Non-N-methyl-d-aspartate glutamate receptors in the lateral hypothalamus modulate cardiac baroreflex responses in conscious rats

P>In the present study, we investigated the effects of inhibition of the lateral hypothalamus (LH) neurotransmission with bilateral microinjection of CoCl(2), a non-selective blocker of neurotransmission, on modulation of cardiac baroreflex responses in conscious rats as well as the involvement of LH glutamatergic neurotransmission in this modulation. Reflex bradycardiac and tachycardiac responses to blood pressure increases (following i.v. infusion of phenylephrine) or decreases (following i.v. infusion of sodium nitroprusside) were investigated in conscious male Wistar rats. Responses were evaluated before and after microinjection of 1 nmol/100 nL CoCl(2), 2 nmol/100 nL 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzoquinoxaline-7-sulphonamide (NBQX; a selective non-N-methyl-d-aspartate (NMDA) glutamate receptor antagonist) or different doses (2, 4 or 8 nmol/100 nL) of the selective NMDA glutamate receptor antagonist LY235959. Microinjection of CoCl(2) into the LH had no effect on the tachycardiac baroreflex response, but did evoke a decrease in the reflex bradycardia caused by increases in blood pressure. Microinjection of NBQX into the LH had a similar effect on reflex bradycardia as CoCl(2), but had no effect on the tachycardiac response. Microinjection of increasing doses of LY235959 into the LH had no effect on the cardiac baroreflex response. In conclusion, the data suggest that the LH has a tonic facilitatory influence on the parasympathetic component of the baroreflex. The results also indicate that this facilitatory influence is mediated by local LH glutamatergic neurotransmission through non-NMDA glutamatergic receptors.

Insular cortex alpha(1)-adrenoceptors modulate the parasympathetic component of the baroreflex in unanesthetized rats

The insular cortex (IC) has been reported to modulate the cardiac parasympathetic activity of the baroreflex in unanesthetized rats. However, which neurotransmitters are involved in this modulation is still unclear. In the present study, we evaluated the possible involvement of local IC-noradrenergic neurotransmission in modulating reflex bradycardiac responses. Bilateral microinjection of the selective alpha(1)-adrenoceptor antagonist WB4101 (15 nmol/100 nL), into the IC of male Wistar rats, increased the gain of reflex bradycardia in response to mean arterial pressure (MAP) increases evoked by intravenous infusion of phenylephrine. However, bilateral microinjection of equimolar doses of either the selective alpha(2)-adrenoceptor antagonist RX821002 or the non-selective beta-adrenoceptor antagonist propranolol into the IC did not affect the baroreflex response. No effects were observed in basal MAP or heart rate values after bilateral microinjection of noradrenergic antagonists into the IC, thus suggesting no tonic influence of IC-noradrenergic neurotransmission on resting cardiovascular parameters. In conclusion, these data provide evidence that local IC-noradrenergic neurotransmission has an inhibitory influence on baroreflex responses to blood pressure increase evoked by phenylephrine infusion through activation of alpha(1)-adrenoceptors. (C) 2009 Elsevier B.V. All rights reserved.

Matrix Metalloproteinase Inhibition Improves Cardiac Dysfunction and Remodeling in 2-Kidney, 1-Clip Hypertension

Background: Enhanced cardiac matrix metalloproteinase activity (MMPs) has been associated with ventricular remodeling and cardiac dysfunction. It is unknown whether MMPs contribute to systolic/diastolic dysfunction and compensatory remodeling in 2-kidney, 1-clip (2K1C) hypertensive rats. To test this hypothesis, we used 2K1C rats after 2 weeks of surgery treated or not with a nonspecific inhibitor of MMPs (doxycycline). Methods and Results: We found that blood pressure and +/-dP/dt increased in 2K1C rats compared with sham groups, and these parameters were attenuated by doxycycline treatment (P < .05). Doxycycline also reversed cardiac hypertrophy observed in 2K1C rats (P < .05). Hypertensive rats showed increased MMP-2 levels in zymograms and in the tissue by immunofluorescence (P < .05) compared with sham groups. Increased total gelatinolytic activity was observed in untreated 2K1C rats when compared with sham groups (P < .05). Doxycycline decreased total gelatinolytic activity in 2K1C rats to control levels (P < .05). Conclusion: An imbalance in gelatinolytic activity, with increased MMP-2 levels and activity underlies the development of morphological and functional alterations found in the compensatory hypertrophy observed in 2K1C hearts. Because function and structure were restored by doxycycline, the inhibition of MMPs or their modulation may provide beneficial effects for therapeutic intervention in cardiac hypertrophy. (J Cardiac Fail 2010;16:599-608)

Changes in hemodynamic and neurohumoral control cause cardiac damage in one-kidney, one-clip hypertensive mice

Borges GR, Salgado HC, Silva CA, Rossi MA, Prado CM, Fazan R Jr. Changes in hemodynamic and neurohumoral control cause cardiac damage in one-kidney, one-clip hypertensive mice. Am J Physiol Regul Integr Comp Physiol 295: R1904-R1913, 2008. First published October 1, 2008; doi:10.1152/ajpregu.00107.2008.-Sympathovagal balance and baroreflex control of heart rate (HR) were evaluated during the development (1 and 4 wk) of one-kidney, one-clip (1K1C) hypertension in conscious mice. The development of cardiac hypertrophy and fibrosis was also examined. Overall variability of systolic arterial pressure (AP) and HR in the time domain and baroreflex sensitivity were calculated from basal recordings. Methyl atropine and propranolol allowed the evaluation of the sympathovagal balance to the heart and the intrinsic HR. Staining of renal ANG II in the kidney and plasma renin activity (PRA) were also evaluated. One and four weeks after clipping, the mice were hypertensive and tachycardic, and they exhibited elevated sympathetic and reduced vagal tone. The intrinsic HR was elevated only 1 wk after clipping. Systolic AP variability was elevated, while HR variability and baroreflex sensitivity were reduced 1 and 4 wk after clipping. Renal ANG II staining and PRA were elevated only 1 wk after clipping. Concentric cardiac hypertrophy was observed at 1 and 4 wk, while cardiac fibrosis was observed only at 4 wk after clipping. In conclusion, these data further support previous findings in the literature and provide new features of neurohumoral changes during the development of 1K1C hypertension in mice. In addition, the 1K1C hypertensive model in mice can be an important tool for studies evaluating the role of specific genes relating to dependent and nondependent ANG II hypertension in transgenic mice.

Monitoring of protein catabolism in neonates and young infants post-cardiac surgery

Aims: To evaluate cell catabolism by balance of nitrogen and phosphate, and creatinine excretion in children post-cardiac surgery; to establish protein and energy requirements to minimize catabolism; and to assess nutritional therapy by following these parameters and serial anthropometric measurements. Methods: A prospective observational study of children with congenital heart disease undergoing cardiac surgery. Blood samples and 24-h urine collections were obtained postoperatively for creatinine measurement and nitrogen and phosphate balance. Anthropometric measurements (weight, mid-arm muscle circumference and triceps skinfold thickness) were obtained preoperatively and at paediatric intensive care unit and hospital discharge. Results: Eleven children were studied for 3-10 postoperative days. Anabolism was associated with higher protein and energy intakes compared to catabolism (1.1 vs. 0.1 g/kg/day and 54 vs. 17 kcal/kg/day, respectively). On days with anabolism, phosphate balance was greater compared with that on days with catabolism. Daily creatinine excretion did not correlate with protein balance. Anthropometric measurements did not change significantly over time. Conclusions: Children with congenital heart disease undergoing cardiac surgery achieved anabolism with > 55 kcal/kg/day and > 1 g/kg/day of protein. Balance of phosphate was useful to monitor cell breakdown. Anthropometric measurements were not valuable to evaluate nutritional therapy in this population.

Effect of Oral Hygiene with 0.12% Chlorhexidine Gluconate on the Incidence of Nosocomial Pneumonia in Children Undergoing Cardiac Surgery

OBJECTIVE. To evaluate the effect of oral hygiene with 0.12% chlorhexidine gluconate on the incidence of nosocomial pneumonia and ventilator-associated pneumonia (VAP) in children undergoing cardiac surgery. DESIGN. Prospective, randomized, double-blind, placebo-controlled trial. SETTING. Pediatric intensive care unit (PICU) at a tertiary care hospital. patients. One hundred sixty children undergoing surgery for congenital heart disease, randomized into 2 groups: chlorhexidine (n = 87) and control (n = 73). INTERVENTIONS. Oral hygiene with 0.12% chlorhexidine gluconate or placebo preoperatively and twice a day postoperatively until PICU discharge or death. RESULTS. Patients in experimental and control groups had similar ages (median, 12.2 vs 10.8 months; P =. 72) and risk adjustment for congenital heart surgery 1 score distribution (66% in category 1 or 2 in both groups; P =. 17). The incidence of nosocomial pneumonia was 29.8% versus 24.6% (Pp. 46) and the incidence of VAP was 18.3% versus 15% (Pp. 57) in the chlorhexidine and the control group, respectively. There was no difference in intubation time (P =. 34), need for reintubation (P =. 37), time interval between hospitalization and nosocomial pneumonia diagnosis (P =. 63), time interval between surgery and nosocomial pneumonia diagnosis (P =. 10), and time on antibiotics (P =. 77) and vasoactive drugs (P =. 16) between groups. Median length of PICU stay (3 vs 4 days; P =. 53), median length of hospital stay (12 vs 11 days; P =. 67), and 28-day mortality (5.7% vs 6.8%; P =. 77) were also similar in the chlorhexidine and the control group. CONCLUSIONS. Oral hygiene with 0.12% chlorhexidine gluconate did not reduce the incidence of nosocomial pneumonia and VAP in children undergoing cardiac surgery.

Risk stratification in neonates and infants submitted to cardiac surgery with cardiopulmonary bypass: A multimarker approach combining inflammatory mediators, N-terminal pro-B-type natriuretic peptide and troponin I

Low cardiac output syndrome (LCOS) is a common problem following cardiac surgery with cardiopulmonary bypass (CPB) in neonates and infants, and its early recognition remains a challenging task. We aimed to test whether a multimarker approach combining inflammatory and cardiac markers provides complementary information for prediction of LCOS and death in children submitted to cardiac surgery with CPB. Forty-six children younger than 18 months with congenital heart defects were prospectively enrolled. No intervention was made. Blood samples were collected pre-operatively, during CPB and post-operatively (PO) for measurement of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Clinical data and outcome variables were recorded. Logistic regression was used to identify predictors of LCOS and death. Multivariate logistic regression identified pre-operative NT-proBNP and IL-8 4 h PO as independent predictors of LCOS, while cTnI 4 h PO and CPB length were independent predictors of death. The use of inflammatory and cardiac markers in combination improved sensitivity, negative predictive value and accuracy of the models. In conclusion, the combined assessment of inflammatory and cardiac biochemical markers can be useful for identifying young children at increased risk for LCOS and death after heart surgery with CPB. (C) 2008 Elsevier Ltd. All rights reserved.

Comparisons of the release of vasodilator substances from left and right cardiac chambers of the isolated perfused rabbit heart: Implications for intraventricular thrombus formation

Prostacyclin (PgI(2)) and endothelium-derived nitric oxide (EDNO) are produced by the arterial and venous endothelium. In addition to their vasodilator action on vascular smooth muscle, both act together to inhibit platelet aggregation and promote platelet disaggregation. EDNO also inhibits platelet adhesion to the endothelium. EDNO and PgI(2) have been shown to be released from the cultured endocardial cells. In this study, we examined the release of vasoactive substances from the intact endocardium by using isolated rabbit hearts perfused with physiological salt solution (95% O(2)/5% CO(2), T = 37 degrees C). The right and left cardiac chambers were perfused through separate constant-flow perfusion loops (physiological salt solution, 8 ml min(-1)). Effluent from left and right cardiac, separately, was bioassayed on canine coronary artery smooth muscle, which had been contracted with prostaglandin F(2 alpha_)(2 x 10(-6) M) and no change in tension was exhibit. However, addition of calcium ionophore A23187 (10(-6) M) to the cardiac chambers` perfusion line induced vasodilation of the bioassay coronary ring, 61.4 +/- 7.4% versus 70.49 +/- 6.1% of initial prostaglandin F(2 alpha) contraction for the left and right cardiac chambers perfusate, respectively (mean +/- SEM, n = 10, p > 0.05). Production of vasodilator was blocked totally in the left heart but, only partially blocked in the right heart by adding indomethacin (10(-5) M) to the perfusate, respectively, 95.2 +/- 2.2% versus 41.5 +/- 4.8% (mean +/- SEM, n = 10, p < 0.05). 6-Keto prostaglandin F(1 alpha), measured in the endocardial superfusion effluent was also higher for the left cardiac chambers than for the right at the time of stimulation with the A23187, respectively, 25385.88 +/- 5495 pg/ml (n = 8) versus 13,132.45 +/- 1839.82 pg/ml (n = 8), (p < 0.05). These results showed that cyclooxygenase pathway plays major role in generating vasoactive substances for the left cardiac chamber endocardium; while it is not the main pathway for the right ventricular endocardium at which EDNO and PgI(2) Could act together and potentiate their antithrombogenic activities in isolated perfused rabbit heart. This may be an explanation for the intraventricular thrombus mostly seen in left ventricle rather than in right ventricle as a complication of myocardial infarction. (C) 2009 Elsevier Inc. All rights reserved.

Nomenclature for congenital and paediatric cardiac disease: Historical perspectives and The International Pediatric and Congenital Cardiac Code

Clinicians working in the field of congenital and paediatric cardiology have long felt the need for a common diagnostic and therapeutic nomenclature and coding system with which to classify patients of all ages with congenital and acquired cardiac disease. A cohesive and comprehensive system of nomenclature, suitable for setting a global standard for multicentric analysis of outcomes and stratification of risk, has only recently emerged, namely, The International Paediatric and Congenital Cardiac Code. This review, will give an historical perspective on the development of systems of nomenclature in general, and specifically with respect to the diagnosis and treatment of patients with paediatric and congenital cardiac disease. Finally, current and future efforts to merge such systems into the paperless environment of the electronic health or patient record on a global scale are briefly explored. On October 6, 2000, The International Nomenclature Committee for Pediatric and Congenital Heart Disease was established. In January, 2005, the International Nomenclature Committee was constituted in Canada as The International Society for Nomenclature of Paediatric and Congenital Heart Disease. This International Society now has three working groups. The Nomenclature Working Group developed The International Paediatric and Congenital Cardiac Code and will continue to maintain, expand, update, and preserve this International Code. It will also provide ready access to the International Code for the global paediatric and congenital cardiology and cardiac surgery communities, related disciplines, the healthcare industry, and governmental agencies, both electronically and in published form. The Definitions Working Group will write definitions for the terms in the International Paediatric and Congenital Cardiac Code, building on the previously published definitions from the Nomenclature Working Group. The Archiving Working Group, also known as The Congenital Heart Archiving Research Team, will link images and videos to the International Paediatric and Congenital Cardiac Code. The images and videos will be acquired from cardiac morphologic specimens and imaging modalities such as echocardiography, angiography, computerized axial tomography and magnetic resonance imaging, as well as intraoperative images and videos. Efforts are ongoing to expand the usage of The International Paediatric and Congenital Cardiac Code to other areas of global healthcare. Collaborative efforts are under-way involving the leadership of The International Nomenclature Committee for Pediatric and Congenital Heart Disease and the representatives of the steering group responsible for the creation of the 11th revision of the International Classification of Diseases, administered by the World Health Organisation. Similar collaborative efforts are underway involving the leadership of The International Nomenclature Committee for Pediatric and Congenital Heart Disease and the International Health Terminology Standards Development Organisation, who are the owners of the Systematized Nomenclature of Medicine or ""SNOMED"". The International Paediatric and Congenital Cardiac Code was created by specialists in the field to name and classify paediatric and congenital cardiac disease and its treatment. It is a comprehensive code that can be freely downloaded from the internet (http://www.IPCCC.net) and is already in use worldwide, particularly for international comparisons of outcomes. The goal of this effort is to create strategies for stratification of risk and to improve healthcare for the individual patient. The collaboration with the World Heath Organization, the International Health Terminology Standards Development Organisation, and the healthcare Industry, will lead to further enhancement of the International Code, and to Its more universal use.

Beyond neuropathy in hereditary sensory and autonomic neuropathy type V: cognitive evaluation

Background and purpose: Hereditary sensory and autonomic neuropathy ( HSAN) type V is a very rare disorder. It is characterized by the absence of thermal and mechanical pain perception caused by decreased number of small diameter neurons in peripheral nerves. Recent genetic studies have pointed out the aetiological role of nerve growth factor beta, which is also involved in the development of the autonomic nervous system and cholinergic pathways in the brain. HSAN type V is usually reported not to cause mental retardation or cognitive decline. However, a structured assessment of the cognitive pro. le of these patients has never been made. Methods and results: We performed a throughout evaluation of four HSAN type V patients and compared their performance with 37 normal individuals. Our patients showed no cognitive deficits, not even mild ones. Discussion and Conclusions: Although newer mutations on this and related disorders are continuously described, their clinical characterization has been restricted to the peripheral aspects of these conditions. A broader characterization of this rare disorder may contribute to better understand the mechanisms of the nociceptive and cognitive aspects of pain.

Report from The International Society for Nomenclature of Paediatric and Congenital Heart Disease: cardiovascular catheterisation for congenital and paediatric cardiac disease (Part 1-Procedural nomenclature)

Interventional cardiology for paediatric and congenital cardiac disease is a relatively young and rapidly evolving field. As the profession begins to establish multi-institutional databases, a universal system of nomenclature is necessary for the field of interventional cardiology for paediatric and congenital cardiac disease. The purpose of this paper is to present the results of the efforts of The International Society for Nomenclature of Paediatric and Congenital Heart Disease to establish a system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease, focusing both on procedural nomenclature and on the nomenclature of complications associated with interventional cardiology. This system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease is a component of The International Paediatric and Congenital Cardiac Code. This manuscript is the first part of a two-part series. Part 1 will cover the procedural nomenclature associated with interventional cardiology as treatment for paediatric and congenital cardiac disease. This procedural nomenclature of The International Paediatric and Congenital Cardiac Code will be used in the IMPACT Registry (TM) (IMproving Pediatric and Adult Congenital Treatment) of the National Cardiovascular Data Registry (R) of The American College of Cardiology. Part 2 will cover the nomenclature of complications associated with interventional cardiology as treatment for paediatric and congenital cardiac disease.

Report from The International Society for Nomenclature of Paediatric and Congenital Heart Disease: cardiovascular catheterisation for congenital and paediatric cardiac disease (Part 2-Nomenclature of complications associated with interventional cardiology)

Interventional cardiology for paediatric and congenital cardiac disease is a relatively young and rapidly evolving field. As the profession begins to establish multi-institutional databases, a universal system of nomenclature is necessary for the field of interventional cardiology for paediatric and congenital cardiac disease. The purpose of this paper is to present the results of the efforts of The International Society for Nomenclature of Paediatric and Congenital Heart Disease to establish a system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease, focusing both on procedural nomenclature and the nomenclature of complications associated with interventional cardiology. This system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease is a component of The International Paediatric and Congenital Cardiac Code. This manuscript is the second part of the two-part series. Part 1 covered the procedural nomenclature associated with interventional cardiology as treatment for paediatric and congenital cardiac disease. Part 2 will cover the nomenclature of complications associated with interventional cardiology as treatment for paediatric and congenital cardiac disease.

Cardiac mast cell proteases do not contribute to the regulation of the rat coronary vascular responsiveness to arterial delivered angiotensin I and II

Cardiac mast cells (MC) are apposed to capillaries within the heart and release renin and proteases capable of metabolizing angiotensins (Ang). Therefore, we hypothesized that mast cell degranulation could alter the rat coronary vascular responsiveness to the arterial delivered Ang I and Ang II, taking into account carboxypeptidase and chymase-1 activities. Hearts from animals that were either pretreated or not with systemic injection of the secretagogue compound 48/80 were isolated and mounted on a Langendorff apparatus to investigate coronary reactivity. The proteolytic activity of the cardiac perfusate from isolated hearts, pretreated or not with the secretagogue, toward Ang I and tetradecapeptide renin substrate was analyzed by HPLC. Coronary vascular reactivity to peptides was not affected by compound 48/80 pretreatment, despite the extensive amount of cardiac MC degranulation. Cardiac MC activation did not modify the generation of both Ang II and Ang 5-10 from Ang I by cardiac perfusate, activities that could be ascribed to MC carboxypeptidase and chymase-1, respectively. An aliskiren-resistant Ang I-forming activity was increased in perfusates from secretagogue-treated hearts. Thus, cardiac MC proteases capable of metabolizing angiotensins do not affect rat coronary reactivity to arterial delivered Ang I and II. (C) 2010 Elsevier Inc. All rights reserved.

The improvement of care for paediatric and congenital cardiac disease across the World: a challenge for the World Society for Pediatric and Congenital Heart Surgery

The diagnosis and treatment for paediatric and congenital cardiac disease has undergone remarkable progress over the last 60 years. Unfortunately, this progress has been largely limited to the developed world. Yet every year approximately 90% of the more than 1,000,000 children who are born with congenital cardiac disease across the world receive either suboptimal care or are totally denied care. While in the developed world the focus has changed from an effort to decrease post-operative mortality to now improving quality of life and decreasing morbidity, which the focus of this Supplement, the rest of the world still needs to develop basic access to congenital cardiac care. The World Society for Pediatric and Congenital Heart Surgery [http://www.wspchs.org/] was established in 2006. The Vision of the World Society is that every child born anywhere in the world with a congenital heart defect should have access to appropriate medical and surgical care. The Mission of the World Society is to promote the highest quality comprehensive care to all patients with pediatric and/or congenital heart disease, from the fetus to the adult, regardless of the patient`s economic means, with emphasis on excellence in education, research and community service. We present in this article an overview of the epidemiology of congenital cardiac disease, the current and future challenges to improve care in the developed and developing world, the impact of the globalization of cardiac surgery, and the role that the World Society should play. The World Society for Pediatric and Congenital Heart Surgery is in a unique position to influence and truly improve the global care of children and adults with congenital cardiac disease throughout the world [http://www.wspchs.org/].

Thyroid gland and cerebella lesions: New risk factors for sudden cardiac death in schizophrenia?

People with schizophrenia show a two to threefold increased risk to die prematurely than those without schizophrenia. Patients` life style, suicide, premature development of cardiovascular disease, high prevalence of metabolic syndrome and sudden cardiac death are well-known causes of the excess mortality. The exact pathophysiological cause of sudden death in schizophrenia is unknown, but it is likely that cardiac arrhythmia and respiratory abnormalities play potential role. Some antipsychotics may be associated with cardiovascular adverse events (e.g., QT interval prolongation) and lesions in specific brain regions, such as cerebella may be associated with respiratory abnormalities, suggesting that metabolic and brain dysfunction could lead to sudden cardiac death in patients with schizophrenia. However, exact knowledge regarding the association of these findings and schizophrenia is lacking. As subclinical hyperthyroidism has been linked with increased risk of cardiovascular disease and cerebella progressive atrophy has been observed in patients with schizophrenia, we propose in this paper that subclinical thyroid dysfunction and cerebella volume loss could be considered as new risk factor for sudden cardiac death in schizophrenia. (C) 2010 Elsevier Ltd. All rights reserved.