Magnesium Supplementation Is Associated with a Lower Cardio-Metabolic Risk in Patients Submitted to Bariatric Surgery.

PURPOSE: Literature has demonstrated an inverse relation between magnesium (Mg) consumption and development of type 2 diabetes mellitus (T2DM), hypertension (HT), and dyslipidemia. After bariatric surgery (BS), micronutrients deficiencies are common, it being important to ensure appropriate supplementation. There is no recommendation about Mg supplementation and to our knowledge, its effect has not been studied to date. Our aim was to evaluate the effect of Mg supplementation in cardio-metabolic risk factors on post-bariatric patients. MATERIALS AND METHODS: A retrospective observational study of patients with obesity who underwent BS was performed. Data was assessed preoperatively and yearly (4-year follow-up). RESULTS: A total of 3363 patients were included. In the first year of follow-up, 79.8% (n = 2123) of the patients were supplemented with Mg, with evidence of slightly decreased percentages in the following years. Mg deficiency (serum Mg < 1.52 mEq/L) was more common among patients who were not supplemented during each year of follow-up (p < 0.05). Among those who underwent Mg supplementation, the percentage of T2DM, HT, or low-density lipoprotein cholesterol (LDL-C) > 130 mg/dL was significantly lower. In the first year post-surgery, the supplementation group had a lower risk of T2DM (OR = 0.545, p < 0.0001), LDL-C > 130 mg/dL (OR = 0.612, p < 0.0001), and HT (OR = 0.584, p < 0.0001). The OR for having these metabolic comorbidities persisted lower during the 4 years' follow-up. Patients who had Mg deficiency had higher prevalence of T2DM and HT. CONCLUSION: Mg supplementation seems to have a protective effect on the development of T2DM, HT, and LDL-C > 130 mg/dL in post-bariatric patients.

A combination of pyridine-2, 4-dicarboxylic acid diethyl ester and resveratrol stabilizes hypoxia-inducible factor 1-alpha and improves hair density in female volunteers.

OBJECTIVE: The aim of this study was first to demonstrate that a combination of pyridine-2, 4-dicarboxylic acid diethyl ester and resveratrol could synergize in vitro on biological pathways associated with hair growth and then to demonstrate the benefit on hair density in a clinical study. METHODS: The effects of pyridine-2, 4-dicarboxylic acid diethyl ester and resveratrol directly on the hypoxic inducible factor-1α protein (HIF-1α) and related genes expression were demonstrated on keratinocytes in culture in vitro using western-blot analysis and real time quantitative polymerase chain reaction analysis. The effect of resveratrol against oxidative stress induced by hydrogen peroxide treatment was studied in hair follicle and hair matrix cells in vitro using the sensitive probe Dichloro-dihydro-fluorescein diacetate (DCFH-DA). Finally, a randomized clinical study on hair density was conducted on 79 Caucasian female subjects to assess the effect of this combination of actives. RESULTS: Pyridine-2, 4-dicarboxylic acid diethyl ester and resveratrol stabilized HIF-1a protein and increased the expression of HIF-1α target genes. Resveratrol significantly reduced the oxygen peroxide-induced oxidative stress generated in hair follicle and hair matrix cells. The clinical study showed that a topical treatment with the combination significantly increased the hair density on women from 1.5 months. CONCLUSION: In addition to the antioxidant properties of resveratrol, the association of pyridine-2, 4-dicarboxylic acid diethyl ester and resveratrol revealed a synergistic effect on the HIF-1α pathway. The results of the clinical study confirmed the importance of such a combination to increase the hair density.

L'alopécie peut affecter 50% des femmes au cours de leur vie ce qui induit une perte de leur estime de soi et une diminution de leur qualité de vie. Au-delà des solutions chirurgicales et des traitements pouvant induire des effets secondaires potentiellement dangereux, il y a un besoin d'améliorer l'efficacité des produits cosmétiques qui permettent de prévenir la chute des cheveux tout en préservant la sécurité des patients. Ainsi, nous avons sélectionné une combinaison de pyridine-2, 4-dicarboxylic acide diethyle ester et de resvératrol pour activer des voies biologiques associées à la croissance du cheveu. Nous avons d'abord montré, in vitro, que la combinaison de pyridine-2, 4-dicarboxylic acide diethyle ester et de resvératrol permet de stabiliser la protéine HIF-1α conduisant ainsi à un effet synergique sur l'expression de gènes clés de la voie HIF-1α. Nous avons aussi démontré, in vitro, que le resvératrol permet de protéger significativement les follicules pileux et les cellules de la matrice du stress oxydatif induit par traitement au peroxide d'hydrogène. En final, une étude clinique randomisée mesurant la densité capillaire a été réalisée sur 79 femmes caucasiennes. Cette étude montre qu'une application topique d'une solution contenant de 5% pyridine-2, 4-dicarboxylic acide diethyle ester et 0.25% de resvératrol augmentent significativement la densité capillaire chez les femmes après 1.5 mois. En conclusion, ces résultats démontrent l'intérêt de stimuler la voie HIF-1α tout en protégeant les cheveux et le scalp du stress oxydatif afin d'améliorer la croissance des cheveux chez les femmes.

Insulin resistance and sex hormone-binding globulin are independently correlated with low free testosterone levels in obese males.

Male obesity is associated with decreased testosterone levels but the pathophysiological mechanisms behind this association are not completely understood. This study aimed to investigate the impact of hyperglycaemia/insulin resistance and sex hormone-binding globulin (SHBG) levels on testosterone levels in a population of obese men. We investigated the impact of several clinical, anthropometric and analytic measures on testosterone levels in 150 obese males. Testosterone deficiency was present in 52.0% of the enrolled patients. This percentage dropped to 17.6% when only calculated free testosterone (FT) was accounted, as SHBG levels were correlated negatively with body mass index (r = -.20; p < .05). Older age (p < .05) and higher homoeostasis model assessment of insulin resistance (HOMA-IR) (p < .01) and lower SHBG levels (p < .05) were independently correlated with lower FT. Weight and fasting plasma glucose lost their statistical significance after multivariate adjustment. Patients with type 2 diabetes mellitus and pre-diabetes had lower FT than those with normal glucose tolerance (p < .05 and p < .01 respectively). Insulin resistance, and not hyperglycaemia and weight per se, seems to be the main determinant of low testosterone levels in obese males. Low SHBG levels are correlated with low FT even after HOMA-IR adjustment. This suggests that SHBG can be associated with testosterone deficiency beyond the influence of insulin resistance unlike previously reported.

Molecular detection of Wolbachia pipientis in natural populations of mosquito vectors of Dirofilaria immitis from continental Portugal: first detection in Culex theileri.

Wolbachia pipientis (Rickettsiales: Rickettsiaceae) protects mosquitoes from infections with arboviruses and parasites. However, the effect of its co-infection on vector competence for Dirofilaria immitis (Spirurida: Onchocercidae) in the wild has not been investigated. This study aimed to screen vectors of D. immitis for wPip, to characterize these, and to investigate a possible association between the occurrence of W. pipientis and that of the nematode. The presence of W. pipientis was assessed in the five mosquito potential vectors of D. immitis in Portugal. Polymerase chain reaction (PCR) products were sequenced, and wPip haplotypes were determined by PCR-restricted fragment length polymorphism (RFLP). Results showed that wPip was detected in 61.5% of Culex pipiens (Diptera: Culicidae) pools and 6.3% of Culex theileri pools. wPip 16s rRNA sequences found in Cx. theileri exactly match those from Cx. pipiens, confirming a mosquito origin, rather than a nematode origin, as some specimens were infected with D. immitis. Only wPip haplotype I was found. No association was found between the presence of wPip and D. immitis in mosquitoes and hence a role for this endosymbiont in influencing vectorial competence is yet to be identified. This study contributes to understanding of wPip distribution in mosquito populations and, to the best of the authors' knowledge, is the first report of natural infections by wPip in Cx. theileri.

IL-4 and IL-6 levels and adipose tissue distribution in HIV-1 patients under antiretroviral therapy.

PURPOSE: Combined antiretroviral therapy (cART) for the treatment of HIV-1 infection has been associated with complications, including lipodystrophy. Several interleukins have been implicated in the pathology and physiology of lipodystrophy. The present study aimed to compare the levels of IL-4 and IL-6 in HIV-1 patients under cART with and without, clinically and fat mass ratio defined, lipodystrophy and in four different groups of fat distribution: (1) no lipodystrophy; (2) isolated central fat accumulation; (3) isolated lipoatrophy and (4) mixed forms of lipodystrophy. METHODS: In the present cross-sectional study we evaluated IL-4 and IL-6 levels, insulin resistance and insulin sensitivity indexes in 86 HIV-infected adults under cART. RESULTS: No significant differences in IL-4 and IL-6 levels between the four groups of body composition were observed. Patients with HOMA-IR >4 presented higher levels of IL-6 and lower levels of IL-4, although without statistical significance. No correlation between IL-6, or IL-4, HOMA-IR and quantitative body fat mass distribution was found. CONCLUSION: Although there was a tendency for patients with isolated lipoatrophy and isolated fat accumulation to present higher IL-6 levels, these differences were not statistically significant. No differences were found relating IL-4 levels.

The role of the immunological background of mice in the genetic variability of Schistosoma mansoni as detected by random amplification of polymorphic DNA.

Schistosomiasis is a parasitic disease caused by flatworms of the genus Schistosoma. Among the Schistosoma species known to infect humans, S. mansoni is the most frequent cause of intestinal schistosomiasis in sub-Saharan Africa and South America: the World Health Organization estimates that about 200,000 deaths per year result from schistosomiasis in sub-Saharan Africa alone. The Schistosoma life cycle requires two different hosts: a snail as intermediate host and a mammal as definitive host. People become infected when they come into contact with water contaminated with free-living larvae (e.g. when swimming, fishing, washing). Although S. mansoni has mechanisms for escaping the host immune system, only a minority of infecting larvae develop into adults, suggesting that strain selection occurs at the host level. To test this hypothesis, we compared the Belo Horizonte (BH) strain of S. mansoni recovered from definitive hosts with different immunological backgrounds using random amplification of polymorphic DNA-polymerase chain reaction (RAPD-PCR). Schistosoma mansoni DNA profiles of worms obtained from wild-type (CD1 and C57BL/6J) and mutant (Jα18- / - and TGFßRIIdn) mice were analysed. Four primers produced polymorphic profiles, which can therefore potentially be used as reference biomarkers. All male worms were genetically distinct from females isolated from the same host, with female worms showing more specific fragments than males. Of the four host-derived schistosome populations, female and male adults recovered from TGFßRIIdn mice showed RAPD-PCR profiles that were most similar to each other. Altogether, these data indicate that host immunological backgrounds can influence the genetic diversity of parasite populations.

Skin penetration of epigallocatechin-3-gallate and quercetin from green tea and Ginkgo biloba extracts vehiculated in cosmetic formulations.

Green tea (Camellia sinensis) and Ginkgo biloba extracts in cosmetic formulations have been suggested to protect the skin against UV-induced damage and skin ageing. Thus, it is very important to assess the human skin penetration of their major flavonoids to verify if they penetrate and remain in the skin to exert their proposed effects. The aim of this study was to evaluate the human skin penetration of epigallocatechin-3-gallate (EGCG) and quercetin from green tea and G. biloba extracts vehiculated in cosmetic formulations. This study was conducted with fresh dermatomed human Caucasian skin from abdominal surgery mounted on static Franz diffusion cells. Skin samples were mounted between two diffusion half-cells and 10 mg/cm(2) of formulations supplemented with 6% of green tea or G. biloba extract were applied on the skin surface. The receptor fluid was removed after 6 and 24 h and analyzed by high-performance liquid chromatography for the quantification of the flavonoids. The stratum corneum was removed by tape stripping and immersed in methanol and the epidermis was mechanically separated from the dermis and triturated in methanol to extract EGCG and quercetin. The results showed that the flavonoids under study penetrated into the skin, without reaching the receptor fluid. The majority of EGCG was quantified in the stratum corneum (0.87 microg/cm(2)), which was statistically higher than the EGCG concentrations found in viable epidermis (0.54 microg/cm(2)) and in the dermis (0.38 microg/cm(2)). The majority of quercetin was quantified in the viable epidermis (0.23 microg/cm(2)), which was statistically higher than the EGCG concentration found in the stratum corneum layer (0.17 microg/cm(2)). Finally, it can be concluded that EGCG and quercetin from green tea and G. biloba extracts vehiculated in cosmetic formulations presented good skin penetration and retention, which can favor their skin effects.

Mortalidad y enfermedades asociadas al síndrome de Down en el primer año de vida: Experiencia de la Policlínica Interdisciplinaria de Atención al niño con síndrome de Down del Servicio de Recién Nacidos del Centro Hospitalario Pereira Rossell / Mortality and disease associated with Down syndrome in the first year of life

Introducción: la Policlínica Interdisciplinaria de Atención al Niño con síndrome de Down brinda asistencia desdeel nacimiento hasta el segundo año de vida.Objetivo: describir la mortalidad observada y las enfermedades asociadas diagnosticadas en el primer año devida en los niños con síndrome de Down atendidos en la policlínica.Material y métodos: niños con síndrome de Down nacidos o derivados al Servicio de Recién Nacidos del CentroHospitalario Pereira Rossell desde el 7 de enero de 2003 al 30 de abril del 2005.Resultados: se asistieron 45 niños. 22 madres eran mayores de 35 años (48,9%). En un caso se realizódiagnóstico prenatal (2,2%). Fallecieron ocho niños (17,8%). En 36 niños se observaron malformaciones asociadas (80,0%). Presentaron cardiopatía congénita 32 niños (71,1%), de los cuales requirieron tratamientoquirúrgico 11 (34,4%). Se diagnosticó hipotiroidismo congénito en un niño (2,2%). De los 37 niños quesobrevivieron al año se detectó hipotiroidismo entre los 6 meses y el año en 8 (21,6%).Conclusiones: la atención por un grupo interdisciplinario permite responder a los múltiples problemas queenfrentan estos niños y sus familias. Permitió un diagnóstico temprano de las enfermedades presentes en estospacientes. Se destaca la alta mortalidad, la alta incidencia de cardiopatía congénita e hipotiroidismo observado.

Introduction: an Interdisciplinary Center for the Attention of Children with Down syndrome provides services forchildren until the age of 2.Objective: describe the mortality incidence and the associated diseases during the first year of life in children withDown syndrome.Material and methods: children with Down syndrome born or derived to the Pereira Rossell Neonatology Servicefrom January 7, 2003 until April 30, 2005.Results: 45 children were assisted. 22 mothers (48,9%) were over 35 years old. Only in one case (2,2%) aprenatal diagnosis was done. 8 children died (17,8%). Associated malformations were observed in 36 children(80%). 32 children (71,1%) had congenital heart disease and 11 (34,4%) required surgery. One children (2,2%)had congenital hypothyroidism. From the 37 children alive after one year, eight had hypothyroidism.Conclusions: these children and families multiple problems are confronted in a better way by an interdisciplinarygroup. This allowed an earlier diagnosis of the different problems. There is a high mortality and a high incidence ofcardiac and thyroid problems.

Prevalence, behavioural and social factors associated with Schistosoma intercalatum and geohelminth infections in São Tomé and Principe.

A pilot study was conducted in schoolchildren from three main districts of São Tome to assess the relationship between the prevalence of infections caused by Schistosoma intercalatum or intestinal helminths and individual behaviour and social conditions. Coprological examination revealed an increase of schistosome infections and a persisting high endemicity for ascariasis and trichuriasis. Infection rates were 36.2% for S. intercalatum and 70.8%, 68.5% and 4.6% for Ascaris lumbricoides, Trichuris trichiura and Ancylostomidae, respectively. Out of the 47 children positive for S. intercalatum, 35 (74.5%) were co-infected with one or more geohelminths. Logistic regression analysis of data collected through questionnaire demonstrate that behaviour and/or social conditions in the house were positively associated with S. intercalatum or T. trichiura. Neither sex nor age groups were associated with infections, suggesting that low personal hygiene and sanitation practices were similar for all groups of children. These data are in accordance to those of other studies and highlight the importance of assessing multivariate factors that may contribute to the transmission of these diseases, in order to design integrated control approaches for schistosomiasis and geohelminthiasis which could have more rapid effects on reduction of infections as well as greater cost-effectiveness.

Sevoflurane with remifentanil allows rapid tracheal intubation without neuromuscular blocking agents.

PURPOSE: After inhalational induction with sevoflurane, we compared the effects of adding remifentanil 1 microg x kg(-1) or remifentanil 2 microg x kg(-1) on conditions for tracheal intubation without neuromuscular blocking agents. METHODS: Before anesthetic induction, all patients were given 0.2 mg of glycopyrrolate iv to counteract the bradycardic effects of remifentanil. Two minutes after inhalational induction with 8% sevoflurane and 50% nitrous oxide, 56 female patients with normal airways scheduled for gynecologic surgery were randomized to receive remifentanil 1 or 2 microg x kg(-1) in a double-blind fashion. One minute later, laryngoscopy was initiated for tracheal intubation. Conditions for tracheal intubation and hemodynamic response to tracheal intubation were assessed. RESULTS: Tracheal intubation was successful in all patients. The incidence of post-intubation coughing was lower in the remifentanil 2 microg x kg(-1) group compared to remifentanil 1 microg x kg(-1) group (11% vs 39%, P <0.02). Optimal intubation conditions were also higher in the remifentanil 2 microg x kg(-1) group at 89% vs 54% (P <0.01). However, the higher dose of remifentanil also resulted in a greater decrease in mean arterial pressure (P <0.05). CONCLUSIONS: The addition of remifentanil after sevoflurane induction allows for rapid tracheal intubation without neuromuscular blocking agents. The higher dose of remifentanil results in improved conditions for tracheal intubation but also caused a greater decrease in mean arterial pressure. Tracheal intubation using sevoflurane and remifentanil may be an alternative to traditional tracheal intubation with neuromuscular blocking agents.

Additive anti-emetic efficacy of prophylactic ondansetron with droperidol in out-patient gynecological laparoscopy.

PURPOSE: To determine the efficacy of ondansetron and droperidol, alone and in combination, administered for prophylaxis of postoperative nausea and vomiting (PONV) in women undergoing general anesthesia for outpatient gynecological laparoscopy. METHODS: Following Institutional Ethics Board approval and patient consent, 160 female out- patients scheduled for laparoscopy were randomly allotted in a double-blind fashion to receive: i) saline (placebo), ii) 4 mg ondansetron, iii) 1.25 mg droperidol, or iv) 4 mg ondansetron and 1.25 mg droperidol combination intravenously on induction. Following a standardized general anesthesia, patients were interviewed and assessed for PONV at various times. RESULTS: During the first 24 hr after surgery, the incidence of PONV in the placebo group was 71%. This was reduced to 61% with droperidol alone (P = 0.334), to 46% with ondansetron alone (P = 0.027), and to 23% with the combination group (P<0.001). A statistically significant difference was observed between combination and droperidol (P<0.001) and between combination and ondansetron (P = 0.036). There were fewer requests for rescue medication from the combination group (7.7%) than from the ondansetron and placebo groups. CONCLUSION: The results of this study suggest that the combination of 4 mg ondansetron and 1.25 mg droperidol is more efficacious as a prophylactic anti-emetic than either agent alone during the 24 hr post-surgery. This additive effect may be due to the different mechanisms of action of ondansetron and droperidol.

Treating "rebound" emesis following outpatient gynecologic laparoscopy: the efficacy of a two-dose regimen of droperidol and ondansetron.

STUDY OBJECTIVE: To evaluate the efficacy of a two-dose combination of droperidol and ondansetron as compared with single-dose droperidol alone, single-dose combined droperidol and ondansetron, and two-dose droperidol alone, for management of postoperative nausea and vomiting (PONV) among gynecologic laparoscopy outpatients. DESIGN: Randomized, double-blind comparison trial. SETTING: Tertiary outpatient gynecologic unit. PATIENTS: A total of 120 female patients scheduled for gynecologic laparoscopy were enrolled. Patients who had experienced nausea or vomiting, or who had taken drugs with antiemetic action in the 24-hour period prior to the study, as well as breast-feeding mothers, were excluded from participation. INTERVENTIONS: Patients were assigned to four treatment groups: i) single dose of droperidol 1.25 mg, ii) two doses of droperidol 1.25 mg, iii) single dose of droperidol 1.25 mg and ondansetron 4 mg in combination, and iv) two doses of droperidol 1.25 mg and ondansetron 4 mg in combination. The first dose of antiemetic was administered prior to induction and the second dose was given by infusion 4 hours later, prior to discharge. MEASUREMENTS AND MAIN RESULTS: A visual analogue scale (VAS, 10 cm) was used to obtain patients' experience of nausea, vomiting, and pain at 0.5, 1.5, 2.5, and 3.5 hours after arrival at the postanesthetic care unit (PACU). Following discharge, approximately 24 hours after arrival at the PACU, the same measures were obtained by a follow-up interview using a verbal 10-point scale. No significant differences in incidence of PONV were noted among the four treatment groups (p = 0.419). However, both single- and two-dose droperidol and ondansetron combination therapy demonstrated attenuation of PONV severity in the 3.5- to 24-hour postinduction period (p < 0.05). CONCLUSIONS: The findings of this study suggest that prophylactic two-dose combined ondansetron and droperidol offers no added benefit over single-dose therapy for routine use in the gynecologic outpatient population.

Prophylactic oral dolasetron mesylate reduces nausea and vomiting after abdominal hysterectomy. The Canadian Dolasetron Study Group.

PURPOSE: The incidence of postoperative nausea and vomiting (PONV) varies from 50% to 75% after gynaecological surgery under general anaesthesia. This study evaluates the dose-response relationships, safety, and efficacy of the new 5-HT3 antagonist, dolasetron mesylate, in the prevention of PONV in women undergoing total abdominal hysterectomy (TAH). METHODS: Three hundred and seventy four women scheduled for TAH under general anaesthesia were studied at 13 Canadian centres. Patients received in a randomized, double-blind manner 25, 50, 100, or 200 mg dolasetron or placebo po one to two hours before induction of anaesthesia. The anesthetic protocol was standardized. Efficacy was evaluated for 24 hr after surgery by comparing the number of emetic episodes, administration of rescue medication, severity of nausea, and patient satisfaction. RESULTS: Analysis of complete response (no emetic episodes and no rescue for 24 hr) revealed a linear dose-response relationship across dolasetron groups (P < 0.002). Dolasetron 100 mg (P < 0.003) and 200 mg (P < 0.01) were superior to placebo. The percentage of patients with no emetic episodes increased from 29.3% (placebo) to 54.1 % (100 mg). Subgroup analysis revealed ASA status (I > II), previous history of PONV, previous history of motion sickness, and total morphine dose (> 55 mg associated with less PONV than < 55 mg) influenced the incidence of emetic symptoms, but did not alter the results of the primary analysis. CONCLUSION: Prophylactic dolasetron (100 mg and 200 mg) reduces the incidence of PONV in patients having total abdominal hysterectomy.

Intracoronary propofol does not decrease myocardial contractile function in the dog.

The intravenous administration of propofol is associated with a considerable decrease in arterial blood pressure. The present study was undertaken to test the hypothesis that myocardial function is not affected by propofol and therefore does not contribute to the hypotensive effect of this anaesthetic agent. Propofol was administered in anaesthetized, open-chest dogs by direct arterial infusion into the left anterior descending coronary artery (LAD). Mean arterial blood pressure, heart rate, left ventricular pressure, dP/dt, regional lactate and oxygen extraction, as well as coronary blood flow were measured. Diastolic function was determined by calculation of the time constant of isovolumetric relaxation from the left ventricular pressure measurement and dP/dt. Contractility was evaluated by measuring regional systolic shortening in an area of the myocardium supplied by the LAD. This was compared with systolic shortening in the distribution of the circumflex (CIRC) artery and with the effects obtained with the intracoronary administration of thiopentone. Intracoronary infusions of propofol and thiopentone did not produce any change in systemic arterial blood pressure, heart rate, or left ventricular end diastolic pressure. Propofol, at a concentration of 5 or 10 micrograms.ml-1 did not decrease systolic shortening in the area perfused by the LAD while thiopentone (40 micrograms.ml-1) reduced systolic shortening by 33% (P < or = 0.05). Neither drug had an effect on systolic shortening in the CIRC area, LAD blood flow or diastolic function. The results of this study suggest that propofol does not have an effect on myocardial contractility. The hypotension associated with the intravascular administration of propofol is more likely due to either a direct vascular or a central effect.

Effect of halothane and isoflurane on postischemic "stunned" myocardium in the dog.

Short periods of coronary artery occlusion are known to produce prolonged periods of ventricular dysfunction. The effects of halothane or isoflurane on contractility and metabolism in postischemic "stunned" myocardium were studied in an open-chest canine model in which the left anterior descending artery (LAD) was occluded for 15 min and then reperfused. Regional function in the LAD and circumflex artery (CIRC) areas were measured with sonomicrometry, and metabolic data were determined from simultaneous arterial and venous measurements of oxygen and lactate. Halothane and isoflurane produced equivalent decreases in systolic shortening in both normal (CIRC) and stunned (LAD) areas of the heart. Furthermore, the amount of depression was similar with either halothane or isoflurane. Halothane 0.75 MAC significantly decreased systolic shortening in both the LAD region (from 38.8 +/- 25.9% to 11.0 +/- 21.8%) and in the CIRC region (from 116.7 +/- 24.7% to 87.5 +/- 23.3%). At equivalent MAC concentrations of isoflurane, the values were 42.5 +/- 45.7 to -7.0 +/- 49.9% in the LAD region and 91.5 +/- 11.9% to 66.9 +/- 23.9% in the CIRC area. At 1.5-MAC halothane, systolic shortening in the LAD region decreased from 47.9 +/- 47.2% to -0.6 +/- 20.3% and in the CIRC area from 114.6 +/- 16.8% to 76.0 +/- 18.7%. Isoflurane at 1.5 MAC produced significant decreases, from 23.4 +/- 54.5% to -15.6 +/- 27.1% in the LAD region and from 94.4 +/- 33.2% to 61.3 +/- 28.2 in the CIRC area.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary vasoconstrictor and vasodilator actions of arachidonic acid in the isolated perfused heart of the rat.

The administration of arachidonic acid (AA) to the isolated perfused heart of the rat usually produced biphasic coronary responses characterized by initial vasoconstriction followed by prolonged vasodilatation. However, some responses were predominantly vasoconstrictor or vasodilator. The non-steroidal anti-inflammatory agents (NSAA) indomethacin (1-5 mg/l) and naproxen (12.5-25 mg/1) reversibly inhibited both phases of the response induced by AA. Pretreatment of animals with indomethacin (5 mg/kg) or naproxen (25 mg/kg) daily, resulted in unaltered coronary response to AA. Subsequent addition of NSAA to the perfusate produced inhibition of the AA effect. Short infusions of acetylsalicylic acid at low concentrations (2.9 micrograms/ml), dipyridamole (0.6 micrograms/ml) and sulphinpyrazone (28.7 micrograms/ml) selectively inhibited the vasoconstrictor phase of the response to AA. It was confirmed that metabolic coronary dilatation induced by cardiostimulation was inhibited by prolonged AA administration; this effect was prevented by NSAA pretreatment. Reactive hyperaemic responses to short lasting occlusions of coronary inflow were unaffected by NSAA. Linolenic, linoleic, dihomo-gamma-linolenic and oleic acid usually produced decreases in coronary flow which were unaffected by NSAA, dipyridamole or sulphinpyrazone. Intra-aortic injections of AA, prostacyclin (PGI2) and prostaglandin E2 (PGE2) in the intact rat produced a dose-dependent decrease in blood pressure with the AA response inhibited by indomethacin. PGI2 and PGE2 produced long lasting coronary vasodilatation in the isolated heart. The coronary actions of AA appear to be due to its transformation, within the easily accessible vascular wall, into prostaglandin and thromboxane-like substances. We suggest that a vasoconstrictor thromboxane A2-like substance may be responsible for coronary vasospasm. Coronary insufficiency may also result from an inhibition of compensatory metabolic coronary dilatation by increased synthesis of PGE2 within the myocardial cell.

Enhancement of noradrenaline-induced metabolic coronary dilatation by ethanol.

Isolated perfused rat hearts receiving noradrenaline as a cardiostimulatory agent show the characteristic metabolic coronary dilatations which correlate with the inotropic effect elicited by noradrenaline. Addition of ethanol (20-400 mg/dl) to the perfusion fluid produced a concentration-dependent enhancement of the metabolic coronary dilatation. The latter was increased by 50% at about 125 mg ethanol/dl. Since the inotropic responses to noradrenaline were not affected by ethanol it is suggested that alcohol produces an alteration in the system that normally adapts the coronary flow to an increased cardiac performance. The effect of ethanol was fully reversible; removal of alcohol from the perfusion fluid restored the metabolic coronary dilatation in response to noradrenaline to control values. At high concentrations, 200-400 mg/dl, ethanol produced a small but significant reduction in contractility of the myocardium (11.1 +/- 2.4%). At these concentrations ethanol enhanced the noradrenaline induced metabolic coronary dilatation by about 100%. These data indicate that ethanol at concentrations that are commonly found in blood in vivo may be beneficial in facilitating the coronary reactions during cardiac exertion. However cardiodepressant effects, particularly at higher concentrations, must also be considered.