineered cardiac tissues with higher maturity in terms of molecular signature markers and functional parameters including twitch force, elastic modulus and sarcomere length, when comparing with static stretch or non-stretched controls. The current study demonstrates that the application of niche cells and mechanical stretch both stimulate the maturation of hESC-CMs in 3D architecture, resulting in more mature cardiac strips. Our results contribute to bioengineering of functional heart tissue strips for drug screening and disease modeling. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Intraperitoneal AAV9-shRNA inhibits target expression in neonatal skeletal and cardiac muscles.
Mayra, Azat; Tomimitsu, Hiroyuki; Kubodera, Takayuki; Kobayashi, Masaki; Piao, Wenying; Sunaga, Fumiko; Hirai, Yukihiko; Shimada, Takashi; Mizusawa, Hidehiro; Yokota, Takanori
2011-02-11
Systemic injections of AAV vectors generally transduce to the liver more effectively than to cardiac and skeletal muscles. The short hairpin RNA (shRNA)-expressing AAV9 (shRNA-AAV9) can also reduce target gene expression in the liver, but not enough in cardiac or skeletal muscles. Higher doses of shRNA-AAV9 required for inhibiting target genes in cardiac and skeletal muscles often results in shRNA-related toxicity including microRNA oversaturation that can induce fetal liver failure. In this study, we injected high-dose shRNA-AAV9 to neonates and efficiently silenced genes in cardiac and skeletal muscles without inducing liver toxicity. This is because AAV is most likely diluted or degraded in the liver than in cardiac or skeletal muscle during cell division after birth. We report that this systemically injected shRNA-AAV method does not induce any major side effects, such as liver dysfunction, and the dose of shRNA-AAV is sufficient for gene silencing in skeletal and cardiac muscle tissues. This novel method may be useful for generating gene knockdown in skeletal and cardiac mouse tissues, thus providing mouse models useful for analyzing diseases caused by loss-of-function of target genes. Copyright © 2011 Elsevier Inc. All rights reserved.
Arslan, Derya; Oran, Bulent; Vatansev, Husamettin; Cimen, Derya; Guvenc, Osman
2013-11-01
The aim of this study was to examine whether asymmetric dimethylarginine (ADMA) concentrations are associated with ventricular function in the infants of mothers with gestational diabetes. Twenty-five term newborns of mothers with gestational diabetes and term newborns as the control group (n = 25) with normal general health status were evaluated at two time points, on the 3rd postnatal day, at the 3th months. Echocardiographic evaluations of all participants were performed and ADMA level was measured. In the first analysis, 10 patients (40%) had a septal thickness of 6 mm or more, indicating septal hypertrophy. In the first and second analysis, interventricular septum end-diastolic thickness (IVSTd) and the left ventricular posterior wall end-diastolic thickness (LVPWTd) in the patient group were higher than the control group. ADMA level measurement was not significantly different between the groups the first and second analysis. There was no difference in ADMA levels of the group with septal thickness ≥6 mm and the group with <6 mm. Newborn cardiac wall thickness was increased in pregnancies complicated by Gestational diabetes mellitus (GDM), and the increase was independent of glycemic control. Diastolic newborn cardiac function was impaired in GDM, and this effect was independent of septal thickness. We found no association between ADMA levels and cardiac systolic, diastolic functions or septum thickness in the GDM newborn.
Banks, Laura; Wells, Greg D; Clarizia, Nadia A; Jean-St-Michel, Emilie; McKillop, Adam L; Redington, Andrew N; McCrindle, Brian W
2016-08-01
We sought to determine whether a 9-day remote ischemic preconditioning (IPC) causes improvements in exercise performance, energetics, and blood pressure. Ten participants (mean age 24 ± 4 years) had no changes in aerobic capacity (preintervention: 38 ± 10 mL/(kg·min)(-1) vs. postintervention: 38 ± 10 mL/(kg·min)(-1)), blood pressure (preintervention: 112 ± 7/66 ± 6 mm Hg vs. postintervention: 112 ± 10/62 ± 5 mm Hg), cardiac phosphocreatinine-to-adenosine-triphosphate ratio (preintervention: 2.1 ± 0.5 vs. postintervention: 2.3 ± 0.4), and postexercise skeletal muscle phosphocreatine recovery (preintervention: 34 ± 11 s vs. postintervention: 31 ± 11 s). Short-term remote IPC may be ineffective in improving these outcomes.
Botta, Amy; Laher, Ismail; Beam, Julianne; Decoffe, Daniella; Brown, Kirsty; Halder, Swagata; Devlin, Angela; Gibson, Deanna L; Ghosh, Sanjoy
2013-01-01
PGC-1α, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1α is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1α on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1α without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNFα) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1α such as NRF-1 and several respiratory genes. Such mismatch between PGC-1α and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1α expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1α mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age.
Maxwell, Aaron W P; Healey, Terrance T; Dupuy, Damian E
2017-09-01
To evaluate the rate of short-term complications associated with microwave ablation of lung tumors located near the heart. This HIPAA-compliant study was performed with a waiver for informed consent. Patients who underwent microwave ablation of lung tumors located 10 mm or less from the heart were identified by retrospective chart review. Both primary and metastatic tumors were included. Only tumors directly adjacent to one of the four cardiac chambers were included. All patients were treated in a single session using CT guidance with continuous electrocardiographic monitoring. Rates of new-onset arrhythmia and myocardial infarction (MI) within 90 days of the procedure were quantified, and evidence of cardiac or pericardiac injury was assessed for using post-ablation contrast-enhanced chest CT, electrocardiography (EKG), and-when available-echocardiography. Complications were graded using the Common Terminology Criteria for Adverse Events (CTCAE) system. Ten patients (four males, six females; mean age 73.1 ± 9.5 years) met all inclusion criteria. Mean tumor distance from the heart was 3 mm (range, 0-6 mm). New-onset arrhythmia was not observed during or following any of the microwave ablation treatments, and there were no documented 90-day MI events. CTCAE Grade 1 complications were observed by CT in eight patients, most commonly mild focal pericardial thickening. EKG and echocardiography were normal in all patients. No major complications (CTCAE Grade 3 or greater) were observed. Microwave ablation of lung tumors located 10 mm or less from the heart appears to have low associated short-term morbidity and may be appropriate in selected patients.
Nakamura, Fabio Y; Pereira, Lucas A; Cal Abad, Cesar C; Cruz, Igor F; Flatt, Andrew A; Esco, Michael R; Loturco, Irineu
2017-02-01
Heart rate variability has been widely used to monitor athletes' cardiac autonomic control changes induced by training and competition, and recently shorter recording times have been sought to improve its practicality. The aim of this study was to test the agreement between the (ultra-short-term) natural log of the root-mean-square difference of successive normal RR intervals (lnRMSSD - measured in only 1 min post-1 min stabilization) and the criterion lnRMSSD (measured in the last 5 min out of 10 min of recording) in young female basketball players. Furthermore, the correlation between training induced delta change in the ultra-short-term lnRMSSD and the criterion lnRMSSD was calculated. Seventeen players were assessed at rest pre- and post-eight weeks of training. Trivial effect sizes (-0.03 in the pre- and 0.10 in the post- treatment) were found in the comparison between the ultra-short-term lnRMSSD (3.29 ± 0.45 and 3.49 ± 0.35 ms, in the pre- and post-, respectively) and the criterion lnRMSSD (3.30 ± 0.40 and 3.45 ± 0.41 ms, in the pre- and post-, respectively) (intraclass correlation coefficient = 0.95 and 0.93). In both cases, the response to training was significant, with Pearson's correlation of 0.82 between the delta changes of the ultra-short-term lnRMSSD and the criterion lnRMSSD. In conclusion, the lnRMSSD can be calculated within only 2 min of data acquisition (the 1 st min discarded) in young female basketball players, with the ultra-short-term measure presenting similar sensitivity to training effects as the standard criterion measure.
Adequacy of the Ultra-Short-Term HRV to Assess Adaptive Processes in Youth Female Basketball Players
Nakamura, Fabio Y; Pereira, Lucas A; Cal Abad, Cesar C; Cruz, Igor F; Flatt, Andrew A; Esco, Michael R; Loturco, Irineu
2017-01-01
Abstract Heart rate variability has been widely used to monitor athletes’ cardiac autonomic control changes induced by training and competition, and recently shorter recording times have been sought to improve its practicality. The aim of this study was to test the agreement between the (ultra-short-term) natural log of the root-mean-square difference of successive normal RR intervals (lnRMSSD - measured in only 1 min post-1 min stabilization) and the criterion lnRMSSD (measured in the last 5 min out of 10 min of recording) in young female basketball players. Furthermore, the correlation between training induced delta change in the ultra-short-term lnRMSSD and the criterion lnRMSSD was calculated. Seventeen players were assessed at rest pre- and post-eight weeks of training. Trivial effect sizes (-0.03 in the pre- and 0.10 in the post- treatment) were found in the comparison between the ultra-short-term lnRMSSD (3.29 ± 0.45 and 3.49 ± 0.35 ms, in the pre- and post-, respectively) and the criterion lnRMSSD (3.30 ± 0.40 and 3.45 ± 0.41 ms, in the pre- and post-, respectively) (intraclass correlation coefficient = 0.95 and 0.93). In both cases, the response to training was significant, with Pearson’s correlation of 0.82 between the delta changes of the ultra-short-term lnRMSSD and the criterion lnRMSSD. In conclusion, the lnRMSSD can be calculated within only 2 min of data acquisition (the 1st min discarded) in young female basketball players, with the ultra-short-term measure presenting similar sensitivity to training effects as the standard criterion measure. PMID:28469745
Satoh, Hiroshi; Sano, Makoto; Suwa, Kenichiro; Saitoh, Takeji; Nobuhara, Mamoru; Saotome, Masao; Urushida, Tsuyoshi; Katoh, Hideki; Hayashi, Hideharu
2014-07-26
The recent development of cardiac magnetic resonance (CMR) techniques has allowed detailed analyses of cardiac function and tissue characterization with high spatial resolution. We review characteristic CMR features in ischemic and non-ischemic cardiomyopathies (ICM and NICM), especially in terms of the location and distribution of late gadolinium enhancement (LGE). CMR in ICM shows segmental wall motion abnormalities or wall thinning in a particular coronary arterial territory, and the subendocardial or transmural LGE. LGE in NICM generally does not correspond to any particular coronary artery distribution and is located mostly in the mid-wall to subepicardial layer. The analysis of LGE distribution is valuable to differentiate NICM with diffusely impaired systolic function, including dilated cardiomyopathy, end-stage hypertrophic cardiomyopathy (HCM), cardiac sarcoidosis, and myocarditis, and those with diffuse left ventricular (LV) hypertrophy including HCM, cardiac amyloidosis and Anderson-Fabry disease. A transient low signal intensity LGE in regions of severe LV dysfunction is a particular feature of stress cardiomyopathy. In arrhythmogenic right ventricular cardiomyopathy/dysplasia, an enhancement of right ventricular (RV) wall with functional and morphological changes of RV becomes apparent. Finally, the analyses of LGE distribution have potentials to predict cardiac outcomes and response to treatments.
Cronberg, Tobias; Lilja, Gisela; Horn, Janneke; Kjaergaard, Jesper; Wise, Matt P; Pellis, Tommaso; Hovdenes, Jan; Gasche, Yvan; Åneman, Anders; Stammet, Pascal; Erlinge, David; Friberg, Hans; Hassager, Christian; Kuiper, Michael; Wanscher, Michael; Bosch, Frank; Cranshaw, Julius; Kleger, Gian-Reto; Persson, Stefan; Undén, Johan; Walden, Andrew; Winkel, Per; Wetterslev, Jørn; Nielsen, Niklas
2015-06-01
Brain injury affects neurologic function and quality of life in survivors after cardiac arrest. To compare the effects of 2 target temperature regimens on long-term cognitive function and quality of life after cardiac arrest. In this multicenter, international, parallel group, assessor-masked randomized clinical trial performed from November 11, 2010, through January 10, 2013, we enrolled 950 unconscious adults with cardiac arrest of presumed cardiac cause from 36 intensive care units in Europe and Australia. Eleven patients were excluded from analysis for a total sample size of 939. Targeted temperature management at 33°C vs 36°C. Cognitive function was measured by the Mini-Mental State Examination (MMSE) and assessed by observers through the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Patients reported their activities in daily life and mental recovery through Two Simple Questions and their quality of life through the Medical Outcomes Study 36-Item Short Form Health Survey, version 2. In the modified intent-to-treat population, including nonsurvivors, the median MMSE score was 14 in the 33°C group (interquartile range [IQR], 0-28) vs 17 in the 36°C group (IQR, 0-29) (P = .77), and the IQCODE score was 115 (IQR, 79-130) vs 115 (IQR, 80-130) (P = .57) in the 33°C and 36°C groups, respectively. The median MMSE score for survivors was within the reference range and similar (33°C group median, 28; IQR, 26-30; vs 36°C group median, 28; IQR, 25-30; P = .61). The median IQCODE score was within the minor deficit range (33°C group median, 79.5; IQR, 78.0-85.9; vs 36°C group median, 80.7; IQR, 78.0-86.9; P = .04). A total of 18.8% vs 17.5% of survivors reported needing help with everyday activities (P = .71), and 66.5% in the 33°C group vs 61.8% in the 36°C group reported that they thought they had made a complete mental recovery (P = .32). The mean (SD) mental component summary score was 49.1 (12.5) vs 49.0 (12.2) (P = .79), and the mean (SD) physical component summary score was 46.8 (13.8) and 47.5 (13.8) (P = .45), comparable to the population norm. Quality of life was good and similar in patients with cardiac arrest receiving targeted temperature management at 33°C or 36°C. Cognitive function was similar in both intervention groups, but many patients and observers reported impairment not detected previously by standard outcome scales. ClinicalTrials.gov NCT01020916.
Awareness of cardiac function in anxious, phobic and hypochondriacal patients.
Tyrer, P; Lee, I; Alexander, J
1980-02-01
Awareness of pulse rate was tested in 60 psychiatric out-patients with anxiety, phobic or hypochondriacal neuroses by asking them to record how fast their hearts were beating during exposure to short film sequences. Correlations between subjective and objective heart rate (ECG) were significantly higher in anxious and hypochondriacal patients than in phobic ones. The results suggest that somatic symptoms in hypochondriacal and anxiety neurosis reflect increased awareness of bodily function.
Weinstock, Michael B; Weingart, Scott; Orth, Frank; VanFossen, Douglas; Kaide, Colin; Anderson, Judy; Newman, David H
2015-07-01
Patients with potentially ischemic chest pain are commonly admitted to the hospital or observed after a negative evaluation in the emergency department (ED) owing to concern about adverse events. Previous studies have looked at 30-day mortality, but no current large studies have examined the most important information regarding ED disposition: the short-term risk for a clinically relevant adverse cardiac event (including inpatient ST-segment elevation myocardial infarction, life-threatening arrhythmia, cardiac or respiratory arrest, or death). To determine the incidence of clinically relevant adverse cardiac events in patients hospitalized for chest pain with 2 troponin-negative findings, nonconcerning initial ED vital signs, and nonischemic, interpretable electrocardiographic findings. We conducted a blinded data review of 45,416 encounters obtained from a prospectively collected database enrolling adult patients admitted or observed with the following inclusion criteria: (1) primary presenting symptom of chest pain, chest tightness, chest burning, or chest pressure and (2) negative findings for serial biomarkers. Data were collected and analyzed from July 1, 2008, through June 30, 2013, from the EDs of 3 community teaching institutions with an aggregate census of more than 1 million visits. We analyzed data extracted by hypothesis-blinded abstractors. The primary outcome was a composite of life-threatening arrhythmia, inpatient ST-segment elevation myocardial infarction, cardiac or respiratory arrest, or death during hospitalization. Of the 45,416 encounters, 11,230 met criteria for inclusion. Mean patient age was 58.0 years. Of the 11 230 encounters, 44.83% of patients arrived by ambulance and 55.00% of patients were women. Relevant history included hypertension in 46.00%, diabetes mellitus in 19.72%, and myocardial infarction in 13.16%. The primary end point occurred in 20 of the 11 230 patients (0.18% [95% CI, 0.11%-0.27%]). After excluding patients with abnormal vital signs, electrocardiographic ischemia, left bundle branch block, or a pacemaker rhythm, we identified a primary end point event in 4 of 7266 patients (0.06% [95% CI, 0.02%-0.14%]). Of these events, 2 were noncardiac and 2 were possibly iatrogenic. In adult patients with chest pain admitted with 2 negative findings for serial biomarkers, nonconcerning vital signs, and nonischemic electrocardiographic findings, short-term clinically relevant adverse cardiac events were rare and commonly iatrogenic, suggesting that routine inpatient admission may not be a beneficial strategy for this group.
Luiz, T; Preisegger, T; Rombach, D; Madler, C
2014-09-01
Provision of medical care is an important element of safety precautions for visitors of sports arenas. The organizational requirements are especially high if cardiac arrest occurs; how this scenario is managed may thus serve as the ultimate indicator of the quality of stadium medical care. The objectives of this study were to analyze the structures and the resources available for the medical care of spectators in German professional soccer stadiums and to identify the frequency and the primary resuscitation success of cardiac arrest. In 2011 a questionnaire-based survey was performed among the clubs of the first and second German soccer leagues regarding medical care of spectators during the seasons 2008/2009 and 2009/2010. The focus was on the qualifications of emergency teams, the equipment and the incidence of cardiac arrest. A total of 15 stadiums were included (38%) in the survey. The mean number of physicians and emergency medical technicians on site was 0.6/10,000 seats and 16/10,000 seats, respectively. Of the latter, a mean of 82% (minimum 20% and maximum 100%) had received training with automatic external defibrillators. In 87% of the stadiums regular advanced life support training (ALS) was required. The mean number of defibrillators per stadium was 2.8/10,000 seats (minimum 1.3 and maximum 3.8) including 1.7 automatic defibrillators (minimum 0.4 and maximum 2.8). For patient transport, a mean of 0.65 ALS ambulance vehicles per 10,000 seats (minimum 0.14 and maximum 1.46) were available on site. In all stadiums staff members were connected via mobile radio communication with the stadium medical control room. A total of 52 cardiac arrests (=0.25/100,000 spectators) were recorded of which 96% of the patients were transported to hospitals with spontaneous circulation. Cardiac arrests are not a rare occurrence in German soccer stadiums. The participating stadiums are overall well prepared for such incidents in terms of organization, staff and technology and due to short response times, the resuscitation success by far surpasses that of the standard emergency medical services. These findings may in addition serve as a motivational example to start resuscitation early in public information campaigns.
β-Adrenergic Regulation of Cardiac Progenitor Cell Death Versus Survival and Proliferation
Khan, Mohsin; Mohsin, Sadia; Avitabile, Daniele; Siddiqi, Sailay; Nguyen, Jonathan; Wallach, Kathleen; Quijada, Pearl; McGregor, Michael; Gude, Natalie; Alvarez, Roberto; Tilley, Douglas G.; Koch, Walter J.; Sussman, Mark A.
2013-01-01
Rationale Short-term β-adrenergic stimulation promotes contractility in response to stress but is ultimately detrimental in the failing heart because of accrual of cardiomyocyte death. Endogenous cardiac progenitor cell (CPC) activation may partially offset cardiomyocyte losses, but consequences of long-term β-adrenergic drive on CPC survival and proliferation are unknown. Objective We sought to determine the relationship between β-adrenergic activity and regulation of CPC function. Methods and Results Mouse and human CPCs express only β2 adrenergic receptor (β2-AR) in conjunction with stem cell marker c-kit. Activation of β2-AR signaling promotes proliferation associated with increased AKT, extracellular signal-regulated kinase 1/2, and endothelial NO synthase phosphorylation, upregulation of cyclin D1, and decreased levels of G protein–coupled receptor kinase 2. Conversely, silencing of β2-AR expression or treatment with β2-antagonist ICI 118, 551 impairs CPC proliferation and survival. β1-AR expression in CPC is induced by differentiation stimuli, sensitizing CPC to isoproterenol-induced cell death that is abrogated by metoprolol. Efficacy of β1-AR blockade by metoprolol to increase CPC survival and proliferation was confirmed in vivo by adoptive transfer of CPC into failing mouse myocardium. Conclusions β-adrenergic stimulation promotes expansion and survival of CPCs through β2-AR, but acquisition of β1-AR on commitment to the myocyte lineage results in loss of CPCs and early myocyte precursors. PMID:23243208
Sato, Yukihito; Nishi, Kiyoto; Saijo, Sayaka; Tanada, Yohei; Goto, Taisuke; Takahashi, Naoki; Yamamoto, Erika; Fukuhara, Rei; Miyamoto, Tadashi; Taniguchi, Ryoji; Fujiwara, Hisayoshi; Takatsu, Yoshiki
2010-07-01
In patients with acutely decompensated heart failure (ADHF), elevated serum concentration of cardiac troponin is an independent predictor of adverse cardiac events. In ADHF with a preserved systolic blood pressure, treatment with intravenous vasodilator is recommended. However, the effect of vasodilators on troponin concentrations has not been elucidated well. Serial high sensitive cardiac troponin I (hs-TnI) was measured in 36 patients presenting with ADHF and preserved systolic blood pressure, of whom 20 were treated with atrial natriuretic peptide (ANP) and 16 with nitrates. The concentrations of hs-TnI ranged from 0.069+/-0.114ng/ml at baseline to 0.076+/-0.121ng/ml at 5h, 0.062+/-0.106ng/ml at 1 day, and 0.056+/-0.089ng/ml at day 7 (n=36,ns). The relative change in hs-TnI between baseline and at 5h, day 1 and day 7 were 1.13+/-0.43, 0.95+/-0.44 and 0.93+/-0.64 in patients treated with ANP, and 1.02+/-0.19, 0.95+/-0.31 and 1.19+/-1.38 in patients treated with nitrates (ns; ANP versus nitrates). On day 7, a hs-TnI change, >20% decrease from baseline, was observed in 55% patients with ANP versus 56% patients with nitrates (ns). The cardiac event rates were similar in both groups. In ADHF patients with preserved systolic blood pressure, the administration of intravenous vasodilators did not decrease hs-TnI over the first 7 days. Treatments with ANP and nitrates were associated with similar short-term decreases in hs-TnI and long-term adverse cardiac events. Copyright 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Cardiovascular function in pulmonary emphysema.
Visca, Dina; Aiello, Marina; Chetta, Alfredo
2013-01-01
Chronic obstructive pulmonary disease (COPD) and chronic cardiovascular disease, such as coronary artery disease, congestive heart failure, and cardiac arrhythmias, have a strong influence on each other, and systemic inflammation has been considered as the main linkage between them. On the other hand, airflow limitation may markedly affect lung mechanics in terms of static and dynamic hyperinflation, especially in pulmonary emphysema, and they can in turn influence cardiac performance as well. Skeletal mass depletion, which is a common feature in COPD especially in pulmonary emphysema patients, may have also a role in cardiovascular function of these patients, irrespective of lung damage. We reviewed the emerging evidence that highlights the role of lung mechanics and muscle mass impairment on ventricular volumes, stroke volume, and stroke work at rest and on exercise in the presence of pulmonary emphysema. Patients with emphysema may differ among COPD population even in terms of cardiovascular function.
The relationship between physical performance and cardiac function in an elderly Russian cohort.
Tadjibaev, Pulod; Frolova, Elena; Gurina, Natalia; Degryse, Jan; Vaes, Bert
2014-01-01
This study aims to determine the cardiac dysfunction prevalence, to investigate the relationship between the Short Physical Performance Battery (SPPB) test and structural and functional echocardiographic parameters and to determine whether SPPB scores and cardiac dysfunction are independent mortality predictors in an elderly Russian population. A random sample of 284 community-dwelling adults aged 65 and older were selected from a population-based register and divided into two age groups (65-74 and ≥75). The SPPB test, echocardiography and all-cause mortality were measured. The prevalence of cardiac dysfunction was 12% in the 65-74 group and 23% in the ≥75 group. The multivariate models could explain 15% and 23% of the SPPB score total variance for the 65-74 and ≥75 age groups, respectively. In the younger age group, the mean follow-up time was 2.6±0.46 years, and the adjusted hazard ratio (HR) for risk of mortality from cardiac dysfunction was 4.9. In the older age group, the mean follow-up time was 2.4±0.61 years, and both cardiac dysfunction and poor physical performance were found to be independent predictors of mortality (adjusted HR=3.4 and adjusted HR=4.2, respectively). The cardiac dysfunction prevalence in this elderly Russian population was found to be comparable to, or even lower than, reported prevalences for Western countries. Furthermore, the observed correlations between echocardiographic abnormalities and SPPB scores were limited. Cardiac dysfunction was shown to be a strong mortality predictor in both age groups, and poor physical performance was identified as an independent mortality predictor in the oldest subjects. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
ERIC Educational Resources Information Center
Herndon, Mary Anne
1978-01-01
In a model of the functioning of short term memory, the encoding of information for subsequent storage in long term memory is simulated. In the encoding process, semantically equivalent paragraphs are detected for recombination into a macro information unit. (HOD)
Cardiovascular Adaptations to Long Duration Head-Down Tilt Bed Rest
NASA Technical Reports Server (NTRS)
Platts, Steven H.; Martin, David S.; Perez, Sondar A.; Ribeiro, Christine; Stenger, Michael B.; Summers, Richard; Meck, Janice V.
2008-01-01
INTRODUCTION: Orthostatic hypotension is a serious risk for crewmembers returning from spaceflight. Numerous cardiovascular mechanisms have been proposed to account for this problem, including vascular and cardiac dysfunction, which we studied during bed rest. METHODS: Thirteen subjects were studied before and during bed rest. Statistical analysis was limited to the first 49-60 days of bed rest, and compared to pre-bed rest data. Ultrasound data were collected on vascular and cardiac structure and function. Tilt testing was conducted for 30 minutes or until presyncopal symptoms intervened. RESULTS: Plasma volume was significantly reduced by day 7 of bed rest. Flow-mediated dilation in the leg was significantly increased at bed rest day 49. Arterial responses to nitroglycerin differed in the arm and leg, but did not change as a result of bed rest. Intimal-medial thickness markedly decreased at bed rest days 21, 35 and 49. Several cardiac functional parameters including isovolumic relaxation time, ejection time and myocardial performance index were significantly increased (indicating a decrease in cardiac function) during bed rest. There was a trend for decreased orthostatic tolerance following 60 days of bed rest. DISCUSSION: These data suggest that 6 head-down tilt bed rest alters cardiovascular structure and function in a pattern similar to short duration spaceflight. Additionally, the vascular alterations are primarily seen in the lower body, while vessels of the upper body are unaffected. KEY WORDS: spaceflight, orthostatic intolerance, hypotension, fluid-shift, plasma volume
Acute pneumonia and the cardiovascular system.
Corrales-Medina, Vicente F; Musher, Daniel M; Shachkina, Svetlana; Chirinos, Julio A
2013-02-09
Although traditionally regarded as a disease confined to the lungs, acute pneumonia has important effects on the cardiovascular system at all severities of infection. Pneumonia tends to affect individuals who are also at high cardiovascular risk. Results of recent studies show that about a quarter of adults admitted to hospital with pneumonia develop a major acute cardiac complication during their hospital stay, which is associated with a 60% increase in short-term mortality. These findings suggest that outcomes of patients with pneumonia can be improved by prevention of the development and progression of associated cardiac complications. Before this hypothesis can be tested, however, an adequate mechanistic understanding of the cardiovascular changes that occur during pneumonia, and their role in the trigger of various cardiac complications, is needed. In this Review, we summarise knowledge about the burden of cardiac complications in adults with acute pneumonia, the cardiovascular response to this infection, the potential effects of commonly used cardiovascular and anti-infective drugs on these associations, and possible directions for future research. Copyright © 2013 Elsevier Ltd. All rights reserved.
Meng, Yong; Liu, Xuelu; Liu, Juan; Cheng, Xianliang
2017-01-15
To prospectively evaluate the impact of metoprolol achieved heart rate (HR) on cardiac-motor function and quality of life (QoL) in chronic heart failure (CHF) patients. Between February 2013 to April 2016, association of HR reduction with haemodynamic indices, motor function and QoL in CHF patients with HR>80bpm receiving metoprolol 23.75mg or 47.5mgq.d was studied. Overall, 154 patients (median age, 66.39years; males, n=101; females, n=53) were enrolled, whose average resting HR decreased significantly from baseline value of 82.72±6.73 to 69.38±3.57, 67.72±2.61, 66.50±3.14 and 64.86±3.21bpm in the 1st, 3rd, 6th and 12th months post metoprolol intervention, respectively (P<0.0001). Similarly, the ejection fraction (r=-0.6461, P<0.0001), cardiac output (r=-0.5238, P<0.0001), cardiac index (r=-0.5378, P<0.0001) and veterans specific activity questionnaire scores (r=-0.4088, P<0.0001) were significantly associated with the reduction in HR after 12months. The improvement in 6-min walk test was independent of HR reduction (P=0.005). Similarly, QoL as measured by short form-8 questionnaire (SF-8) but not Minnesota Living with Heart Failure was significantly improved at the 12th-month. However, this was not associated with the reductions in HR. Metoprolol achieved HR control was associated with improvement in cardiac performance and motor function but not QoL in patients with CHF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Ramjee, Vimal; Grossestreuer, Anne V; Yao, Yuan; Perman, Sarah M; Leary, Marion; Kirkpatrick, James N; Forfia, Paul R; Kolansky, Daniel M; Abella, Benjamin S; Gaieski, David F
2015-11-01
Determination of clinical outcomes following resuscitation from cardiac arrest remains elusive in the immediate post-arrest period. Echocardiographic assessment shortly after resuscitation has largely focused on left ventricular (LV) function. We aimed to determine whether post-arrest right ventricular (RV) dysfunction predicts worse survival and poor neurologic outcome in cardiac arrest patients, independent of LV dysfunction. A single-center, retrospective cohort study at a tertiary care university hospital participating in the Penn Alliance for Therapeutic Hypothermia (PATH) Registry between 2000 and 2012. 291 in- and out-of-hospital adult cardiac arrest patients at the University of Pennsylvania who had return of spontaneous circulation (ROSC) and post-arrest echocardiograms. Of the 291 patients, 57% were male, with a mean age of 59 ± 16 years. 179 (63%) patients had LV dysfunction, 173 (59%) had RV dysfunction, and 124 (44%) had biventricular dysfunction on the initial post-arrest echocardiogram. Independent of LV function, RV dysfunction was predictive of worse survival (mild or moderate: OR 0.51, CI 0.26-0.99, p<0.05; severe: OR 0.19, CI 0.06-0.65, p=0.008) and neurologic outcome (mild or moderate: OR 0.33, CI 0.17-0.65, p=0.001; severe: OR 0.11, CI 0.02-0.50, p=0.005) compared to patients with normal RV function after cardiac arrest. Echocardiographic findings of post-arrest RV dysfunction were equally prevalent as LV dysfunction. RV dysfunction was significantly predictive of worse outcomes in post-arrest patients after accounting for LV dysfunction. Post-arrest RV dysfunction may be useful for risk stratification and management in this high-mortality population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels
Weisbrod, David; Khun, Shiraz Haron; Bueno, Hanna; Peretz, Asher; Attali, Bernard
2016-01-01
The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca2+-activated K+ channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity. PMID:26725737
Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels.
Weisbrod, David; Khun, Shiraz Haron; Bueno, Hanna; Peretz, Asher; Attali, Bernard
2016-01-01
The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca(2+)-activated K(+) channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity.
2014-01-01
Background Physical activity has well-established positive health-related effects. Sedentary behaviour has been associated with postoperative complications and mortality after cardiac surgery. Patients undergoing cardiac surgery often suffer from impaired lung function postoperatively. The association between physical activity and lung function in cardiac surgery patients has not previously been reported. Methods Patients undergoing cardiac surgery were followed up two months postoperatively. Physical activity was assessed on a four-category scale (sedentary, moderate activity, moderate regular exercise, and regular activity and exercise), modified from the Swedish National Institute of Public Health’s national survey. Formal lung function testing was performed preoperatively and two months postoperatively. Results The sample included 283 patients (82% male). Two months after surgery, the level of physical activity had increased (p < 0.001) in the whole sample. Patients who remained active or increased their level of physical activity had significantly better recovery of lung function than patients who remained sedentary or had decreased their level of activity postoperatively in terms of vital capacity (94 ± 11% of preoperative value vs. 91 ± 9%; p = 0.03), inspiratory capacity (94 ± 14% vs. 88 ± 19%; p = 0.008), and total lung capacity (96 ± 11% vs. 90 ± 11%; p = 0.01). Conclusions An increased level of physical activity, compared to preoperative level, was reported as early as two months after surgery. Our data shows that there could be a significant association between physical activity and recovery of lung function after cardiac surgery. The relationship between objectively measured physical activity and postoperative pulmonary recovery needs to be further examined to verify these results. PMID:24678691
On short-term memory of prefrontal cortex using near-infrared spectroscopy
NASA Astrophysics Data System (ADS)
Li, Chengjun; Gan, Zhuo; Gong, Hui; Luo, Qingming; Zeng, Shaoqun
2003-12-01
For studying prefrontal cortical function in short-term memory two tasks were designed. In task one, a plus expression appears on screen for 300 milliseconds every other 2 seconds and the subject is required to give it"s answer but not to remember it. In task two, an Arabic numeral presents on screen as the same frequency as in task one. While a number is present, the subject need adding it to the sum he got last time. As subjects, 26 children participated in the work. Blood volume changes(BVCs) of right prefrontal cortex(PC) under two cognitive tasks were examined using functional near infrared imaging(fNIRI), a noninvasive technique for localizing regional BVCs which correlate with neural activities. The BVCs caused by short-term memory for numbers were retrieved from BVCs by task one and task two. Results revealed that short-term memory is related to PC and the near-infrared spectroscopy(NIRS) can be used to study prefrontal cortical function in short-term memory.
Wang, Ting; Miller, Kenneth E
2016-08-04
The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia (ICG) for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside ICG. In the present study, rat ICG neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) ICG contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial ICG contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT; (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG neurons could help in better understanding the function of the intrinsic cardiac nervous system. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
Cardiac injury biomarkers in paediatric age: Are we there yet?
Neves, Ana L; Henriques-Coelho, Tiago; Leite-Moreira, Adelino; Areias, José C
2016-11-01
The aim of this article is to evaluate the clinical utility of cardiac injury biomarkers in paediatric age. In December 2015, a literature search was performed (PubMed access to MEDLINE citations; http://www.ncbi.nlm.nih.gov/PubMed/ ). The search strategy included the following medical subject headings and text terms for the key words: "cardiac injury biomarkers", "creatine kinase-MB", "myoglobin", "troponin", "children", "neonate/s", "newborn/s", "infant/s" and echocardiography. In the paediatric population, troponins show a good correlation with the extent of myocardial damage following cardiac surgery and cardiotoxic medication and can be used as predictors of subsequent cardiac recovery and mortality. Elevation of cardiac injury biomarkers may also have diagnostic value in cases when cardiac contusion or pericarditis is suspected. Cardiac injury biomarkers are very sensitive markers for the detection of myocardial injury and have been studied in healthy newborns, after tocolysis, intrauterine growth restriction, respiratory distress and asphyxia. The proportion of newborns with elevated troponin was higher than that in ill infants, children, and adolescents and in healthy adults, suggesting that myocardial injury, although clinically occult, is common in this young age group. Results suggest that significant elevation of cord troponin is an excellent early predictor of severity of hypoxic-ischaemic encephalopathy and mortality in term infants. Cardiac biomarkers may also benefit centres without on-site echocardiography with evidence showing good correlation with echo-derived markers of myocardial function. Further studies are needed to better clarify the role of cardiac biomarkers in paediatric age and their correlation with echocardiographic parameters.
Jin, Hong; Stojnic, Robert; Adryan, Boris; Ozdemir, Anil; Stathopoulos, Angelike; Frasch, Manfred
2013-01-01
The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP) from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of ∼50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites. PMID:23326246
Wdowczyk, Joanna; Makowiec, Danuta; Gruchała, Marcin; Wejer, Dorota; Struzik, Zbigniew R.
2018-01-01
It is commonly believed that higher values of heart rate variability (HRV) indices account for better organization of the network of feedback reflexes driving an organism's response to actual bodily needs. In order to evaluate this organization in heart transplant (HTX) recipients, 58 nocturnal Holter signals of 14 HTX patients were analyzed. Their dynamical properties were evaluated by short-term HRV indices and measures grounded on entropy. Estimates grouped according to the patients' clinical progress: free of complications versus with complications, and arranged in order of the length of time since the HTX, lead us to the conclusion that higher HRV is associated with a worse outcome for HTX patients. Moreover, short-term HRV indices that are constant, rather than increasing over time, serve well in the prognosis of the future state of a HTX patient. These findings suggest that increases observed in HRV indices are related to erratic rhythms resulting from remodeling of the cardiac tissue (including heterogeneous innervation) in long-term HTX patients. Therefore, we hypothesize that dynamical landscape markers (entropy and fragmentation measures together with the short-term HRV indices) can serve as a tool in the exploration of the genesis of (non-respiratory sinus) arrhythmia. PMID:29686620
Kember, Guy; Ardell, Jeffrey L; Shivkumar, Kalyanam; Armour, J Andrew
2017-01-01
The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as 'free-floating' in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease.
House, Stacey L.; Wang, Joy; Castro, Angela M.; Weinheimer, Carla; Kovacs, Attila; Ornitz, David M.
2015-01-01
Abstract Fibroblast growth factor 2 (FGF2) is cardioprotective in in vivo models of myocardial infarction; however, whether FGF2 has a protective role in in vivo ischemia‐reperfusion (IR) injury, a model that more closely mimics acute myocardial infarction in humans, is not known. To assess the cardioprotective efficacy of endogenous FGF2, mice lacking a functional Fgf2 gene (Fgf2−/−) and wild‐type controls were subjected to closed‐chest regional cardiac IR injury (90 min ischemia, 7 days reperfusion). Fgf2−/− mice had significantly increased myocardial infarct size and significantly worsened cardiac function compared to wild‐type controls at both 1 and 7 days post‐IR injury. Pathophysiological analysis showed that at 1 day after IR injury Fgf2−/− mice have worsened cardiac strain patterns and increased myocardial cell death. Furthermore, at 7 days post‐IR injury, Fgf2−/− mice showed a significantly reduced cardiac hypertrophic response, decreased cardiac vessel density, and increased vessel diameter in the peri‐infarct area compared to wild‐type controls. These data reveal both acute cardioprotective and a longer term proangiogenic potential of endogenous FGF2 in a clinically relevant, in vivo, closed‐chest regional cardiac IR injury model that mimics acute myocardial infarction. PMID:25626875
Effects of increasing left ventricular filling pressure in patients with acute myocardial infarction
Russell, Richard O.; Rackley, Charles E.; Pombo, Jaoquin; Hunt, David; Potanin, Constantine; Dodge, Harold T.
1970-01-01
Left ventricular performance in 19 patients with acute myocardial infarction has been evaluated by measuring left ventricular response in terms of cardiac output, stroke volume, work, and power to progressive elevation of filling pressure accomplished by progressive expansion of blood volume with rapid infusion of low molecular weight dextran. Such infusion can elevate the cardiac output, stroke volume, work, and power and thus delineate the function of the left ventricle by Frank-Starling function curves. Left ventricular filling pressure in the range of 20-24 mm Hg was associated with the peak of the curves and when the filling pressure exceeded this range, the curves became flattened or decreased. An increase in cardiac output could be maintained for 4 or more hr. Patients with a flattened function curve had a high mortality in the ensuing 8 wk. The function curve showed improvement in myocardial function during the early convalescence. When left ventricular filling pressure is monitored directly or as pulmonary artery end-diastolic pressure, low molecular weight dextran provides a method for assessment of left ventricular function. Images PMID:5431663
Hopkins, Susan R; Prisk, G Kim
2010-12-01
Since the lung receives the entire cardiac output, sophisticated imaging techniques are not required in order to measure total organ perfusion. However, for many years studying lung function has required physiologists to consider the lung as a single entity: in imaging terms as a single voxel. Since imaging, and in particular functional imaging, allows the acquisition of spatial information important for studying lung function, these techniques provide considerable promise and are of great interest for pulmonary physiologists. In particular, despite the challenges of low proton density and short T2* in the lung, noncontrast MRI techniques to measure pulmonary perfusion have several advantages including high reliability and the ability to make repeated measurements under a number of physiologic conditions. This brief review focuses on the application of a particular arterial spin labeling (ASL) technique, ASL-FAIRER (flow sensitive inversion recovery with an extra radiofrequency pulse), to answer physiologic questions related to pulmonary function in health and disease. The associated measurement of regional proton density to correct for gravitational-based lung deformation (the "Slinky" effect (Slinky is a registered trademark of Pauf-Slinky incorporated)) and issues related to absolute quantification are also discussed. Copyright © 2010 Wiley-Liss, Inc.
Kruse, Marie; Sørensen, Jan; Davidsen, Michael; Gyrd-Hansen, Dorte
2009-06-01
The aim of this study was to analyse to what extent individuals with coronary heart disease (CHD) leave the labour market earlier than individuals without CHD and to discuss the implications for rehabilitation. Individuals with CHD were identified from the Danish National Cohort study and were followed from the year of their first hospital admission for CHD and onwards for up to 23 years. Individuals with CHD were individually matched with individuals without CHD. We analysed their short-term labour market participation and compared the long-term withdrawal risk for the two groups through Cox regression. In the year after the first CHD-related admission, 79% of individuals with CHD maintained their labour force participation compared with 93% of individuals without CHD. Individuals with CHD had a hazard ratio of 1.32 for withdrawal compared with their matched counterparts. This means that the individuals with CHD were on the labour market, on average, for 0.8 years less than the individuals without CHD. Stratified analyses showed that, in particular, individuals with CHD aged below 60 years and individuals employed as manual labour may benefit from cardiac rehabilitation, which aims to maintain labour market participation. Individuals with CHD have a significantly increased risk of withdrawing from the labour market. Especially younger individuals and those employed as manual labour seem to have greater problems in maintaining labour market participation. This suggests that greater focus in cardiac rehabilitation on returning these individuals to the labour market might be worthwhile.
Equivalent cardioprotection induced by ischemic and hypoxic preconditioning.
Xiang, Xujin; Lin, Haixia; Liu, Jin; Duan, Zeyan
2013-04-01
We aimed to compare cardioprotection induced by various hypoxic preconditioning (HPC) and ischemic preconditioning (IPC) protocols. Isolated rat hearts were randomly divided into 7 groups (n = 7 per group) and received 3 or 5 cycles of 3-minute ischemia or hypoxia followed by 3-minute reperfusion (IPC33 or HPC33 or IPC53 or HPC53 group), 3 cycles of 5-minute ischemia or hypoxia followed by 5-minute reperfusion (IPC35 group or HPC35 group), or 30-minute perfusion (ischemic/reperfusion group), respectively. Then all the hearts were subjected to 50-minute ischemia and 120-minute reperfusion. Cardiac function, infarct size, and coronary flow rate (CFR) were evaluated. Recovery of cardiac function and CFR in IPC35, HPC35, and HPC53 groups was significantly improved as compared with I/R group (p < 0.01). There were no significant differences in cardiac function parameters between IPC35 and HPC35 groups. Consistently, infarct size was significantly reduced in IPC35, HPC35, and HPC53 groups compared with ischemic/reperfusion group. Multiple-cycle short duration HPC exerted cardioprotection, which was as powerful as that of IPC. Georg Thieme Verlag KG Stuttgart · New York.
Kotovskaia, A R; Koloteva, M I; Luk'ianiuk, V Iu; Stepanova, G P; Filatova, L M; Buĭlov, S P; Zhernavkov, A F; Kondratiuk, L L
2007-01-01
Analyzed were deviations in cardiac function in 29 cosmonauts with previous aviation and other occupations ranging of 29 to 61 y.o. who made 8- to 30-day space flights (totai number of flights = 34) between 1982 and 2006. The deviations were identified in ECG records collected during clinical selection, clinical physiological examination (CPE) before flight, insertion and deorbit in transport vehicles, and post-flight CPE. Based on the analysis, the cosmonauts were distributed into three groups. The first group (55.2% of the cosmonauts) did not exhibit noticeable shifts and unfavorable trends in ECG at any time of the period of observation. The second group (34.5%) showed some deviations during selection and pre-flight CPE that became more apparent in the period of deorbit and were still present in post-flight ECG records. The third group (10.3%) displayed health-threatening deviations in cardiac function during deorbit. These findings give start to important investigations with the purpose to define permissible medical risks and ensuing establishment and perfection of medical criteria for candidates to cosmonauts with certain health problems.
Large pericardial effusion induced by minoxidil.
Çilingiroğlu, Mehmet; Akkuş, Nuri; Sethi, Salil; Modi, Kalgi A
2012-04-01
A 53-year-old male admitted with increased shortness of breath. In the physical examination, he had dyspnea, tachycardia and tachypnea. An echocardiogram showed large pericardial effusion (PE) as well as significant pulmonary hypertension. He had been started recently on minoxidil for blood pressure control. PE was reported to occur with minoxidil treatment both in patients undergoing dialysis and those with normal renal function. Pulmonary hypertension has been reported to affect the cardiac tamponade physiology. Because of significant pulmonary hypertension in our patient, a right heart catheterization was also done, which prevented cardiac tamponade. He was treated conservatively without any intervention, and PE resolved spontaneously after discontinuation of minoxidil.
Mechanisms and management of the heart in Myotonic Dystrophy
McNally, Elizabeth M.; Sparano, Dina
2015-01-01
Myotonic dystrophy (DM) is the most common form of adult onset muscular dystrophy and is caused by expansion of short nucleotide repeats that, in turn, produce toxic RNA aggregates within cells. DM is multisystemic, and the heart is primary site of pathology. DM patients exhibit cardiac conduction disorders including atrial fibrillation, atrio-ventricular heart block and ventricular arrhythmias. DM patients are also at risk for cardiomyopathy and congestive heart failure. Myotonic dystrophy is also characterized by myotonia, muscle weakness, and profound fatigue. The management of these symptoms requires input from the cardiologist and a team approach to minimize the debilitating aspects of the disorder and optimize cardiac function. PMID:21642660
How to Connect Cardiac Excitation to the Atomic Interactions of Ion Channels.
Silva, Jonathan R
2018-01-23
Many have worked to create cardiac action potential models that explicitly represent atomic-level details of ion channel structure. Such models have the potential to define new therapeutic directions and to show how nanoscale perturbations to channel function predispose patients to deadly cardiac arrhythmia. However, there have been significant experimental and theoretical barriers that have limited model usefulness. Recently, many of these barriers have come down, suggesting that considerable progress toward creating these long-sought models may be possible in the near term. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Marwaha, Puneeta; Sunkaria, Ramesh Kumar
2017-02-01
Multiscale entropy (MSE) and refined multiscale entropy (RMSE) techniques are being widely used to evaluate the complexity of a time series across multiple time scales 't'. Both these techniques, at certain time scales (sometimes for the entire time scales, in the case of RMSE), assign higher entropy to the HRV time series of certain pathologies than that of healthy subjects, and to their corresponding randomized surrogate time series. This incorrect assessment of signal complexity may be due to the fact that these techniques suffer from the following limitations: (1) threshold value 'r' is updated as a function of long-term standard deviation and hence unable to explore the short-term variability as well as substantial variability inherited in beat-to-beat fluctuations of long-term HRV time series. (2) In RMSE, entropy values assigned to different filtered scaled time series are the result of changes in variance, but do not completely reflect the real structural organization inherited in original time series. In the present work, we propose an improved RMSE (I-RMSE) technique by introducing a new procedure to set the threshold value by taking into account the period-to-period variability inherited in a signal and evaluated it on simulated and real HRV database. The proposed I-RMSE assigns higher entropy to the age-matched healthy subjects than that of patients suffering from atrial fibrillation, congestive heart failure, sudden cardiac death and diabetes mellitus, for the entire time scales. The results strongly support the reduction in complexity of HRV time series in female group, old-aged, patients suffering from severe cardiovascular and non-cardiovascular diseases, and in their corresponding surrogate time series.
Brida, Margarita; Diller, Gerhard-Paul; Gatzoulis, Michael A
2018-01-30
The systemic right ventricle (SRV) is commonly encountered in congenital heart disease representing a distinctly different model in terms of its anatomic spectrum, adaptation, clinical phenotype, and variable, but overall guarded prognosis. The most common clinical scenarios where an SRV is encountered are complete transposition of the great arteries with previous atrial switch repair, congenitally corrected transposition of the great arteries, double inlet right ventricle mostly with previous Fontan palliation, and hypoplastic left heart syndrome palliated with the Norwood-Fontan protocol. The reasons for the guarded prognosis of the SRV in comparison with the systemic left ventricle are multifactorial, including distinct fibromuscular architecture, shape and function, coronary artery supply mismatch, intrinsic abnormalities of the tricuspid valve, intrinsic or acquired conduction abnormalities, and varied SRV adaptation to pressure or volume overload. Management of the SRV remains an ongoing challenge because SRV dysfunction has implications on short- and long-term outcomes for all patients irrespective of underlying cardiac morphology. SRV dysfunction can be subclinical, underscoring the need for tertiary follow-up and timely management of target hemodynamic lesions. Catheter interventions and surgery have an established role in selected patients. Cardiac resynchronization therapy is increasingly used, whereas pharmacological therapy is largely empirical. Mechanical assist device and heart transplantation remain options in end-stage heart failure when other management strategies have been exhausted. The present report focuses on the SRV with its pathological subtypes, pathophysiology, clinical features, current management strategies, and long-term sequelae. Although our article touches on issues applicable to neonates and children, its main focus is on adults with SRV. © 2018 American Heart Association, Inc.
Functional chloroplasts in metazoan cells - a unique evolutionary strategy in animal life
2009-01-01
Background Among metazoans, retention of functional diet-derived chloroplasts (kleptoplasty) is known only from the sea slug taxon Sacoglossa (Gastropoda: Opisthobranchia). Intracellular maintenance of plastids in the slug's digestive epithelium has long attracted interest given its implications for understanding the evolution of endosymbiosis. However, photosynthetic ability varies widely among sacoglossans; some species have no plastid retention while others survive for months solely on photosynthesis. We present a molecular phylogenetic hypothesis for the Sacoglossa and a survey of kleptoplasty from representatives of all major clades. We sought to quantify variation in photosynthetic ability among lineages, identify phylogenetic origins of plastid retention, and assess whether kleptoplasty was a key character in the radiation of the Sacoglossa. Results Three levels of photosynthetic activity were detected: (1) no functional retention; (2) short-term retention lasting about one week; and (3) long-term retention for over a month. Phylogenetic analysis of one nuclear and two mitochondrial loci revealed reciprocal monophyly of the shelled Oxynoacea and shell-less Plakobranchacea, the latter comprising a monophyletic Plakobranchoidea and paraphyletic Limapontioidea. Only species in the Plakobranchoidea expressed short- or long-term kleptoplasty, most belonging to a speciose clade of slugs bearing parapodia (lateral flaps covering the dorsum). Bayesian ancestral character state reconstructions indicated that functional short-term retention arose once in the last common ancestor of Plakobranchoidea, and independently evolved into long-term retention in four derived species. Conclusion We propose a sequential progression from short- to long-term kleptoplasty, with different adaptations involved in each step. Short-term kleptoplasty likely arose as a deficiency in plastid digestion, yielding additional energy via the release of fixed carbon. Functional short-term retention was an apomorphy of the Plakobranchoidea, but the subsequent evolution of parapodia enabled slugs to protect kleptoplasts against high irradiance and further prolong plastid survival. We conclude that functional short-term retention was necessary but not sufficient for an adaptive radiation in the Plakobranchoidea, especially in the genus Elysia which comprises a third of all sacoglossan species. The adaptations necessary for long-term chloroplast survival arose independently in species feeding on different algal hosts, providing a valuable study system for examining the parallel evolution of this unique trophic strategy. PMID:19951407
Vincke, Eveline
2017-01-01
Previous research indicates that drinking large quantities of alcohol could function as a short-term mating strategy for young adults in mating situations. However, no study investigated whether this is actually the case. Therefore, in this article, the link between short-term mating motivations and drinking high amounts of alcohol is tested. First, a survey study ( N = 345) confirmed that young adults who engage in binge drinking are more short-term oriented in their mating strategy than young adults who never engage in binge drinking. Also, the more short-term-oriented young adults were in their mating strategy, the more often binge drinking behavior was conducted. In addition, an experimental study ( N = 229) empirically verified that short-term mating motivations increase young adults' drinking behavior, more so than long-term mating motivations. Results of the experiment clearly showed that young men and young women are triggered to drink more alcoholic beverages in a short-term mating situation compared to a long-term mating situation. Furthermore, the mating situation also affected young adults' perception of drinking behavior. Young adults in a short-term mating context perceived a higher amount of alcoholic beverages as heavy drinking compared to peers in a long-term mating context. These findings confirm that a high alcohol consumption functions as a short-term mating strategy for both young men and young women. Insights gained from this article might be of interest to institutions aimed at targeting youth alcohol (ab)use.
Brown, D. Mark; Holt, David W.; Edwards, Jeff T.; Burnett, Robert J.
2006-01-01
Abstract: Oxygen pressure field theory (OPFT) was originally described in the early 1900s by Danish physiologist, Dr. August Krogh. This revolutionary theory described microcirculation of blood gases at the capillary level using a theoretical cylindrical tissue model commonly referred to as the Krogh cylinder. In recent years, the principles and benefits of OPFT in long-term extracorporeal circulatory support (ECMO) have been realized. Cardiac clinicians have successfully mastered OPFT fundamentals and incorporated them into their clinical practice. These clinicians have experienced significantly improved survival rates as a result of OPFT strategies. The objective of this study was to determine if a hyperoxic strategy can lead to equally beneficial outcomes for short-term support as measured by total ventilator time and total length of stay in intensive care unit (ICU) in the cardiopulmonary bypass (CPB) patient at a private institution. Patients receiving traditional blood gas management while on CPB (group B, n = 17) were retrospectively compared with hyperoxic patients (group A, n = 19). Hyperoxic/OPFT management was defined as paO2 values of 300–350 mmHg and average VSAT > 75%. Traditional blood gas management was defined as paO2 values of 150–250 mmHg and average VSAT < 75%. No significant differences between treatment groups were found for patient weight, CPB/AXC times, BSA, pre/post Hgb, pre/post-platelet (PLT) counts, pre/post-creatinine levels, pre/post-BUN, UF volumes, or CPB urine output. Additionally, no significant statistical differences were found between treatment groups for total time in ICU (T-ICU) or total time on ventilator (TOV). Hyperoxic management strategies provided no conclusive evidence of outcome improvement for patients receiving CPB for routine cardiac surgical repair. Additional studies into the impact of hyperoxia in short-term extracorporeal circulatory support are needed. PMID:17089511
Volf, Martin; Redmond, Conor; Albert, Ágnes J; Le Bagousse-Pinguet, Yoann; Biella, Paolo; Götzenberger, Lars; Hrázský, Záboj; Janeček, Štěpán; Klimešová, Jitka; Lepš, Jan; Šebelíková, Lenka; Vlasatá, Tereza; de Bello, Francesco
2016-04-01
The functional structures of communities respond to environmental changes by both species replacement (turnover) and within-species variation (intraspecific trait variability; ITV). Evidence is lacking on the relative importance of these two components, particularly in response to both short- and long-term environmental disturbance. We hypothesized that such short- and long-term perturbations would induce changes in community functional structure primarily via ITV and turnover, respectively. To test this we applied an experimental design across long-term mown and abandoned meadows, with each plot containing a further level of short-term management treatments: mowing, grazing and abandonment. Within each plot, species composition and trait values [height, shoot biomass, and specific leaf area (SLA)] were recorded on up to five individuals per species. Positive covariations between the contribution of species turnover and ITV occurred for height and shoot biomass in response to both short- and long-term management, indicating that species turnover and intraspecific adjustments selected for similar trait values. Positive covariations also occurred for SLA, but only in response to long-term management. The contributions of turnover and ITV changed depending on both the trait and management trajectory. As expected, communities responded to short-term disturbances mostly through changes in intraspecific trait variability, particularly for height and biomass. Interestingly, for SLA they responded to long-term disturbances by both species turnover and intraspecific adjustments. These findings highlight the importance of both ITV and species turnover in adjusting grassland functional trait response to environmental perturbation, and show that the response is trait specific and affected by disturbance regime history.
Chen, Yan; Chen, Hongmei; Birnbaum, Yochai; Nanhwan, Manjyot K; Bajaj, Mandeep; Ye, Yumei; Qian, Jinqiao
2017-03-01
To assess the effects of Aleglitazar on hyperglycaemia-induced apoptosis. We incubated human cardiomyocytes, cardiomyocytes from cardiac-specific peroxisome proliferator-activated receptor-γ knockout or wild-type mice in normoglycaemic or hyperglycaemic conditions (glucose 25 mM). Cells were treated with different concentrations of Aleglitazar for 48 h. We measured viability, apoptosis, caspase-3 activity, cytochrome-C release, total antioxidant capacity and reactive oxygen species formation in the treated cardiomyocytes. Human cardiomyocytes were transfected with short interfering RNA against peroxisome proliferator-activated receptor-α or peroxisome proliferator-activated receptor-γ. Aleglitazar attenuated hyperglycaemia-induced apoptosis, caspase-3 activity and cytochrome-C release and increased viability in human cardiomyocyte, cardiomyocytes from cardiac-specific peroxisome proliferator-activated receptor-γ knockout and wild-type mice. Hyperglycaemia reduced the antioxidant capacity and Aleglitazar significantly blunted this effect. Hyperglycaemia-induced reactive oxygen species production was attenuated by Aleglitazar in both human cardiomyocyte and wild-type mice cardiomyocytes. Aleglitazar improved cell viability in cells exposed to hyperglycaemia. The protective effect was partially blocked by short interfering RNA against peroxisome proliferator-activated receptor-α alone and short interfering RNA against peroxisome proliferator-activated receptor-γ alone and completely blocked by short interfering RNA to both peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ. Aleglitazar protects cardiomyocytes against hyperglycaemia-induced apoptosis by combined activation of both peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ in a short-term vitro model.
Takotsubo-like syndrome triggered by fludrocortisone overdose for Addison's disease: a case report.
Campean, Radu; Hasun, Matthias; Stöllberger, Claudia; Bucher, Johannes; Finsterer, Josef; Schnack, Christoph; Weidinger, Franz
2016-10-12
Reversible left ventricular dysfunction, also termed Takotsubo cardiomyopathy, is rarely reported in Addison's disease after initiation of hormone replacement therapy. The pathogenesis of this cardiomyopathy is unknown. A 41-year-old white woman with a history of autoimmune Hashimoto thyroiditis diagnosed 3 years earlier and acute adrenal insufficiency diagnosed 3 weeks earlier presented with new onset of heart failure New York Heart Association class IV, which had started shortly after initiation of hormone replacement therapy with hydrocortisone 20 mg/day and fludrocortisone 0.3 mg/day. Nine days before admission she had collapsed because of dizziness and had a cerebral concussion and open fracture of her nasal bone, however, no further investigations were carried out at that time. A physical examination revealed leg edema, tachycardia, tachypnea, bilateral basal crepitations, and blood pressure 110/70 mmHg. An electrocardiogram showed sinus tachycardia, low voltage, negative T-waves in V 5 and V 6 and a corrected QT interval of 590 ms. Echocardiography revealed a reduced left ventricular systolic function with an ejection fraction of 30 %, and septal, apical, and anterior wall akinesia. Cardiac magnetic resonance imaging showed relative enhancement of gadolinium, indicating hyperemia and capillary leakage, and no myocardial scars. Because of the improvement in her cardiac function, lack of cardiovascular risk factors, and lack of signs for ischemia on magnetic resonance imaging, no coronary angiography was carried out. The results of sellar and renal magnetic resonance imaging were normal. Her troponin T was slightly elevated. Bisoprolol and ramipril were started. Her fludrocortisone dose was reduced to 0.05 mg/day. Her electrocardiogram and systolic function, documented by echocardiography and magnetic resonance imaging, normalized within 6 months. Although we could not exclude coronary artery disease by coronary angiography, her clinical course and instrumental findings suggest Takotsubo cardiomyopathy of the apical type. Fludrocortisone overdosage and increased myocardial vulnerability due to cortisol deficiency might be pathogenetic factors, whereas myocarditis is unlikely. When hormone replacement in patients with Addison's disease is initiated, cardiac function should be monitored by electrocardiogram and echocardiography.
Respiratory modulation of cardiovascular rhythms before and after short-duration human spaceflight.
Verheyden, B; Beckers, F; Couckuyt, K; Liu, J; Aubert, A E
2007-12-01
Astronauts commonly return from space with altered short-term cardiovascular dynamics and blunted baroreflex sensitivity. Although many studies have addressed this issue, post-flight effects on the dynamic circulatory control remain incompletely understood. It is not clear how long the cardiovascular system needs to recover from spaceflight as most post-flight investigations only extended between a few days and 2 weeks. In this study, we examined the effect of short-duration spaceflight (1-2 weeks) on respiratory-mediated cardiovascular rhythms in five cosmonauts. Two paced-breathing protocols at 6 and 12 breaths min(-1) were performed in the standing and supine positions before spaceflight, and after 1 and 25 days upon return. Dynamic baroreflex function was evaluated by transfer function analysis between systolic pressure and the RR intervals. Post-flight orthostatic blood pressure control was preserved in all cosmonauts. In the standing position after spaceflight there was an increase in heart rate (HR) of approx. 20 beats min(-1) or more. Averaged for all five cosmonauts, respiratory sinus dysrhythmia and transfer gain reduced to 40% the day after landing, and had returned to pre-flight levels after 25 days. Low-frequency gain decreased from 6.6 (3.4) [mean (SD)] pre-flight to 3.9 (1.6) post-flight and returned to 5.7 (1.3) ms mmHg(-1) after 25 days upon return to Earth. Unlike alterations in the modulation of HR, blood pressure dynamics were not significantly different between pre- and post-flight sessions. Our results indicate that short-duration spaceflight reduces respiratory modulation of HR and decreases cardiac baroreflex gain without affecting post-flight arterial blood pressure dynamics. Altered respiratory modulation of human autonomic rhythms does not persist until 25 days upon return to Earth.
Lin, Yi-Dong; Chang, Ming-Yao; Cheng, Bill; Liu, Yen-Wen; Lin, Lung-Chun; Chen, Jyh-Hong; Hsieh, Patrick C H
2015-05-01
Accumulating evidence suggests that the benefits of cell therapy for cardiac repair are modest and transient due to progressive harmful cardiac remodeling as well as loss of transplanted cells. We previously demonstrated that injection of peptide nanofibers (NFs) reduces ventricular remodeling and facilitates cell retention at 1 month after acute myocardial infarction (MI) in pigs. However, it remains unclear whether these benefits still persist as the material is being degraded. In this study, 2 mL of placebo or NFs, with or without 1×10(8) mononuclear cells (MNCs), was injected into the pig myocardium after MI (n≥5 in each group), and cardiac function was assessed by echocardiography, including myocardial deformation analyses and catheterization at 3 months post-MI. Our results reveal that MNC-only injection slightly improved cardiac systolic function at 1 month post-MI, but this benefit was lost at later time points (ejection fraction: 42.0±2.3 in MI+normal saline [NS] and 43.5±1.1 in MI+MNCs). In contrast, NF-only injection resulted in improved cardiac diastolic function and reduced pathological remodeling at 3 months post-MI. Furthermore, combined injection of MNCs/NFs provided a greater and longer term cardiac performance (52.1±1.2 in MI+MNCs/NFs, p<0.001 versus MI+NS and MI+MNCs) and 11.3-fold transplanted cell retention. We also found that about 30% NFs remained at 3 months after injection; however, endogenous myofibroblasts were recruited to the NF-injected microenvironment to replace the degraded NFs and preserved cardiac dimensions and mechanics. In conclusion, we demonstrated that injection of NFs contributes to preservation of ventricular mechanical integrity and sustains MNC efficacy at 3 months postinjection.
Vildagliptin and caloric restriction for cardioprotection in pre-diabetic rats.
Tanajak, Pongpan; Pintana, Hiranya; Siri-Angkul, Natthaphat; Khamseekaew, Juthamas; Apaijai, Nattayaporn; Chattipakorn, Siriporn C; Chattipakorn, Nipon
2017-02-01
Long-term high-fat diet (HFD) consumption causes cardiac dysfunction. Although calorie restriction (CR) has been shown to be useful in obesity, we hypothesized that combined CR with dipeptidyl peptidase-4 (DPP-4) inhibitor provides greater efficacy than monotherapy in attenuating cardiac dysfunction and metabolic impairment in HFD-induced obese-insulin resistant rats. Thirty male Wistar rats were divided into 2 groups to be fed on either a normal diet (ND, n = 6) or a HFD (n = 24) for 12 weeks. Then, HFD rats were divided into 4 subgroups (n = 6/subgroup) to receive just the vehicle, CR diet (60% of mean energy intake and changed to ND), vildagliptin (3 mg/kg/day) or combined CR and vildagliptin for 4 weeks. Metabolic parameters, heart rate variability (HRV), cardiac mitochondrial function, left ventricular (LV) and fibroblast growth factor (FGF) 21 signaling pathway were determined. Rats on a HFD developed insulin and FGF21 resistance, oxidative stress, cardiac mitochondrial dysfunction and impaired LV function. Rats on CR alone showed both decreased body weight and visceral fat accumulation, whereas vildagliptin did not alter these parameters. Rats in CR, vildagliptin and CR plus vildagliptin subgroups had improved insulin sensitivity and oxidative stress. However, vildagliptin improved heart rate variability (HRV), cardiac mitochondrial function and LV function better than the CR. Chronic HFD consumption leads to obese-insulin resistance and FGF21 resistance. Although CR is effective in improving metabolic regulation, vildagliptin provides greater efficacy in preventing cardiac dysfunction by improving anti-apoptosis and FGF21 signaling pathways and attenuating cardiac mitochondrial dysfunction in obese-insulin-resistant rats. © 2017 Society for Endocrinology.
Plasma cardiac troponin I concentration and cardiac death in cats with hypertrophic cardiomyopathy.
Borgeat, K; Sherwood, K; Payne, J R; Luis Fuentes, V; Connolly, D J
2014-01-01
The use of cardiac biomarkers to assist in the diagnosis of occult and symptomatic hypertrophic cardiomyopathy (HCM) in cats has been established. There is limited data describing their prognostic utility in cats with HCM. Circulating concentrations of N-terminal B-type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) predict cardiac death in cats with HCM. Forty-one cats diagnosed with HCM at a veterinary teaching hospital, between February 2010 and May 2011. Prospective investigational study. Plasma samples were collected from cats diagnosed with HCM and concentrations of NTproBNP and cTnI were analyzed at a commercial laboratory. Echocardiographic measurements from the day of blood sampling were recorded. Long-term outcome data were obtained. Associations with time to cardiac death were analyzed using Cox proportional hazards models. When controlling for the presence/absence of heart failure and echocardiographic measures of left atrial size and function, cTnI > 0.7 ng/mL was independently associated with time to cardiac death. In univariable analysis, NTproBNP > 250 pmol/L was associated with cardiac death (P = .023), but this did not remain significant (P = .951) when controlling for the effect of clinical signs or left atrial size/function. Plasma concentration of cTnI (cutoff >0.7 ng/mL) is a predictor of cardiac death in cats with HCM that is independent of the presence of heart failure or left atrial dilatation. Copyright © 2014 by the American College of Veterinary Internal Medicine.
Corno, Antonio F
2016-07-01
To attract the interest of all people potentially involved in humanitarian activities in the emerging economies, in particular giving attention to the basic requirements of the organization of paediatric cardiac surgery activities, the requirements for a successful partnership with the local existing organizations and the basic elements of a patient-centred multidisciplinary integrated approach. Unfortunately, for many years, the interventions in the low and middle income countries were largely limited to short-term medical missions, not inappropriately nicknamed 'surgical safari', because of negative general and specific characteristics. The negative aspects and the limits of the short-term medical missions can be overcome only by long-term educational programmes. The most suitable and consistent models of long-term educational programmes have been combined and implemented with the personal experience to offer a proposal for a long-term educational project, with the following steps: (i) site selection; (ii) demographic research; (iii) site assessment; (iv) organization of surgical educational teams; (v) regular frequency of surgical educational missions; (vi) programme evolution and maturation; (vii) educational outreach and interactive support. Potential limits of a long-term educational surgical programme are: (i) financial affordability; (ii) basic legal needs; (iii) legal support; (iv) non-profit indemnification. The success should not be measured by the number of successful operations of any given mission, but by the successful operations that our colleagues perform after we leave. Considering that the children in need outnumber by far the people able to provide care, in this humanitarian medicine there should be plenty of room for cooperation rather than competition. The main goal should be to provide teaching to local staff and implement methods and techniques to support the improvement of the care of the patients in the long run. This review focuses on the organization of paediatric cardiac activities in the emerging economies, but 'the less privileged parts of the world' can be anywhere, not necessarily limited to economic constraints. Lack of diversity because of social, intellectual, educational and professional growth, the last consisting in cultural stagnation, is responsible for the lack of scientific progress and development. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Giorgini, Paolo; Rubenfire, Melvyn; Das, Ritabrata; Gracik, Theresa; Wang, Lu; Morishita, Masako; Bard, Robert L; Jackson, Elizabeth A; Fitzner, Craig A; Ferri, Claudio; Brook, Robert D
2015-10-01
Fine particulate matter air pollution (PM2.5) and extreme temperatures have both been associated with alterations in blood pressure (BP). However, few studies have evaluated their joint haemodynamic actions among individuals at high risk for cardiovascular events. We assessed the effects of short-term exposures during the prior week to ambient PM2.5 and outdoor temperature levels on resting seated BP among 2078 patients enrolling into a cardiac rehabilitation programme at the University of Michigan (from 2003 to 2011) using multiple linear regression analyses adjusting for age, sex, BMI, ozone and the same-day alternate environmental factor (i.e. PM2.5 or temperature). Mean PM2.5 and temperature levels were 12.6 ± 8.2 μg/m and 10.3 ± 10.4°C, respectively. Each standard deviation elevation in PM2.5 concentration during lag days 4-6 was associated with significant increases in SBP (2.1-3.5 mmHg) and DBP (1.7-1.8 mmHg). Conversely, higher temperature levels (per 10.4°C) during lag days 4-6 were associated with reductions in both SBP (-3.6 to -2.3 mmHg) and DBP (-2.5 to -1.8 mmHg). There was little evidence for consistent effect modification by other covariates (e.g. demographics, seasons, medication usage). Short-term exposures to PM2.5, even at low concentrations within current air quality standards, are associated with significant increases in BP. Contrarily, higher ambient temperatures prompt the opposite haemodynamic effect. These findings demonstrate that both ubiquitous environmental exposures have clinically meaningful effects on resting BP among high-risk cardiac patients.
Wakisaka, Shiori; Nagai, Hajime; Mura, Emi; Matsumoto, Takehiro; Moritani, Toshio; Nagai, Narumi
2012-01-01
Although previous reports suggested that carbonated water drinking was effective against gastrointestinal symptoms, there is little information about the effects of carbonated water on gastric and appetite sensation. We therefore investigated the effect of carbonated water on short-term fullness with respect to gastric and cardiac responses in 19 healthy young women. Each subject was tested on three separate days at approximately 9 a.m. after an overnight fast. Gastric motility, evaluated by electrogastrography (EGG) and heart rate (HR), was measured for 20 min in the fasting state and 40 min after ingestion of water. Preloads consisted of an equivalent amount (250 mL) of water (W) or carbonated water (CW) and no drinking (blank). Fullness scores were measured using visual analog scales. To determine gastric motility, we assessed the component of bradygastria (1-2 cycles/min [cpm]), normogastria (2-4 cpm), tachygastria (4-9 cpm), and dominant frequency of the EGG power spectrum. After ingestion of CW, significant increases in fullness scores were observed compared with W. All postprandial EGG powers were significantly greater than preprandial, but no group difference was found. However, a dominant frequency tended to shift toward a lower band after ingestion of W. A significantly higher HR was found following consumption of CW as opposed to W. Multiple regression analysis revealed that increased HR was a significant variable contributing to the variances in fullness after ingestion of CW at 40 min. Our data suggest that CW may induce a short-term, but significant, satiating effect through enhanced postprandial gastric and cardiac activities due possibly to the increased sympathetic activity and/or withdrawal of parasympathetic activity.
Baker, Kimberly; Sanchez-de-Toledo, Joan; Munoz, Ricardo; Orr, Richard; Kiray, Shareen; Shiderly, Dana; Clemens, Michele; Wearden, Peter; Morell, Victor O; Chrysostomou, Constantinos
2012-01-01
Objective. Infants with critical congenital heart disease (CHD) can have genetic and other extracardiac malformations, which add to the short- and long-term risk of morbidity and perhaps mortality. We sought to examine our center's practice of screening for extracardiac anomalies and to determine the yield of these tests among specific cardiac diagnostic categories. Design. Retrospective review of infants admitted to the cardiac intensive care unit with a new diagnosis of CHD. Subjects were categorized into six groups: septal defects (SD), conotruncal defects (CTD), single-ventricle physiology (SV), left-sided obstructive lesions (LSO), right-sided obstructive lesions (RSO), and "other" (anomalous pulmonary venous return, Ebstein's anomaly). Screening modalities included genetic testing (karyotype and fluorescent in situ hybridization for 22q11.2 deletion), renal ultrasound (RUS), and head ultrasound (HUS). Results. One hundred forty-one patients were identified. The incidence of cardiac anomalies was: CTD (36%), SD (18%), SV (18%), LSO (14%), RSO (3%), and "other" (8%). Overall 14% had an abnormal karyotype, 5% had a deletion for 22q11.2, 28% had an abnormal RUS and 22% had abnormal HUS. Patients in SD and SV had the highest incidence of abnormal karyotype (36% and 17%); 22q11.2 deletion was present only in CTD and LSO groups (9% and 7%, respectively); abnormal RUS and HUS were seen relatively uniformly in all categories. Premature infants had significantly higher incidence of renal 43% vs. 24%, and intracranial abnormalities 46% vs. 16%. Conclusion. Infants with critical CHD and particularly premature infants have high incidence of genetic and other extracardiac anomalies. Universal screening for these abnormalities with ultrasonographic and genetic testing maybe warranted because early detection could impact short and long-term outcomes. © 2011 Wiley Periodicals, Inc.
Neonatal and pediatric extracorporeal membrane oxygenation in developing Latin American countries.
Kattan, Javier; González, Álvaro; Castillo, Andrés; Caneo, Luiz Fernando
To review the principles of neonatal-pediatric extracorporeal membrane oxygenation therapy, prognosis, and its establishment in limited resource-limited countries in Latino America. The PubMed database was explored from 1985 up to the present, selecting from highly-indexed and leading Latin American journals, and Extracorporeal Life Support Organization reports. Extracorporeal membrane oxygenation provides "time" for pulmonary and cardiac rest and for recovery. It is used in the neonatal-pediatric field as a rescue therapy for more than 1300 patients with respiratory failure and around 1000 patients with cardiac diseases per year. The best results in short- and long-term survival are among patients with isolated respiratory diseases, currently established as a standard therapy in referral centers for high-risk patients. The first neonatal/pediatric extracorporeal membrane oxygenation Program in Latin America was established in Chile in 2003, which was also the first program in Latin America to affiliate with the Extracorporeal Life Support Organization. New extracorporeal membrane oxygenation programs have been developed in recent years in referral centers in Argentina, Colombia, Brazil, Mexico, Perú, Costa Rica, and Chile, which are currently funding the Latin American Extracorporeal Life Support Organization chapter. The best results in short- and long-term survival are in patients with isolated respiratory diseases. Today extracorporeal membrane oxygenation therapy is a standard therapy in some Latin American referral centers. It is hoped that these new extracorporeal membrane oxygenation centers will have a positive impact on the survival of newborns and children with respiratory or cardiac failure, and that they will be available for an increasing number of patients from this region in the near future. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.
Leiria, Tiago Luiz Luz; Glavinovic, Tamara; Armour, J Andrew; Cardinal, René; de Lima, Gustavo Glotz; Kus, Teresa
2011-04-26
In canines, excessive activation of select mediastinal nerve inputs to the intrinsic cardiac nervous system induces atrial fibrillation (AF). Since ablation of neural elements is proposed as an adjunct to circumferential pulmonary vein ablation for AF, we investigated the short and long-term effects of mediastinal nerve ablation on AF inducibility. Under general anesthesia, in 11 dogs several mediastinal nerve sites were identified on the superior vena cava that, when stimulated electrically during the atrial refractory period, reproducibly initiated AF. Cryoablation of one nerve site was then performed and inducibility retested early (1-2 months post Cryo; n=7) or late (4 months post Cryo; n=4). Four additional dogs that underwent a sham procedure were retested 1 to 2 months post-surgery. Stimulation induced AF at 91% of nerve sites tested in control versus 21% nerve sites early and 54% late post-ablation (both P<0.05). Fewer stimuli were required to induce AF in controls versus the Early Cryo group; this capacity returned to normal values in the Late Cryo group. AF episodes were longer in control versus the Early or Late Cryo groups. Heart rate responses to vagal or stellate ganglion stimulation, as well as to local nicotine infusion into the right coronary artery, were similar in all groups. In conclusion, focal damage to intrinsic cardiac neuronal inputs causes short-term stunning of neuronal inducibility of AF without major loss of overall adrenergic or cholinergic efferent neuronal control. That recovery of AF inducibility occurs rapidly post-surgery indicates the plasticity of intrathoracic neuronal elements to focal injury. Copyright © 2011 Elsevier B.V. All rights reserved.
Yannopoulos, Demetris; Bartos, Jason A.; George, Stephen A.; Sideris, George; Voicu, Sebastian; Oestreich, Brett; Matsuura, Timothy; Shekar, Kadambari; Rees, Jennifer; Aufderheide, Tom P.
2017-01-01
Introduction Sodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms. Hypothesis SNPeCPR will increase short term (4-hour) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model. Methods Sixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5 minutes. Basic life support was performed for 10 minutes. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3 minutes. CPR continued for a total of 45 minutes, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60 minutes, if unsuccessful. SNPeCPR animals received 2 mg of SNP at minute 10 followed by 1 mg every 5 minutes until ROSC. Standard ACLS animals received 0.5 mg epinephrine every 5 minutes until ROSC. Primary endpoints were ROSC and 4-hour survival. Results All SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-hour survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019. Conclusion SNPeCPR significantly improved ROSC and 4-hour survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest. PMID:27771299
Yannopoulos, Demetris; Bartos, Jason A; George, Stephen A; Sideris, George; Voicu, Sebastian; Oestreich, Brett; Matsuura, Timothy; Shekar, Kadambari; Rees, Jennifer; Aufderheide, Tom P
2017-01-01
Sodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms. SNPeCPR will increase short term (4-h) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model. Sixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5min. Basic life support was performed for 10min. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3min. CPR continued for a total of 45min, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60min, if unsuccessful. SNPeCPR animals received 2mg of SNP at minute 10 followed by 1mg every 5min until ROSC. Standard ACLS animals received 0.5mg epinephrine every 5min until ROSC. Primary endpoints were ROSC and 4-h survival. All SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-h survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019. SNPeCPR significantly improved ROSC and 4-h survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Characterizing short-term stability for Boolean networks over any distribution of transfer functions
Seshadhri, C.; Smith, Andrew M.; Vorobeychik, Yevgeniy; ...
2016-07-05
Here we present a characterization of short-term stability of random Boolean networks under arbitrary distributions of transfer functions. Given any distribution of transfer functions for a random Boolean network, we present a formula that decides whether short-term chaos (damage spreading) will happen. We provide a formal proof for this formula, and empirically show that its predictions are accurate. Previous work only works for special cases of balanced families. Finally, it has been observed that these characterizations fail for unbalanced families, yet such families are widespread in real biological networks.
Anderson, Jeffrey B; Grenier, Michelle; Edwards, Nicholas M; Madsen, Nicolas L; Czosek, Richard J; Spar, David S; Barnes, Allison; Pratt, Jesse; King, Eileen; Knilans, Timothy K
2014-12-01
Sudden cardiac death in the young (SCDY) is the leading cause of death in young athletes during sport. Screening young athletes for high-risk cardiac defects is controversial. The purpose of this study was to assess the utility and feasibility of a comprehensive cardiac screening protocol in an adolescent population. Adolescent athletes were recruited from local schools and/or sports teams. Each subject underwent a history and/or physical examination, an electrocardiography (ECG), and a limited echocardiography (ECHO). The primary outcome measure was identification of cardiac abnormalities associated with an elevated risk for sudden death. We secondarily identified cardiac abnormalities not typically associated with a short-term risk of sudden death. A total of 659 adolescent athletes were evaluated; 64% men. Five subjects had cardiac findings associated with an elevated risk for sudden death: prolonged QTc >500 ms (n = 2) and type I Brugada pattern (n = 1), identified with ECG; dilated cardiomyopathy (n = 1) and significant aortic root dilation; and z-score = +5.5 (n = 1). History and physical examination alone identified 76 (11.5%) subjects with any cardiac findings. ECG identified 76 (11.5%) subjects in which a follow-up ECHO or cardiology visit was recommended. Left ventricular mass was normal by ECHO in all but 1 patient with LVH on ECG. ECHO identified 34 (5.1%) subjects in whom a follow-up ECHO or cardiology visit was recommended. In conclusion, physical examination alone was ineffective in identification of subjects at elevated risk for SCDY. Screening ECHO identified patients with underlying cardiac disease not associated with immediate risk for SCDY. Cost of comprehensive cardiac screening is high. Copyright © 2014 Elsevier Inc. All rights reserved.
Brown, Armand O.; Mann, Beth; Gao, Geli; Hankins, Jane S.; Humann, Jessica; Giardina, Jonathan; Faverio, Paola; Restrepo, Marcos I.; Halade, Ganesh V.; Mortensen, Eric M.; Lindsey, Merry L.; Hanes, Martha; Happel, Kyle I.; Nelson, Steve; Bagby, Gregory J.; Lorent, Jose A.; Cardinal, Pablo; Granados, Rosario; Esteban, Andres; LeSaux, Claude J.; Tuomanen, Elaine I.; Orihuela, Carlos J.
2014-01-01
Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1β was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD. PMID:25232870
Tian, Li; Wei, Chang; Zhu, Jun; Liu, Lisheng; Liang, Yan; Li, Jiandong; Yang, Yanmin
2013-12-01
The prognostic value of diabetes mellitus (DM) on the long-term outcomes of patients after myocardial infarction has been well established. The correlation between DM, including newly diagnosed DM, and short-term outcomes needs to be validated. A total of 5410 ST-segment elevation myocardial infarction (STEMI) patients with typical chest pain onset in the past 12 h were enrolled. Follow-ups were carried out on days 7 and 30 after hospital admission. According to 2013 Standards of Medical Care in Diabetes, the study population was stratified into the following three groups: no diabetes, newly diagnosed diabetes, and previously known diabetes. The primary outcomes of our study were mortality from all causes and major adverse cardiac events (MACE) at days 7 and 30. Patients with previously known diabetes were older and had a higher incidence of previous history of cardiovascular disease compared with the other groups. The 7-day and 30-day mortality was similar between patients without DM and patients with newly diagnosed DM. For both groups, this was significantly lower than that in patients with DM. Similar results were observed for 7-day and 30-day MACE. Multivariable Cox regression analysis indicated that newly diagnosed diabetes did not correlate with 30-day MACE (hazard ratio, 0.901; 95% confidence interval, 0.759-1.069), but that previously known DM correlated with short-term MACE (hazard ratio, 1.211; 95% confidence interval, 1.009-1.453). Previously known DM, but not newly diagnosed DM, was an independent predictor for short-term MACE in patients with STEMI. To reduce the incidence of short-term MACE and the detrimental effects of stress hyperglycemia after STEMI, intensive insulin therapy should be provided to diabetic patients with STEMI.
den Uil, Corstiaan A; Akin, Sakir; Jewbali, Lucia S; Dos Reis Miranda, Dinis; Brugts, Jasper J; Constantinescu, Alina A; Kappetein, Arie Pieter; Caliskan, Kadir
2017-07-01
Short-term mechanical circulatory support (MCS) is increasingly used as a bridge to decision in patients with refractory cardiogenic shock. Subsequently, these patients might be bridged to durable MCS either as a bridge to candidacy/transplantation, or as destination therapy. The aim of this study was to review support duration and clinical outcome of short-term MCS in cardiogenic shock, and to analyse application of this technology as a bridge to long-term cardiac support (left ventricular assist device, LVAD) from 2006 till June 2016. Using Cochrane Register of Trials, Embase and Medline, a systematic review was performed on patients with cardiogenic shock from acute myocardial infarction, end-stage cardiomyopathy, or acute myocarditis, receiving short-term MCS. Studies on periprocedural, post-cardiotomy and cardiopulmonary resuscitation support were excluded. Thirty-nine studies, mainly registries of heterogeneous patient populations (n = 4151 patients), were identified. Depending on the device used (intra-aortic balloon pump, TandemHeart, Impella 2.5, Impella 5.0, CentriMag and peripheral veno-arterial extracorporeal membrane oxygenation), mean support duration was (range) 1.6-25 days and the mean proportion of short-term MCS patients discharged was (range) 45-66%. The mean proportion of bridge to durable LVAD was (range) 3-30%. Bridge to durable LVAD was most frequently performed in patients with end-stage cardiomyopathy (22 [12-35]%). We conclude that temporary MCS can be used to bridge patients with cardiogenic shock towards durable LVAD. Clinicians are encouraged to share their results in a large multicentre registry in order to investigate optimal device selection and best duration of support. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Satoh, Hiroshi; Sano, Makoto; Suwa, Kenichiro; Saitoh, Takeji; Nobuhara, Mamoru; Saotome, Masao; Urushida, Tsuyoshi; Katoh, Hideki; Hayashi, Hideharu
2014-01-01
The recent development of cardiac magnetic resonance (CMR) techniques has allowed detailed analyses of cardiac function and tissue characterization with high spatial resolution. We review characteristic CMR features in ischemic and non-ischemic cardiomyopathies (ICM and NICM), especially in terms of the location and distribution of late gadolinium enhancement (LGE). CMR in ICM shows segmental wall motion abnormalities or wall thinning in a particular coronary arterial territory, and the subendocardial or transmural LGE. LGE in NICM generally does not correspond to any particular coronary artery distribution and is located mostly in the mid-wall to subepicardial layer. The analysis of LGE distribution is valuable to differentiate NICM with diffusely impaired systolic function, including dilated cardiomyopathy, end-stage hypertrophic cardiomyopathy (HCM), cardiac sarcoidosis, and myocarditis, and those with diffuse left ventricular (LV) hypertrophy including HCM, cardiac amyloidosis and Anderson-Fabry disease. A transient low signal intensity LGE in regions of severe LV dysfunction is a particular feature of stress cardiomyopathy. In arrhythmogenic right ventricular cardiomyopathy/dysplasia, an enhancement of right ventricular (RV) wall with functional and morphological changes of RV becomes apparent. Finally, the analyses of LGE distribution have potentials to predict cardiac outcomes and response to treatments. PMID:25068019
Cardiac parasympathetic reactivation following exercise: implications for training prescription.
Stanley, Jamie; Peake, Jonathan M; Buchheit, Martin
2013-12-01
The objective of exercise training is to initiate desirable physiological adaptations that ultimately enhance physical work capacity. Optimal training prescription requires an individualized approach, with an appropriate balance of training stimulus and recovery and optimal periodization. Recovery from exercise involves integrated physiological responses. The cardiovascular system plays a fundamental role in facilitating many of these responses, including thermoregulation and delivery/removal of nutrients and waste products. As a marker of cardiovascular recovery, cardiac parasympathetic reactivation following a training session is highly individualized. It appears to parallel the acute/intermediate recovery of the thermoregulatory and vascular systems, as described by the supercompensation theory. The physiological mechanisms underlying cardiac parasympathetic reactivation are not completely understood. However, changes in cardiac autonomic activity may provide a proxy measure of the changes in autonomic input into organs and (by default) the blood flow requirements to restore homeostasis. Metaboreflex stimulation (e.g. muscle and blood acidosis) is likely a key determinant of parasympathetic reactivation in the short term (0-90 min post-exercise), whereas baroreflex stimulation (e.g. exercise-induced changes in plasma volume) probably mediates parasympathetic reactivation in the intermediate term (1-48 h post-exercise). Cardiac parasympathetic reactivation does not appear to coincide with the recovery of all physiological systems (e.g. energy stores or the neuromuscular system). However, this may reflect the limited data currently available on parasympathetic reactivation following strength/resistance-based exercise of variable intensity. In this review, we quantitatively analyse post-exercise cardiac parasympathetic reactivation in athletes and healthy individuals following aerobic exercise, with respect to exercise intensity and duration, and fitness/training status. Our results demonstrate that the time required for complete cardiac autonomic recovery after a single aerobic-based training session is up to 24 h following low-intensity exercise, 24-48 h following threshold-intensity exercise and at least 48 h following high-intensity exercise. Based on limited data, exercise duration is unlikely to be the greatest determinant of cardiac parasympathetic reactivation. Cardiac autonomic recovery occurs more rapidly in individuals with greater aerobic fitness. Our data lend support to the concept that in conjunction with daily training logs, data on cardiac parasympathetic activity are useful for individualizing training programmes. In the final sections of this review, we provide recommendations for structuring training microcycles with reference to cardiac parasympathetic recovery kinetics. Ultimately, coaches should structure training programmes tailored to the unique recovery kinetics of each individual.
Feola, Mauro; Chauvie, Stephane; Biggi, Alberto; Testa, Marzia
2015-01-01
(123)I-iobenguane myocardial scintigraphy (MIBG) has been shown to be a predictor of sudden cardiac mortality in patients with heart failure. One patient with recent anterior myocardial infarction (MI) treated with coronary angioplasty and having left ventricular ejection fraction (LVEF) of 30% underwent early MIBG myocardial scintigraphy/tetrofosmin single-photon emission computed tomography (SPECT) in order to help evaluate his eligibility for implantable cardioverter defibrillator (ICD). The late heart/mediastinum (H/M) ratio was calculated to be 1.32% and the washout rate was 1%. At 40-day follow-up after angioplasty, LVEF proved to be 32%, New York Heart Association (NYHA) class was still II-III, and an ICD was placed in order to reduce mortality from ventricular arrhythmias. MIBG myocardial scintigraphy might be a promising method for evaluating left ventricular recovery in post-MI patients.
Debouk, Haifa; de Bello, Francesco; Sebastià, Maria-Teresa
2015-01-01
Plant functional traits underlie vegetation responses to environmental changes such as global warming, and consequently influence ecosystem processes. While most of the existing studies focus on the effect of warming only on species diversity and productivity, we further investigated (i) how the structure of community plant functional traits in temperate grasslands respond to experimental warming, and (ii) whether species and functional diversity contribute to a greater stability of grasslands, in terms of vegetation composition and productivity. Intact vegetation turves were extracted from temperate subalpine grassland (highland) in the Eastern Pyrenees and transplanted into a warm continental, experimental site in Lleida, in Western Catalonia (lowland). The impacts of simulated warming on plant production and diversity, functional trait structure, and vegetation compositional stability were assessed. We observed an increase in biomass and a reduction in species and functional diversity under short-term warming. The functional structure of the grassland communities changed significantly, in terms of functional diversity and community-weighted means (CWM) for several traits. Acquisitive and fast-growing species with higher SLA, early flowering, erect growth habit, and rhizomatous strategy became dominant in the lowland. Productivity was significantly positively related to species, and to a lower extent, functional diversity, but productivity and stability after warming were more dependent on trait composition (CWM) than on diversity. The turves with more acquisitive species before warming changed less in composition after warming. Results suggest that (i) the short-term warming can lead to the dominance of acquisitive fast growing species over conservative species, thus reducing species richness, and (ii) the functional traits structure in grassland communities had a greater influence on the productivity and stability of the community under short-term warming, compared to diversity effects. In summary, short-term climate warming can greatly alter vegetation functional structure and its relation to productivity.
Debouk, Haifa; de Bello, Francesco; Sebastià, Maria-Teresa
2015-01-01
Plant functional traits underlie vegetation responses to environmental changes such as global warming, and consequently influence ecosystem processes. While most of the existing studies focus on the effect of warming only on species diversity and productivity, we further investigated (i) how the structure of community plant functional traits in temperate grasslands respond to experimental warming, and (ii) whether species and functional diversity contribute to a greater stability of grasslands, in terms of vegetation composition and productivity. Intact vegetation turves were extracted from temperate subalpine grassland (highland) in the Eastern Pyrenees and transplanted into a warm continental, experimental site in Lleida, in Western Catalonia (lowland). The impacts of simulated warming on plant production and diversity, functional trait structure, and vegetation compositional stability were assessed. We observed an increase in biomass and a reduction in species and functional diversity under short-term warming. The functional structure of the grassland communities changed significantly, in terms of functional diversity and community-weighted means (CWM) for several traits. Acquisitive and fast-growing species with higher SLA, early flowering, erect growth habit, and rhizomatous strategy became dominant in the lowland. Productivity was significantly positively related to species, and to a lower extent, functional diversity, but productivity and stability after warming were more dependent on trait composition (CWM) than on diversity. The turves with more acquisitive species before warming changed less in composition after warming. Results suggest that (i) the short-term warming can lead to the dominance of acquisitive fast growing species over conservative species, thus reducing species richness, and (ii) the functional traits structure in grassland communities had a greater influence on the productivity and stability of the community under short-term warming, compared to diversity effects. In summary, short-term climate warming can greatly alter vegetation functional structure and its relation to productivity. PMID:26513148
The crystalloid cardioplegia: advantages with a word of caution.
Angeli, E
2011-05-01
Technical success and absence of iatrogenic injury from inadequate myocardial protection are the foremost targets of every cardiac surgical procedure. The current trends of pediatric cardiac surgery are aimed to achieve definitive repair of complex cardiac defects at birth as to avoid the risks related with palliative surgery and to reduce the long term impact of the untreated defect on the cardiac function. Thus, even newborn patients are exposed to a prolonged time of myocardial ischemia. The aim of this paper is to describe the impact of crystalloid HKT Custodiol cardioplegia infusion on myocardial protection in the early and late outcome of newborn patients who underwent arterial switch operation (ASO) for transposition of the great arteries (TGA). Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Does marital conflict predict infants' physiological regulation? A short-term prospective study.
Porter, Christin L; Dyer, W Justin
2017-06-01
Prior research has linked marital conflict to children's internalizing/externalizing disorders, insecure attachment, and poor emotional regulation (e.g., Cummings & Davies, 2010; Cummings, Iannotti, & Zahn-Waxler, 1985). Although investigators have examined the impact of marital discord on older children (e.g., Crockenberg & Langrock, 2001), few have explored direct links in infancy (e.g., Cowan & Cowan, 1999). This study extends earlier work by examining linkages between marital functioning (conflict and harmony) and infants' cardiac vagal tone and developmental status across 2 time points using a cross-lag approach. Differential findings were found for boys and girls, with concurrent linkages between marital love and vagal tone at 6 months for boys and girls but only for boys at 12 months. In addition, marital conflict at 6 months predicted lower cardiac vagal tone in girls at 12 months but not boys. Finally, infants' developmental status at 6 months was found to predict marital conflict at 12 months. Higher scores on the Psychomotor Development Index (PDI) predicted greater marital conflict whereas higher scores on the Mental Development Index (MDI) predicted lower conflict. These findings are discussed in the context of the emotional security hypothesis and the spillover framework as well as differential susceptibilities to early developmental contexts. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Maturation status of sarcomere structure and function in human iPSC-derived cardiac myocytes.
Bedada, Fikru B; Wheelwright, Matthew; Metzger, Joseph M
2016-07-01
Human heart failure due to myocardial infarction is a major health concern. The paucity of organs for transplantation limits curative approaches for the diseased and failing adult heart. Human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) have the potential to provide a long-term, viable, regenerative-medicine alternative. Significant progress has been made with regard to efficient cardiac myocyte generation from hiPSCs. However, directing hiPSC-CMs to acquire the physiological structure, gene expression profile and function akin to mature cardiac tissue remains a major obstacle. Thus, hiPSC-CMs have several hurdles to overcome before they find their way into translational medicine. In this review, we address the progress that has been made, the void in knowledge and the challenges that remain. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
Images as drivers of progress in cardiac computational modelling
Lamata, Pablo; Casero, Ramón; Carapella, Valentina; Niederer, Steve A.; Bishop, Martin J.; Schneider, Jürgen E.; Kohl, Peter; Grau, Vicente
2014-01-01
Computational models have become a fundamental tool in cardiac research. Models are evolving to cover multiple scales and physical mechanisms. They are moving towards mechanistic descriptions of personalised structure and function, including effects of natural variability. These developments are underpinned to a large extent by advances in imaging technologies. This article reviews how novel imaging technologies, or the innovative use and extension of established ones, integrate with computational models and drive novel insights into cardiac biophysics. In terms of structural characterization, we discuss how imaging is allowing a wide range of scales to be considered, from cellular levels to whole organs. We analyse how the evolution from structural to functional imaging is opening new avenues for computational models, and in this respect we review methods for measurement of electrical activity, mechanics and flow. Finally, we consider ways in which combined imaging and modelling research is likely to continue advancing cardiac research, and identify some of the main challenges that remain to be solved. PMID:25117497
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lin, Xinchun
Introduction: The aim of the present study was to evaluate the effects of the novel kinin B1 receptor antagonist BI113823 on postinfarction cardiac remodeling and heart failure, and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin 1 converting enzyme (ACE) inhibitor in rats. Methods and results: Sprague Dawley rats were subjected to permanent occlusion of the left coronary artery. Cardiovascular function was determined at 6 weeks postinfarction. Treatment with either B1 receptor antagonist (BI113823) or an ACE inhibitor (lisinopril) alone or in combination significantly reduced the heart weight-to-body weight and lung weight-to-body weight ratios, andmore » improved postinfarction cardiac function as evidenced by greater cardiac output, the maximum rate of left ventricular pressure rise (± dP/dtmax), left ventricle ejection fraction, fractional shorting, better wall motion, and attenuation of elevated left ventricular end diastolic pressure (LVEDP). Furthermore, all three treatment groups exhibited significant reduction in cardiac interstitial fibrosis, collagen deposition, CD68 positive macrophages, neutrophils, and proinflammatory cytokine production (TNF-α and IL-1β), compared to vehicle controls. Conclusion: The present study shows that treatment with the novel kinin B1 receptor antagonist, BI113823, reduces postinfarction cardiac remodeling and heart failure, and does not influence the cardiovascular effects of the ACE inhibitor. - Highlights: • We examined the role of kinin B1 receptors in the development of heart failure. • Kinin B1 receptor blockade attenuates post-infarction cardiac remodeling. • Kinin B1 receptor blockade improves dysfunction, and prevented heart failure. • B1 receptor blockade does not affect the cardio-protection of an ACE inhibitor.« less
Oghli, Mostafa Ghelich; Dehlaghi, Vahab; Zadeh, Ali Mohammad; Fallahi, Alireza; Pooyan, Mohammad
2014-07-01
Assessment of cardiac right-ventricle functions plays an essential role in diagnosis of arrhythmogenic right ventricular dysplasia (ARVD). Among clinical tests, cardiac magnetic resonance imaging (MRI) is now becoming the most valid imaging technique to diagnose ARVD. Fatty infiltration of the right ventricular free wall can be visible on cardiac MRI. Finding right-ventricle functional parameters from cardiac MRI images contains segmentation of right-ventricle in each slice of end diastole and end systole phases of cardiac cycle and calculation of end diastolic and end systolic volume and furthermore other functional parameters. The main problem of this task is the segmentation part. We used a robust method based on deformable model that uses shape information for segmentation of right-ventricle in short axis MRI images. After segmentation of right-ventricle from base to apex in end diastole and end systole phases of cardiac cycle, volume of right-ventricle in these phases calculated and then, ejection fraction calculated. We performed a quantitative evaluation of clinical cardiac parameters derived from the automatic segmentation by comparison against a manual delineation of the ventricles. The manually and automatically determined quantitative clinical parameters were statistically compared by means of linear regression. This fits a line to the data such that the root-mean-square error (RMSE) of the residuals is minimized. The results show low RMSE for Right Ventricle Ejection Fraction and Volume (≤ 0.06 for RV EF, and ≤ 10 mL for RV volume). Evaluation of segmentation results is also done by means of four statistical measures including sensitivity, specificity, similarity index and Jaccard index. The average value of similarity index is 86.87%. The Jaccard index mean value is 83.85% which shows a good accuracy of segmentation. The average of sensitivity is 93.9% and mean value of the specificity is 89.45%. These results show the reliability of proposed method in these cases that manual segmentation is inapplicable. Huge shape variety of right-ventricle led us to use a shape prior based method and this work can develop by four-dimensional processing for determining the first ventricular slices.
[Dynamics of the dominance of identified cardioregulatory neurons in the snail Achatina fulica] .
Zhuravlev, V L; Bugaĭ, V V; Safronova, T A
2000-08-01
9 cardioregulating neurones belonging to 5 different functional groups were studied in visceral and right parietal ganglia of the Giant African snail Achatina fulica. The neuronal network included multimodal and multifunctional cells exerting short- or long-lasting chronoionotropic effects on the cardiac electro- and mechanograms. Mechanisms of the differences in the cardioregulating effectiveness of these groups were discussed.
GPCR-autoantibodies in chronic heart failure.
Boivin-Jahns, Valerie; Jahns, Roland
2018-06-01
Chronic heart failure (CHF) is a syndrome characterized by shortness of breath, fluid retention, and a progressive reduction in cardiac function. More than 60% of the cases are ischemic in origin (i.e., due to myo-cardial infarction) and about 30% are caused by non-ischemic myocardial damage (i.e., due to genetic or non-genetic causes like myocardial inflammation). Because of alterations in both cellular and humoral immunity patients with non-ischemic CHF often develop abnormal or misled immune responses, including cross-reacting antibodies and/or autoantibodies to various cardiac anti-gens. Non-ischemic myo-cardial damage was found to progress to CHF particularly, when associated (a) with the generation of autoantibodies directed against distinct myocyte membrane proteins critically involved in cardiac function - like G-protein coup-led membrane receptors (GPCRs), or (b) with virus persistence in the myocardium. This article will review current knowledge on the pathophysiological relevance of GPCR-autoreactivity in CHF by giving an overview on the so far available evidence from pre-clinical, clinical and epidemiological studies on the CHF-inducing potential of GPCR-autoantibodies and thereon based novel therapeutic approaches in GPCR autoantibody-associated CHF.
Detrended fluctuation analysis of short datasets: An application to fetal cardiac data
NASA Astrophysics Data System (ADS)
Govindan, R. B.; Wilson, J. D.; Preißl, H.; Eswaran, H.; Campbell, J. Q.; Lowery, C. L.
2007-02-01
Using detrended fluctuation analysis (DFA) we perform scaling analysis of short datasets of length 500-1500 data points. We quantify the long range correlation (exponent α) by computing the mean value of the local exponents αL (in the asymptotic regime). The local exponents are obtained as the (numerical) derivative of the logarithm of the fluctuation function F(s) with respect to the logarithm of the scale factor s:αL=dlog10F(s)/dlog10s. These local exponents display huge variations and complicate the correct quantification of the underlying correlations. We propose the use of the phase randomized surrogate (PRS), which preserves the long range correlations of the original data, to minimize the variations in the local exponents. Using the numerically generated uncorrelated and long range correlated data, we show that performing DFA on several realizations of PRS and estimating αL from the averaged fluctuation functions (of all realizations) can minimize the variations in αL. The application of this approach to the fetal cardiac data (RR intervals) is discussed and we show that there is a statistically significant correlation between α and the gestation age.
Senzolo, M; Bassanello, M; Graziotto, A; Zucchetta, P; Cillo, U; Maraglino, G; Loreno, M; Bellotto, F; Davià, G; Burra, P
2008-01-01
Up to 15% of liver transplant candidates have asymptomatic coronary artery diseases, which increase the risk of cardiac complications during and after transplantation. The aim of this study was to prospectively investigate the usefulness of an integrated cardiological approach in cirrhotic patients undergoing liver transplantation. Twenty-four consecutive patients undergoing evaluation for liver transplantation were studied by assessing risk factors for coronary artery diseases, electrocardiogram with QTc interval determination, chest X-ray, echocardiography, 24-hour Holter monitor, myocardial perfusion scintigraphy (99mTc)MIBI-GSPECT at rest and after dipyridamole infusion. Cardiac (123)I-metaiodobenzylguanidine (MIBG) scan and coronarography were performed in patients with myocardial perfusion defects. Twenty three of 24 patients underwent successful liver transplantation; one patient died on the waiting list. Before liver transplantation, 29% of patients were diabetic and 41% were smokers. Eleven of 24 patients had a prolonged QTc interval, and 3/24 had positive myocardioscintigraphy after dipyridamole infusion: in two coronarography was negative, while the (123)I-MIBG washout was altered. No cardiac events were recorded during the short-and long-term follow-up after surgery. Predictive value of positive cardiac (99mTc)MIBI-GSPECT in patients with liver cirrhosis is low, and this may be due to alterations of cardiac microvascular tone as showed by cardiac (123)I-MIBG scan.
Gelsomino, Sandro; Lozekoot, Pieter W J; Lorusso, Roberto; de Jong, Monique M J; Parise, Orlando; Matteucci, Francesco; Lucà, Fabiana; La Meir, Mark; Gensini, Gian Franco; Maessen, Jos G
2016-05-01
We compare a short and a standard-size balloon with same filling volumes to verify the differences in terms of visceral flow, coronary circulation and haemodynamic performance during aortic counterpulsation in an animal model of myocardial ischaemia-reperfusion injury. Eighteen healthy pigs underwent 120-min ligation of the left anterior descending coronary artery followed by 6 h of reperfusion, and they were randomly assigned to have intra-aortic balloon counterpulsation (IABP) with a 40-ml short-balloon (n = 6) or a 40-ml standard-length balloon (n = 6), or to undergo no IABP implantation (controls, n = 6). Haemodynamics and visceral and coronary flows were measured at baseline (t0), at 2 h of ischaemia (t1) and every hour thereafter until 6 h of reperfusion (from tR1 to tR6), respectively. Mesenteric flows increased significantly at tR1 only in the short-balloon group (P < 0.001) and it was constantly higher than in the standard-balloon group regardless of mean arterial pressure, systemic vascular resistance and cardiac output (CO; all, P < 0.001). Renal blood flows were significantly increased during IABP treatment with values constantly and significantly higher in short balloons at any following experimental step (all, P < 0.05). IABP improved CO and coronary blood flow, and reduced afterload, myocardial resistances and myocardial oxygen consumption without differences between the short and the standard-length balloon (all, P > 0.05). The short balloon prevents visceral ischaemia and, compared with the standard-size balloon, it does not lose IABP beneficial cardiac and coronary-related effects. Further studies are warranted to confirm our findings. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Proteostasis and REDOX state in the heart
Christians, Elisabeth S.
2012-01-01
Force-generating contractile cells of the myocardium must achieve and maintain their primary function as an efficient mechanical pump over the life span of the organism. Because only half of the cardiomyocytes can be replaced during the entire human life span, the maintenance strategy elicited by cardiac cells relies on uninterrupted renewal of their components, including proteins whose specialized functions constitute this complex and sophisticated contractile apparatus. Thus cardiac proteins are continuously synthesized and degraded to ensure proteome homeostasis, also termed “proteostasis.” Once synthesized, proteins undergo additional folding, posttranslational modifications, and trafficking and/or become involved in protein-protein or protein-DNA interactions to exert their functions. This includes key transient interactions of cardiac proteins with molecular chaperones, which assist with quality control at multiple levels to prevent misfolding or to facilitate degradation. Importantly, cardiac proteome maintenance depends on the cellular environment and, in particular, the reduction-oxidation (REDOX) state, which is significantly different among cardiac organelles (e.g., mitochondria and endoplasmic reticulum). Taking into account the high metabolic activity for oxygen consumption and ATP production by mitochondria, it is a challenge for cardiac cells to maintain the REDOX state while preventing either excessive oxidative or reductive stress. A perturbed REDOX environment can affect protein handling and conformation (e.g., disulfide bonds), disrupt key structure-function relationships, and trigger a pathogenic cascade of protein aggregation, decreased cell survival, and increased organ dysfunction. This review covers current knowledge regarding the general domain of REDOX state and protein folding, specifically in cardiomyocytes under normal-healthy conditions and during disease states associated with morbidity and mortality in humans. PMID:22003057
Cardiac dimensions and function in female handball players.
Malmgren, A; Dencker, M; Stagmo, M; Gudmundsson, P
2015-04-01
Long-term intensive endurance training leads to increased left ventricular mass and increased left ventricular end-diastolic and left atrial end-systolic diameters. Different types of sports tend to give rise to distinct morphological forms of the athlete's heart. However, the sport-specific aspects have not been fully investigated in female athletes. The purpose of the present study was to investigate differences in left and right cardiac dimensions, cardiac volumes, and systolic and diastolic function in elite female handball players compared to sedentary controls. A cross-sectional study of 33 elite female handball players was compared to 33 matched sedentary controls. Mean age was 21.5±2 years. The subjects underwent echocardiography examinations, both 2-dimensional (2DE) and 3-dimensional (3DE). Cardiac dimensions and volumes were quantified using M-mode, 2DE and 3DE. Systolic and diastolic left ventricular functions were also evaluated. All cardiac dimensions and volumes were adjusted for body surface area (BSA). Left atrium and left ventricle volumes were significantly (P<0.001) larger in elite female handball players compared with sedentary controls. Even right atrium area as well as right ventricular end-diastolic and end-systolic area were significantly (P<0.001) larger in elite female handball players. Significant differences were observed in three out of five systolic parameters. Most diastolic function parameters did not differ between the two groups. The findings from the present study suggest that similar cardiac remodeling takes place in elite female handball players as it does in athletes pursuing endurance or team game sports.
Proteostasis and REDOX state in the heart.
Christians, Elisabeth S; Benjamin, Ivor J
2012-01-01
Force-generating contractile cells of the myocardium must achieve and maintain their primary function as an efficient mechanical pump over the life span of the organism. Because only half of the cardiomyocytes can be replaced during the entire human life span, the maintenance strategy elicited by cardiac cells relies on uninterrupted renewal of their components, including proteins whose specialized functions constitute this complex and sophisticated contractile apparatus. Thus cardiac proteins are continuously synthesized and degraded to ensure proteome homeostasis, also termed "proteostasis." Once synthesized, proteins undergo additional folding, posttranslational modifications, and trafficking and/or become involved in protein-protein or protein-DNA interactions to exert their functions. This includes key transient interactions of cardiac proteins with molecular chaperones, which assist with quality control at multiple levels to prevent misfolding or to facilitate degradation. Importantly, cardiac proteome maintenance depends on the cellular environment and, in particular, the reduction-oxidation (REDOX) state, which is significantly different among cardiac organelles (e.g., mitochondria and endoplasmic reticulum). Taking into account the high metabolic activity for oxygen consumption and ATP production by mitochondria, it is a challenge for cardiac cells to maintain the REDOX state while preventing either excessive oxidative or reductive stress. A perturbed REDOX environment can affect protein handling and conformation (e.g., disulfide bonds), disrupt key structure-function relationships, and trigger a pathogenic cascade of protein aggregation, decreased cell survival, and increased organ dysfunction. This review covers current knowledge regarding the general domain of REDOX state and protein folding, specifically in cardiomyocytes under normal-healthy conditions and during disease states associated with morbidity and mortality in humans.
Sridharan, Vijayalakshmi; Tripathi, Preeti; Aykin-Burns, Nukhet; Krager, Kimberly J; Sharma, Sunil K.; Moros, Eduardo G.; Melnyk, Stepan B.; Pavliv, Oleksandra; Hauer-Jensen, Martin; Boerma, Marjan
2015-01-01
Radiation-induced heart disease (RIHD) is a common and sometimes severe late side effect of radiation therapy for intrathoracic and chest wall tumors. We have previously shown that local heart irradiation in a rat model caused prolonged changes in mitochondrial respiration and increased susceptibility to mitochondrial permeability transition pore (mPTP) opening. Because tocotrienols are known to protect against oxidative stress-induced mitochondrial dysfunction, in this study, we examined the effects of tocotrienols on radiation-induced alterations in mitochondria, and structural and functional manifestations of RIHD. Male Sprague-Dawley rats received image-guided localized X irradiation to the heart to a total dose of 21 Gy. Twenty-four hours before irradiation, rats received a tocotrienol-enriched formulation or vehicle by oral gavage. Mitochondrial function and mitochondrial membrane parameters were studied at 2 weeks and 28 weeks after irradiation. In addition, cardiac function and histology were examined at 28 weeks. A single oral dose of the tocotrienol-enriched formulation preserved Bax/Bcl2 ratios and prevented mPTP opening and radiation-induced alterations in succinate-driven mitochondrial respiration. Nevertheless, the late effects of local heart irradiation pertaining to myocardial function and structure were not modified. Our studies suggest that a single dose of tocotrienols protects against radiation-induced mitochondrial changes, but these effects are not sufficient against long-term alterations in cardiac function or remodeling. PMID:25710576
Sridharan, Vijayalakshmi; Tripathi, Preeti; Aykin-Burns, Nukhet; Krager, Kimberly J; Sharma, Sunil K; Moros, Eduardo G; Melnyk, Stepan B; Pavliv, Oleksandra; Hauer-Jensen, Martin; Boerma, Marjan
2015-03-01
Radiation-induced heart disease (RIHD) is a common and sometimes severe late side effect of radiation therapy for intrathoracic and chest wall tumors. We have previously shown that local heart irradiation in a rat model caused prolonged changes in mitochondrial respiration and increased susceptibility to mitochondrial permeability transition pore (mPTP) opening. Because tocotrienols are known to protect against oxidative stress-induced mitochondrial dysfunction, in this study, we examined the effects of tocotrienols on radiation-induced alterations in mitochondria, and structural and functional manifestations of RIHD. Male Sprague-Dawley rats received image-guided localized X irradiation to the heart to a total dose of 21 Gy. Twenty-four hours before irradiation, rats received a tocotrienol-enriched formulation or vehicle by oral gavage. Mitochondrial function and mitochondrial membrane parameters were studied at 2 weeks and 28 weeks after irradiation. In addition, cardiac function and histology were examined at 28 weeks. A single oral dose of the tocotrienol-enriched formulation preserved Bax/Bcl2 ratios and prevented mPTP opening and radiation-induced alterations in succinate-driven mitochondrial respiration. Nevertheless, the late effects of local heart irradiation pertaining to myocardial function and structure were not modified. Our studies suggest that a single dose of tocotrienols protects against radiation-induced mitochondrial changes, but these effects are not sufficient against long-term alterations in cardiac function or remodeling.
Mimic, Branko; Ilic, Slobodan; Vulicevic, Irena; Milovanovic, Vladimir; Tomic, Danijela; Mimic, Ana; Stankovic, Sanja; Zecevic, Tatjana; Davies, Ben; Djordjevic, Miroslav
2016-01-01
OBJECTIVES This study investigates the effects of high glucose content on patients undergoing cold crystalloid versus cold blood cardioplegia in terms of early clinical results, functional myocardial recovery and ischaemia–reperfusion injury in patients undergoing repair of acyanotic cardiac lesions. METHODS Patients were randomly assigned to receive either crystalloid (n = 31) or blood cardioplegia (n = 31). Early clinical results were assessed. Changes in left ventricular fractional shortening, arterial blood lactate levels, central venous saturation, cardiac Troponin I release and blood glucose concentration were measured during the first 24 h after ischaemia. RESULTS There was no significant difference in clinical outcomes and postoperative complication rates between groups. The postoperative changes in left ventricular function, lactate levels, central venous saturation and Troponin I were not significantly different between groups. The use of crystalloid cardioplegia was associated with significant increases in serum glucose compared with blood cardioplegia. CONCLUSIONS A high glucose content blood cardioplegia does not show any advantage compared with crystalloid cardioplegia in terms of clinical outcomes, functional recovery and the degree of ischaemic injury in infants and children undergoing repair of acyanotic heart lesions. High glucose concentration of the cardioplegic solution might potentiate ischaemia–reperfusion injury and diminish the beneficial effects of blood cardioplegia. PMID:26831677
Nazem, Shima; Rabiee, Farzaneh; Ghaedi, Kamran; Babashah, Sadegh; Sadeghizadeh, Majid; Nasr-Esfahani, Mohammad Hossein
2018-06-01
Fibronectin type III domain-containing 5 protein (Fndc5) is a glycosylated protein with elevated expression in high energy demanded tissues as heart, brain, and muscle. It has been shown that upregulation of Fndc5 is regulated by peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α), which is known as a master regulator of mitochondrial function and biogenesis. Also, our group indicated that Fndc5 expression increases gradually during cardiac differentiation of mouse embryonic stem cells (mESCs). In this paper, to clarify the importance of Fndc5 in cardiac differentiation, we south to knock down Fndc5 expression by generation a stably transduced mESC line that derives the expression of a short hairpin RNA (shRNA) against Fndc5 gene following doxycycline (Dox) induction. Knock-down of Fndc5 demonstrated a considerable decrease in expression of cardiac progenitor and cardiomyocyte markers. Considering the fact that mitochondria play a crucial role in cardiac differentiation of ESCs, we investigated the role of Fndc5, as a downstream target of PGC1-α, on mitochondrial indices. Results showed that expression of nuclear encoded mitochondrial genes including PGC1-α, Atp5b, Ndufb5, and SOD2 significantly decreased. Moreover, mitochondrial membrane potential (ΔΨm) and relative ATP content of cardiomyocytes decreased markedly with relative ROS level increase. Together, our results suggest that Fndc5 attenuates process of cardiac differentiation of mESCs which is associated with modulation of mitochondrial function and gene expression. © 2017 Wiley Periodicals, Inc.
Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs
2017-10-01
Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.
Haji Mohd Yasin, Nur A B; Herbison, Peter; Saxena, Pankaj; Praporski, Slavica; Konstantinov, Igor E
2014-01-01
Remote ischemic preconditioning (RIPC) appears to protect distant organs from ischemia-reperfusion injury. We undertook meta-analysis of clinical studies to evaluate the effects of RIPC on organ protection and clinical outcomes in patients undergoing cardiac surgery. A review of evidence for cardiac, renal, and pulmonary protection after RIPC was performed. We also did meta-regressions on RIPC variables, such as duration of ischemia, cuff pressure, and timing of application of preconditioning. Secondary outcomes included length of hospital and intensive care unit stay, duration of mechanical ventilation, and mortality at 30 days. Randomized control trials (n = 25) were included in the study for quantitative analysis of cardiac (n = 16), renal (n = 6), and pulmonary (n = 3) protection. RIPC provided statistically significant cardiac protection (standardized mean difference [SMD], -0.77; 95% confidence interval [CI], -1.15, -0.39; Z = 3.98; P < 0.0001) and on subgroup analysis, the protective effect remained consistent for all types of cardiac surgical procedures. However, there was no evidence of renal protection (SMD, 0.74; 95% CI, 0.53, 1.02; Z = 1.81; P = 0.07) or pulmonary protection (SMD, -0.03; 95% CI, -0.56, 0.50; Z = 0.12; P = 0.91). There was no statistical difference in the short-term clinical outcomes between the RIPC and control groups. RIPC provides cardiac protection, but there is no evidence of renal or pulmonary protection in patients undergoing cardiac surgery using cardiopulmonary bypass. Larger multicenter trials are required to define the role of RIPC in surgical practice. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.
Shaefi, Shahzad; Mittel, Aaron; Loberman, Dan; Ramakrishna, Harish
2018-04-04
Surgical coronary artery bypass grafting (CABG) is the standard of care for revascularization of left main or three-vessel coronary artery disease. The off-pump coronary artery bypass graft (OPCAB) procedure avoids the use of cardiopulmonary bypass. Theoretically, OPCAB may improve long-term outcomes by reducing the rates of perioperative myocardial injury, stroke, neurocognitive impairment, and cardiac-related mortality. Several high-quality clinical trials have been conducted since OPCAB became popular in the 1990s and have demonstrated no benefit of OPCAB over traditional CABG with respect to these outcomes despite favorable short-term reductions in transfusion requirements and other postoperative complications. Ultimately, OPCAB is associated with less effective myocardial revascularization and does not entirely prevent complications traditionally associated with cardiopulmonary bypass. This article reviews major high-quality trials of OPCAB versus traditional CABG with respect to both short- and long-term clinical outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.
Skuta, G; Fischer, G M; Janaky, T; Kele, Z; Szabo, P; Tozser, J; Sumegi, B
1999-12-15
The short-term cardiac side effects of 2',3'-dideoxycytidine (ddC, zalcitabine) were studied in rats in order to understand the biochemical events contributing to the development of ddC-induced cardiomyopathy. In developing animals, ddC treatment provoked a surprisingly rapid appearance of cardiac malfunctions characterized by prolonged RR, PR, and QT intervals and J point depression. The energy metabolism in the heart was compromised, characterized by a decreased creatine phosphate/creatine ratio (from 2.05 normal value to 0.75) and a decreased free ATP/ADP ratio (from 332 normal value to 121). The activity of respiratory complexes (NADH: cytochrome c oxidoreductase and cytochrome oxidase) also decreased significantly. Southern blot and polymerase chain reaction analysis did not show deletions or a decrease in the quantity of mitochondrial DNA (mtDNA) deriving from ddC-treated rat hearts, indicating that under our experimental conditions, ddC-induced heart abnormalities were not the direct consequence of mtDNA-related damage. The ddC treatment of rats significantly increased the formation of reactive oxygen species (ROS) in heart and skeletal muscle as determined by the oxidation of non-fluorescent dihydrorhodamine123 to fluorescent rhodamine123 and the oxidation of cellular proteins determined from protein carbonyl content. An activation of the nuclear poly-(ADP-ribose) polymerase (EC 2.4.2.30) and an increase in the mono-ADP-ribosylation of glucose-regulated protein and desmin were observed in the cardiac tissue from ddC-treated animals. A decrease in the quantity of heat shock protein (HSP)70s was also detected, while the level of HSP25 and HSP60 remained unchanged. Surprisingly, ddC treatment induced a skeletal muscle-specific decrease in the quantity of three proteins, one of which was identified by N-terminal sequencing as myoglobin, and another by tandem mass spectrometer sequencing as triosephosphate isomerase (EC 5.3.1.1). These data show that the short term cardiotoxicity of ddC is partially based on ROS-mediated signalling through poly- and mono-ADP-ribosylation reactions and depression of HSP70 levels, whose processes represent a new mtDNA independent mechanism for ddC-induced cell damage.
Shu, Janet; Lo, Stephen; Phillips, Margot; Sun, Fangui; Seldin, David C; Berenbaum, Isidore; Berk, John L; Sanchorawala, Vaishali
2016-09-01
Our study examines depression and anxiety in patients with immunoglobulin light chain (AL) amyloidosis, and determines the associations between the mental health problems and patient characteristics (age, gender, race, marital status, alcohol consumption, smoking status and cardiac involvement). Patients with AL amyloidosis who completed the 36-item Short Form General Health Survey (SF-36) during initial evaluation at a single center were studied. The SF-36 included assessments of depression, anxiety, role limitation due to emotional problems and the mental health subscale score. From 1226 patients with AL amyloidosis, 37.0% reported depression and 46.7% reported anxiety. Patients with cardiac amyloidosis reported more anxiety (odds ratio (OR) = 1.29, 95% confidence interval (CI) 1.03-1.61) and role limitation due to emotional problems (OR = 1.32, 95%CI 1.05-1.65). No significant association between cardiac involvement and depression was found (OR = 1.22, 95%CI 0.97-1.54). Men reported less anxiety (OR = 0.72, 95%CI 0.57-0.91). Patients ≥65 years experienced greater role limitation (OR = 1.36, 95%CI 1.08-1.71). Smokers (p = 0.019) and women (p = 0.006) scored lower on mental health subscales. Many patients with AL amyloidosis suffer from depression, anxiety and functional limitations. Psychiatric assessment and treatment is important, and further research is needed to clarify the long-term effects of depression and anxiety in AL amyloidosis. This current study was registered in ClinicalTrials.gov as NCT00898235.
Cardiac rehabilitation after myocardial infarction.
Contractor, Aashish S
2011-12-01
Cardiac rehabilitation/secondary prevention programs are recognized as integral to the comprehensive care of patients with coronary heart disease (CHD), and as such are recommended as useful and effective (Class I) by the American Heart Association and the American College of Cardiology in the treatment of patients with CHD. The term cardiac rehabilitation refers to coordinated, multifaceted interventions designed to optimize a cardiac patient's physical, psychological, and social functioning, in addition to stabilizing, slowing, or even reversing the progression of the underlying atherosclerotic processes, thereby reducing morbidity and mortality. Cardiac rehabilitation, aims at returning the patient back to normal functioning in a safe and effective manner and to enhance the psychosocial and vocational state of the patient. The program involves education, exercise, risk factor modification and counselling. A meta-analysis based on a review of 48 randomized trials that compared outcomes of exercise-based rehabilitation with usual medical care, showed a reduction of 20% in total mortality and 26% in cardiac mortality rates, with exercise-based rehabilitation compared with usual medical care. Risk stratification helps identify patients who are at increased risk for exercise-related cardiovascular events and who may require more intensive cardiac monitoring in addition to the medical supervision provided for all cardiac rehabilitation program participants. During exercise, the patients' ECG is continuously monitored through telemetry, which serves to optimize the exercise prescription and enhance safety. The safety of cardiac rehabilitation exercise programs is well established, and the occurrence of major cardiovascular events during supervised exercise is extremely low. As hospital stays decrease, cardiac rehabilitation is assuming an increasingly important role in secondary prevention. In contrast with its growing importance internationally, there are very few cardiac rehabilitation centers in India at the present moment.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Applefeld, M.M.; Slawson, R.G.; Spicer, K.M.
1982-04-01
The long-term cardiac effects of anterior-weighted thoracic mantle field radiotherapy were assessed in 25 patients treated for Hodgkin's disease. These patients underwent an evaluation that included a careful history and physical examination, ECG, M-mode echocardiogram, exercise ECG-gated radionuclide ventriculography, and cardiac catheterization. In these 25 patients evaluated 37-144 months (median, 96) after completion of thoracic mantle radiotherapy, eight had constrictive pericarditis; eight had occult constrictive pericarditis; three had an abnormal response to fluid challenge; three had suspected or proven occlusive coronary artery disease; and one each had a cardiomyopathy and diminished functional capacity on exercise testing. Only one patient appearsmore » to be normal after evaluation. The clinical spectrum of delayed-appearing radiation-induced cardiac disease in patients treated by anterior-weighted thoracic mantle fields and our suggestions for its treatment are discussed.« less
Functional optical coherence tomography for live dynamic analysis of mouse embryonic cardiogenesis
NASA Astrophysics Data System (ADS)
Wang, Shang; Lopez, Andrew L.; Larina, Irina V.
2018-02-01
Blood flow, heart contraction, and tissue stiffness are important regulators of cardiac morphogenesis and function during embryonic development. Defining how these factors are integrated is critically important to advance prevention, diagnostics, and treatment of congenital heart defects. Mammalian embryonic development is taking place deep within the female body, which makes cardiodynamic imaging and analysis during early developmental stages in humans inaccessible. With thousands of mutant lines available and well-established genetic manipulation tools, mouse is a great model to understand how biomechanical factors are integrated with molecular pathways to regulate cardiac function and development. Dynamic imaging and quantitative analysis of the biomechanics of live mouse embryos have become increasingly important, which demands continuous advancements in imaging techniques and live assessment approaches. This has been one of the major drives to keep pushing the frontier of embryonic imaging for better resolution, higher speed, deeper penetration, and more diverse and effective contrasts. Optical coherence tomography (OCT) has played a significant role in addressing such demands, and its features in non-labeling imaging, 3D capability, a large working distance, and various functional derivatives allow OCT to cover a number of specific applications in embryonic imaging. Recently, our group has made several technical improvements in using OCT to probe the biomechanical aspects of live developing mouse embryos at early stages. These include the direct volumetric structural and functional imaging of the cardiodynamics, four-dimensional quantitative Doppler imaging and analysis of the cardiac blood flow, and fourdimensional blood flow separation from the cardiac wall tissue in the beating embryonic heart. Here, we present a short review of these studies together with brief descriptions of the previous work that demonstrate OCT as a valuable and useful imaging tool for the research in developmental cardiology.
Ardell, Jeffrey L.; Shivkumar, Kalyanam; Armour, J. Andrew
2017-01-01
The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as ‘free-floating’ in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease. PMID:28692680
ERIC Educational Resources Information Center
Staiano, Amanda E.; Abraham, Anisha A.; Calvert, Sandra L.
2012-01-01
Exergames are videogames that require gross motor activity, thereby combining gaming with physical activity. This study examined the role of competitive versus cooperative exergame play on short-term changes in executive function skills, following a 10-week exergame training intervention. Fifty-four low-income overweight and obese African American…
Hedley, Jeffrey S; Al Mheid, Ibhar; Alikhani, Zoubin; Pernetz, Maria A; Kim, Jonathan H
2017-08-01
Arrhythmogenic right ventricular cardiomyopathy, a genetically inherited disease that results in fibrofatty replacement of normal cardiac myocytes, has been associated with sudden cardiac death in athletes. Long-term participation in endurance exercise hastens the development of both the arrhythmic and structural arrhythmogenic right ventricular cardiomyopathy phenotypes. We describe the unusual case of a 34-year-old, symptomatic, female endurance athlete who had arrhythmogenic right ventricular cardiomyopathy in the presence of a structurally normal right ventricle. Clinicians should be aware of this infrequent presentation when evaluating athletic patients who have ventricular arrhythmias and normal findings on cardiac imaging studies.
Reparative resynchronization in ischemic heart failure: an emerging strategy.
Yamada, Satsuki; Terzic, Andre
2014-08-01
Cardiac dyssynchrony refers to disparity in cardiac wall motion, a serious consequence of myocardial infarction associated with poor outcome. Infarct-induced scar is refractory to device-based cardiac resynchronization therapy, which relies on viable tissue. Leveraging the prospect of structural and functional regeneration, reparative resynchronization has emerged as a potentially achievable strategy. In proof-of-concept studies, stem-cell therapy eliminates contractile deficit originating from infarcted regions and secures long-term synchronization with tissue repair. Limited clinical experience suggests benefit of cell interventions in acute and chronic ischemic heart disease as adjuvant to standard of care. A regenerative resynchronization option for dyssynchronous heart failure thus merits validation.
Differential cardiac effects in rats exposed to atmospheric ...
The results of this study demonstrate that atmospheric smog generated from both isoprene and toluene cause cardiac effects in rats. In addition, it appears that smog from toluene is more toxic in terms of cardiac arrhythmogenicity. Smog, which is a complex mixture of particulate matter and gaseous irritants (ozone, sulfur dioxide, reactive aldehydes), as well as components which react with sunlight to form secondary pollutants, has recently been linked to increased risk of adverse cardiac responses. The components, and therefore health effects, of atmospheric smog are determined by the fuel used to generate them. In this study we examined the difference between isoprene- and toluene-generated smog in causing cardiac effects in rats and hypothesized that both atmospheres would cause cardiac electrical and functional changes in rats. Male Wistar-Kyoto rats were exposed to either atmospheric smog generated by the USEPA’s mobile reaction chamber using either isoprene or toluene, or filtered air for four hours. One day later, rats were anesthetized and left ventricular functional responses to dobutamine were measured using a Millar probe and arrhythmia sensitivity to aconitine. Baseline left ventricular pressure (LVP) was lower in toluene-exposed animals but not isoprene when compared to air. Increases in LVP with increasing doses of dobutamine were impaired only in toluene-exposed rats. Both isoprene and toluene impaired the rate of ventri
A minimal-contact intervention for cardiac inpatients: long-term effects on smoking cessation.
Bolman, Catherine; de Vries, Hein; van Breukelen, Gerard
2002-08-01
This study examined the 1-year effects of a minimal-contact smoking cessation intervention for cardiac inpatients. The multicenter study included cardiac inpatients who had smoked prior to hospitalization. A pretest-posttest quasi-experimental design was used. Patients' experimental condition depended on the hospital they were assigned to. The design was partially randomized: 4 of the 11 hospitals selected the experimental condition themselves (2 experimental, 2 control), while the remaining 7 hospitals were randomly assigned. The experimental group consisted of patients of 5 hospitals (N = 388). Patients of 6 other hospitals served as the control group (N = 401). The intervention included stop-smoking advice by the cardiologist, brief counseling by the nurse, the provision of self-help materials, and aftercare by the cardiologist. Logistic regression analyses controlling for baseline differences and covariates did not show significant intervention effects on point prevalence and continuous abstinence. The study also showed that the outcomes were not significantly related to the way hospitals were assigned to the experimental condition. While short-term effects were found, the minimal-contact intervention did not result in significant effects after 12 months, at least if patients lost to follow-up were treated as posttest smokers. Efforts should be made to improve the intervention, especially the aftercare.
Potential clinical relevance of the 'little brain' on the mammalian heart.
Armour, J A
2008-02-01
It is hypothesized that the heart possesses a nervous system intrinsic to it that represents the final relay station for the co-ordination of regional cardiac indices. This 'little brain' on the heart is comprised of spatially distributed sensory (afferent), interconnecting (local circuit) and motor (adrenergic and cholinergic efferent) neurones that communicate with others in intrathoracic extracardiac ganglia, all under the tonic influence of central neuronal command and circulating catecholamines. Neurones residing from the level of the heart to the insular cortex form temporally dependent reflexes that control overlapping, spatially determined cardiac indices. The emergent properties that most of its components display depend primarily on sensory transduction of the cardiovascular milieu. It is further hypothesized that the stochastic nature of such neuronal interactions represents a stabilizing feature that matches cardiac output to normal corporal blood flow demands. Thus, with regard to cardiac disease states, one must consider not only cardiac myocyte dysfunction but also the fact that components within this neuroaxis may interact abnormally to alter myocyte function. This review emphasizes the stochastic behaviour displayed by most peripheral cardiac neurones, which appears to be a consequence of their predominant cardiac chemosensory inputs, as well as their complex functional interconnectivity. Despite our limited understanding of the whole, current data indicate that the emergent properties displayed by most neurones comprising the cardiac neuroaxis will have to be taken into consideration when contemplating the targeting of its individual components if predictable, long-term therapeutic benefits are to accrue.
Mlakar, Polona; Salobir, Barbara; Cobo, Nusret; Jug, Borut; Terčelj, Marjeta; Sabovič, Mišo
2014-03-01
High-sensitivity C-reactive protein (hsCRP) is an important biomarker of risk for coronary heart disease morbidity and mortality. We investigated the influence of short-term cardiac rehabilitation (CR) after acute myocardial infarction (AMI) on values of hsCRP and classical risk factors, including metabolic syndrome. hsCRP and classical risk factors were measured before and after completed 2-week CR program in 30 men after AMI. The comparison group comprised 30 age-balanced healthy men, with no risk factors for coronary heart disease. As expected, in comparison to healthy individuals, patients had higher values of hsCRP; furthermore, smokers had significantly higher hsCRP values than nonsmokers. Patients had more expressed markers of metabolic syndrome and due to pharmacological therapy lower blood pressure, total cholesterol and low-density lipoprotein cholesterol (LDL-C). After CR was completed, a significant drop in hsCRP (P=0.006) and improvement of metabolic syndrome parameters (lower body mass index, blood pressure, LDL-C, triglycerides) was observed in nonsmokers, whereas no such changes occurred in smokers. Our study revealed that hsCRP and metabolic syndrome parameters can be substantially reduced by a 2-week CR program; however, this effect is present only in nonsmokers. Thus, all patients entering the CR program after AMI should be advised to quit smoking before entering the program to achieve optimal benefits.
Dahlquist, Marcus; Raza, Auriba; Bero-Bedada, Getahun; Hollenberg, Jacob; Lind, Tomas; Orsini, Nicola; Sjögren, Bengt; Svensson, Leif; Ljungman, Petter L
2016-07-01
Associations have been reported between daily ambient temperature and all-cause and cardiovascular mortality. However, the potential harmful effect of temperature on out-of-hospital cardiac arrest (OHCA) is insufficiently studied. The objective of this study was to investigate the short-term association between ambient temperature and the occurrence of OHCA. In 5961 cases of OHCAs treated by Emergency Medical Service occurring in Stockholm County we investigated the association between the preceding 24-h and 1h mean ambient temperature, obtained from a fixed monitoring station, and OHCA using a time-stratified case-crossover design. We observed a V-shaped relationship between preceding mean 24-h and 1-h ambient temperature and the occurrence of OHCAs. For mean 24-h temperature we observed an odds ratio (OR) of 1.05 (1.00-1.11) for each 5°C below the optimum temperature and 1.05 (0.96-1.18) for each 5°C above the optimum. We observed similar results for 1-h mean temperature exposure. Results for temperatures above the optimum temperature showed evidence of confounding by ozone. Ambient temperature below an optimum temperature was associated with increased risk of OHCA in Stockholm. Temperature above an optimum temperature was not significantly associated with OHCA. Copyright © 2016 Elsevier GmbH. All rights reserved.
Fatalism and short-termism as cultural barriers to cardiac rehabilitation among underprivileged men.
Savage, Mathieu; Dumas, Alex; Stuart, Stephen A
2013-11-01
Cardiovascular diseases are a leading cause of death and disability in Canada, and individuals of low socioeconomic status appear particularly vulnerable to such disorders. Although many health-related institutions have promoted cardiovascular health and have created cardiac rehabilitation programmes, they have not attained their desired outcomes, especially amongst socioeconomically deprived men. Drawing on Pierre Bourdieu's sociocultural theory, this qualitative study aims to understand the social mechanisms underpinning the lifestyles and health practices of men who had suffered a cardiovascular incident requiring hospitalisation. In all, 20 interviews were conducted with francophone men aged 40 to 65 years living in the province of Québec, Canada. The analysis strongly suggests that the respondents' living conditions and disease were significant obstacles to their adoption of a healthy lifestyle. Their despair and pessimism, apparently originating in the harshness of their financial realities, physical limitations and social networks, led them to believe that they could do little to control their lives, thereby limiting the fulfillment of any long-term ambitions. Therefore, the adoption of a habitus characterised by fatalistic and short-term perceptions of health influenced their lifestyle choices, leading them to maintain lives that were in stark contrast with the recommendations made by health promotion experts. © 2013 The Authors. Sociology of Health & Illness © 2013 Foundation for the Sociology of Health & Illness/John Wiley & Sons Ltd.
NASA Astrophysics Data System (ADS)
Hong, Inki; Cho, Sanghee; Michel, Christian J.; Casey, Michael E.; Schaefferkoetter, Joshua D.
2014-09-01
A new data handling method is presented for improving the image noise distribution and reducing bias when reconstructing very short frames from low count dynamic PET acquisition. The new method termed ‘Complementary Frame Reconstruction’ (CFR) involves the indirect formation of a count-limited emission image in a short frame through subtraction of two frames with longer acquisition time, where the short time frame data is excluded from the second long frame data before the reconstruction. This approach can be regarded as an alternative to the AML algorithm recently proposed by Nuyts et al, as a method to reduce the bias for the maximum likelihood expectation maximization (MLEM) reconstruction of count limited data. CFR uses long scan emission data to stabilize the reconstruction and avoids modification of algorithms such as MLEM. The subtraction between two long frame images, naturally allows negative voxel values and significantly reduces bias introduced in the final image. Simulations based on phantom and clinical data were used to evaluate the accuracy of the reconstructed images to represent the true activity distribution. Applicability to determine the arterial input function in human and small animal studies is also explored. In situations with limited count rate, e.g. pediatric applications, gated abdominal, cardiac studies, etc., or when using limited doses of short-lived isotopes such as 15O-water, the proposed method will likely be preferred over independent frame reconstruction to address bias and noise issues.
Bianchi, Maria Otilia; Cheung, Po-Yin; Phillipos, Ernest; Aranha-Netto, Abimael; Joynt, Chloe
2015-08-01
Despite the advancement in the postoperative care of neonates with congenital heart disease (CHD), there is little information on preoperative management of systemic and regional hemodynamics, which may be related to outcomes. We aimed to determine the preoperative effect of milrinone, a phosphodiesterase III inhibitor, on cardiac output and splanchnic and cerebral perfusion in neonates with CHD. Neonates with CHD requiring cardiac surgery were enrolled in a prospective, single-blinded study once a clinical decision of starting milrinone (0.75 μg/kg per minute intravenously) using institutional criteria was made. Demographic and clinical variables and outcomes were recorded. Combined cardiac output and measures of splanchnic (superior mesenteric and celiac arteries) and cerebral (anterior and middle cerebral arteries) perfusion were determined by Doppler studies at 0, 6, 24, and 48 h after milrinone infusion. Investigators were unaware of intervention time points and patients in analyzing blood flow measurements. Seventeen term (39.2 ± 1.3 weeks) neonates were included with hypoplastic left-sided heart syndrome (78.5%) as the most common diagnosis. Combined cardiac output increased by 28% within 48 h (613 ± 154 vs. 479 ± 147 mL/kg per minute at baseline, P < 0.05). Superior mesenteric artery mean velocity increased at 6 h and throughout 48 h of milrinone infusion (P < 0.05). Peak and mean velocities at cerebral arteries increased with milrinone infusion (P < 0.05~0.08), and the corresponding changes at celiac artery were modest. There were no significant changes in splanchnic and cerebral resistive and pulsatility indices during milrinone infusion. Milrinone increases cardiac output with concurrent effects on splanchnic and cerebral blood flows during the short-term preoperative use in neonates with CHD.
Suzuki, Hideaki; Arakawa, Yasuhiro; Ito, Masaki; Yamada, Hisashi; Horiguchi-Yamada, Junko
2006-01-01
To elucidate the molecular pathogenesis behind increased levels of laminin in cardiac muscle cells in cardiomyopathy by using a yeast hybrid screen. The present study reports the cloning of a newly identified heart-specific troponin I isoform, which is putatively linked to laminin. Future studies will explore the functional significance of this connection. Yeast two-hybrid screen analysis was performed using MLF1-interacting protein (amino acids 1 to 318) as bait. The human heart complementary DNA library was screened by using the yeast-mating method for overnight culture. Two final positive clones from the heart library were isolated. These two clones encoded the same protein, a short isoform of human cardiac troponin I (TnI) that lacked TnI exons 5 and 6. The TnI isoform has a heart-specific expression pattern and it shares several sequence features with human cardiac TnI; however, it lacks the troponin T binding portion. The heart-specific segment of the human cardiac TnI isoform shares several sequence features with human cardiac TnI, but it lacks the troponin T binding portion. These results suggest that the heart-specific TnI isoform may be involved in cardiac development and disease.
Suzuki, Hideaki; Arakawa, Yasuhiro; Ito, Masaki; Yamada, Hisashi; Horiguchi-Yamada, Junko
2006-01-01
OBJECTIVE To elucidate the molecular pathogenesis behind increased levels of laminin in cardiac muscle cells in cardiomyopathy by using a yeast hybrid screen. The present study reports the cloning of a newly identified heart-specific troponin I isoform, which is putatively linked to laminin. Future studies will explore the functional significance of this connection. METHODS Yeast two-hybrid screen analysis was performed using MLF1-interacting protein (amino acids 1 to 318) as bait. The human heart complementary DNA library was screened by using the yeast-mating method for overnight culture. RESULTS Two final positive clones from the heart library were isolated. These two clones encoded the same protein, a short isoform of human cardiac troponin I (TnI) that lacked TnI exons 5 and 6. The TnI isoform has a heart-specific expression pattern and it shares several sequence features with human cardiac TnI; however, it lacks the troponin T binding portion. CONCLUSION The heart-specific segment of the human cardiac TnI isoform shares several sequence features with human cardiac TnI, but it lacks the troponin T binding portion. These results suggest that the heart-specific TnI isoform may be involved in cardiac development and disease. PMID:18651010
Sørhus, Elin; Incardona, John P.; Karlsen, Ørjan; Linbo, Tiffany; Sørensen, Lisbet; Nordtug, Trond; van der Meeren, Terje; Thorsen, Anders; Thorbjørnsen, Maja; Jentoft, Sissel; Edvardsen, Rolf B.; Meier, Sonnich
2016-01-01
Recent studies have shown that crude oil exposure affects cardiac development in fish by disrupting excitation-contraction (EC) coupling. We previously found that eggs of Atlantic haddock (Melanogrammus aeglefinus) bind dispersed oil droplets, potentially leading to more profound toxic effects from uptake of polycyclic aromatic hydrocarbons (PAHs). Using lower concentrations of dispersed crude oil (0.7–7 μg/L ∑PAH), here we exposed a broader range of developmental stages over both short and prolonged durations. We quantified effects on cardiac function and morphogenesis, characterized novel craniofacial defects, and examined the expression of genes encoding potential targets underlying cardiac and craniofacial defects. Because of oil droplet binding, a 24-hr exposure was sufficient to create severe cardiac and craniofacial abnormalities. The specific nature of the craniofacial abnormalities suggests that crude oil may target common craniofacial and cardiac precursor cells either directly or indirectly by affecting ion channels and intracellular calcium in particular. Furthermore, down-regulation of genes encoding specific components of the EC coupling machinery suggests that crude oil disrupts excitation-transcription coupling or normal feedback regulation of ion channels blocked by PAHs. These data support a unifying hypothesis whereby depletion of intracellular calcium pools by crude oil-derived PAHs disrupts several pathways critical for organogenesis in fish. PMID:27506155
Pleger, Sven T.; Shan, Changguang; Ksienzyk, Jan; Bekeredjian, Raffi; Boekstegers, Peter; Hinkel, Rabea; Schinkel, Stefanie; Leuchs, Barbara; Ludwig, Jochen; Qiu, Gang; Weber, Christophe; Kleinschmidt, Jürgen A.; Raake, Philip; Koch, Walter J.; Katus, Hugo A.; Müller, Oliver J.; Most, Patrick
2014-01-01
As a prerequisite to clinical application, we determined the long-term therapeutic effectiveness and safety of adeno-associated viral (AAV) S100A1 gene therapy in a preclinical, large animal model of heart failure. S100A1, a positive inotropic regulator of myocardial contractility, becomes depleted in failing cardiomyocytes in humans and various animal models, and myocardial-targeted S100A1 gene transfer rescues cardiac contractile function by restoring sarcoplasmic reticulum calcium Ca2+ handling in acutely and chronically failing hearts in small animal models. We induced heart failure in domestic pigs by balloon-occlusion of the left circumflex coronary artery, resulting in myocardial infarction. After 2 weeks, when the pigs displayed significant left ventricular contractile dysfunction, we administered through retrograde coronary venous delivery, AAV9-S100A1 to the left ventricular non-infarcted myocardium. AAV9-luciferase and saline treatment served as control. At 14 weeks, both control groups showed significantly decreased myocardial S100A1 protein expression along with progressive deterioration of cardiac performance and left ventricular remodeling. AAV9-S100A1 treatment prevented and reversed this phenotype by restoring cardiac S100A1 protein levels. S100A1 treatment normalized cardiomyocyte Ca2+ cycling, sarcoplasmic reticulum calcium handling and energy homeostasis. Transgene expression was restricted to cardiac tissue and extra-cardiac organ function was uncompromised indicating a favorable safety profile. This translational study shows the pre-clinical feasibility, long-term therapeutic effectiveness and a favorable safety profile of cardiac AAV9-S100A1 gene therapy in a preclinical model of heart failure. Our study presents a strong rational for a clinical trial of S100A1 gene therapy for human heart failure that could potentially complement current strategies to treat end-stage heart failure. PMID:21775667
Rababa'h, Abeer M; Alzoubi, Karem H; Atmeh, Ala'a
2018-06-01
Impairment of learning and memory has been associated with accumulation of reactive oxygen species in the body. It has also been found that antioxidants enhance learning and memory. Levosimendan is a cardiac inotropic and vasodilator agent that has pleotropic effects including antioxidant, anti-inflammatory, and smooth muscle vasodilatory actions. In this study, we investigated the effect of levosimendan on learning and memory in rats. Levosimendan (12 µg/kg, intraperitoneally) or vehicle was administered once a week for 8 weeks. The radial arm water maze was used to assess spatial learning and memory. In addition, hippocampus levels of antioxidant biomarkers/enzyme - reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase, superoxide dismutase, catalase, and thiobarbituric acid reactive substance - were assessed. Levosimendan significantly enhanced short-term (30 min) and long-term (5 h) memory. Levosimendan also significantly increased levels of glutathione peroxidase and GSH and decreased thiobarbituric acid reactive substance. There were no significant effects on the level of other oxidative stress biomarkers. In conclusion, levosimendan enhanced short-term and long-term memory by potentiating antioxidant defense mechanism in the hippocampus.
DiBona, G F; Sawin, L L
1999-07-06
Long-term metoprolol therapy improves cardiac performance and decreases mortality in patients with chronic congestive heart failure (CHF). This study examined the effect of long-term metoprolol therapy on renal sodium handling in an experimental rat model of CHF. Rats with left coronary ligation and myocardial infarction-induced CHF were treated with metoprolol (1.5 mg. kg-1. h-1) or vehicle for 3 weeks by osmotic minipump. They were then evaluated for their ability to excrete a short-term sodium load (5% body weight isotonic saline infusion over 30 minutes) and a long-term sodium load (change from low- to high-sodium diet over 8 days). All CHF rats had left ventricular end-diastolic pressure >10 mm Hg, and heart weight/body weight ratios averaged 0.68+/-0.02% (versus control of approximately 0.40%). Compared with vehicle CHF rats (n=19), metoprolol CHF rats (n=18) had lower basal values of mean arterial pressure (122+/-3 versus 112+/-3 mm Hg) and heart rate (373+/-14 versus 315+/-9 bpm) and decreased heart rate responses to intravenous doses of isoproterenol. During short-term isotonic saline volume loading, metoprolol CHF rats excreted 54+/-4% more of the sodium load than vehicle CHF rats. During long-term dietary sodium loading, metoprolol CHF rats retained 28+/-3% less sodium than vehicle CHF rats. Metoprolol treatment of rats with CHF results in an improved ability to excrete both short- and long-term sodium loads.
The Effect of Blood Transfusion on Outcomes in Aortic Surgery.
Velasquez, Camilo A; Singh, Mrinal; Bin Mahmood, Syed Usman; Brownstein, Adam J; Zafar, Mohammad A; Saeyeldin, Ayman; Ziganshin, Bulat A; Elefteriades, John A
2017-09-01
The use of blood transfusion in cardiac surgery varies widely. The beneficial effects of blood products are offset by an increase in morbidity and mortality. Despite multiple studies showing an association between blood product exposure and adverse short- and long-term events, it is difficult to determine causality. Nevertheless, the implication is sufficient to warrant the search for alternative strategies to reduce the use of blood products while providing a standard of care that optimizes postoperative outcomes. Aortic surgery, in particular, is associated with an increased risk of bleeding requiring a blood transfusion. There is a paucity of evidence within aortic surgery regarding the deleterious effects of blood products. Here, we review the current evidence regarding patient outcomes after blood transfusion in cardiac surgery, with special emphasis on aortic surgery.
Topical minoxidil: cardiac effects in bald man.
Leenen, F H; Smith, D L; Unger, W P
1988-01-01
Systemic cardiovascular effects during chronic treatment with topical minoxidil vs placebo were evaluated using a double-blind, randomized design for two parallel groups (n = 20 for minoxidil, n = 15 for placebo). During 6 months of follow-up, blood pressure did not change, whereas minoxidil increased heart rate by 3-5 beats min-1. Compared with placebo, topical minoxidil caused significant increases in LV end-diastolic volume, in cardiac output (by 0.751 min-1) and in LV mass (by 5 g m-2). We conclude that in healthy subjects short-term use of topical minoxidil is likely not to be detrimental. However, safety needs to be established regarding ischaemic symptoms in patients with coronary artery disease as well as for the possible development of LV hypertrophy in healthy subjects during years of therapy. PMID:3191000
CardioNet: a human metabolic network suited for the study of cardiomyocyte metabolism.
Karlstädt, Anja; Fliegner, Daniela; Kararigas, Georgios; Ruderisch, Hugo Sanchez; Regitz-Zagrosek, Vera; Holzhütter, Hermann-Georg
2012-08-29
Availability of oxygen and nutrients in the coronary circulation is a crucial determinant of cardiac performance. Nutrient composition of coronary blood may significantly vary in specific physiological and pathological conditions, for example, administration of special diets, long-term starvation, physical exercise or diabetes. Quantitative analysis of cardiac metabolism from a systems biology perspective may help to a better understanding of the relationship between nutrient supply and efficiency of metabolic processes required for an adequate cardiac output. Here we present CardioNet, the first large-scale reconstruction of the metabolic network of the human cardiomyocyte comprising 1793 metabolic reactions, including 560 transport processes in six compartments. We use flux-balance analysis to demonstrate the capability of the network to accomplish a set of 368 metabolic functions required for maintaining the structural and functional integrity of the cell. Taking the maintenance of ATP, biosynthesis of ceramide, cardiolipin and further important phospholipids as examples, we analyse how a changed supply of glucose, lactate, fatty acids and ketone bodies may influence the efficiency of these essential processes. CardioNet is a functionally validated metabolic network of the human cardiomyocyte that enables theorectical studies of cellular metabolic processes crucial for the accomplishment of an adequate cardiac output.
Potluri, Phani R; Chamoun, Jean; Cooke, James A; Badr, Myriam; Guse, Joanna A; Rayes, Roni; Cordina, Nicole M; McCamey, Dane; Fajer, Piotr G; Brown, Louise J
2017-12-01
The absence of a crystal structure of the calcium free state of the cardiac isoform of the troponin complex has hindered our understanding of how the simple binding of Ca 2+ triggers conformational changes in troponin which are then propagated to enable muscle contraction. Here we have used continuous wave (CW) and Double Electron-Electron Resonance (DEER) pulsed EPR spectroscopy to measure distances between TnI and TnC to track the movement of the functionally important regulatory 'switch' region of cardiac Tn. Spin labels were placed on the switch region of Troponin I and distances measured to Troponin C. Under conditions of high Ca 2+ , the interspin distances for one set (TnI151/TnC84) were 'short' (9-10Å) with narrow distance distribution widths (3-8Å) indicating the close interaction of the switch region with the N-lobe of TnC. Additional spin populations representative of longer interspin distances were detected by DEER. These longer distance populations, which were ∼16-19Å longer than the short distance populations, possessed notably broader distance distribution widths (14-29Å). Upon Ca 2+ removal, the interspin population shifted toward the longer distances, indicating the release of the switch region from TnC and an overall increase in disorder for this region. Together, our results suggest that under conditions of low Ca 2+ , the close proximity of the TnI switch region to TnC in the cardiac isoform is necessary for promoting the interaction between the regulatory switch helix with the N-lobe of cardiac Troponin C, which, unlike the skeletal isoform, is largely in a closed conformation. Copyright © 2017 Elsevier Inc. All rights reserved.
Eme, John; Rhen, Turk; Tate, Kevin B; Gruchalla, Kathryn; Kohl, Zachary F; Slay, Christopher E; Crossley, Dane A
2013-06-01
Reptile embryos tolerate large decreases in the concentration of ambient oxygen. However, we do not fully understand the mechanisms that underlie embryonic cardiovascular short- or long-term responses to hypoxia in most species. We therefore measured cardiac growth and function in snapping turtle embryos incubated under normoxic (N21; 21% O₂) or chronic hypoxic conditions (H10; 10% O₂). We determined heart rate (fH) and mean arterial pressure (Pm) in acute normoxic (21% O₂) and acute hypoxic (10% O₂) conditions, as well as embryonic responses to cholinergic, adrenergic, and ganglionic pharmacological blockade. Compared with N21 embryos, chronic H10 embryos had smaller bodies and relatively larger hearts and were hypotensive, tachycardic, and following autonomic neural blockade showed reduced intrinsic fH at 90% of incubation. Unlike other reptile embryos, cholinergic and ganglionic receptor blockade both increased fH. β-Adrenergic receptor blockade with propranolol decreased fH, and α-adrenergic blockade with phentolamine decreased Pm. We also measured cardiac mRNA expression. Cholinergic tone was reduced in H10 embryos, but cholinergic receptor (Chrm2) mRNA levels were unchanged. However, expression of adrenergic receptor mRNA (Adrb1, Adra1a, Adra2c) and growth factor mRNA (Igf1, Igf2, Igf2r, Pdgfb) was lowered in H10 embryos. Hypoxia altered the balance between cholinergic receptors, α-adrenoreceptor and β-adrenoreceptor function, which was reflected in altered intrinsic fH and adrenergic receptor mRNA levels. This is the first study to link gene expression with morphological and cardioregulatory plasticity in a developing reptile embryo.
Lesizza, Pierluigi; Prosdocimo, Giulia; Martinelli, Valentina; Sinagra, Gianfranco; Zacchigna, Serena; Giacca, Mauro
2017-04-14
Recent evidence indicates that a few human microRNAs (miRNAs), in particular hsa-miR-199a-3p and hsa-miR-590-3p, stimulate proliferation of cardiomyocytes and, once expressed in the mouse heart using viral vectors, induce cardiac regeneration after myocardial infarction. Viral vectors, however, are not devoid of safety issues and, more notably, drive expression of the encoded miRNAs for indefinite periods of time, which might not be desirable in light of human therapeutic application. As an alternative to the use of viral vectors, we wanted to assess the efficacy of synthetic miRNA mimics in inducing myocardial repair after single intracardiac injection using synthetic lipid formulations. We comparatively analyzed the efficacy of different lipid formulations in delivering hsa-miR-199a-3p and hsa-miR-590-3p both in primary neonatal mouse cardiomyocytes and in vivo. We established a transfection protocol allowing persistence of these 2 mimics for at least 12 days after a single intracardiac injection, with minimal dispersion to other organs and long-term preservation of miRNA functional activity, as assessed by monitoring the expression of 2 mRNA targets. Administration of this synthetic formulation immediately after myocardial infarction in mice resulted in marked reduction of infarct size and persistent recovery of cardiac function. A single administration of synthetic miRNA-lipid formulations is sufficient to stimulate cardiac repair and restoration of cardiac function. © 2017 American Heart Association, Inc.
Maleckar, Mary M; Edwards, Andrew G; Louch, William E; Lines, Glenn T
2017-01-01
Excitation-contraction coupling in cardiac myocytes requires calcium influx through L-type calcium channels in the sarcolemma, which gates calcium release through sarcoplasmic reticulum ryanodine receptors in a process known as calcium-induced calcium release, producing a myoplasmic calcium transient and enabling cardiomyocyte contraction. The spatio-temporal dynamics of calcium release, buffering, and reuptake into the sarcoplasmic reticulum play a central role in excitation-contraction coupling in both normal and diseased cardiac myocytes. However, further quantitative understanding of these cells' calcium machinery and the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease requires accurate knowledge of cardiac ultrastructure, protein distribution and subcellular function. As current imaging techniques are limited in spatial resolution, limiting insight into changes in calcium handling, computational models of excitation-contraction coupling have been increasingly employed to probe these structure-function relationships. This review will focus on the development of structural models of cardiac calcium dynamics at the subcellular level, orienting the reader broadly towards the development of models of subcellular calcium handling in cardiomyocytes. Specific focus will be given to progress in recent years in terms of multi-scale modeling employing resolved spatial models of subcellular calcium machinery. A review of the state-of-the-art will be followed by a review of emergent insights into calcium-dependent etiologies in heart disease and, finally, we will offer a perspective on future directions for related computational modeling and simulation efforts.
Sommer, J Ulrich; Kraus, Marius; Birk, Richard; Schultz, Johannes D; Hörmann, Karl; Stuck, Boris A
2014-03-01
Continuous positive airway pressure (CPAP) is the gold standard in the treatment of obstructive sleep apnea (OSA), but its impact on ciliary function is unclear to date. Furthermore, CPAP is associated with numerous side effects related to the nose and upper airway. Humidified CPAP is used to relieve these symptoms, but again, little is known regarding its effect on ciliary function of the nasal respiratory epithelium. In this prospective, randomized, crossover trial, 31 patients with OSA (AHI >15/h) were randomized to two treatment arms: nasal continuous positive airway pressure (nCPAP) with humidification or nCPAP without humidification for one night in each modality to assess short-term effects of ciliary beat frequency (CBF) and mucus transport time (MTT) and consecutively for 8 weeks in each modality to assess long-term effects in a crossover fashion. The baseline CBF was 4.8 ± 0.6 Hz, and baseline MTT was 540 ± 221 s. After one night of CPAP with and without humidification, ciliary function increased moderately yet with statistical significance (p <0.05). The short-term groups with and without humidification did not differ statistically significant. Regarding long-term effects of CPAP, a statistically significant increase in ciliary function above the baseline level and above the short-term level was shown without humidification (7.2 ± 0.4 Hz; 402 ± 176 s; p <0.01). The increase above baseline level was even more pronounced with humidification (9.3 ± 0.7 Hz; 313 ± 95 s; p <0.01). There was a statistically significant difference between both groups at long-term assessment with regard to CBF (p <0.01). Independent of airway humidification, nCPAP has moderate effects on short-term ciliary function of the nasal respiratory epithelium. However, a significant increase in ciliary function-both in terms of an increased CBF and a decreased MTT-was detected after long-term use. The effect was more pronounced when humidification was used during nCPAP.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.
One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation.more » - Highlights: • Dexamethasone accelerates Ca{sup 2+} transient decay in hESC-CMs. • Dexamethasone enhances SERCA and NCX function in hESC-CMs. • Dexamethasone increases force of contraction and sarcomere length in hESC-CMs. • Dexamethasone does not alter I{sub Ca,L} and action potential characteristics in hESC-CMs.« less
Zijlstra, Jolande A; Beesems, Stefanie G; De Haan, Rob J; Koster, Rudolph W
2015-07-01
We studied the short-term psychological impact and post-traumatic stress disorder (PTSD)-related symptoms in lay rescuers performing cardiopulmonary resuscitation (CPR) after a text message (TM)-alert for out-of-hospital-cardiac arrest, and assessed which factors contribute to a higher level of PTSD-related symptoms. The lay rescuers received a TM-alert and simultaneously an email with a link to an online questionnaire. We analyzed all questionnaires from February 2013 until October 2014 measuring the short-term psychological impact. We interviewed by telephone all first arriving lay rescuers performing bystander CPR and assessed PTSD-related symptoms with the Impact of Event Scale (IES) 4-6 weeks after the resuscitation. IES-scores 0-8 reflected no stress, 9-25 mild, 26-43 moderate, and 44-75 severe stress. A score ≥ 26 indicated PTSD symptomatology. Of all alerted lay rescuers, 6572 completed the online questionnaire. Of these, 1955 responded to the alert and 507 assisted in the resuscitation. We interviewed 203 first arriving rescuers of whom 189 completed the IES. Of these, 41% perceived no/mild short-term impact, 46% bearable impact and 13% severe impact. On the IES, 81% scored no stress and 19% scored mild stress. None scored moderate or severe stress. Using a multivariable logistic regression model we identified three factors with an independent impact on mild stress level: no automated external defibrillator connected by the lay rescuer, severe short-term impact, and no (very) positive experience. Lay rescuers alerted by text messages, do not show PTSD-related symptoms 4-6 weeks after performing bystander CPR, even if they perceive severe short-term psychological impact. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Automatic attention towards face or body as a function of mating motivation.
Lu, Hui Jing; Chang, Lei
2012-03-22
Because women's faces and bodies carry different cues of reproductive value, men may attend to different perceptual cues as functions of their long-term versus short-term mating motivations. We tested this hypothesis in three experiments on 135 male and 132 female participants. When influenced by short-term rather than long-term mating motivations, men's attention was captured by (Study 1), was shifted to (Study 2), and was distracted by (Study 3) the waist/hip area rather than the face on photographs of attractive women. Similar effects were not found among the female participants in response to photographs of attractive men. These results support the evolutionary view that, similar to the attentional selectivity found in other domains of life, male perceptual attention has evolved to selectively capture and hold reproductive information about the opposite sex as a function of short-term versus long-term mating goals.
Auditory-Cortex Short-Term Plasticity Induced by Selective Attention
Jääskeläinen, Iiro P.; Ahveninen, Jyrki
2014-01-01
The ability to concentrate on relevant sounds in the acoustic environment is crucial for everyday function and communication. Converging lines of evidence suggests that transient functional changes in auditory-cortex neurons, “short-term plasticity”, might explain this fundamental function. Under conditions of strongly focused attention, enhanced processing of attended sounds can take place at very early latencies (~50 ms from sound onset) in primary auditory cortex and possibly even at earlier latencies in subcortical structures. More robust selective-attention short-term plasticity is manifested as modulation of responses peaking at ~100 ms from sound onset in functionally specialized nonprimary auditory-cortical areas by way of stimulus-specific reshaping of neuronal receptive fields that supports filtering of selectively attended sound features from task-irrelevant ones. Such effects have been shown to take effect in ~seconds following shifting of attentional focus. There are findings suggesting that the reshaping of neuronal receptive fields is even stronger at longer auditory-cortex response latencies (~300 ms from sound onset). These longer-latency short-term plasticity effects seem to build up more gradually, within tens of seconds after shifting the focus of attention. Importantly, some of the auditory-cortical short-term plasticity effects observed during selective attention predict enhancements in behaviorally measured sound discrimination performance. PMID:24551458
Aimé, Ezio; Rovida, Marina; Contardi, Danilo; Ricci, Cristian; Gaeta, Maddalena; Innocenti, Ester; Cabral Tantchou-Tchoumi, Jacques
2014-10-01
The primary aim of this pilot study was to prospectively assess a flowchart to screen and diagnose paced patients (pts) affected by sleep apnoeas, by crosschecking indexes derived from pacemakers (minute ventilation sensor on-board) with Sleep-Lab Polygraphy (PG) outcomes. Secondarily, "smoothed" long-term pacemaker indexes (all the information between two consecutive follow-up visits) have been retrospectively compared vs. standard short-term pacemaker indexes (last 24h) at each follow-up (FU) visit, to test their correlation and diagnostic concordance. Data from long-term FU of 61 paced pts were collected. At each visit, the standard short-term apnoea+hypopnoea (PM_AHI) index was retrieved from the pacemaker memory. Patients showing PM_AHI ≥ 30 at least once during FU were proposed to undergo a PG for diagnostic confirmation. Smoothed pacemaker (PM_SAHI) indexes were calculated by averaging the overall number of apnoeas/hypopnoeas over the period between two FU visits, and retrospectively compared with standard PM_AHI. Data were available from 609 consecutive visits (overall 4.64 ± 1.78 years FU). PM_AHI indexes were positive during FU in 40/61 pts (65.6%); 26/40 pts (65%) accepted to undergo a PG recording; Sleep-Lab confirmed positivity in 22/26 pts (84.6% positive predictive value for PM_AHI). A strong correlation (r=0.73) and a high level of concordance were found between smoothed and standard indexes (multivariate analysis, Cohen's-k and Z-score tests). Pacemaker-derived indexes may help in screening paced pts potentially affected by sleep apnoeas. Long-term "smoothed" apnoea indexes could improve the accuracy of pacemaker screening capability, even though this hypothesis must be prospectively confirmed by larger studies. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
Than, Martin; Cullen, Louise; Reid, Christopher M; Lim, Swee Han; Aldous, Sally; Ardagh, Michael W; Peacock, W Frank; Parsonage, William A; Ho, Hiu Fai; Ko, Hiu Fai; Kasliwal, Ravi R; Bansal, Manish; Soerianata, Sunarya; Hu, Dayi; Ding, Rongjing; Hua, Qi; Seok-Min, Kang; Sritara, Piyamitr; Sae-Lee, Ratchanee; Chiu, Te-Fa; Tsai, Kuang-Chau; Chu, Fang-Yeh; Chen, Wei-Kung; Chang, Wen-Han; Flaws, Dylan F; George, Peter M; Richards, A Mark
2011-03-26
Patients with chest pain contribute substantially to emergency department attendances, lengthy hospital stay, and inpatient admissions. A reliable, reproducible, and fast process to identify patients presenting with chest pain who have a low short-term risk of a major adverse cardiac event is needed to facilitate early discharge. We aimed to prospectively validate the safety of a predefined 2-h accelerated diagnostic protocol (ADP) to assess patients presenting to the emergency department with chest pain symptoms suggestive of acute coronary syndrome. This observational study was undertaken in 14 emergency departments in nine countries in the Asia-Pacific region, in patients aged 18 years and older with at least 5 min of chest pain. The ADP included use of a structured pre-test probability scoring method (Thrombolysis in Myocardial Infarction [TIMI] score), electrocardiograph, and point-of-care biomarker panel of troponin, creatine kinase MB, and myoglobin. The primary endpoint was major adverse cardiac events within 30 days after initial presentation (including initial hospital attendance). This trial is registered with the Australia-New Zealand Clinical Trials Registry, number ACTRN12609000283279. 3582 consecutive patients were recruited and completed 30-day follow-up. 421 (11.8%) patients had a major adverse cardiac event. The ADP classified 352 (9.8%) patients as low risk and potentially suitable for early discharge. A major adverse cardiac event occurred in three (0.9%) of these patients, giving the ADP a sensitivity of 99.3% (95% CI 97.9-99.8), a negative predictive value of 99.1% (97.3-99.8), and a specificity of 11.0% (10.0-12.2). This novel ADP identifies patients at very low risk of a short-term major adverse cardiac event who might be suitable for early discharge. Such an approach could be used to decrease the overall observation periods and admissions for chest pain. The components needed for the implementation of this strategy are widely available. The ADP has the potential to affect health-service delivery worldwide. Alere Medical (all countries), Queensland Emergency Medicine Research Foundation and National Health and Medical Research Council (Australia), Christchurch Cardio-Endocrine Research Group (New Zealand), Medquest Jaya Global (Indonesia), Science International (Hong Kong), Bio Laboratories Pte (Singapore), National Heart Foundation of New Zealand, and Progressive Group (Taiwan). Copyright © 2011 Elsevier Ltd. All rights reserved.
Takahashi, Eiki; Niimi, Kimie; Itakura, Chitoshi
2010-10-25
Ca(V)2.1 is highly expressed in the nervous system and plays an essential role in the presynaptic modulation of neurotransmitter release machinery. Recently, the antiepileptic drug levetiracetam was reported to inhibit presynaptic Ca(V)2.1 functions, reducing glutamate release in the hippocampus, although the precise physiological role of Ca(V)2.1-regulated synaptic functions in cognitive performance at the system level remains unknown. This study examined whether Ca(V)2.1 mediates hippocampus-dependent spatial short-term memory using the object location and Y-maze tests, and perirhinal cortex-dependent nonspatial short-term memory using the object recognition test, via a combined pharmacological and genetic approach. Heterozygous rolling Nagoya (rol/+) mice carrying the Ca(V)2.1alpha(1) mutation had normal spatial and nonspatial short-term memory. A 100mg/kg dose of levetiracetam, which is ineffective in wild-type controls, blocked spatial short-term memory in rol/+ mice. At 5mg/kg, the N-methyl-D-aspartate (NMDA) receptor blocker (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), which is ineffective in wild-type controls, also blocked the spatial short-term memory in rol/+ mice. Furthermore, a combination of subthreshold doses of levetiracetam (25 mg/kg) and CPP (2.5mg/kg) triggered a spatial short-term memory deficit in rol/+ mice, but not in wild-type controls. Similar patterns of nonspatial short-term memory were observed in wild-type and rol/+ mice when injected with levetiracetam (0-300 mg/kg). These results indicate that Ca(V)2.1-mediated NMDA receptor signaling is critical in hippocampus-dependent spatial short-term memory and differs in various regions. The combination subthreshold pharmacological and genetic approach presented here is easily performed and can be used to study functional signaling pathways in neuronal circuits. Copyright © 2010 Elsevier B.V. All rights reserved.
Max dD/Dt: A Novel Parameter to Assess Fetal Cardiac Contractility and a Substitute for Max dP/Dt.
Fujita, Yasuyuki; Kiyokoba, Ryo; Yumoto, Yasuo; Kato, Kiyoko
2018-07-01
Aortic pulse waveforms are composed of a forward wave from the heart and a reflection wave from the periphery. We focused on this forward wave and suggested a new parameter, the maximum slope of aortic pulse waveforms (max dD/dt), for fetal cardiac contractility. Max dD/dt was calculated from fetal aortic pulse waveforms recorded with an echo-tracking system. A normal range of max dD/dt was constructed in 105 healthy fetuses using linear regression analysis. Twenty-two fetuses with suspected fetal cardiac dysfunction were divided into normal and decreased max dD/dt groups, and their clinical parameters were compared. Max dD/dt of aortic pulse waveforms increased linearly with advancing gestational age (r = 0.93). The decreased max dD/dt was associated with abnormal cardiotocography findings and short- and long-term prognosis. In conclusion, max dD/dt calculated from the aortic pulse waveforms in fetuses can substitute for max dP/dt, an index of cardiac contractility in adults. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.
Decrease of cardiac chaos in congestive heart failure
NASA Astrophysics Data System (ADS)
Poon, Chi-Sang; Merrill, Christopher K.
1997-10-01
The electrical properties of the mammalian heart undergo many complex transitions in normal and diseased states. It has been proposed that the normal heartbeat may display complex nonlinear dynamics, including deterministic chaos,, and that such cardiac chaos may be a useful physiological marker for the diagnosis and management, of certain heart trouble. However, it is not clear whether the heartbeat series of healthy and diseased hearts are chaotic or stochastic, or whether cardiac chaos represents normal or abnormal behaviour. Here we have used a highly sensitive technique, which is robust to random noise, to detect chaos. We analysed the electrocardiograms from a group of healthy subjects and those with severe congestive heart failure (CHF), a clinical condition associated with a high risk of sudden death. The short-term variations of beat-to-beat interval exhibited strongly and consistently chaotic behaviour in all healthy subjects, but were frequently interrupted by periods of seemingly non-chaotic fluctuations in patients with CHF. Chaotic dynamics in the CHF data, even when discernible, exhibited a high degree of random variability over time, suggesting a weaker form of chaos. These findings suggest that cardiac chaos is prevalent in healthy heart, and a decrease in such chaos may be indicative of CHF.
Weaver, Anne M; Wellenius, Gregory A; Wu, Wen-Chih; Hickson, DeMarc A; Kamalesh, Masoor; Wang, Yi
2016-06-13
Cardiovascular disease (CVD), including heart failure, is a major cause of morbidity and mortality, particularly among African Americans. Exposure to ambient air pollution, such as that produced by vehicular traffic, is believed to be associated with heart failure, possibly by impairing cardiac function. We evaluated the cross-sectional association between residential proximity to major roads, a marker of long-term exposure to traffic-related pollution, and echocardiographic indicators of left and pulmonary vascular function in African Americans enrolled in the Jackson Heart Study (JHS): left ventricular ejection fraction, E-wave velocity, isovolumic relaxation time, left atrial diameter index, and pulmonary artery systolic pressure. We examined these associations using multivariable linear or logistic regression, adjusting for potential confounders. Of 4866 participants at study enrollment, 106 lived <150 m, 159 lived 150-299 m, 1161 lived 300-999 m, and 3440 lived ≥1000 m from a major roadway. We did not observe any associations between residential distance to major roads and these markers of cardiac function. Results were similar with additional adjustment for diabetes and hypertension, when considering varying definitions of major roadways, or when limiting analyses to those free from cardiovascular disease at baseline. Overall, we observed little evidence that residential proximity to major roads was associated with cardiac function among African Americans.
Viveiros Monteiro, André; Fiarresga, António; Cacela, Duarte; de Sousa, Lídia; Ramos, Ruben; Galrinho, Ana; Branco, Luísa; Cruz Ferreira, Rui
2016-09-01
Acromegaly is a rare disease, mostly caused by a growth hormone (GH)-secreting benign pituitary tumor, with an increased production of GH and insulin-like growth factor 1 (IGF-1). Cardiovascular complications are common and are associated with cardiomyocyte apoptosis and concentric cardiac hypertrophy. Suppression of GH and IGF-1 appears to improve cardiac function only in the short term, with little or no decrease in left ventricular mass or improvement in cardiac function after prolonged treatment. Alcohol septal ablation (ASA) has emerged as a minimally invasive alternative to septal myectomy, with significant improvement in symptoms, gradients and left ventricular remodeling. In this report, we describe the case of a 73-year-old woman with acromegaly due to a pituitary adenoma diagnosed and treated surgically at the age of 38 but with recurrence and reoperation at the age of 50. She was referred to our cardiology department due to a three-month history of progressively worsening exercise-induced dyspnea and orthopnea under optimal medical therapy. Echocardiography and magnetic resonance imaging revealed severe basal hypertrophy of the interventricular septum (19 mm), dynamic left ventricular outflow tract obstruction with a gradient of 70 mmHg at rest and 120 mmHg with Valsalva maneuver, and systolic anterior movement (SAM). Genetic testing excluded the most frequent forms of familial hypertrophic cardiomyopathy. ASA was performed with injection of 2 cc of alcohol in the first septal branch of the left coronary artery, without complications. At one-year reassessment, significant clinical and echocardiographic improvement was noted, with disappearance of SAM. To our knowledge, there have been no previously reported cases of ASA in hypertrophic cardiomyopathy due to acromegaly. We report a case of successful ASA in acromegalic cardiomyopathy. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.
Lindfors, Olavi; Knekt, Paul; Heinonen, Erkki; Virtala, Esa
2014-01-01
Quality of object relations and self-concept reflect clinically relevant aspects of personality functioning, but their prediction as suitability factors for psychotherapies of different lengths has not been compared. This study compared their prediction on psychiatric symptoms and work ability in short- and long-term psychotherapy. Altogether 326 patients, 20-46 years of age, with mood and/or anxiety disorder, were randomized to short-term (solution-focused or short-term psychodynamic) psychotherapy and long-term psychodynamic psychotherapy. The Quality of Object Relations Scale (QORS) and the Structural Analysis of Social Behavior (SASB) self-concept questionnaire were measured at baseline, and their prediction on outcome during the 3-year follow-up was assessed by the Symptom Check List Global Severity Index and the Anxiety Scale, the Beck Depression Inventory and by the Work Ability Index, Social Adjustment Scale work subscale and the Perceived Psychological Functioning scale. Negative self-concept strongly and self-controlling characteristics modestly predicted better 3-year outcomes in long-term therapy, after faster early gains in short-term therapy. Patients with a more positive or self-emancipating self-concept, or more mature object relations, experienced more extensive benefits after long-term psychotherapy. The importance of length vs. long-term therapy technique on the differences found is not known. Patients with mild to moderate personality pathology, indicated by poor self-concept, seem to benefit more from long-term than short-term psychotherapy, in reducing risk of depression. Long-term therapy may also be indicated for patients with relatively good psychological functioning. More research is needed on the relative importance of these characteristics in comparison with other patient-related factors. © 2013 Published by Elsevier B.V.
ERIC Educational Resources Information Center
Webster, Raymond E.
1980-01-01
A significant two-way input modality by output modality interaction suggested that short term memory capacity among the groups differed as a function of the modality used to present the items in combination with the output response required. (Author/CL)
Roncaglia, Paola; Howe, Douglas G.; Laulederkind, Stanley J.F.; Khodiyar, Varsha K.; Berardini, Tanya Z.; Tweedie, Susan; Foulger, Rebecca E.; Osumi-Sutherland, David; Campbell, Nancy H.; Huntley, Rachael P.; Talmud, Philippa J.; Blake, Judith A.; Breckenridge, Ross; Riley, Paul R.; Lambiase, Pier D.; Elliott, Perry M.; Clapp, Lucie; Tinker, Andrew; Hill, David P.
2018-01-01
Background: A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. Methods and Results: In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. Conclusions: We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects. PMID:29440116
Lovering, Ruth C; Roncaglia, Paola; Howe, Douglas G; Laulederkind, Stanley J F; Khodiyar, Varsha K; Berardini, Tanya Z; Tweedie, Susan; Foulger, Rebecca E; Osumi-Sutherland, David; Campbell, Nancy H; Huntley, Rachael P; Talmud, Philippa J; Blake, Judith A; Breckenridge, Ross; Riley, Paul R; Lambiase, Pier D; Elliott, Perry M; Clapp, Lucie; Tinker, Andrew; Hill, David P
2018-02-01
A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects. © 2018 The Authors.
Fechner, H; Suckau, L; Kurreck, J; Sipo, I; Wang, X; Pinkert, S; Loschen, S; Rekittke, J; Weger, S; Dekkers, D; Vetter, R; Erdmann, V A; Schultheiss, H-P; Paul, M; Lamers, J; Poller, W
2007-02-01
Impaired function of the phospholamban (PLB)-regulated sarcoplasmic reticulum Ca(2+) pump (SERCA2a) contributes to cardiac dysfunction in heart failure (HF). PLB downregulation may increase SERCA2a activity and improve cardiac function. Small interfering (si)RNAs mediate efficient gene silencing by RNA interference (RNAi). However, their use for in vivo gene therapy is limited by siRNA instability in plasma and tissues, and by low siRNA transfer rates into target cells. To address these problems, we developed an adenoviral vector (AdV) transcribing short hairpin (sh)RNAs against rat PLB and evaluated its potential to silence the PLB gene and to modulate SERCA2a-mediated Ca(2+) sequestration in primary neonatal rat cardiomyocytes (PNCMs). Over a period of 13 days, vector transduction resulted in stable > 99.9% ablation of PLB-mRNA at a multiplicity of infection of 100. PLB protein gradually decreased until day 7 (7+/-2% left), whereas SERCA, Na(+)/Ca(2+) exchanger (NCX1), calsequestrin and troponin I protein remained unchanged. PLB silencing was associated with a marked increase in ATP-dependent oxalate-supported Ca(2+) uptake at 0.34 microM of free Ca(2+), and rapid loss of responsiveness to protein kinase A-dependent stimulation of Ca(2+) uptake was maintained until day 7. In summary, these results indicate that AdV-derived PLB-shRNA mediates highly efficient, specific and stable PLB gene silencing and modulation of active Ca(2+) sequestration in PNCMs. The availability of the new vector now enables employment of RNAi for the treatment of HF in vivo.
Aurensanz Clemente, Esther; Ayerza Casas, Ariadna; Samper Villagrasa, Pilar; Ruiz Frontera, Pablo; Bueno Lozano, Gloria
2017-02-09
Small for gestational age (SGA) patients have an increased risk of developing a cardiovascular pathology, as well as a metabolic syndrome. Our objective is to evaluate the cardiac morphology and function of SGA children treated with growth hormone (GH), identifying changes that could potentially have long-term consequences. We selected 23 SGA school-age patients and 23 healthy children. We measured their weight, height, blood pressure and heart rate. Using transthoracic echocardiography, we evaluated cardiac chamber size, ascending and abdominal aortic diameter as well as the systolic and diastolic function of both ventricles. SGA children have a higher systolic and diastolic blood pressure (P<.05) without significant changes in their heart rate. They also have a thicker interventricular septum (SGA Z-score 1.57 vs. 0.89; P=.026) and a worse right ventricular systolic function, with a lower TAPSE (SGA Z-score -0.98 vs. 0.95; P=.000), as well as a lower blood flow rate in the pulmonary artery (SGA 0.85m/s vs. 0.97m/s; P=.045). No significant difference was observed in the patients' left ventricular function. SGA patients' ascending aortic diameter was greater (SGA Z-score -1.09 vs. -1.93; P=.026), whereas the systolic abdominal aortic diameter was smaller (SGA Z-score-0.89 vs. -0.19; P=.015). We found functional and morphological cardiac changes in SGA school-age patients treated with GH. It is important to follow-up this patient group in order to determine if these changes contribute to an increased cardiac morbidity in adulthood. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.
Striated Muscle Function, Regeneration, and Repair
Shadrin, I.Y.; Khodabukus, A.; Bursac, N.
2016-01-01
As the only striated muscle tissues in the body, skeletal and cardiac muscle share numerous structural and functional characteristics, while exhibiting vastly different size and regenerative potential. Healthy skeletal muscle harbors a robust regenerative response that becomes inadequate after large muscle loss or in degenerative pathologies and aging. In contrast, the mammalian heart loses its regenerative capacity shortly after birth, leaving it susceptible to permanent damage by acute injury or chronic disease. In this review, we compare and contrast the physiology and regenerative potential of native skeletal and cardiac muscles, mechanisms underlying striated muscle dysfunction, and bioengineering strategies to treat muscle disorders. We focus on different sources for cellular therapy, biomaterials to augment the endogenous regenerative response, and progress in engineering and application of mature striated muscle tissues in vitro and in vivo. Finally, we discuss the challenges and perspectives in translating muscle bioengineering strategies to clinical practice. PMID:27271751
Peng, Feng; Lin, Jinxiu; Lin, Liming; Tang, Hong
2012-12-01
The aim of this study was to compare the effectiveness of transient prehypertensive treatment with losartan compared with amlodipine in spontaneously hypertensive rats (SHRs) on long-term blood pressure (BP), cardiac and renal protection. SHRs were prehypertensively treated with losartan, amlodipine or saline. Rats were followed up until 46 weeks of age. The left ventricular (LV) geometry and function were assessed by echocardiography. Angiotensin II (Ang II) and aldosterone (Aldo) were measured by radioimmunoassay. Ang II type 1 (AT1R) and type 2 (AT2R) receptor protein expression was determined by western blotting. The systolic blood pressure (SBP) in losartan-treated SHRs (SHR-Los) was persistently reduced until 46 weeks of age, but returned to untreated SHR levels in amlodipine-treated SHRs (SHR-Aml) from 30 weeks onwards. Compared to untreated SHRs, the albuminuria excretion in SHR-Los at week 46 was markedly decreased, the plasma, myocardium and renal tissue Ang II and Aldo levels in SHR-Los at week 46 were markedly decreased; AT1R and TGF-β1 protein expression was downregulated and AT2R protein was upregulated. Compared to untreated SHRs, the left ventricular mass index (LVMI) and collagen volume fraction (CVF) in SHR-Los were markedly decreased until week 46, and the left ventricular ejection fraction (LVEF) and cardiac brain natriuretic peptide mRNA expression were improved, whereas similar LVMI and elevated CVF were observed in SHR-Aml, and the LVEF decreased significantly below that of untreated SHRs at week 46, with cardiac BNP mRNA expression increasing slightly. Prehypertensive treatment with losartan was more effective than amlodipine on delaying long-term BP increase and ameliorating cardiac, renal structure and function, which may be related to the permanent attenuation of the circulating and local renin-angiotensin systems.
Barra, Nicole G; Lisyansky, Maria; Vanduzer, Taylor A; Raha, Sandeep; Holloway, Alison C; Hardy, Daniel B
2017-12-01
Smoking throughout pregnancy can lead to complications during gestation, parturition and neonatal development. Thus, nicotine replacement therapies are a popular alternative thought to be safer than cigarettes. However, recent studies in rodents suggest that fetal and neonatal nicotine exposure alone results in cardiac dysfunction and high blood pressure. While it is well known that perinatal nicotine exposure causes increased congenital abnormalities, the mechanisms underlying longer-term deficits in cardiac function are not completely understood. Recently, our laboratory demonstrated that nicotine impairs placental protein disulfide isomerase (PDI) triggering an increase in endoplasmic reticulum stress, leading us to hypothesize that this may also occur in the heart. At 3 months of age, nicotine-exposed offspring had 45% decreased PDI levels in the absence of endoplasmic reticulum stress. Given the association of PDI and superoxide dismutase enzymes, we further observed that antioxidant superoxide dismutase-2 levels were reduced by 32% in these offspring concomitant with a 26-49% decrease in mitochondrial complex proteins (I, II, IV and V) and tissue inhibitor of metalloproteinase-4, a critical matrix metalloprotease for cardiac contractility and health. Collectively, this study suggests that perinatal nicotine exposure decreases PDI, which can promote oxidative damage and mitochondrial damage, associated with a premature decline in cardiac function. Copyright © 2017 John Wiley & Sons, Ltd.
Insensitivity of visual short-term memory to irrelevant visual information.
Andrade, Jackie; Kemps, Eva; Werniers, Yves; May, Jon; Szmalec, Arnaud
2002-07-01
Several authors have hypothesized that visuo-spatial working memory is functionally analogous to verbal working memory. Irrelevant background speech impairs verbal short-term memory. We investigated whether irrelevant visual information has an analogous effect on visual short-term memory, using a dynamic visual noise (DVN) technique known to disrupt visual imagery (Quinn & McConnell, 1996b). Experiment I replicated the effect of DVN on pegword imagery. Experiments 2 and 3 showed no effect of DVN on recall of static matrix patterns, despite a significant effect of a concurrent spatial tapping task. Experiment 4 showed no effect of DVN on encoding or maintenance of arrays of matrix patterns, despite testing memory by a recognition procedure to encourage visual rather than spatial processing. Serial position curves showed a one-item recency effect typical of visual short-term memory. Experiment 5 showed no effect of DVN on short-term recognition of Chinese characters, despite effects of visual similarity and a concurrent colour memory task that confirmed visual processing of the characters. We conclude that irrelevant visual noise does not impair visual short-term memory. Visual working memory may not be functionally analogous to verbal working memory, and different cognitive processes may underlie visual short-term memory and visual imagery.
Sherr, Jennifer; Tamborlane, William V; Xing, Dongyuan; Tsalikian, Eva; Mauras, Nelly; Buckingham, Bruce; White, Neil H; Arbelaez, Ana Maria; Beck, Roy W; Kollman, Craig; Ruedy, Katrina
2012-04-01
To determine exposure to hyper- and hypoglycemia using blinded continuous glucose monitoring (CGM) profiles in youth with type 1 diabetes (T1D) with residual β-cell function during the first year of insulin treatment. Blinded, 3-7 day CGM profiles were obtained in 16 short-term T1D patients (age 8-18 years, T1D duration 6-52 weeks) who had peak C-peptide levels ranging from 0.46 to 1.96 nmol/L during a mixed-meal tolerance test. Results in this short-term group were compared with those in 34 patients with well-controlled, longer-term T1D (duration ≥5 years), matched for age and A1C with the short-term T1D group, and with those in 26 age-matched nondiabetic individuals. Despite matching for A1C, and therefore similar mean sensor glucose levels in the two T1D groups, short-term T1D participants had a lower frequency of hypoglycemia (0.3 vs. 7.6%, P < 0.001), a trend toward less hyperglycemia (17 vs. 32%, P = 0.15), and a greater percentage in the target range (median 77 vs. 60%, P = 0.02). Indeed, the percentage of sensor glucose levels ≤70 mg/dL in the short-term T1D group (0.3%) did not differ from those in the nondiabetic group (1.7%, P = 0.73). The coefficient of variation of sensor glucose levels (an index of glucose variability) was lower in short-term vs. longer-term T1D participants (27 vs. 42%, respectively, P < 0.001). In youth with short-term T1D who retain residual β-cell function, there is negligible exposure to hypoglycemia and lower glucose variability than in youth with well-controlled T1D of longer duration.
Xu, Bin; Xu, Hao; Cao, Heng; Liu, Xiaoxiao; Qin, Chunhuan; Zhao, Yanzhou; Han, Xiaolin; Li, Hongli
2017-01-01
Emerging evidence has suggested that intermedin (IMD), a novel member of the calcitonin gene-related peptide (CGRP) family, has a wide range of cardioprotective effects. The present study investigated the effects of long-term administration of IMD on cardiac function and sympathetic neural remodeling in heart failure (HF) rats, and studied potential underlying mechanism. HF was induced in rats by myocardial infarction (MI). Male Sprague Dawley rats were randomly assigned to either saline or IMD (0.6 µg/kg/h) treatment groups for 4 weeks post-MI. Another group of sham-operated rats served as controls. Cardiac function was assessed by echocardiography, cardiac catheterization and plasma level of B-type natriuretic peptide (BNP). Cardiac sympathetic neural remodeling was assessed by immunohistochemistical study of tyrosine hydroxylase (TH) and growth associated protein 43 (GAP43) immunoreactive nerve fibers. The protein expression levels of nerve growth factor (NGF), TH and GAP43 in the ventricular myocardium were studied by western blotting. Ventricular fibrillation threshold (VFT) was determined to evaluate the incidence of ventricular arrhythmia. Oxidative stress was assessed by detecting the activity of superoxide dismutase and the level of malondialdehyde. Compared with rats administrated with saline, IMD significantly improved cardiac function, decreased the plasma BNP level, attenuated sympathetic neural remodeling, increased VFT and suppressed oxidative stress. In conclusion, these results indicated that IMD prevents ventricle remodeling and improves the performance of a failing heart. In addition, IMD attenuated sympathetic neural remodeling and reduced the incidence of ventricular arrhythmia, which may contribute to its anti-oxidative property. These results implicate IMD as a potential therapeutic agent for the treatment of HF. PMID:28627670
Jackson, Ellen E; Rendina-Ruedy, Elisabeth; Smith, Brenda J; Lacombe, Veronique A
2015-01-01
Diabetes is a chronic inflammatory disease that carries a high risk of cardiovascular disease. However, the pathophysiological link between these disorders is not well known. We hypothesize that TLR4 signaling mediates high fat diet (HFD)-induced peripheral and cardiac glucose metabolic derangements. Mice with a loss-of-function mutation in TLR4 (C3H/HeJ) and age-matched control (C57BL/6) mice were fed either a high-fat diet or normal diet for 16 weeks. Glucose tolerance and plasma insulin were measured. Protein expression of glucose transporters (GLUT), AKT (phosphorylated and total), and proinflammatory cytokines (IL-6, TNF-α and SOCS-3) were quantified in the heart using Western Blotting. Both groups fed a long-term HFD had increased body weight, blood glucose and insulin levels, as well as impaired glucose tolerance compared to mice fed a normal diet. TLR4-mutant mice were partially protected against long-term HFD-induced insulin resistance. In control mice, feeding a HFD decreased cardiac crude membrane GLUT4 protein content, which was partially rescued in TLR4-mutant mice. TLR4-mutant mice fed a HFD also had increased expression of GLUT8, a novel isoform, compared to mice fed a normal diet. GLUT8 content was positively correlated with SOCS-3 and IL-6 expression in the heart. No significant differences in cytokine expression were observed between groups, suggesting a lack of inflammation in the heart following a HFD. Loss of TLR4 function partially restored a healthy metabolic phenotype, suggesting that TLR4 signaling is a key mechanism in HFD-induced peripheral and cardiac insulin resistance. Our data further suggest that TLR4 exerts its detrimental metabolic effects in the myocardium through a cytokine-independent pathway.
Eichler, Sarah; Salzwedel, Annett; Reibis, Rona; Nothroff, Jörg; Harnath, Axel; Schikora, Martin; Butter, Christian; Wegscheider, Karl; Völler, Heinz
2017-02-01
Background In the last decade, transcatheter aortic valve implantation has become a promising treatment modality for patients with aortic stenosis and a high surgical risk. Little is known about influencing factors of function and quality of life during multicomponent cardiac rehabilitation. Methods From October 2013 to July 2015, patients with elective transcatheter aortic valve implantation and a subsequent inpatient cardiac rehabilitation were enrolled in the prospective cohort multicentre study. Frailty-Index (including cognition, nutrition, autonomy and mobility), Short Form-12 (SF-12), six-minute walk distance (6MWD) and maximum work load in bicycle ergometry were performed at admission and discharge of cardiac rehabilitation. The relation between patient characteristics and improvements in 6MWD, maximum work load or SF-12 scales were studied univariately and multivariately using regression models. Results One hundred and thirty-six patients (80.6 ± 5.0 years, 47.8% male) were enrolled. 6MWD and maximum work load increased by 56.3 ± 65.3 m ( p < 0.001) and 8.0 ± 14.9 watts ( p < 0.001), respectively. An improvement in SF-12 (physical 2.5 ± 8.7, p = 0.001, mental 3.4 ± 10.2, p = 0.003) could be observed. In multivariate analysis, age and higher education were significantly associated with a reduced 6MWD, whereas cognition and obesity showed a positive predictive value. Higher cognition, nutrition and autonomy positively influenced the physical scale of SF-12. Additionally, the baseline values of SF-12 had an inverse impact on the change during cardiac rehabilitation. Conclusions Cardiac rehabilitation can improve functional capacity as well as quality of life and reduce frailty in patients after transcatheter aortic valve implantation. An individually tailored therapy with special consideration of cognition and nutrition is needed to maintain autonomy and empower octogenarians in coping with challenges of everyday life.
Functional TRPV2 and TRPV4 channels in human cardiac c-kit(+) progenitor cells.
Che, Hui; Xiao, Guo-Sheng; Sun, Hai-Ying; Wang, Yan; Li, Gui-Rong
2016-06-01
The cellular physiology and biology of human cardiac c-kit(+) progenitor cells has not been extensively characterized and remains an area of active research. This study investigates the functional expression of transient receptor potential vanilloid (TRPV) and possible roles for this ion channel in regulating proliferation and migration of human cardiac c-kit(+) progenitor cells. We found that genes coding for TRPV2 and TRPV4 channels and their proteins are significantly expressed in human c-kit(+) cardiac stem cells. Probenecid, an activator of TRPV2, induced an increase in intracellular Ca(2+) (Ca(2+) i ), an effect that may be attenuated or abolished by the TRPV2 blocker ruthenium red. The TRPV4 channel activator 4α-phorbol 12-13-dicaprinate induced Ca(2+) i oscillations, which can be inhibited by the TRPV4 blocker RN-1734. The alteration of Ca(2+) i by probenecid or 4α-phorbol 12-13-dicprinate was dramatically inhibited in cells infected with TRPV2 short hairpin RNA (shRNA) or TRPV4 shRNA. Silencing TRPV2, but not TRPV4, significantly reduced cell proliferation by arresting cells at the G0/G1 boundary of the cell cycle. Cell migration was reduced by silencing TRPV2 or TRPV4. Western blot revealed that silencing TRPV2 decreased expression of cyclin D1, cyclin E, pERK1/2 and pAkt, whereas silencing TRPV4 only reduced pAkt expression. Our results demonstrate for the first time that functional TRPV2 and TRPV4 channels are abundantly expressed in human cardiac c-kit(+) progenitor cells. TRPV2 channels, but not TRPV4 channels, participate in regulating cell cycle progression; moreover, both TRPV2 and TRPV4 are involved in migration of human cardiac c-kit(+) progenitor cells. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
NASA Astrophysics Data System (ADS)
Chamakuri, Nagaiah; Engwer, Christian; Kunisch, Karl
2014-09-01
Optimal control for cardiac electrophysiology based on the bidomain equations in conjunction with the Fenton-Karma ionic model is considered. This generic ventricular model approximates well the restitution properties and spiral wave behavior of more complex ionic models of cardiac action potentials. However, it is challenging due to the appearance of state-dependent discontinuities in the source terms. A computational framework for the numerical realization of optimal control problems is presented. Essential ingredients are a shape calculus based treatment of the sensitivities of the discontinuous source terms and a marching cubes algorithm to track iso-surface of excitation wavefronts. Numerical results exhibit successful defibrillation by applying an optimally controlled extracellular stimulus.
The Role of Short Term Synaptic Plasticity in Temporal Coding of Neuronal Networks
ERIC Educational Resources Information Center
Chandrasekaran, Lakshmi
2008-01-01
Short term synaptic plasticity is a phenomenon which is commonly found in the central nervous system. It could contribute to functions of signal processing namely, temporal integration and coincidence detection by modulating the input synaptic strength. This dissertation has two parts. First, we study the effects of short term synaptic plasticity…
Robotic cardiac surgery in Brazil
Toschi, Alisson P.; Pope, Renato B.; Montanhesi, Paola K.; Santos, Ricardo S.; Teruya, Alexandre; Hatanaka, Dina M.; Rusca, Gabriel F.; Fischer, Claudio H.; Vieira, Marcelo C.; Makdisse, Marcia R.
2017-01-01
Background Brazil, the largest country and economy in South America, is a major driving force behind the development of new medical technologies in the region. Robotic cardiac surgery (RCS) has been evolving rapidly since 2010, when the first surgery using the DaVinci® robotic system was performed in Latin America. The aim of this article is to evaluate short and mid-term results in patients undergoing robotic cardiac surgery in Brazil. Methods From March 2010 to December 2015, 39 consecutive patients underwent robotic cardiac surgery. Twenty-seven patients were male (69.2%), with the mean age of 51.3±17.9 years. Participants had a mean ejection fraction of 62±5%. The procedures included in this study were mitral valve surgery, surgical treatment of atrial fibrillation, atrial septal defect closure, resection of intra-cardiac tumors, totally endoscopic coronary artery bypass and pericardiectomy. Results The mean time spent on cardiopulmonary bypass (CPB) during RCS was 154.9±94.2 minutes and the mean aortic cross-clamp time was 114.48±75.66 minutes. Thirty-two patients (82%) were extubated in the operating room immediately after surgery. The median intensive care unit (ICU) length of stay was 1 day (ranging from 0 to 25) and the median hospital length of stay was 5 days (ranging from 3 to 25). For each type of procedure, endpoints were individually reported. There were no conversions to sternotomy and no intra-operative complications. Patient follow-up was complete in 100% of the participants, with two early deaths unrelated to the procedures and no re-operations at mid-term. Conclusions Despite the heterogeneity of this series, RCS appears to be feasible, safe and effective when used for the correction of various intra- and extra-cardiac pathologies. Adopting the robotic system has been a challenge in Brazil, where its limited clinical application may be related to the lack of specific training and the high cost of technology. PMID:28203537
Robotic cardiac surgery in Brazil.
Poffo, Robinson; Toschi, Alisson P; Pope, Renato B; Montanhesi, Paola K; Santos, Ricardo S; Teruya, Alexandre; Hatanaka, Dina M; Rusca, Gabriel F; Fischer, Claudio H; Vieira, Marcelo C; Makdisse, Marcia R
2017-01-01
Brazil, the largest country and economy in South America, is a major driving force behind the development of new medical technologies in the region. Robotic cardiac surgery (RCS) has been evolving rapidly since 2010, when the first surgery using the DaVinci ® robotic system was performed in Latin America. The aim of this article is to evaluate short and mid-term results in patients undergoing robotic cardiac surgery in Brazil. From March 2010 to December 2015, 39 consecutive patients underwent robotic cardiac surgery. Twenty-seven patients were male (69.2%), with the mean age of 51.3±17.9 years. Participants had a mean ejection fraction of 62±5%. The procedures included in this study were mitral valve surgery, surgical treatment of atrial fibrillation, atrial septal defect closure, resection of intra-cardiac tumors, totally endoscopic coronary artery bypass and pericardiectomy. The mean time spent on cardiopulmonary bypass (CPB) during RCS was 154.9±94.2 minutes and the mean aortic cross-clamp time was 114.48±75.66 minutes. Thirty-two patients (82%) were extubated in the operating room immediately after surgery. The median intensive care unit (ICU) length of stay was 1 day (ranging from 0 to 25) and the median hospital length of stay was 5 days (ranging from 3 to 25). For each type of procedure, endpoints were individually reported. There were no conversions to sternotomy and no intra-operative complications. Patient follow-up was complete in 100% of the participants, with two early deaths unrelated to the procedures and no re-operations at mid-term. Despite the heterogeneity of this series, RCS appears to be feasible, safe and effective when used for the correction of various intra- and extra-cardiac pathologies. Adopting the robotic system has been a challenge in Brazil, where its limited clinical application may be related to the lack of specific training and the high cost of technology.
Low-carbohydrate diets: what are the potential short- and long-term health implications?
Bilsborough, Shane A; Crowe, Timothy C
2003-01-01
Low-carbohydrate diets for weight loss are receiving a lot of attention of late. Reasons for this interest include a plethora of low-carbohydrate diet books, the over-sensationalism of these diets in the media and by celebrities, and the promotion of these diets in fitness centres and health clubs. The re-emergence of low-carbohydrate diets into the spotlight has lead many people in the general public to question whether carbohydrates are inherently 'bad' and should be limited in the diet. Although low-carbohydrate diets were popular in the 1970s they have resurged again yet little scientific fact into the true nature of how these diets work or, more importantly, any potential for serious long-term health risks in adopting this dieting practice appear to have reached the mainstream literature. Evidence abounds that low-carbohydrate diets present no significant advantage over more traditional energy-restricted, nutritionally balanced diets both in terms of weight loss and weight maintenance. Studies examining the efficacy of using low-carbohydrate diets for long-term weight loss are few in number, however few positive benefits exist to promote the adoption of carbohydrate restriction as a realistic, and more importantly, safe means of dieting. While short-term carbohydrate restriction over a period of a week can result in a significant loss of weight (albeit mostly from water and glycogen stores), of serious concern is what potential exists for the following of this type of eating plan for longer periods of months to years. Complications such as heart arrhythmias, cardiac contractile function impairment, sudden death, osteoporosis, kidney damage, increased cancer risk, impairment of physical activity and lipid abnormalities can all be linked to long-term restriction of carbohydrates in the diet. The need to further explore and communicate the untoward side-effects of low-carbohydrate diets should be an important public health message from nutrition professionals.
Natural history of echocardiographic abnormalities in mucopolysaccharidosis III.
Wilhelm, Carolyn M; Truxal, Kristen V; McBride, Kim L; Kovalchin, John P; Flanigan, Kevin M
2018-06-01
Mucopolysaccharidosis (MPS) type III, Sanfilippo Syndrome, is an autosomal recessive lysosomal storage disorder. MPS I and II patients often develop cardiac involvement leading to early mortality, however there are limited data in MPS III. The objective of this study is to describe cardiac abnormalities in a large group of MPS III patients followed in a longitudinal natural history study designed to determine outcome measures for gene transfer trials. A single center study of MPS III patients who were enrolled in the Nationwide Children's Hospital natural history study in 2014. Two cardiologists reviewed all patient echocardiograms for anatomic, valvular, and functional abnormalities. Valve abnormalities were defined as abnormal morphology, trivial mitral regurgitation (MR) with abnormal morphology or at least mild MR, and any aortic regurgitation (AR). Abnormal left ventricular (LV) function was defined as ejection fraction < 50%. Group comparisons were assessed using two-sample t-tests or Wilcoxon rank sum tests for continuous variables and chi-square or Fisher's exact tests for categorical variables. Twenty-five patients, 15 Type A and 10 Type B MPS III, underwent 45 echocardiograms. Fifteen patients (60%) demonstrated an abnormal echocardiographic finding with age at first abnormal echocardiogram within the study being 6.8 ± 2.8 years. Left-sided valve abnormalities were common over time: 7 mitral valve thickening, 2 mitral valve prolapse, 16 MR (8 mild, 8 trivial), 3 aortic valve thickening, and 9 AR (7 mild, 2 trivial). Two patients had asymmetric LV septal hypertrophy. No valvular stenosis or ventricular function abnormalities were noted. Incidental findings included: mild aortic root dilation (2), bicommissural aortic valve (1), and mild tricuspid regurgitation (3). Individuals with Sanfilippo A and B demonstrate a natural history of cardiac involvement with valvular abnormalities most common. In short-term follow up, patients demonstrated only mild progression of abnormalities, none requiring intervention. Valvular disease prevalence is similar to MPS I and II, but appears less severe. These findings raise no specific concerns for gene transfer trials in patients in this age range. Copyright © 2018 Elsevier Inc. All rights reserved.
Haggerty, Christopher M; Kramer, Sage P; Binkley, Cassi M; Powell, David K; Mattingly, Andrea C; Charnigo, Richard; Epstein, Frederick H; Fornwalt, Brandon K
2013-08-27
Advanced measures of cardiac function are increasingly important to clinical assessment due to their superior diagnostic and predictive capabilities. Cine DENSE cardiovascular magnetic resonance (CMR) is ideal for quantifying advanced measures of cardiac function based on its high spatial resolution and streamlined post-processing. While many studies have utilized cine DENSE in both humans and small-animal models, the inter-test and inter-observer reproducibility for quantification of advanced cardiac function in mice has not been evaluated. This represents a critical knowledge gap for both understanding the capabilities of this technique and for the design of future experiments. We hypothesized that cine DENSE CMR would show excellent inter-test and inter-observer reproducibility for advanced measures of left ventricular (LV) function in mice. Five normal mice (C57BL/6) and four mice with depressed cardiac function (diet-induced obesity) were imaged twice, two days apart, on a 7T ClinScan MR system. Images were acquired with 15-20 frames per cardiac cycle in three short-axis (basal, mid, apical) and two long-axis orientations (4-chamber and 2-chamber). LV strain, twist, torsion, and measures of synchrony were quantified. Images from both days were analyzed by one observer to quantify inter-test reproducibility, while inter-observer reproducibility was assessed by a second observer's analysis of day-1 images. The coefficient of variation (CoV) was used to quantify reproducibility. LV strains and torsion were highly reproducible on both inter-observer and inter-test bases with CoVs ≤ 15%, and inter-observer reproducibility was generally better than inter-test reproducibility. However, end-systolic twist angles showed much higher variance, likely due to the sensitivity of slice location within the sharp longitudinal gradient in twist angle. Measures of synchrony including the circumferential (CURE) and radial (RURE) uniformity of strain indices, showed excellent reproducibility with CoVs of 1% and 3%, respectively. Finally, peak measures (e.g., strains) were generally more reproducible than the corresponding rates of change (e.g., strain rate). Cine DENSE CMR is a highly reproducible technique for quantification of advanced measures of left ventricular cardiac function in mice including strains, torsion and measures of synchrony. However, myocardial twist angles are not reproducible and future studies should instead report torsion.
Maraviroc (Celsentri) for multidrug-resistant human immunodeficiency virus (HIV)-1.
Ndegwa, S
2007-12-01
(1) Maraviroc belongs to a new class of antiretroviral drugs designed to block entry of HIV-1 into CD4+ T-cells via the CCR5 coreceptor. It is indicated for combination therapy in treatment-experienced adults infected with CCR5-tropic HIV-1 that is resistant to multiple antiretroviral agents. (2) Results from two randomized controlled trials (RCTs) indicate that in treatment experienced patients, maraviroc, combined with optimized background therapy (OBT), significantly decreases the level of HIV-1 RNA in the blood (viral load) when compared with OBT alone. The number of patients achieving undetectable viral loads and CD4+ cell count increases were also significantly higher in those receiving maraviroc. (3) Most patients experiencing treatment failure with maraviroc exhibit tropism changes from CCR5-tropic to CXCR4-using virus, but there is no evidence of disease progression. (4) Adverse effects reported with maraviroc include cough, fever, upper respiratory tract infections, rash, muscle and joint pain, abdominal pain, and postural hypotension (dizziness). No significant increases in cardiovascular events, hepatotoxicity, infections or malignancies have been reported with short-term maraviroc therapy. Several post-marketing studies will assess maraviroc's long-term safety for immune function, liver function, malignancy, cardiac events, and risks associated with changes in tropism. (5) Results from an ongoing trial in treatment naive patients suggest that maraviroc may not be superior in terms of viral suppression to standard therapy, but may significantly increase the number of CD4+ T-cells.
Esteban, Cristóbal; Arostegui, Inmaculada; Garcia-Gutierrez, Susana; Gonzalez, Nerea; Lafuente, Iratxe; Bare, Marisa; Fernandez de Larrea, Nerea; Rivas, Francisco; Quintana, José M
2015-12-22
Creating an easy-to-use instrument to identify predictors of short-term (30/60-day) mortality after an exacerbation of chronic obstructive pulmonary disease (eCOPD) could help clinicians choose specific measures of medical care to decrease mortality in these patients. The objective of this study was to develop and validate a classification and regression tree (CART) to predict short term mortality among patients evaluated in an emergency department (ED) for an eCOPD. We conducted a prospective cohort study including participants from 16 hospitals in Spain. COPD patients with an exacerbation attending the emergency department (ED) of any of the hospitals between June 2008 and September 2010 were recruited. Patients were randomly divided into derivation (50%) and validation samples (50%). A CART based on a recursive partitioning algorithm was created in the derivation sample and applied to the validation sample. Two thousand four hundred eighty-seven patients, 1252 patients in the derivation sample and 1235 in the validation sample, were enrolled in the study. Based on the results of the univariate analysis, five variables (baseline dyspnea, cardiac disease, the presence of paradoxical breathing or use of accessory inspiratory muscles, age, and Glasgow Coma Scale score) were used to build the CART. Mortality rates 30 days after discharge ranged from 0% to 55% in the five CART classes. The lowest mortality rate was for the branch composed of low baseline dyspnea and lack of cardiac disease. The highest mortality rate was in the branch with the highest baseline dyspnea level, use of accessory inspiratory muscles or paradoxical breathing upon ED arrival, and Glasgow score <15. The area under the receiver-operating curve (AUC) in the derivation sample was 0.835 (95% CI: 0.783, 0.888) and 0.794 (95% CI: 0.723, 0.865) in the validation sample. CART was improved to predict 60-days mortality risk by adding the Charlson Comorbidity Index, reaching an AUC in the derivation sample of 0.817 (95% CI: 0.776, 0.859) and 0.770 (95% CI: 0.716, 0.823) in the validation sample. We identified several easy-to-determine variables that allow clinicians to classify eCOPD patients by short term mortality risk, which can provide useful information for establishing appropriate clinical care. NCT02434536.
Marques, Francine Z; Nelson, Erin; Chu, Po-Yin; Horlock, Duncan; Fiedler, April; Ziemann, Mark; Tan, Jian K; Kuruppu, Sanjaya; Rajapakse, Niwanthi W; El-Osta, Assam; Mackay, Charles R; Kaye, David M
2017-03-07
Dietary intake of fruit and vegetables is associated with lower incidence of hypertension, but the mechanisms involved have not been elucidated. Here, we evaluated the effect of a high-fiber diet and supplementation with the short-chain fatty acid acetate on the gut microbiota and the prevention of cardiovascular disease. Gut microbiome, cardiorenal structure/function, and blood pressure were examined in sham and mineralocorticoid excess-treated mice with a control diet, high-fiber diet, or acetate supplementation. We also determined the renal and cardiac transcriptome of mice treated with the different diets. We found that high consumption of fiber modified the gut microbiota populations and increased the abundance of acetate-producing bacteria independently of mineralocorticoid excess. Both fiber and acetate decreased gut dysbiosis, measured by the ratio of Firmicutes to Bacteroidetes, and increased the prevalence of Bacteroides acidifaciens . Compared with mineralocorticoid-excess mice fed a control diet, both high-fiber diet and acetate supplementation significantly reduced systolic and diastolic blood pressures, cardiac fibrosis, and left ventricular hypertrophy. Acetate had similar effects and markedly reduced renal fibrosis. Transcriptome analyses showed that the protective effects of high fiber and acetate were accompanied by the downregulation of cardiac and renal Egr1 , a master cardiovascular regulator involved in cardiac hypertrophy, cardiorenal fibrosis, and inflammation. We also observed the upregulation of a network of genes involved in circadian rhythm in both tissues and downregulation of the renin-angiotensin system in the kidney and mitogen-activated protein kinase signaling in the heart. A diet high in fiber led to changes in the gut microbiota that played a protective role in the development of cardiovascular disease. The favorable effects of fiber may be explained by the generation and distribution of one of the main metabolites of the gut microbiota, the short-chain fatty acid acetate. Acetate effected several molecular changes associated with improved cardiovascular health and function. © 2016 American Heart Association, Inc.
Zhang, Yijie; Bao, Mingwei; Dai, Mingyan; Wang, Xin; He, Wenbo; Tan, Tuantuan; Lin, Dandan; Wang, Wei; Wen, Ying; Zhang, Rui
2015-06-03
Fatty acid (FA) catabolism abnormality has been proved to play an important role in obesity-related cardiomyopathy. We hypothesized that cardiospecific suppression of CD36, the predominant membrane FA transporter, would protect against obesity-related cardiomyopathy. Four-wk-old male C57BL/6 J mice were fed with either high-fat-diet (HFD) or control-normal-diet for 2 wk. Then they were subjected to intramyocardial injection with recombinant lentiviral vectors containing short hairpin RNAs to selectively downregulate the expression of either cardiac CD36 or irrelevant gene by RNA interference. After a 10-wk continuation of the diet, biochemical, functional, morphological, histological, metabolic and molecular profiles were assessed. HFD administration elicited obesity, cardiac hypertrophy and systolic dysfunction accompanied with elevated serum levels of blood urea nitrogen (BUN), creatinine, fasting serum glucose (FSG), total cholesterol (TC) and triglyceride. Additionally, HFD consumption promoted lipid accumulation and reactive oxygen species (ROS) generation in the cardiomyocytes. Cardiospecific CD36 inhibition protected against HFD induced cardiac remodeling by decreasing heart/body weight ratio, increasing left ventricular (LV) ejection fraction and fractional shortening as well as normalizing LV diameter, without influencing body weight gain. Inhibition of cardiac CD36 also mitigated obesity induced alteration in BUN, creatinine and triglyceride, but had no effect on FSG or TC. Moreover, cardiospecific CD36 deficiency corrected myocardial lipid overaccumulation and intracellular ROS overproduction that were induced by HFD feeding. Cardiospecific CD36 inhibition protects against the aggravation of cardiac functional and morphological changes associated with HFD induced obesity. CD36 represents a potential therapeutic target for obesity cardiomyopathy.
2D to 3D fusion of echocardiography and cardiac CT for TAVR and TAVI image guidance.
Khalil, Azira; Faisal, Amir; Lai, Khin Wee; Ng, Siew Cheok; Liew, Yih Miin
2017-08-01
This study proposed a registration framework to fuse 2D echocardiography images of the aortic valve with preoperative cardiac CT volume. The registration facilitates the fusion of CT and echocardiography to aid the diagnosis of aortic valve diseases and provide surgical guidance during transcatheter aortic valve replacement and implantation. The image registration framework consists of two major steps: temporal synchronization and spatial registration. Temporal synchronization allows time stamping of echocardiography time series data to identify frames that are at similar cardiac phase as the CT volume. Spatial registration is an intensity-based normalized mutual information method applied with pattern search optimization algorithm to produce an interpolated cardiac CT image that matches the echocardiography image. Our proposed registration method has been applied on the short-axis "Mercedes Benz" sign view of the aortic valve and long-axis parasternal view of echocardiography images from ten patients. The accuracy of our fully automated registration method was 0.81 ± 0.08 and 1.30 ± 0.13 mm in terms of Dice coefficient and Hausdorff distance for short-axis aortic valve view registration, whereas for long-axis parasternal view registration it was 0.79 ± 0.02 and 1.19 ± 0.11 mm, respectively. This accuracy is comparable to gold standard manual registration by expert. There was no significant difference in aortic annulus diameter measurement between the automatically and manually registered CT images. Without the use of optical tracking, we have shown the applicability of this technique for effective fusion of echocardiography with preoperative CT volume to potentially facilitate catheter-based surgery.
Jiang, Yong; Wang, Hui-Yan; Zheng, Sheng; Mu, Shang-Qiang; Ma, Meng-Ni; Xie, Xin; Zhang, Yang-Yang; Zhang, Chun-Xue; Cai, Jian-Hui
2015-01-01
Hypertension is the most common risk factor for various cardiovascular and cerebrovascular diseases that affects approximately 61 million, or 25% of the population in United States. The dietary salt intake is one of the most important but modifiable factors for hypertension. In the current study, we aim to elucidate the role of aquaporin 1 in high-salt-induced hypertension and cardiac injuries and whether angiotensin II receptor blocker valsartan could ameliorate the effect of high salt on blood pressure. Mice were fed with normal diet, high-salt diet in the presence or absence of valsartan for 4 weeks. The body weight gain, feeding behavior, blood pressure, and cardiac pathology changes were monitored after 4 weeks. The expression of aquaporin 1, vascular endothelial growth factor, transforming growth factor β1, and basic fibroblast growth factor were analyzed using quantitative real-time polymerase chain reaction, Western blot, and immunohistochemical staining. Valsartan partially reversed the effects of high-salt diet on hypertension, cardiac injuries such as fibrosis and inflammatory cell infiltration, and inhibition of aquaporin 1 and angiogenic factors; valsartan alone did not exert such effects. The current data demonstrated that the reduction of cardiac aquaporin 1 and angiogenic factor expression level might be associated with high-salt-induced hypertension and cardiac injuries in mice, which could be ameliorated by angiotensin II receptor blocker treatment. Copyright © 2015 Elsevier Inc. All rights reserved.