Observations on PCBs and mercury in common loons (Gavia immer) collected from southwestern Lake Michigan.

The death of common loons (Gavia immer) was associated with a small spill of bunker-C oil off the Chicago shoreline of Lake Michigan. Petroleum oil was not found on the feathers or in the lungs of the birds. Botulinus toxins C and E were found in heart blood. Because the carcasses were autolysed, botulism toxins could have been produced postmortem. An average of 97 micrograms PCBs (Aroclor 1254 standard) and 2.2 micrograms dieldrin/g of body fat also were found. Concentrations of heavy metals in one bird were 0.25 microgram of total mercury and 0.5 microgram of lead/g of liver, respectively. The loons had abundant body fat suggesting they were not debilitated at the time of death.

pH standardization for phosphorus-31 magnetic resonance heart spectroscopy at different temperatures.

Intracellular pH typically is measured by NMR using the calibrated chemical shift of the inorganic phosphate peak in phosphorus-31 spectra. Heart spectroscopy experiments often require measurements of intracellular pH at temperatures from 5 to 37 degrees C. This paper provides NMR pH calibrations for this range of temperatures, a summary of calibration data reported to date, and a discussion of the factors influencing pH standardization.

Dietary effects on cardiac metabolic properties in rodents.

Previous studies have shown that dietary provision of carbohydrate can alter cardiac isomyosin distribution in hormonally deficient rats. The main objective of this study was to determine if varying the heart's potential to utilize carbohydrate for energy provision can influence the cardiac isomyosin expression in normal weanling rats. Animals were assigned to one of five groups according to dietary and/or metabolic treatment: (1) mixed-control--(M); (2) high carbohydrate--(H); (3) low carbohydrate--(L); (4) mixed-diet supplemented with oxfenicine, a cardiospecific fatty acid oxidation inhibitor--(MO); and (5) high carbohydrate diet supplemented with oxfenicine--(HO). The results show that 4 weeks of dietary manipulations aimed to either increase or decrease carbohydrate supply to the heart, failed to induce any alterations in either cardiac myosin ATPase activity or isoenzyme pattern. However, extremes in carbohydrate provision altered the metabolic properties of both heart and skeletal muscle. A low carbohydrate diet increased 3-hydroxyacyl CoA dehydrogenase (P less than 0.05) and citrate synthase activities (P less than 0.05) and decreased glycogen content in both heart and soleus muscle; whereas, a high carbohydrate diet, in conjunction with oxfenicine, tended to increase hexokinase activity in these same tissues. These alterations provide indirect evidence that the contributions of both fat and carbohydrate to the energy balance of the heart and skeletal muscle were altered by the imposed dietary interventions. Collectively, these results suggest that although the substrate utilization patterns of the normal weanling heart can be modified via dietary manipulation, such shifts do not exert any regulatory influence on cardiac isomyosin expression.

Cardiac-type excitation-contraction coupling in dysgenic skeletal muscle injected with cardiac dihydropyridine receptor cDNA.

There are dihydropyridine (DHP)-sensitive calcium currents in both skeletal and cardiac muscle cells, although the properties of these currents are very different in the two cell types (for simplicity, we refer to currents in both tissues as L-type). The mechanisms of depolarization-contraction coupling also differ. As the predominant voltage-dependent calcium current of cardiac cells, the L-type current represents a major pathway for entry of extracellular calcium. This entry triggers the subsequent large release of calcium from the sarcoplasmic reticulum (SR). In contrast, depolarization of skeletal muscle releases calcium from the SR without the requirement for entry of extracellular calcium through L-type calcium channels. To investigate the molecular basis for these differences in calcium currents and in excitation-contraction (E-C) coupling, we expressed complementary DNAs for the DHP receptors from skeletal and cardiac muscle in dysgenic skeletal muscle. We compared the properties of the L-type channels produced and showed that expression of a cardiac calcium channel in skeletal muscle cells results in E-C coupling resembling that of cardiac muscle.

Effects of potassium or potassium/magnesium supplementation on potassium content of body tissues and fluids in furosemide-treated rats on magnesium-deficient or magnesium-sufficient diet.

Persistent Mg2+ deficiency may interfere with restoration of normal tissue K+ levels. This study examined: a) the effects of chronic furosemide treatment on K+ of sartorius, aorta and ventricle of rats fed Mg2(+)-deficient (100 ppm) or Mg2(+)-sufficient (400 ppm) diet and deionized water; b) whether normal tissue K+ is restored by oral K+ or K+/Mg2+ supplementation with continued furosemide therapy. Levels of Mg2+ were also measured. Furosemide (20 mg/kg i.p.) decreased K+ in sartorius, aorta and ventricle by 5.5, 4.3 and 19.9 microEq/gm (p less than .05), respectively, in rats fed 100 ppm Mg2+ diet. Furosemide did not alter K+ levels in rats fed 400 ppm Mg2+ diet. K+ supplementation (1 mEq/kg for 7 days) restored K+ to normal in sartorius but the addition of Mg2+ supplementation was necessary to restore K+ levels to normal in ventricle and aorta. These data indicate that furosemide can decrease tissue K+ in rats on a Mg2(+)-deficient diet. This decrease can be reversed during diuretic administration by K+ supplementation in sartorius, or K+ plus Mg2+ supplementation in ventricle and aorta.

Changes in ventricular creatine-kinase with progression and regression of cardiac hypertrophy in hypertensive rats.

We studied the distribution of four isoenzymes of creatine-kinase (MM, MB, BB and the mitochondrial) in 13 renovascular hypertensive rats and five age-matched controls. After 6 weeks of hypertension, seven rats were treated with captopril (2 mg/kg daily) for 4 weeks and the other six were left untreated for 4 weeks. After the rats were killed an adaptive increase in MB and BB was found at the expense of MM in the hypertensive rats compared with the controls. The captopril-treated rats displayed persistently higher levels of both MB and BB than the controls. Therefore, the regression in cardiac hypertrophy that is achieved by captopril is accompanied by persistence of the isoenzymic pattern that leads to better use of energy-rich phosphates.

Regulation of cardiac beta-adrenergic receptors by captopril. Implications for congestive heart failure.

The interaction of the renin-angiotensin system and the sympathetic nervous system in patients with congestive heart failure is not well understood. We tested the hypothesis that angiotensin-converting enzyme inhibitors can resensitize the beta-adrenergic receptor system. Guinea pigs were given captopril, isoproterenol, or both for 2 weeks. At death, cardiac sarcolemmal and light vesicle fractions and intact mononuclear leukocytes were prepared. Captopril treatment led to an up-regulation of cardiac beta 1- but not mononuclear leukocyte beta 2-adrenergic receptors and an increase in isoproterenol-stimulated adenylate cyclase activity in the heart. Animals treated with isoproterenol developed cardiac hypertrophy, had increased plasma norepinephrine levels, and had a decreased number and responsiveness of both cardiac and mononuclear leukocyte beta-adrenergic receptors. Concomitant treatment with captopril attenuated alterations of heart weight, plasma norepinephrine levels, and cardiac beta-receptor density and function. In contrast to its cardiac effects, captopril treatment did not diminish the down-regulation of mononuclear leukocyte beta 2-adrenergic receptors by isoproterenol. Our data suggest that captopril may resensitize the cardiac but not the mononuclear leukocyte beta-adrenergic receptor-adenylate cyclase system after long-term catecholamine exposure.

Trace elements intake in the Faroe Islands. III. Element concentrations in human organs in populations from Bergen (Norway) and the Faroe Islands.

Flameless as well as flame atomic absorption spectrophotometry were used for the analysis of six elements (calcium, iron, zinc, selenium, cadmium and mercury) in human organs (liver, kidney cortex and medulla, heart, pancreas and spleen) from 13 bodies from Bergen and 10 from the Faroe Islands. Samples were taken at autopsy and the organs selected were without pathological signs. All patients were born between 1899 and 1923. Element concentrations in the organs studied were comparable to previous studies, except for high mercury and selenium values in the liver, the kidney cortex and medulla of subjects from the Faroe Islands. The high mercury and selenium values may be explained by the high consumption of pilot whales by the Faroe Islands population.

Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel.

In cardiac muscle, where Ca2+ influx across the sarcolemma is essential for contraction, the dihydropyridine (DHP)-sensitive L-type calcium channel represents the major entry pathway of extracellular Ca2+. We have previously elucidated the primary structure of the rabbit skeletal muscle DHP receptor by cloning and sequencing the complementary DNA. An expression plasmid carrying this cDNA, microinjected into cultured skeletal muscle cells from mice with muscular dysgenesis, has been shown to restore both excitation-contraction coupling and slow calcium current missing from these cells, so that a dual role for the DHP receptor in skeletal muscle transverse tubules is suggested. We report here the complete amino-acid sequence of the rabbit cardiac DHP receptor, deduced from the cDNA sequence. We also show that messenger RNA derived from the cardiac DHP receptor cDNA is sufficient to direct the formation of a functional DHP-sensitive calcium channel in Xenopus oocytes. Furthermore, higher calcium-channel activity is observed when mRNA specific for the polypeptide of relative molecular mass approximately 140,000 (alpha 2-subunit) associated with skeletal muscle DHP receptor is co-injected.

Mulberry heart disease in young pigs without vitamin E and selenium deficiency.

Mulberry heart disease persists among young pigs in Denmark although abundant supplies of selenium and vitamin E are added to feedstuffs for sows and pigs. The concentrations of selenium and vitamin E in the liver and heart tissues of young pigs which had died suddenly, and had the characteristic lesions of mulberry heart disease post mortem, were not significantly different from the concentrations found in pigs of the same age which had died suddenly for other reasons. The concentrations of selenium and vitamin E in the livers (0.3 mg/kg and 4 mg/kg, respectively) appeared to be satisfactory in all the pigs examined.

Calcitonin gene-related peptide (CGRP) in normotensive and spontaneously hypertensive rats.

With the techniques of specific radioimmunoassay and gel filtration it was found that CGRP was distributed in various tissues of normotensive (WKY) and spontaneously hypertensive rats (SHR) with the highest concentration in the lumbar spinal cord (1197 +/- 94.8 pg/mg tissue) and the lowest in the auricle (15.0 +/- 2.1 pg/mg tissue). In comparison with WKY, CGRP concentration in the plasma was decreased and in the abdominal aorta and hypothalamus was increased in SHR. Gel filtration revealed only one major CGRP molecular form in the tissues. In addition, CGRP reduced the mean arterial pressure (MAP) in SHR in a dose-dependent manner. These data suggest that CGRP may play an important role in the pathogenesis of hypertension and its possible therapy.

Plasma lipids, lipoproteins, and fecal excretion of neutral sterols and bile acids in rats fed various high fat diets or a low fat/high sucrose diet.

The effect of feeding various diets on plasma lipids and lipoproteins and on fecal excretion of neutral sterols and bile acids was studied in rats fed for 7 wk diets containing 42% of energy as either coconut oil (CO), sunflower seed oil (SO), fish body oil (FBO), cod liver oil (CLO), or a low fat/high sucrose diet (SU). Triacylglycerols (TG) in whole plasma and VLDL + LDL were lower in rats fed high amounts of polyunsaturated fatty acids (PUFA) than in those fed the CO diet. Plasma HDL2 components in FBO and CLO groups were generally lower than in the other groups. Percentages of liver and heart linoleic and arachidonic acid were higher in the SO group, but lower in groups fed marine oils, than in the CO group. There was a high relative amount of eicosapentaenoic and docosahexaenoic acid in liver and heart of rats fed marine oils. Fecal excretion of bile acids was lower in the PUFA groups than in the CO group, whereas the sum of neutral sterols was similar in all groups. Plasma HDL2 (and VLDL + LDL) correlated positively, but HDL3 negatively, with fecal bile acid excretion. Accordingly, increased bile acid excretion does not seem to account for hypolipemia following intake of PUFA diets.

Specific block of calcium channel expression by a fragment of dihydropyridine receptor cDNA.

Although the structure of rabbit skeletal muscle dihydropyridine (DHP) receptor, deduced from cDNA sequence, indicates that this protein is the channel-forming subunit of voltage-dependent calcium channel (VDCC), no functional proof for this prediction has been presented. Two DNA oligonucleotides complementary to DHP-receptor RNA sequences coding for putative membrane-spanning regions of the DHP receptor specifically suppress the expression of the DHP-sensitive VDCC from rabbit and rat heart in Xenopus oocytes. However, these oligonucleotides do not suppress the expression of the DHP-insensitive VDCC and of voltage-dependent sodium and potassium channels. Thus, the gene for DHP receptor of rabbit skeletal muscle is closely related, or identical to, a gene expressed in heart that encodes a component of the DHP-sensitive VDCC. The DHP-sensitive and DHP-insensitive VDCCs are distinct molecular entities.

Dynamics of n-3 and n-6 fatty acids in phospholipids of heart muscle.

The purpose of this paper is to describe the dynamics of n-3 and n-6 polyunsaturated fatty acids in major phospholipids of heart muscle. The profile of n-3 and n-6 fatty acids was examined in rats in relation to various risk factors of coronary heart disease such as stress (catecholamines), ageing and dietary fat. The level of n-3 and n-6 fatty acids in cardiac phospholipids was also examined in relation to coronary heart disease and sudden cardiac death in man. Severe stress caused great changes in the fatty acid profile of phospholipids. Corresponding changes were observed during adaptation to neonatal stress. Rats fed diets containing cod liver oil, butter or corn oil showed different fatty acid composition of individual phospholipids in sarcolemma. Repeated epinephrine administration induced similar changes in the three dietary groups despite large differences in initial levels of individual n-3 and n-6 fatty acids. Fatal ventricular fibrillation in rats and sudden cardiac death in man were accompanied by a high ratio of 20:4 n-6/22:6 n-3. The balance between n-6 and n-3 fatty acids in cellular phospholipids seem to play an important role in sudden cardiac death.

Cytosolic sodium concentration regulates contractility of cardiac muscle.

The present chapter provides experimental evidence to show that intracellular Na+ concentration regulates cardiac contractility effectively by altering intracellular Ca2+ concentration via the Na-Ca exchange. This steep coupling between the Na+ and Ca2+ electrochemical gradients implies that a change in intracellular Na+ concentration is accompanied by a concomitant change in intracellular Ca2+ concentration (and, therefore, contractility). Under the physiologic conditions, each cardiac action potential alters intracellular Na+ concentration in a dynamic manner. Therefore, Na-Ca exchange can regulate cardiac contraction from a beat-to-beat basis.

Relationship between lipid parameters and the occurrence and severity of lesions in the heart: a study on rats fed low erucic acid rapeseed oil.

Fifty-six male Wistar SPF rats were fed a diet containing low erucic acid rapeseed (LEAR) oil (15% by weight) as the only source of lipids for 18 wk. Lipid parameters (fatty acid composition and contents of lipid classes) and the occurrence and severity of focal lesions were both determined on the heart of each animal. Four groups were constituted according to the severity of cardiac lesions. Statistical analyses were applied to the data to find a relationship between the lipid parameters and the severity of heart lesions. None of the measured parameters (heart contents of neutral lipids, total phospholipids, phosphatidylcholine, phosphatidylethanolamine, diphosphatidylglycerol, sphingomyelin and fatty acid composition of each phospholipid class) appeared to be related with the grading of the lesions. Therefore, we failed to find a direct support for the assumption that heart lesions, induced by LEAR oil, are mediated by changes in the lipid and/or fatty acid composition of heart membranes. However, this hypothesis can not be discarded.

[The content of lipid peroxidation products and the activity of antioxidant enzymes in the myocardium and liver of rats with various vitamin E allowances]. / Soderzhanie produktov perekisnogo okisleniia lipidov i aktivnosti antioksidantnykh fermentov v miokarde i pecheni krys pri razlichnoi obespechennosti vitaminom E.

After 2 month of feeding vitamin E-supplemented diet (100.6 and 0 mg/kg; group I-control, II and III, respectively) the concentration of lipid peroxidation products (diene conjugates, malondialdehyde, Schiff's bases) and activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase) was estimated in rat heart and liver. Although the content of alpha-tocopherol in organs of group II was significantly decreased, the concentration of peroxidation products and enzyme activities was unchanged. Moreover, these parameters were constant in rat liver of group III. The heart was more sensitive because in group III to vitamin E deficiency (the alpha-tocopherol level was dropped fourfold) the concentration of diene conjugates and malondialdehyde was increased and superoxide dismutase activity was decreased. Thus insufficiency of vitamin E may result in selective alterations of myocardial functions. In addition, vitamin E may be useful instrument for correction of free radical oxidation and antioxidant system activity in the heart.

Structure and regulation of the rat 1,25-dihydroxyvitamin D3 receptor.

Complementary DNA clones encoding the entire rat 1,25-dihydroxyvitamin D3 receptor were isolated, and the total 423-amino acid sequence was deduced. The amino acid sequence of the rat receptor is similar but not identical to the reported human receptor sequence. The cysteine-rich DNA-binding domain is completely conserved and the steroid-binding domain is greater than 93% conserved between rat and human. The cDNA was used as a probe in blot analysis of polyadenylylated RNA to show that the 1,25-dihydroxyvitamin D3 receptor mRNA is a single 4.4-kilobase mRNA that is expressed in intestine and kidney, slightly expressed in heart, and not detectable in liver and spleen. The receptor mRNA concentration is markedly increased during development of the rat intestine between day 14 and day 21, in accord with previous results obtained by measurement of receptor concentration by ligand binding or immunoblotting.

The carnitine-deprived newborn rabbit: a potential model to study carnitine deficiency.

This report describes the novel development of an animal model for neonatal carnitine deficiency using the artificially fed newborn rabbit. Each litter was separated from the mother following the first colostrum feeding and divided into 2 groups, one of which was fed a purified rabbit formula that was essentially free of carnitine; the other received the same formula supplemented with L-carnitine (100 mg/l). At 9-13 d of age, rabbit pups receiving the carnitine-free formula had lower concentrations of total, free and acylcarnitine in plasma and urine, as well as lower total acid soluble carnitine concentrations in liver, muscle, heart and brown adipose tissue than those receiving the same formula supplemented with L-carnitine. Their plasma and tissue levels were also lower, but their urinary carnitine concentrations were higher than those in naturally-raised pups. The findings suggest that the described animal model may prove to be a useful tool for the investigation of certain aspects of neonatal carnitine deficiency.