Atrial fibrillation: much heat, a little light.
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Atrial Fibrillation↗
Biomedical subjects
Mark A McGuire
Publications and source records attributed to Mark A McGuire.
Characterization and incidence of inducible monomorphic ventricular tachycardia in a postinfarction rabbit model.
OBJECTIVE: Ventricular tachycardia (VT), occurring late after myocardial infarction, is an important cause of sudden death. Animal models are useful for the investigation of this arrhythmia. The aim of this study is to develop and characterize a model of late postinfarction monomorphic VT in the rabbit. METHODS AND RESULTS: Myocardial infarction was created by ligation of the left circumflex artery. Cardiac electrophysiologic studies were performed 10 to 17 days postinfarction in 39 rabbits, in 10 sham-operated rabbits, and 6 control rabbits. Ventricular tachycardia was defined as a broad-complex tachycardia with a cycle length of more than 100 milliseconds, a duration of more than 10 seconds, and monomorphic QRS complexes. Using programmed stimulation, we induced VT in 9 rabbits (23%) in the infarct group but in none of the sham or control animals. The mean infarct size was 23% +/- 9% (mean +/- SD) of the left ventricle. CONCLUSION: Coronary ligation in the rabbit creates a substrate, which allows the induction of sustained monomorphic VT with programmed stimulation. Monomorphic VT is not inducible in rabbits without myocardial infarction. This model might allow the testing of interventions that reduce the incidence of VT late after myocardial infarction.
Animals↗
Transfer of mouse embryonic stem cells to sheep myocardium.
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Animals↗
Differential biohydrogenation and isomerization of [U-(13)C]oleic and [1-(13)C]oleic acids by mixed ruminal microbes.
The additional mass associated with 13C in metabolic tracers may interfere with their metabolism. The comparative isomerization and biohydrogenation of oleic, [1-(13)C]oleic, and [U-13C]oleic acids by mixed ruminal microbes was used to evaluate this effect. The percent of stearic, cis-14 and -15, and trans-9 to -16 18:1 originating from oleic acid was decreased for [U-(13)C]oleic acid compared with [1-(13)C]oleic acid. Conversely, microbial utilization of [U-(13)C]oleic acid resulted in more of the 13C label in cis-9 18:1 compared with [1-(13)C]oleic acid (53.7 vs. 40.1%). The isomerization and biohydrogenation of oleic acid by ruminal microbes is affected by the mass of the labeled tracer.
Analysis of Variance↗
cis-9, trans-11 conjugated linoleic acid is synthesized directly from vaccenic acid in lactating dairy cattle.
The utilization of (13)C-labeled vaccenic acid (VA) by lactating dairy cows to synthesize cis-9, trans-11 conjugated linoleic acid (CLA) was investigated. Primiparous ruminally cannulated Holstein cows (n = 3) were abomasally infused with 1.5 g of VA-1-(13)C. Blood and milk samples were taken frequently before and after VA infusion. Milk and plasma lipid were extracted using chloroform:methanol. Plasma lipid was separated into triacylglycerol (TG), cholesterol ester (CE), phospholipid (PL), nonesterified fatty acid (NEFA), and mono- and diacylglycerol (MDG) fractions. Lipid was methylated, converted to dimethyl disulfide and Diels-Alder adducts, and analyzed by GC-MS. Increased enrichment of (13)C was determined using a 2-sample t test for each sample time compared with -24 h, with significance declared at P < 0.05. Enrichment in milk fat VA was detected at 4 (3.0%), 8 (8.3%), 12 (4.1%), 16 (2.2%), and 20 h (0.8%). Enrichment in VA was also detected in plasma TG, NEFA, PL, and MDG. Enrichment in milk fat cis-9, trans-11 CLA, the Delta9-desaturase product of VA, was detected at 4 (2.6%), 8 (6.6%), 12 (3.4%), 16 (1.7%), and 24 h (0.7%). Enrichment was not detected in cis-9, trans-11 CLA for any plasma lipid fraction. Modeling of the data showed the exponential decay in (13)C enrichment over time for both VA and cis-9, trans-11 CLA in milk fat. Conversion of dietary VA to cis-9, trans-11 CLA endogenously was confirmed with the mammary gland being the primary site of Delta9-desaturase activity; approximately 80% of milk fat cis-9, trans-11 CLA originated from VA.
Animal Feed↗
Cis-9, trans-11 conjugated linoleic acid is synthesized from vaccenic acid in lactating women.
We studied the incorporation of the trans-11 vaccenic-1-(13)C acid ((13)C-VA) into milk and endogenous synthesis of cis-9, trans-11 conjugated linoleic acid (CLA) in lactating women. Subjects (n = 4) were 247 +/- 30 d postpartum, weighed 70.8 +/- 3.7 kg, breast-fed at least 6 times/d and consumed self-selected diets. After an overnight fast, they consumed the (13)C-VA (2.5 mg/kg body wt). Milk samples were obtained by complete breast expression at 0, 2, 4, 8, 12, 18, 24, and 48 h post-(13)C-VA ingestion. Lipid was extracted using chloroform:methanol. Fatty acids were methylated and converted to dimethyl disulfide and Diels-Alder derivatives before analysis by gas chromatography mass spectrometry. The mean (13)C-enrichment of milk VA was 3.1% at 8 h and reached maximal enrichment of 7.6% at 18 h. The (13)C enrichment of milk cis-9, trans-11 CLA reached a maximum of 0.4% at 18 h, confirming its conversion of VA to the Delta9-desaturase enzyme product. In the subjects examined, a portion (<10%) of the cis-9, trans-11 CLA present in milk was endogenously synthesized from VA.
Carbon Isotopes↗
Sudden death in the young.
BACKGROUND: Sudden death is rare in young people, but it has a disproportionate impact on the community. OBJECTIVES: The purpose of this study was to determine the causes of sudden, natural death in persons aged 5-35 years. METHODS: All autopsies conducted at a forensic medicine facility in the years 1995-2004 (inclusive) were reviewed. This facility serves more than 2.5 million people in the eastern part of Sydney, Australia. Data collected included subject age, height, weight, gender, circumstances of death, and pathologic findings at autopsy. Deaths caused by trauma, accidental causes, drowning, and drug toxicity were excluded from analysis. RESULTS: There were 427 nontraumatic, sudden deaths in the 10-year period (70.7% male). Cardiac causes accounted for 56.4%, noncardiac causes 39.3%, and undetermined cause 4.3%. The most common cardiac cause of sudden death was presumed arrhythmia in those with no or minimal structural heart disease (29.0%). Other cardiac causes were acute myocardial infarction (24.5%), myocarditis (11.6%), hypertrophic cardiomyopathy (5.8%), aortic dissection (5.4%), and dilated cardiomyopathy (5.4%). More than two thirds of deaths caused by acute myocardial infarction occurred in the age group from 30-35 years. Sudden cardiac death occurred during physical activity in 10.8% of cases. Sudden cardiac death was reported in a first-degree relative in 4.5% of decedents. The most common noncardiac causes of sudden death were epilepsy (23.8%), intracerebral hemorrhage (23.8%), asthma (16.1%), and pulmonary embolism (12.5%). CONCLUSION: Presumed cardiac arrhythmia is the most common cause of sudden, natural death in the young. There was no reported history of sudden death among the relatives of most decedents.
Adolescent↗
trans Fatty acids in milk produced by women in the United States.
BACKGROUND: trans Fatty acids (FAs) have been identified as negatively affecting human health. The trans FA composition of human milk fat must be examined to establish its influence on the nutritional quality of milk consumed by infants. OBJECTIVE: We sought to ascertain the individual and total trans FA isomers (sum of FAs containing at least one trans double bond) in human milk and to identify relations between individual FAs and milk fat concentration (% by wt). DESIGN: The FA composition of milk samples (n = 81) from women living in the southwestern United States was ascertained. The individual 18:1t isomers were separated. Correlations between each FA, total trans FAs, groups of similar FAs, and milk fat concentrations were examined. RESULTS: The mean total trans FA concentration was 7.0 +/- 2.3% (range: 2.5-13.8%). The concentration of total 18:1t was 5.1 +/- 2.0% (range: 1.5-11.6%), and Delta10t (range: Delta9-12t) was the most abundant isomer. CONCLUSIONS: Milk fat from women living in the United States contains concentrations of trans FAs similar to those in milk from Canadian women but greater than those reported in milk from women in other countries. In decreasing order of concentration, the Delta10t, Delta11t, Delta9t, and Delta12t isomers represented 78.9% of the total 18:1t. These FAs generally originate from partially hydrogenated vegetable oils and ruminant fat in the diet. No relation was found between the concentration of total trans FAs and milk fat concentration.
Adult↗
Dietary fat type influences total milk fat content in lean women.
Trans fatty acids (TFA) are found naturally in some foods (e.g., dairy products) as well as many processed foods made with partially hydrogenated vegetable oils (PHVO). Data from a growing literature suggest that some TFA decrease milk fat in lactating animals. Because the physiologic effects of TFA in lactating women are unknown, this study was designed to investigate the effects of TFA consumption on human milk fat. A randomized, crossover design (n = 12) was used to study the effect of 3 dietary treatments: high PHVO (regular margarine), low PHVO (low TFA margarine), or low PHVO but high in naturally occurring TFA (butter) on milk fat. Treatments were administered for 5 d, with 7-d washout periods. Maternal adiposity was estimated by dual-energy X-ray absorptiometry. Milk and blood were collected on d 5 of each intervention period. In general, milk and serum fatty acid concentrations mirrored those of the dietary treatments. There were significant interactions between treatment and maternal adiposity on milk fat and infant milk consumption, as well as on serum glucose and nonesterified fatty acid (NEFA) concentrations. Consumption of regular margarine, compared with low TFA margarine, resulted in lower milk fat in leaner, but not in more obese women. Consumption of either regular or low TFA margarine, compared with butter, elevated serum NEFA concentrations in the more obese women. In summary, consumption of regular margarine, compared with low TFA margarine, decreased milk fat in lean women. Further studies are required to determine whether infant milk consumption might compensate for this potentially important change in milk composition.
Absorptiometry, Photon↗
Consumption of conjugated linoleic acid (CLA) from CLA-enriched cheese does not alter milk fat or immunity in lactating women.
Isomers of conjugated linoleic acid (CLA) decreased milk fat, altered immunity, and reduced the risk for cardiovascular disease (CVD) in some animals. The major form of CLA in the human diet is c9,t11-18:2 (rumenic acid; RA). We studied the effects of high RA consumption on plasma and milk RA concentration, milk composition, immunity, and CVD risk factors in lactating women (n = 36) assigned to 1 of 3 treatments: control, low CLA cheese (LCLA; 160 mg RA/d), or high CLA cheese (HCLA; 346 mg RA/d). The increase in plasma RA concentration between baseline and 8 wk in women consuming HCLA cheese was significantly greater than that of controls. At study completion (8 wk), milk RA concentration among women consuming HCLA cheese was greater (P < 0.05) than that of controls (0.37 vs. 0.26% of fatty acids). Treatment did not affect milk fat, protein, or lactose concentrations, immune indices (e.g., plasma T-helper cells and interleukin-2), or measured risk factors for CVD (e.g., plasma triacylglyceride and cholesterol). In summary, consumption of a RA-enriched cheese modestly increased plasma and milk RA concentrations without affecting total milk fat, plasma and milk indices of immunity, or selected risk factors for CVD.
Adult↗
Should patients with severely impaired left ventricular function following myocardial infarction receive an implantable defibrillator?
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Journal Article↗
Development and testing of a high-density cDNA microarray resource for cattle.
A cDNA microarray resource has been developed with the goal of providing integrated functional genomics resources for cattle. The National Bovine Functional Genomics Consortium's (NBFGC) expressed sequence tag (EST) collection was established in 2001 to develop resources for functional genomics research. The NBFGC EST collection and microarray contains 18,263 unique transcripts, derived from many different tissue types and various physiologically important states within these tissues. The NBFGC microarray has been tested for false-positive rates using self-self hybridizations and was shown to yield robust results in test microarray experiments. A web-accessible database has been established to provide pertinent data related to NBFGC clones, including sequence data, BLAST results, and ontology information. The NBFGC microarray represents the largest cDNA microarray for a livestock species prepared to date and should prove to be a valuable tool in studying genome-wide gene expression in cattle.
Animals↗
Determination of c9,t11-CLA in major human plasma lipid classes using a combination of methylating methodologies.
Isomeric CLA exhibit several significant biological activities in animals and humans and are easily isomerized to their corresponding t,t-CLA isomers during methylation with various acid-catalyzed reagents. To minimize such isomerization and provide a valid quantification of human plasma CLA content, several methylation methods were tested. Plasma neutral lipid, nonesterified FA (NEFA), and polar lipid classes were separated into the following fractions: (i) cholesteryl ester (CE, 1.2 mg/12 mL, 37.5% lipids), (ii) TAG (0.8 mg/12 mL, 25% lipids), (iii) NEFA (0.2 mg/12 mL, 6.2% lipids), (iv) MAG/DAG/cholesterol (0.3 mg/12 mL, 9.4% lipids), and (v) phospholipid (PL, 0.5 mg/20 mL, 15.6% lipids). Data showed that c9,t11-CLA found in TAG, MAG/DAG/cholesterol, and PL fractions were converted to methyl esters with sodium methoxide within 2 h at 55 degrees C. However, the c9,t11-CLA in the CE fraction could not be completely converted to methyl esters by sodium methoxide/acetylchloride in methanol or methanolic KOH; instead, CE was treated with sodium methoxide and methyl acetate in diethyl ether for 1 h. NEFA were converted to methyl esters with trimethylsilyldiazomethane (TMSDAM). All reaction mixtures were monitored by TLC prior to GLC analysis. The highest enrichment of c9,t11-18:2 (% FA) was in TAG (0.31%), followed by CE (0.14%) and PL (0.13%). The above methylation methods were then applied to a small subset (n = 10) of nonfasting plasma lipid fractions to confirm the applicability of these data. Results from this subset of samples also indicated that the greatest enrichment of c9,t11-CLA was present in the TAG fraction (0.39%), followed by CE (0.27%) and PL (0.22%). These data indicate that different plasma fractions have different c9,t11-CLA contents.
Adult↗
Tyramide signal amplification enhances the detectable distribution of connexin-43 positive gap junctions across the ventricular wall of the rabbit heart.
Previous mapping studies examinig the distribution and pattern of staining for connexin-43 expression (the major ventricular gap junction protein) across the ventricular wall have yielded variable findings. The aim of this study was to determine if variations in the distribution of connexin-43 were due to histochemical detection problems, i.e. cross-linking of antigenic sites as a consequence of aldehyde fixation and/or due to low levels of protein expression within the epicardial or endocardial regions of the heart. Immunoperoxidase staining of connexin-43 using the ABC method was carried out in crosssections of rabbit hearts at the level of the papillary muscle. The following treatments were examined: the antibody (Ab) only, Ab with 1/2 Tyramide Signal Amplification (TSA) or full TSA; antibody with microwave antigen retrieval (AR); Ab + 1/2 TSA + AR and finally Ab + TSA + AR. Under light microscopy and using computerized image analysis the percentages of ventricular cross-sectional transmural staining for the different treatment groups were calculated: Ab amounted to only 55%; Ab + 1/2 TSA 63%; Ab + TSA 78%; Ab + AR 72%; Ab + AR + 1/2 TSA 72% and Ab + AR + TSA 88%. The percentages of transumural connexin-43 staining in both TSA + Ab and Ab + TSA + AR groups when compared to Ab only were significantly greater p < 0.01. The antigenic cross-linking due to aldehyde fixation and low levels expression of connexin-43 are contributing factors that influence the immunohistochemical detection of connexin-43 in the mammalian heart. Methodological enhancement for the detection of connexin-43 in this study was derived primarily from amplification of low background levels of connexin-43 being expressed using the TSA protocol. This is supported by the significant differences encountered when TSA was utilized in the protocol and compared with antibody treatment only.
Animals↗
Maternal supplementation with CLA decreases milk fat in humans.
CLA refers to isomers of octadecadienoic acid with conjugated double bonds. The most abundant form of CLA (rumenic acid (RA): c9,t11-18:2) is found in milk and beef fat. Further, CLA supplements containing RA and t10,c12-18:2 are now available. Consumption of commercially produced CLA has been shown to decrease adipose accretion in growing laboratory and production animals and cause milk fat depression in cows. We tested the hypothesis that CLA supplementation would increase milk CLA concentration and decrease milk fat content in humans. Breastfeeding women (n = 9) participated in this double-blind, placebo-controlled, crossover study divided into three periods: intervention I (5 d), washout (7 d), and intervention II (5 d). Women were randomized to treatment order. During each intervention period, women consumed 1.5 g of CLA supplement or placebo (olive oil) daily; during the washout period, no supplements were consumed. Milk was collected by complete breast expression on the final day of each period; milk output was estimated by 24-h weighing on the penultimate day of each intervention period. Milk RA and t10,c12-18:2 concentrations were greater (P < 0.05) during the CLA treatment period as compared to the placebo period. Milk fat content was significantly lower during the CLA treatment, as compared to the placebo treatment (P < 0.05). Data indicate no effect of treatment on milk output. Therefore, it would be prudent that lactating women not consume commercially available CLA supplements at this time.
Breast Feeding↗