Computational prediction of drug response in short QT syndrome type 1 based on measurements of compound effect in stem cell-derived cardiomyocytes.

Short QT (SQT) syndrome is a genetic cardiac disorder characterized by an abbreviated QT interval of the patient's electrocardiogram. The syndrome is associated with increased risk of arrhythmia and sudden cardiac death and can arise from a number of ion channel mutations. Cardiomyocytes derived from induced pluripotent stem cells generated from SQT patients (SQT hiPSC-CMs) provide promising platforms for testing pharmacological treatments directly in human cardiac cells exhibiting mutations specific for the syndrome. However, a difficulty is posed by the relative immaturity of hiPSC-CMs, with the possibility that drug effects observed in SQT hiPSC-CMs could be very different from the corresponding drug effect in vivo. In this paper, we apply a multistep computational procedure for translating measured drug effects from these cells to human QT response. This process first detects drug effects on individual ion channels based on measurements of SQT hiPSC-CMs and then uses these results to estimate the drug effects on ventricular action potentials and QT intervals of adult SQT patients. We find that the procedure is able to identify IC50 values in line with measured values for the four drugs quinidine, ivabradine, ajmaline and mexiletine. In addition, the predicted effect of quinidine on the adult QT interval is in good agreement with measured effects of quinidine for adult patients. Consequently, the computational procedure appears to be a useful tool for helping predicting adult drug responses from pure in vitro measurements of patient derived cell lines.

Application of Zebrafish Model in the Suppression of Drug-Induced Cardiac Hypertrophy by Traditional Indian Medicine Yogendra Ras.

Zebrafish is an elegant vertebrate employed to model the pathological etiologies of human maladies such as cardiac diseases. Persistent physiological stresses can induce abnormalities in heart functions such as cardiac hypertrophy (CH), which can lead to morbidity and mortality. In the present study, using zebrafish as a study model, efficacy of the traditional Indian Ayurveda medicine "Yogendra Ras" (YDR) was validated in ameliorating drug-induced cardiac hypertrophy. YDR was prepared using traditionally described methods and composed of nano- and micron-sized metal particles. Elemental composition analysis of YDR showed the presence of mainly Au, Sn, and Hg. Cardiac hypertrophy was induced in the zebrafish following a pretreatment with erythromycin (ERY), and the onset and reconciliation of disease by YDR were determined using a treadmill electrocardiogram, heart anatomy analysis, C-reactive protein release, and platelet aggregation time-analysis. YDR treatment of CH-induced zebrafish showed comparable results with the Standard-of-care drug, verapamil, tested in parallel. Under in-vitro conditions, treatment of isoproterenol (ISP)-stimulated murine cardiomyocytes (H9C2) with YDR resulted in the suppression of drug-stimulated biomarkers of oxidative stress: COX-2, NOX-2, NOX-4, ANF, troponin-I, -T, and cardiolipin. Taken together, zebrafish showed a strong disposition as a model for studying the efficacy of Ayurvedic medicines towards drug-induced cardiopathies. YDR provided strong evidence for its capability in modulating drug-induced CH through the restoration of redox homeostasis and exhibited potential as a viable complementary therapy.

Marijuana in pediatric and adult congenital heart disease heart transplant listing: A survey of provider practices and attitudes.

Despite increasing legalization and use of marijuana, there is no consensus among pediatric heart transplant institutions or providers regarding users' eligibility for cardiac transplant. We sent a survey to pediatric and ACHD transplant providers (physicians, surgeons, transplant coordinators, and pharmacists) assessing their current institution's policies and their personal opinions about marijuana use in patients being considered for heart transplantation. Of the respondents, 84% practice in the United States and Canada. Most providers (80%) care for both pediatric and ACHD patients. Respondents included cardiologists (77%) and surgeons (11%), with the remaining being coordinators and pharmacists. Most providers (73%) reported their institution had no policy regarding marijuana use in heart transplant candidates. Only 20% of respondents' institutions consider mode of consumption, with 87% and 53% approving of oral and transdermal routes, respectively, and only 7% approving of vaporized or smoked routes. While 73% of providers would consider illegal marijuana use an absolute/relative contraindication to heart transplant listing, the number decreases to 57% for legal recreational users and 21% for legal medical users. Most providers personally believe marijuana to be physically and mentally/emotionally harmful to pediatric patients (67% and 72%, respectively). Many institutions lack a policy regarding marijuana use in pediatric and ACHD heart transplant candidates, and there is considerable disagreement among providers on the best practice. With increasing legalization and use of marijuana, each institution will have to address this issue thoughtfully to continue to provide high-quality, consistent, and equitable care for pediatric and ACHD heart transplant candidates.

Pharmacological therapy in adult congenital heart disease: growing need, yet limited evidence.

Congenital heart disease (CHD) is the most common inborn defect. Due to advances in paediatric care, surgical, and catheter procedures the number of adults with CHD has grown remarkably in recent years. Most of these patients, however, have residua from their original operation/s and require life-long care, many of them are subjected to further haemodynamic and electrophysiological interventions during adulthood. While such re-do surgical or catheter interventions together with device therapy and transplantation play a key therapeutic role, increasingly, adults with CHD require drug therapy for late complications namely heart failure (HF), arrhythmias, pulmonary and systemic hypertension, thromboembolic events, etc. Unlike other cardiovascular areas, drug therapy in adult CHD is based on scarce clinical data and remains largely empiric. Consequently, pharmacological therapies are individualized to ameliorate patients' symptoms and/or degree of haemodynamic impairment. Thus far, recommendations have been difficult to make and formalized guidelines on drug therapy are lacking. We review herewith the rationale, limited evidence and knowledge gaps regarding drug therapy in this growing cardiovascular field and discuss pharmacotherapy options in specific conditions namely HF, arrhythmias, thrombosis, pulmonary arterial hypertension, contraception, and pregnancy.

Therapeutic Effect and Mechanism of Action of Abnormal Savda Munziq in Development of Degenerative Atherosclerotic Aortic Valve Disease.

BACKGROUND The aim of this study was to investigate the therapeutic effect of abnormal Savda Munziq (ASMq) on the development of degenerative atherosclerotic aortic valve disease and its underlying mechanisms. MATERIAL AND METHODS We randomly divided 80 rabbits into 4 groups: a normal control group (group N, n=20); a high-fat diet group (group HC, n=20); a high-fat diet and Atorvastatin calcium intervention group (group AI, n=20); and a high-fat diet and ASMq intervention group (group MI, n=20). For evaluation of blood lipid profiles, blood samples were collected at week 0 and at the end of week 8. Aortic valve samples were taken at weeks 0, 2, 4, 6, and 8 for atomic force microscopy (AFM) examination of endothelial cell nanostructures, and at week 8 for pathological examinations. RESULTS Triglyceride (TG), cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein HDL levels of rabbits in group HC were significantly different from those in group N (P<0.01). TG, TC, LDL, and HDL values of rabbits in group MI were significantly different from rabbits in group HC (P<0.05). Pathological examination revealed that the aortic valves from rabbits in group MI were visibly clear, with strong endothelial cell continuity. No infiltration of macrophages or other inflammatory cells nor subendothelial calcium deposition was found when compared with rabbits in group HC. CONCLUSIONS ASMq therapy can delay the onset of degenerative calcific aortic valve disease, and its effects are similar to those of Atorvastatin.

CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy.

BACKGROUND: The CHInese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES) study was an international randomized double-blind placebo-controlled trial of MLC601 (NeuroAiD) in subjects with cerebral infarction of intermediate severity within 72 h. CHIMES-E (Extension) aimed at evaluating the effects of the initial 3-month treatment with MLC601 on long-term outcome for up to 2 years. METHODS: All subjects randomized in CHIMES were eligible for CHIMES-E. Inclusion criteria for CHIMES were age ≥18, baseline National Institute of Health Stroke Scale of 6-14, and pre-stroke modified Rankin Scale (mRS) ≤1. Initial CHIMES treatment allocation blinding was maintained, although no further study treatment was provided in CHIMES-E. Subjects received standard care and rehabilitation as prescribed by the treating physician. mRS, Barthel Index (BI), and occurrence of medical events were ascertained at months 6, 12, 18, and 24. The primary outcome was mRS at 24 months. Secondary outcomes were mRS and BI at other time points. RESULTS: CHIMES-E included 880 subjects (mean age 61.8 ± 11.3; 36% women). Adjusted OR for mRS ordinal analysis was 1.08 (95% CI 0.85-1.37, p = 0.543) and mRS dichotomy ≤1 was 1.29 (95% CI 0.96-1.74, p = 0.093) at 24 months. However, the treatment effect was significantly in favor of MLC601 for mRS dichotomy ≤1 at 6 months (OR 1.49, 95% CI 1.11-2.01, p = 0.008), 12 months (OR 1.41, 95% CI 1.05-1.90, p = 0.023), and 18 months (OR 1.36, 95% CI 1.01-1.83, p = 0.045), and for BI dichotomy ≥95 at 6 months (OR 1.55, 95% CI 1.14-2.10, p = 0.005) but not at other time points. Subgroup analyses showed no treatment heterogeneity. Rates of death and occurrence of vascular and other medical events were similar between groups. CONCLUSIONS: While the benefits of a 3-month treatment with MLC601 did not reach statistical significance for the primary endpoint at 2 years, the odds of functional independence defined as mRS ≤1 was significantly increased at 6 months and persisted up to 18 months after a stroke.

Comparison of six generic vancomycin products for treatment of methicillin-resistant Staphylococcus aureus experimental endocarditis in rabbits.

Concerns have recently emerged about the potency and the quality of generic vancomycin (VAN) products approved for use in humans, based on experiments in a neutropenic mouse thigh infection model. However, other animal models may be more appropriate to decipher the bactericidal activities of VAN generics in vivo and to predict their efficacy in humans. We aimed to compare the bactericidal activities of six generic VAN products currently used in France (Mylan and Sandoz), Spain (Hospira), Switzerland (Teva), and the United States (Akorn-Strides and American Pharmaceutical Products [APP]) in a rabbit model of aortic valve endocarditis induced by 8 × 10(7) CFU of methicillin-resistant Staphylococcus aureus (MRSA) strain COL (VAN MIC, 1.5 µg/ml). In vitro, there were no significant differences in the time-kill curve studies performed with the six generic VAN products. Ten rabbits in each group were treated with intravenous (i.v.) VAN, 60 mg/kg of body weight twice a day (b.i.d.) for 4 days. Mean peak serum VAN levels, measured 45 min after the last injection, ranged from 35.5 (APP) to 45.9 µg/ml (Teva). Mean trough serum VAN levels, measured 12 h after the last injection, ranged from 2.3 (Hospira) to 9.2 (APP) µg/ml. All generic VAN products were superior to controls (no treatment) in terms of residual organisms in vegetations (P < 0.02 for each comparison) and in the spleen (P < 0.005 for each comparison). Pairwise comparisons of generic VAN products found no significant differences. In conclusion, a stringent MRSA endocarditis model found no significant differences in the bactericidal activities of six generic VAN products currently used in Europe and America.

Nifekalant enlarged the transmural activation-recovery interval difference as well as the peak-to-end interval on surface ECG in a patient with short-QT syndrome.

A 38-year-old woman with type 1 short-QT syndrome (SQTS) was referred to our hospital. Her ECG showed short QT/QTc interval and peaked T wave. Activation-recovery intervals (ARIs) were calculated from the intracardiac endocardial and epicardial electrode catheters placed in the left ventricle (LV). Intravenous administration of nifekalant prolonged effective refractory period at multiple ventricular sites as well as the QT/QTc interval (from 260/300 to 364/419 ms) on the surface ECG. Nifekalant also enlarged the transmural ARI dispersion of the ventricular repolarization, which was measured by the difference between the longest endocardial ARI and the shortest epicardial ARI during atrial pacing at 90 bpm, from 73 to 103-105 ms. These values corresponded to the intervals between the peak and end of the T wave on the surface ECG. Nifekalant-induced QT interval prolongation on the surface ECG may not indicate attenuation of the arrhythmogenic potential in the heart of SQTS patients.

[Intervention of astragalus injection on the kidney injury after cardiopulmonary bypass of infants with congenital heart disease].

OBJECTIVE: To study the intervention of astragalus injection in the kidney injury of infants with congenital heart disease after cardiopulmonary bypass, thus providing a new method for protection of the kidney injury in them. METHODS: Forty infants undergoing cardiac surgery with cardiopulmonary bypass were randomly assigned to the test group and the control group, twenty in each group. Astragalus Injection (at the dose of 2 mL/kg) was added in the perfusion fluid before giving to infants in the test group before bypass, while the normal saline of the same volume was added in the perfusion fluid before giving to infants in the control group (P < 0.01). The concentrations of serum tumor necrosis factor-alpha (TNF)-alpha, interleukin-6 (IL-6), cystatin C (CysC), and N-acetyl-beta-D-glucosaminidase (NAG) were detected with ELISA at the following time points, i.e., before bypass (T1), by the end of the surgery (T2), 2 h after surgery (T3), 6 h after surgery (T4), and 24 h after surgery (T5). RESULTS: The serum CysC concentrations were not significantly higher after CPB (P > 0.05). The urinary NAG level increased significantly in the control group after surgery (P < 0.05), but no obvious increase of the urinary NAG level was found in the test group after surgery (P > 0.05). It was obviously lower than that of the control group (P < 0.05). After CPB serum TNF-alpha and IL-6 levels increased significantly in the control group (P < 0.05), while they were lower in the test group than in the control group (P < 0.01). CONCLUSIONS: CPB may result in the renal tubular injury in infants with congenital heart disease. The application of Astragalus Injection before the CPB plays a role in protecting renal tubular functions.

Alternativas terapéuticas para la insuficiencia cardíaca en los ancianos: [revisión] / Therapeutic alternatives for treating heart failure in elderly patients: [review]

La insuficiencia cardíaca (IC) es una importante causa de mortalidad en todo el mundo y el principal motivo de hospitalización de origen no quirúrgico en muchos países. Existe un gran número de variables predictivas acerca del pronóstico de pacientes con IC, una de ellas es la edad. Además, la comorbilidad por causa no cardíaca dificulta el tratamiento en un importante grupo de pacientes ancianos con IC y casi la mitad de los pacientes con síntomas de IC presenta una fracción de eyección del ventrículo izquierdo conservada. Sin embargo, los ensayos clínicos en IC no se han centrado ni en el grupo de pacientes ancianos ni en aquellos con fracción de eyección conservada. Por esta razón no se han establecido recomendaciones específicas para este grupo. Este artículo revisará los estudios más importantes sobre IC realizados en los últimos años y analizará los resultados en pacientes de edad igual o superior a 65 años. Esta revisión incluye los betabloqueantes, inhibidores de la enzima convertidora de angiotensina, antagonistas del receptor de la angiotensina, antagonistas de los receptores de la aldosterona, nitratos más hidralazina, digoxina, estatinas, el desfibrilador automático implantable y la resincronización cardíaca.(AU)

Alternativas terapéuticas para la insuficiencia cardíaca en los ancianos: [revisión] / Therapeutic alternatives for treating heart failure in elderly patients: [review]

La insuficiencia cardíaca (IC) es una importante causa de mortalidad en todo el mundo y el principal motivo de hospitalización de origen no quirúrgico en muchos países. Existe un gran número de variables predictivas acerca del pronóstico de pacientes con IC, una de ellas es la edad. Además, la comorbilidad por causa no cardíaca dificulta el tratamiento en un importante grupo de pacientes ancianos con IC y casi la mitad de los pacientes con síntomas de IC presenta una fracción de eyección del ventrículo izquierdo conservada. Sin embargo, los ensayos clínicos en IC no se han centrado ni en el grupo de pacientes ancianos ni en aquellos con fracción de eyección conservada. Por esta razón no se han establecido recomendaciones específicas para este grupo. Este artículo revisará los estudios más importantes sobre IC realizados en los últimos años y analizará los resultados en pacientes de edad igual o superior a 65 años. Esta revisión incluye los betabloqueantes, inhibidores de la enzima convertidora de angiotensina, antagonistas del receptor de la angiotensina, antagonistas de los receptores de la aldosterona, nitratos más hidralazina, digoxina, estatinas, el desfibrilador automático implantable y la resincronización cardíaca.

Successful transcatheter cryoablation in infants with drug-resistant supraventricular tachycardia: a case series.

PURPOSE: Drug-resistant supraventricular tachycardia can cause hemodynamic instability, especially in infants. There are no case-series reports of transcatheter cryoablation treatment for infants with drug-resistant supraventricular tachycardia. Our purpose is to report our experience with transcatheter cryoablation in three infants with drug-resistant supraventricular tachycardia. METHODS: We reviewed clinical and electrophysiologic data from infants who underwent cryothermal ablation for drug-resistant supraventricular tachycardia (SVT) at our institution. RESULTS: Three patients (age 10-42 days) underwent transcatheter cryothermal ablation over a 1-year period. None had arrhythmia suppression on medical management, and all had hemodynamic instability from persistent SVT episodes. Cryothermal mapping (-30 C) localized the suspected foci. All foci were adjacent to the AV node. Cryoablation lesions were delivered at and around mapped foci. In one patient, cryothermal energy application eliminated the SVT but resulted in transient right bundle branch block that resolved later. Two patients had hemodynamically insignificant episodes of SVT in the immediate post-ablation period that resolved with standard antiarrhythmic treatment. One died of sepsis but remained SVT free for 10 days after the procedure without antiarrhythmic medications. Neither of the two surviving patients had SVT recurrence at 6-month follow-up off medications. CONCLUSIONS: In our series, transcatheter cryoablation was an effective treatment for drug-resistant SVT in infants. We encountered some early nonsustained post-procedure SVT; however, such episodes did not predict procedural failure.

Infants and children with tachycardia: natural history and drug administration.

Tachyarrhythmias can occur at any age from the developing fetus through adulthood. However, in deference to adult-onset ischemic cardiac issues, abnormal heart rhythms occurring in the young are often due to developmental alterations of the cardiac conduction tissue, genetically-inherited changes of myocardial cellular ion membrane properties and both pre- and post-surgical repair of associated structural congenital heart anatomical defects. And different from adults, abnormal rhythms occurring in the young can spontaneously disappear with progressive patient growth. Both supra- and ventricular tachyarrhythmias occur in the young although atrial rhythm abnormalities far exceed those of the ventricle. In both, pharmacologic therapies to alter tissue conduction and refractoriness remain the mainstay for initial intervention in the infant and young child, reserving more invasive and potentially harmful ablation therapies for drug-refractory cases. The purpose of the review is to present common and uncommon tachyarrhythmias which can occur in the fetus and throughout infancy. Emphasis will be placed on their electrocardiographic identification, recognition of any associated structural congenital heart defects and recommended pharmacologic management. Drug therapies will be divided according to mechanism of action and discussions of which particular agent is potentially best-suited to treat which specific tachyarrhythmia. A listing of current pharmacologic agents used in the young with appropriate dosages is included.

[Effects of Shenfu Injection on inflammatory cytokines during cardiopulmonarbypass in infants].

OBJECTIVE: To evaluate the effects of Shenfu Injection (SF) on cytokines during cardiopulmonary bypass (CPB) in infants. METHODS: Twenty-four infants with congenital heart disease, aged below three years, were randomly assigned to the control group and the SF group equally. In the SF group, 1 mL/kg of SF was given through center vein pump after center vein puncture being performed, while only normal saline was given instead in the control group. Blood sample was obtained for measurement of serum necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) concentration by ELISA, at various time points in the process, i.e. right after anesthesia induction (T1), beginning of CPB (T2), aortic off-clamping (T3), 20 min after CPB (T4), the end of CPB (T5), and 6 h (T6) and 24 h (T7) after CPB. RESULTS: The time for reverting to sinus heart rhythm and analepsia after CPB was shorter in the SF group than in the control group (P < 0.05). Serum concentration of TNF-a and IL-6 was equal in the two groups at T1; they increased significantly after CPB (P < 0.05), reached the peak value at T4 and reduced to the normal level at T7 in the control group. TNF-alpha concentration was significantly lower at T3, T4 and T5, and IL-6 concentration was lower at T4 in the SF group than that in the control group at corresponding time point (P < 0.05). CONCLUSION: SF could shorten the time for reverting to sinus heart rhythm and analepsia after CPB in infants, and suppress the inflammatory response caused by CPB.

Folate intake and the primary prevention of non-neural birth defects.

OBJECTIVES: To investigate whether maternal periconceptional folate intake is associated with a reduction in selected non-neural birth defects in Western Australia (WA). METHODS: Case-control study of folate intake in women whose infants had orofacial clefts (62); congenital heart defects (151); urinary tract defects (117); limb reduction defects (26); or other major birth defects (119); and 578 control women. RESULTS: Neither folic acid supplements nor dietary folate intake in women not using supplements was significantly associated with a reduction in risk in any of the case groups. In contrast to neural tube defects, WA population data for orofacial clefts, heart defects, limb reduction defects and urinary tract defects showed no fall in prevalence since the introduction of folate promotion and voluntary food fortification. CONCLUSIONS: This study provides no evidence of folate being an important factor in the prevention of birth defects other than neural tube defects.

Nutrition care for newborns with congenital heart disease.

Those health care professionals entrusted with the care of infants with congenital heart disease require an understanding of the unique nutritional needs of this population. This article defines the congenital, physiologic, and nutritional variables encountered in this population. The nutritional needs, multi-factorial sources of undernutrition, and consequences of inadequate nutrition in infants with congenital heart disease are discussed, as well as medical and nutritional management strategies intended to optimize growth and reduce morbidity.

Prostaglandin E1 treatment in patent ductus arteriosus dependent congenital heart defects.

Prostaglandin E1 (PGE1) treatment can be life saving in patients suffering from ductus dependent congenital heart defect. We analyzed the indications and side-effects of PGE1 therapy over a five-year period. The purpose of the study was also to examine whether a change in serum electrolyte levels could be detected. Forty-nine patients were treated with PGE1 during this period. PGE1 treatment was indicated by ductus dependent systemic circulation in 16 cases, ductus dependent pulmonary circulation in 17 cases, transposition of the great arteries in 13 cases and pulmonary hypertension (persistent fetal circulation) in three cases. As early side-effects of the treatment, fever occurred in 27/49 cases while apnoea was observed in 15 patients. In a one-week-old neonate with coarctation of the aorta grade III intraventricular hemorrhage developed. A mild decrease of sodium, potassium and chloride levels and a slight shift of pH levels toward metabolic alkalosis could be detected after one day and one week of PGE1 treatment. Because of these side-effects of PGE1 patients should be monitored in an intensive care unit. According to our observations electrolyte levels may exhibit a slight decrease; however, in the case of a short-term therapy extra salt supplementation is not necessary.

Palivizumab: a review of its use as prophylaxis for serious respiratory syncytial virus infection.

Palivizumab (Synagi) is a humanized monoclonal antibody that provides immunoprophylaxis against serious lower respiratory tract infections (LRTIs) caused by respiratory syncytial virus (RSV). RSV is the leading cause of hospitalization for LRTIs in infants, causing winter- or wet-season epidemics. In two double-blind, placebo-controlled trials, intramuscular palivizumab 15 mg/kg every 30 days for 5 months significantly reduced RSV-related hospitalizations by 55% in 1502 infants with prematurity and/or bronchopulmonary dysplasia/chronic lung disease (BPD/CLD) and by 45% in 1287 infants with hemodynamically significant congenital heart disease (HSCHD). Reductions were statistically significant versus placebo in infants with BPD/CLD, with all degrees of prematurity, and with acyanotic/other heart disease. Palivizumab was generally well tolerated, with < or =1.9% of recipients discontinuing treatment for tolerability reasons. In placebo-controlled trials, the most common potentially drug-related adverse events were fever, nervousness, injection-site reactions, and diarrhea. Drug-related events occurred in 7.2-11% of palivizumab recipients in controlled trials (vs 6.9-10% with placebo) and 0-7.9% in open-label trials. Very few serious potentially drug-related adverse events occurred in clinical trials; four occurred in 2 of 285 patients in one open-label trial. No significant anti-palivizumab antibodies developed during palivizumab use. Palivizumab trough serum concentrations were below the recommended 40 microg/mL in about 33% and up to 14% of children prior to their second and third palivizumab injections. In pharmacoeconomic studies, the cost of palivizumab per hospitalization averted was generally lowest in the highest-risk infants. Drug cost was generally the most influential factor in sensitivity analyses. In conclusion, prophylaxis with palivizumab significantly reduces the incidence of RSV-related hospitalization relative to placebo and is generally well tolerated in high-risk infants aged <2 years, including those with prematurity and BPD/CLD or HSCHD, which are risk factors for early or serious RSV infection. Palivizumab is approved for use in these patients. Other high-risk infants in whom palivizumab has not been formally assessed, such as those with immunodeficiency, cystic fibrosis, or location-specific risk factors (including extended hospital stays) might potentially benefit from palivizumab. The use of palivizumab in these other high-risk populations is likely to be determined as much by pharmacoeconomic considerations as by efficacy outcomes.

Antioxidant therapy with Salvia miltiorrhiza decreases plasma endothelin-1 and thromboxane B2 after cardiopulmonary bypass in patients with congenital heart disease.

OBJECTIVE: The endothelium-derived vasoconstrictor endothelin-1 is increased after cardiopulmonary bypass in children with congenital heart defects. This study determines whether antioxidant therapy with Salvia miltiorrhiza injection, an herb extract containing phenolic compounds, prevents the postoperative increase of endothelin-1. The relationship between endothelin-1 and the endothelium-derived prostacyclin (prostaglandin I2) and thromboxane A2 postoperatively is also investigated. METHODS: Twenty children with congenital heart defects and pulmonary hypertension were randomly assigned to group A (placebo control, n=10) or B (200 mg/kg Salvia miltiorrhiza intravenously after anesthesia induction and at the time of rewarming, respectively; n =10) before cardiac surgery. Central venous blood samples were taken before operation (T(0)), 10 (T(1)) and 30 minutes (T(2)) after starting cardiopulmonary bypass, 10 (T(3)) and 30 minutes (T(4)) after aortic declamping, and 30 minutes (T(5)) and 24 hours (T(6)) after termination of cardiopulmonary bypass. Plasma lipid peroxidation product malondialdehyde, myocardial specific creatine kinase-MB activity, thromboxane B2, and 6-keto-prostaglandin F(1 alpha) (stable metabolites of thromboxane A2 and prostaglandin I2) were measured. RESULTS: Malondialdehyde increased significantly at T(1) in group A and remained significantly higher than in group B thereafter (P <.05). Malondialdehyde in group B did not significantly increase over time. At T(5), plasma creatine kinase-MB, thromboxane B2, and endothelin-1 in group B were lower than in group A (P <.05); malondialdehyde correlated significantly with creatine kinase-MB (r = 0.71, P =.0005). At T(6), endothelin-1 negatively correlated with the 6-keto-prostaglandin F(1 alpha)/thromboxane B2 ratio (r = -0.64, P =.0025). CONCLUSION: Antioxidant therapy reduces myocardial damage and attenuates postoperative vasoactive mediator imbalance.