Impact of hormone receptor status and tumor subtypes of breast cancer in young BRCA carriers.

BACKGROUND: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes. PATIENTS AND METHODS: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]. RESULTS: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype). CONCLUSIONS: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.

Lasofoxifene versus fulvestrant for ER+/HER2- metastatic breast cancer with an ESR1 mutation: results from the randomized, phase II ELAINE 1 trial.

BACKGROUND: Acquired estrogen receptor alpha (ER/ESR1) mutations commonly cause endocrine resistance in ER+ metastatic breast cancer (mBC). Lasofoxifene, a novel selective ER modulator, stabilizes an antagonist conformation of wild-type and ESR1-mutated ER-ligand binding domains, and has antitumor activity in ESR1-mutated xenografts. PATIENTS AND METHODS: In this open-label, randomized, phase II, multicenter, ELAINE 1 study (NCT03781063), we randomized women with ESR1-mutated, ER+/human epidermal growth factor receptor 2 negative (HER2-) mBC that had progressed on an aromatase inhibitor (AI) plus a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) to oral lasofoxifene 5 mg daily or IM fulvestrant 500 mg (days 1, 15, and 29, and then every 4 weeks) until disease progression/toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were safety/tolerability. RESULTS: A total of 103 patients received lasofoxifene (n = 52) or fulvestrant (n = 51). The most current efficacy analysis showed that lasofoxifene did not significantly prolong median PFS compared with fulvestrant: 24.2 weeks (∼5.6 months) versus 16.2 weeks (∼3.7 months; P = 0.138); hazard ratio 0.699 (95% confidence interval 0.434-1.125). However, PFS and other clinical endpoints numerically favored lasofoxifene: clinical benefit rate (36.5% versus 21.6%; P = 0.117), objective response rate [13.2% (including a complete response in one lasofoxifene-treated patient) versus 2.9%; P = 0.124], and 6-month (53.4% versus 37.9%) and 12-month (30.7% versus 14.1%) PFS rates. Most common treatment-emergent adverse events with lasofoxifene were nausea, fatigue, arthralgia, and hot flushes. One death occurred in the fulvestrant arm. Circulating tumor DNA ESR1 mutant allele fraction (MAF) decreased from baseline to week 8 in 82.9% of evaluable lasofoxifene-treated versus 61.5% of fulvestrant-treated patients. CONCLUSIONS: Lasofoxifene demonstrated encouraging antitumor activity versus fulvestrant and was well tolerated in patients with ESR1-mutated, endocrine-resistant mBC following progression on AI plus CDK4/6i. Consistent with target engagement, lasofoxifene reduced ESR1 MAF, and to a greater extent than fulvestrant. Lasofoxifene may be a promising targeted treatment for patients with ESR1-mutated mBC and warrants further investigation.

[Probiotics in asthma treatment]. / Les probiotiques dans le traitement de l'asthme.

Asthma is the most prevalent chronic inflammatory airway disease worldwide. The gut microbiota possesses an important link with the development of the immunity in youth and a dysregulation of the gut flora was implicated in the asthmatic disease emergence. Moreover, a dysregulation of the intestinal microbiota exists in asthmatic individual. Probiotics are micro-organisms that can regulate our microbiome conferring potential beneficial effects on health. Thereby, their use in asthma prevention and treatment is attractive and could lead to new therapeutic perspectives. Indeed, they are well tolerated and safe and possess anti-inflammatory and immunoregulatory properties. This article is intended to update the current state of knowledge regarding the use of probiotics in the context of asthma.

: L'asthme est la maladie respiratoire chronique inflammatoire la plus prévalente dans le monde. Le microbiote intestinal est reconnu pour être intimement lié avec le développement de l'immunité dans le jeune âge et un dérèglement de cette flore intestinale a été impliqué dans l'apparition de la maladie asthmatique. De plus, une dérégulation du microbiote existe chez l'individu asthmatique. Les probiotiques sont des micro-organismes qui peuvent réguler notre microbiome, conférant un effet bénéfique potentiel sur la santé. De ce fait, leur utilisation dans la prévention et la prise en charge de l'asthme est attractive et pourrait ouvrir de nouvelles perspectives thérapeutiques. En effet, les probiotiques sont très bien tolérés et présentent une grande sécurité d'emploi, tout en possédant des propriétés anti-inflammatoires et immunorégulatrices. Cet article permet de faire le point sur l'état actuel des connaissances quant à leur utilisation dans le cadre de l'asthme.

[Asthma in clinical practice: from inflammatory phenotypes to personalized treatment]. / L'asthme bronchique en pratique clinique : des phénotypes inflammatoires au traitement personnalisé.

Asthma is a chronic inflammatory disease of the airways. Classification of asthma in different phenotypes has therapeutic implications and may lead to personalized medicine. Induced sputum is the gold standard for asthma phenotyping but is complex, time-consuming and not widely available. The combination of different biomarkers such as exhaled nitric oxide, blood eosinophils and total serum IgE levels allows the prediction of inflammatory phenotype in 58% of asthmatic patients when sputum is not available. We recently demonstrated the interest of measuring volatile organic compounds in exhaled breath to phenotype asthma. These compounds could play an important role in the future to predict the response to expensive biologicals available in severe asthma to reduce exacerbations and the use of systemic corticosteroids.

: L'asthme est une pathologie inflammatoire chronique des voies respiratoires. Classer l'asthme en différents phénotypes inflammatoires a des implications thérapeutiques importantes et peut conduire à un traitement personnalisé. Le gold standard pour l'établissement du phénotype inflammatoire est l'analyse de l'expectoration induite qui est une technique complexe, difficilement accessible en routine. La combinaison de plusieurs biomarqueurs d'intérêt tels le monoxyde d'azote dans l'air exhalé, l'éosinophilie systémique et le taux d'IgE sérique permet de prédire correctement le phénotype inflammatoire dans 58% des cas. Récemment, nous avons également mis en évidence l'intérêt de la détection de molécules dans l'haleine. Ces composés organiques volatiles pourraient représenter des biomarqueurs futurs de la réponse au traitement, spécialement dans l'asthme sévère, pour lequel des traitements ciblés coûteux sont actuellement disponibles en vue de réduire les exacerbations et le recours aux corticostéroïdes oraux.

Asthma in elderly is characterized by increased sputum neutrophils, lower airway caliber variability and air trapping.

BACKGROUND: Elderly asthmatics represent an important group that is often excluded from clinical studies. In this study we wanted to present characteristics of asthmatics older than 70 years old as compared to younger patients. METHODS: We conducted a retrospective analysis on a series of 758 asthmatics subdivided in three groups: lower than 40, between 40 and 70 and older than 70. All the patients who had a successful sputum induction were included in the study. RESULTS: Older patients had a higher Body Mass Index, had less active smokers and were more often treated with Long Acting anti-Muscarinic Agents. We found a significant increase in sputum neutrophil counts with ageing. There was no significant difference in blood inflammatory cell counts whatever the age group. Forced expiratory volume in one second (FEV1) and FEV1/FVC values were significantly lower in elderly who had lower bronchial hyperresponsiveness and signs of air trapping. We found a lower occurrence of the allergic component in advanced ages. Asthmatics older than 70 years old had later onset of the disease and a significant longer disease duration. CONCLUSION: Our study highlights that asthmatics older than 70 years old have higher bronchial neutrophilic inflammation, a poorer lung function, signs of air trapping and lower airway variability. The role of immunosenescence inducing chronic low-grade inflammation in this asthma subtype remains to be elucidated.

Chronic oral corticosteroids use and persistent eosinophilia in severe asthmatics from the Belgian severe asthma registry.

BACKGROUND: Severe asthma (SA) may require frequent courses or chronic use of oral corticosteroids (OCS), inducing many known side effects and complications. Therefore, it is important to identify risk factors of chronic use of OCS in SA, considering the heterogeneity of clinical and inflammatory asthma phenotypes. Another aim of the present analysis is to characterize a subpopulation of severe asthmatics, in whom blood eosinophil counts (BEC) remain elevated despite chronic OCS treatment. METHODS: In a cross-sectional analysis of 982 SA patients enrolled in the Belgian Severe Asthma Registry (BSAR) between March 2009 and February 2019, we investigated the characteristics of the OCS treated patients with special attention to their inflammatory profile. RESULTS: At enrollment, 211 (21%) SA patients were taking maintenance OCS (median dose: 8 [IQR: 5-10]) mg prednisone equivalent). BEC was high (> 400/mm3) in 44% of the OCS treated population. Multivariable logistic regression analysis showed that risk factors for chronic use of OCS in SA were late-onset asthma (i.e. age of onset > 40 yr), frequent exacerbations (i.e. ≥2 exacerbations in the previous year) and non-atopic asthma. Late-onset asthma was also a predictor for persistently high BEC in OCS treated SA patients. CONCLUSION: These data showed a significant association between a persistently high BEC and late-onset asthma in OCS treated SA patients. Whether it is poor compliance to treatment or corticosteroid insensitivity the reasons for this association warrants further investigation.

Predictors of a good response to inhaled corticosteroids in obesity-associated asthma.

INTRODUCTION: Asthma in obese subjects is poorly understood. According to GINA guidelines, pulmonologists increase ICS in case of poor asthma control but lung volume restriction may also worsen respiratory symptoms in obese asthmatics leading to overtreatment in this subpopulation. METHODS: We conducted a retrospective study on 1217 asthmatics recruited from University Hospital of Liege. 92 patients with a BMI ≥30 came at least two times at the asthma clinic (mean interval: 335 days). In this obese population, we identified predictors of good (decrease in ACQ ≥0.5) versus poor response (rise in ACQ ≥0.5) to ICS step-up therapy. RESULTS: Obese asthmatics had a poorer asthma control and quality of life as compared to non-obese and exhibited reduced FVC, higher levels of blood leucocytes and markers of systemic inflammation. The proportion of asthma inflammatory phenotypes was similar to that observed in a general population of asthmatics. Among uncontrolled obese asthmatics receiving ICS step-up therapy, 53% improved their asthma control while 31% had a worsening of their asthma. Uncontrolled obese asthmatics showing a good response to increase in ICS had higher ACQ, lower CRP levels, higher sputum eosinophil counts and higher FeNO levels at visit 1. Uncontrolled obese asthmatics that worsened after increasing the dose of ICS had lower FVC, lower sputum eosinophil counts and higher sputum neutrophil counts. CONCLUSION: We observed poorer asthma control in obese asthmatics despite similar bronchial inflammation. Managing obese asthmatics according to ACQ alone seems to underestimate asthma control and the contribution of restriction to dyspnea. Increasing the dose of ICS in the absence of sputum eosinophilic inflammation or in the presence of restriction or bronchial neutrophilia led to poorer asthma control. In those patients, management of obesity should be the first choice.

Risk of stroke after bereavement-a systematic literature review.

Several studies have suggested that psychological stress may increase the risk of stroke. However, this link remains a controversial issue because of conflicting findings. Bereavement, the loss of a close relative, is considered a severely stressful life event. Increased risk of stroke could thus be expected after bereavement if stress plays a causal role. We aimed to evaluate the association between bereavement and stroke by performing a systematic review of the existing literature. The literature search was conducted according to the PRISMA guidelines for systematic reviews. A search in Medline and Embase identified eligible studies, which were reviewed by two researchers independently according to specific inclusion criteria. We included six studies: five cohort studies and one case-crossover study. Five studies found that loss of a first-degree relative was associated with a 1.1- to 2.4-fold higher risk of stroke. However, one study found a statistically significant overall risk only for women. Five studies evaluated the risk of stroke according to time since the loss; one study found no association, two studies indicated short-term effect, one study indicated long-term effect, and one study indicated both short-term and long-term effect. Three studies stratified their analysis by sex; two found higher association in bereaved women than men. Our systematic review suggests that bereavement-related stress is associated with a higher risk of stroke. As relatively few studies were identified, new studies are needed to verify this association. These should aim to quantify the risk, describe the effect of time since bereavement, and identify risk-modifying factors.

Habitual physical activity is associated with improved anthropometric and androgenic profile in PCOS: a cross-sectional study.

PURPOSE: To examine the effect of habitual physical activity (PA) on the metabolic and hormonal profiles of women with polycystic ovary syndrome. MATERIALS AND METHODS: Anthropometric, metabolic and hormonal assessment and determination of habitual PA levels with a digital pedometer were evaluated in 84 women with PCOS and 67 age- and body mass index (BMI)-matched controls. PA status was defined according to number of steps (≥7500 steps, active, or <7500 steps, sedentary). RESULTS: BMI was lower in active women from both groups. Active PCOS women presented lower waist circumference (WC) and lipid accumulation product (LAP) values versus sedentary PCOS women. In the control group, active women also had lower WC, lower values for fasting and 120-min insulin, and lower LAP than sedentary controls. In the PCOS group, androgen levels were lower in active versus sedentary women (p = 0.001). In the control group, free androgen index (FAI) was also lower in active versus sedentary women (p = 0.018). Homeostasis model assessment of insulin resistance and 2000 daily step increments were independent predictors of FAI. Each 2000 daily step increment was associated with a decrease of 1.07 in FAI. CONCLUSIONS: Habitual PA was associated with a better anthropometric and androgenic profile in PCOS.

Effects of orlistat vs. metformin on weight loss-related clinical variables in women with PCOS: systematic review and meta-analysis.

AIMS: The aim of this study was to assess the effects of orlistat on weight loss-related clinical variables in overweight/obese women with polycystic ovary syndrome (PCOS) and to compare treatment with orlistat vs. metformin in this group. METHODS: We conducted a systematic review and meta-analysis of the evidence about the use of orlistat in women with PCOS. We searched the literature published until May 2015 in MEDLINE, Cochrane Central Register of Controlled Trials and LILACS. RESULTS: Of 3951 studies identified, nine were included in the systematic review (three prospective, non-randomised studies and six randomised control trials). Eight studies used the Rotterdam criteria and 1 used NIH criteria to diagnose PCOS. Data suggest that orlistat promotes a significant reduction in BMI/weight in overweight/obese PCOS women. Eight studies evaluated orlistat impact on testosterone. Seven reported an improvement in testosterone levels. Eight studies evaluated impact on insulin resistance, and five reported improvement. Finally, five studies evaluated impact on lipid profile, and four reported improvement. Three randomised control trials were included in the fixed effects model meta-analysis for a total of 121 women with PCOS. Orlistat and metformin had similar positive effects on BMI (-0.65%, 95% CI: -2.03 to 0.73), HOMA (-3.60%, 95% CI: -16.99 to 9.78), testosterone (-2.08%, 95% CI: -13.08 to 8.93) and insulin (-5.51%, 95% CI: -22.27 to 11.26). CONCLUSION(S): The present results suggest that orlistat leads to significant reduction in BMI/body weight in PCOS. In addition, the available evidence indicates that orlistat and metformin have similar effects in reducing BMI, HOMA, testosterone and insulin in overweight/obese PCOS women. This study was registered in PROSPERO under number CRD42014012877.

Changing places: policies to make a healthy choice the easy choice.

The environments where people live, learn, work and play have a profound influence on health. Policies affecting physical activity, access to healthy foods, and the prevalence of tobacco products in our neighbourhoods can either promote or discourage behaviour associated with cancer and other chronic diseases. Given the regulatory landscape in the USA, where federal law controls venues with the widest possible scope (such as television and the Internet), states and cities have tremendous latitude in regulating the physical environments that residents experience every day. This paper explores innovative and meaningful ways to improve public health through policy initiatives targeted specifically at places such as homes and neighbourhoods, schools, shops, restaurants, bars and recreational areas.

Development of a standardized susceptibility test for campylobacter with quality-control ranges for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem.

A standardized agar dilution susceptibility testing method was developed for Campylobacter that consisted of testing on Mueller-Hinton medium supplemented with 5% defibrinated sheep blood in an atmosphere of 10% CO2, 5% O2, and 85% N2. Campylobacter jejuni ATCC 33560 was identified as a quality-control (QC) strain. Minimal inhibitory concentration (MIC) QC ranges were determined for two incubation time/temperature combinations: 36 degrees C for 48 hr and 42 degrees C for 24 hr. Quality-control ranges were determined for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem. For all antimicrobial agents tested at both temperatures, 95-100% of the QC MIC results fell within recommended QC ranges. Twenty-one Campylobacter clinical isolates, encompassing five species of Campylobacter (C. jejuni, C. coli, C. jejuni, subsp. doylei, C. fetus, and C. lari) were tested in conjunction with the C. jejuni QC strain. While C. jejuni and C. coli could be reliably tested under both test conditions, growth of C. jejuni subsp. doylei, C. fetus, and C. lari isolates was inconsistent when incubated at 42 degrees C. Therefore, it is recommended that these species only be tested at 36 degrees C.

BOD5 estimation for pulp and paper mill effluent using UV absorbance.

A novel method based on UV absorbance, is presented for estimating the BOD5 in pulp and paper mill effluent. This method could eventually be incorporated into an on-line sensor for BOD5 that is suitable for process control applications. Two streams, the reactor entrance and the final effluent, from two different mills were studied. One mill employed the Kraft pulping process, while the second mill was a thermo-mechanical one. The absorbance over the range 200-350 nm showed significant differences between the two mills. Because the two mills use very distinct processes, separate correlations were used to relate the absorbance to the BOD5 for both the mills. Results indicate that prediction of reactor entrance BOD5 was reasonable, whereas prediction of final effluent BOD5 was inaccurate, for both mills. Also studied was the effect of aeration on BOD5 results obtained at low BOD5 values for the Kraft mill.

High-risk population health management--achieving improved patient outcomes and near-term financial results.

OBJECTIVE: A managed care organization sought to achieve efficiencies in care delivery and cost savings by anticipating and better caring for its frail and least stable members. STUDY DESIGN: Time sequence case study of program intervention across an entire managed care population in its first year compared with the prior baseline year. PATIENTS AND METHODS: Key attributes of the intervention included predictive registries of at-risk members based on existing data, relentless focus on the high-risk group, an integrated clinical and psychosocial approach to assessments and are planning, a reengineered care management process, secured Internet applications enabling rapid implementation and broad connectivity, and population-based outcomes metrics derived from widely used measures of resource utilization and functional status. RESULTS: Concentrating on the highest-risk group, which averaged just 1.1% prevalence in the total membership, yielded bottom line results. When the year before program implementation (July 1997 through June 1998) was compared with the subsequent year, the total population's annualized commercial admission rate was reduced 5.3%, and seniors' was reduced 3.0%. A claims-paid analysis exclusively of the highest-risk group revealed that their efficiencies and savings overwhelmingly contributed to the membershipwide effect. This subgroup's costs dropped 35.7% from preprogram levels of $2590 per member per month (excluding pharmaceuticals). During the same time, patient-derived cross-sectional functional status rose 12.5%. CONCLUSIONS: A sharply focused, Internet-deployed case management strategy achieved economic and functional status results on a population basis and produced systemwide savings in its first year of implementation.

Effects of gender on the autonomic modulation of the cardiovascular responses to lower body negative pressure.

BACKGROUND: The cardiovascular responses to submaximal lower body negative pressure (LBNP) appear to differ between genders, but the underlying mechanisms are uncertain. HYPOTHESIS: These differences are due to differences in the autonomic modulation of the cardiovascular system. METHODS: There were 14 women and 13 men who underwent LBNP to -50 mmHg in 10 mmHg increments of 6 min each. Heart rate (HR), stroke volume (SV), BP, forearm blood flow and R-R interval data were acquired. Spectral analysis of the R-R interval data was used to assess autonomic modulation with the low frequency component (LF) set at 0.04 to 0.15 Hz and the high frequency component (HF) at 0.15 to 0.4 Hz. RESULTS: The responses to LBNP to -40 mmHg did not differ between groups. LBNP of -50 mmHg evoked greater HR increases in the women than the men (7.2 +/- 1.0 vs. 3.8 +/- 1.1 bpm; p < 0.05), while SV, cardiac output and total peripheral conductance decreased more (-15 +/- 2 vs. -8 +/- 2 ml x beat(-1); -0.668 +/- 0.131 vs. -0.1778 +/- 0.124 L x min(-1); -0.009 +/- 0.002 vs. -0.004 +/- 0.001 units; p < 0.05). Normalized HF, an indicator of the vagal influence on HR variability, declined below rest at -40 mmHg while the LF/HF ratio, an indicator of sympathetic neural modulation of HR variability, increased above rest at -40 mmHg. These responses did not differ significantly between groups. CONCLUSIONS: These results suggest that gender differences in the cardiovascular responses to LBNP are not due to gross differences in modulation of the autonomic nervous systems.

Cellular alterations in collembolan midgut cells as a marker of heavy metal exposure: ultrastructure and intracellular metal distribution.

The ultrastructure of the midgut epithelial cells of Tetrodontophora bielanensis (Collembola) fed either with lead-, cadmium- or zinc-enriched food or kept under control conditions was compared by transmission electron microscopy (TEM). Atomic absorption spectrophotometry (AAS) showed accumulation of these three metals in the body tissues of the collembolans. Intracellular localization of zinc in the midgut epithelial cells was investigated by electron spectroscopic imaging (ESI) and electron energy loss spectroscopy (EELS). The presence of lead in the midgut tissue was shown by laser microprobe mass spectrometry (LAMMS). Under heavy metal conditions, the midgut cells showed different ultrastructural alterations, the degree of which was found to be dose-dependent. Independent of the type of the metal in the food, the endoplasmic reticulum appeared fenestrated or vesiculated, and often large vacuoles, which were shown to be ER-derived, occurred throughout the cells. Also the mitochondrial membranes were affected by heavy metal stress. In epithelial cells of individuals exposed to either lead or cadmium, an increase of myelin-like structures could be observed. In the case of exposure to zinc in the highest applied concentration, the cytoplasm showed condensation and portions of the microvillous border appeared destroyed. Additionally, an increase of mineral congregations (type-A spherites) could be observed under heavy metal influence. Intracellularly stored zinc could be localised at highly affected mitochondrial membranes, in the microvillous border, and in the heterochromatin.

Fracture of the distal radius: classification of treatment and indications for external fixation.

A number of classifications have been created for fractures of the distal radius. We describe those of Older et al., Frykman, Thomas, Melone, McMurtry, Fernandez, the Mayo and the AO/ASIF. These classifications help to identify unstable fractures and offer insight into the indications for external skeletal fixation.

Acute gout after carpal tunnel release.

A carpal tunnel release was performed on three patients with known gout of the lower extremity but not of the upper extremity. Each patient had a postoperative inflammatory reaction in a treated hand, and there was some suspicion of an infection in two patients. However, the inflammatory reaction resolved only when treated with a combination of anti-inflammatory and anti-gout medication.

Free radical scavenger mechanisms in experimentally induced ischemia in the rabbit heart and protective effect of verapamil.

The protective effect of verapamil on the free radical generation in the ischemic myocardium of rabbit has been studied. A significant decrease of the lactate dehydrogenase activity in the ischemic zone was observed compared to the nonischemic control myocardial tissue. The level of malondialdehyde was found to be elevated in the ischemic zone and in other parts of the myocardium. However, there was no alteration in glutathione content in both zones. In addition, an increase in the activity of myeloperoxidase was observed in the ischemic part of the myocardium. At lower doses (30 micrograms/kg), verapamil protected the animals from ischemic changes but did not do so at higher doses (100 micrograms/kg). These results suggest that, in the rabbit, the free radical scavenging mechanism of the heart is not adversely affected during ischemia.