Plasma delipidation process induces rapid regression of atherosclerosis and mobilisation of adipose tissue.

Cholesterol is a major component of atherosclerotic plaques. Cholesterol accumulation within the arterial intima and atherosclerotic plaques is determined by the difference of cellular cholesterol synthesis and/or influx from apo B-containing lipoproteins and cholesterol efflux. In humans, apo A-1 Milano infusion has led to rapid regression of atherosclerosis in coronary arteries. We hypothesised that a multifunctional plasma delipidation process (PDP) would lead to rapid regression of experimental atherosclerosis and probably impact on adipose tissue lipids. In hyperlipidemic animals, the plasma concentrations of cholesterol, triglyceride and phospholipid were, respectively, 6-, 157-, and 18-fold higher than control animals, which consequently resulted in atherosclerosis. PDP consisted of delipidation of plasma with a mixture of butanol-diisopropyl ether (DIPE). PDP removed considerably more lipid from the hyperlipidemic animals than in normolipidemic animals. PDP treatment of hyperlipidemic animals markedly reduced intensity of lipid staining materials in the arterial wall and led to dramatic reduction of lipid in the adipose tissue. Five PDP treatments increased apolipoprotein A1 concentrations in all animals. Biochemical and hematological parameters were unaffected during PDP treatment. These results show that five PDP treatments led to marked reduction in avian atherosclerosis and removal of lipid from adipose tissue. PDP is a highly effective method for rapid regression of atherosclerosis.

Effects of simvastatin on blood lipids, vitamin E, coenzyme Q10 levels and left ventricular function in humans.

BACKGROUND: As statin therapy has been reported to reduce antioxidants such as vitamin E and coenzyme Q10 and there are indications that this reduction may cause impairment of left ventricular function (LVF), we studied the influence of simvastatin on LVF and serum vitamin E and coenzyme Q10 levels in humans. MATERIAL AND METHODS: We assessed the effect of simvastatin on left ventricular function and coenzyme Q10 levels in 21 (11 male, 10 female) hypercholesterolaemic subjects (mean age = 56 years) with normal LVF, over a period of 6 months. Subjects were re-tested after a 1-month wash-out period (7 months). Echocardiography was performed on all subjects before commencement of simvastatin (20 mg day(-1)), and at 1, 3, 6 and 7 months after initiation of treatment. Fasting blood samples were also collected at these intervals to assess lipids, apoproteins, vitamin E and coenzyme Q10. RESULTS: Serum lipids showed the expected reductions. Plasma vitamin E and coenzyme Q10 levels were reduced by 17 +/- 4% (P < 0.01) and 12 +/- 4% (P < 0.03) at 6 months. However, the coenzyme Q10/LDL-cholesterol ratio and vitamin E/LDL-cholesterol ratio increased significantly. Left ventricular ejection fraction (EF) decreased transiently after 1 month, while no significant change was observed at 3 and 6 months. Other markers of left ventricular function did not change significantly at any time point. CONCLUSION: Despite reduced plasma vitamin E and coenzyme Q10, 20 mg of simvastatin therapy is associated with a significantly increased coenzyme Q10/LDL-cholesterol ratio and vitamin E/LDL-cholesterol ratio. Simvastatin treatment is not associated with impairment in left ventricular systolic or diastolic function in hypercholesterolaemic subjects after 6 months of treatment.

Nutraceuticals: vitamins and other nutrients in coronary heart disease.

Nutraceuticals and specifically vitamins, oils and herbs are increasingly being taken by patients. Some supplements may improve cardiovascular outcome, most are unproved, and some could potentially cause harm. Marine lipid supplementation needs to be considered in all patients who have manifest coronary heart disease. For most supplements more data are needed before confident recommendations can be made.

Pravastatin therapy and the risk of stroke.

BACKGROUND: Several epidemiologic studies have concluded that there is no relation between total cholesterol levels and the risk of stroke. In some studies that classified strokes according to cause, there was an association between increasing cholesterol levels and the risk of ischemic stroke and a possible association between low cholesterol levels and the risk of hemorrhagic stroke. Recent reviews of trials of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have suggested that these agents may reduce the risk of stroke. METHODS: In a double-blind trial (the Long-Term Intervention with Pravastatin in Ischaemic Disease study), we compared the effects of pravastatin on mortality due to coronary heart disease (the primary end point) with the effects of placebo among 9014 patients with a history of myocardial infarction or unstable angina and a total cholesterol level of 155 to 271 mg per deciliter (4.0 to 7.0 mmol per liter). Our goal in the present study was to assess effects on stroke from any cause and nonhemorrhagic stroke, which were secondary end points. RESULTS: There were 419 strokes among 373 patients over a follow-up period of six years. A total of 309 strokes were classified as ischemic, 31 as hemorrhagic, and 79 as of unknown type. Among the patients given placebo, the risk of stroke was 4.5 percent, as compared with 3.7 percent among those given pravastatin (relative reduction in risk, 19 percent; 95 percent confidence interval, 0 to 34 percent; P=0.05). Non-hemorrhagic stroke occurred in 4.4 percent of the patients given placebo, as compared with 3.4 percent of those given pravastatin (reduction in risk, 23 percent; 95 percent confidence interval, 5 to 38 percent; P=0.02). Pravastatin had no effect on hemorrhagic stroke (incidence, 0.2 percent in the placebo group vs. 0.4 percent in the pravastatin group; P=0.28). CONCLUSIONS: Pravastatin has a moderate effect in reducing the risk of stroke from any cause and the risk of nonhemorrhagic stroke in patients with previous myocardial infarction or unstable angina.

Food for prevention of coronary heart disease: Beyond the low fat, low cholesterol diet.

The single major cause of death throughout the world is coronary heart disease. Prevalence is stable or decreasing in North America, Australasia and most of Europe, while rapidly increasing in eastern Europe, Asia and Africa. Atherosclerosis is the underlying pathology. This is one of the classic lifestyle diseases on the background of genetic susceptibility. Diet plays a key role in the initiation and progression of coronary heart disease. A low total fat diet is almost universally recommended throughout the world. However, the most successful secondary prevention diet trials have used modification of fat, rather than decrease in total fat per se. Successful diet trials suggest that diet modification is as effective as accepted drug therapy to prevent recurrent coronary events, and importantly is very cost effective. Marine lipid supplementation has been demonstrated beyond reasonable doubt to decrease total mortality and in particular sudden death in patients who have survived their first myocardial infarction. Large-scale diet intervention trials are indicated to improve the scientific basis for dietary recommendations to prevent initial and recurrrent coronary heart disease.

Interdependence of serum concentrations of vitamin K1, vitamin E, lipids, apolipoprotein A1, and apolipoprotein B: importance in assessing vitamin status.

Vitamin E (alpha-tocopherol) and vitamin K1 (phylloquinone) are fat-soluble vitamins and are important nutrients in health and disease. In this study serum concentrations of vitamin E and vitamin K1, lipids and apolipoproteins A1 and B were measured in neonates, normal and hyperlipidaemic individuals in an attempt to establish their interrelationships. A high degree of correlation was observed between the concentrations of the vitamins and those of lipids and apolipoproteins (r ranged from 0.42 to 0.92; p<0.001). Stepwise linear regression methods determined that serum concentrations of both vitamin E and vitamin K1 could best be predicted by using equations excluding lipids but containing only apolipoprotein A1 and B concentrations. Correlation coefficients between predicted and measured values were 0.89 for serum vitamin E, and 0.83 for serum vitamin K1 concentrations. To test the validity of the derived formulae, measured and estimated vitamin K1 and vitamin E concentrations in serum were determined in another group of neonates, normal adults and hypercholesterolemic adults and the comparisons were shown to be very good. These results indicate that the serum levels of both vitamins depend critically on the concentration of the lipoprotein carriers, apolipoproteins A1 and B. Hence, in order to identify variations in serum vitamin K1 and vitamin E concentrations, which are independent of variations in carrier concentration, it will be necessary to express these serum vitamins as ratios of vitamins to apolipoprotein A1 and B carriers.

Lecithin-cholesterol acyltransferase activity in normocholesterolaemic and hypercholesterolaemic roosters: modulation by lipid apheresis.

Lipid apheresis, a recently described procedure for the elimination of lipid but not apolipoproteins from plasma, was applied to normocholesterolaemic and hypercholesterolaemic roosters. Lipid apheresis resulted in an immediate reduction in plasma unesterified cholesterol concentration, which was sustained for 150 min. The reduction in unesterified cholesterol concentration was higher in the normocholesterolaemic animals than in the hypercholesterolaemic animals. Lipid apheresis induced changes in the ratio of plasma unesterified to total cholesterol in normocholesterolamic animals but not in hypercholesterolaemic animals. In hypercholesterolaemic animals, lecithin-cholesterol acyltransferase (LCAT) activity was not affected by lipid apheresis, whereas in normocholesterolaemic animals LCAT activity was acutely reduced for 150 min after lipid apheresis. Saturated LCAT kinetics occurred in the hypercholesterolaemic animals but not in the normocholesterolaemic animals. LCAT obeyed Michaelis-Menten kinetics. After lipid apheresis, there was a pool of unesterified cholesterol that was available as substrate for LCAT to a greater extent in hypercholesterolaemic animals than in normocholesterolaemic animals. These observations may have important implications for lipid apheresis as a treatment for atherosclerosis.

Lipid apheresis in an animal model causes in vivo changes in lipoprotein electrophoretic patterns.

Lipid apheresis, a new extracorporeal procedure based on plasma delipidation and showing promise as a possible treatment for atherosclerosis, was recently reported for the first time from this laboratory [Cham et al., J Clin Apheresis 10:61-69, 1995]. In the present study lipid apheresis was applied to hypercholesterolemic and normocholesterolemic roosters to examine its effect on plasma lipoprotein particles. This procedure resulted in conspicuous changes in electrophoretic patterns of plasma lipoproteins. The electrophoretic mobilities of all the lipoprotein fractions had changed considerably. Lipid stainable material was present in at least three bands in the alpha-globulin area. In particular, changes in the electrophoretic region of high-density lipoproteins were observed. Lipid apheresis markedly induced the anti-atherogenic pre- beta-high-density lipoproteins. The observed changes induced by lipid apheresis were more pronounced in the hyperlipidemic animals compared with the normocholesterolemic controls. A novel pre-alpha-lipoprotein band was observed soon after lipid apheresis. This lipoprotein band had a density larger than 1.21. At approximately 150 minutes after lipid apheresis, the electrophoretic pattern had almost returned to its original base pattern. Lipid apheresis results in plasma lipoprotein changes which may induce reverse cholesterol transport and shows promise as a possible treatment of atherosclerosis.

Phenolic content of olive oil is reduced in extraction and refining.

Three grades of olive oil and ten vegetable cooking oils were analysed for their phenolic content. It was hypothesised that as olive oil passed through the chemical extraction process, polyphenols would also be removed, thus reducing the antioxidant properties of olive oil. Other commonly used edible vegetable oils were analysed for comparative reasons. Extra virgin olive oil was found to have the greatest amount (48 µg/gram of oil) of polyphenols, when compared with other olive or vegetable oils. No polyphenols were detected in sunflower, walnut, peanut or almond oils. All other oils tested had a polyphenolic content between 2 and 10 µg/gram of oil. The results of the study confirms the above hypothesis that the phenolic content of olive oil is reduced by chemical extraction and refining.

Lipid apheresis: an in vivo application of plasma delipidation with organic solvents resulting in acute transient reduction of circulating plasma lipids in animals.

Despite primary and secondary prevention of coronary disease with lowering plasma cholesterol by diet and drug therapy, coronary heart disease remains the major cause of death in Western countries. Low density lipoprotein apheresis had the potential to make a significant impact as it acutely leads to a marked reduction in plasma cholesterol. However, recent preliminary results suggest that low density lipoprotein apheresis may not be more effective in preventing progression of coronary disease than current drug therapy. We have devised a new technique, termed lipid apheresis, which removes cholesterol and triglycerides from plasma but retains the apolipoproteins. This procedure shows great promise in stimulating regression beyond current therapy. Lipid apheresis, a new extracorporeal procedure based on plasma delipidation with the organic solvent mixture butanol-diisopropyl ether, was applied to hypercholesterolemic and normocholesterolemic roosters. Approximately 25% of the calculated blood volume was removed from the animals. The plasma was separated from the blood cells. The plasma was delipidated for 20 min with the organic solvent mixture. The delipidated plasma containing all proteins, including the apolipoproteins and other ionic constituents, was remixed with the blood cells and infused back into the identical donor animals. Analyses of serial blood samples collected from lipid apheresed and sham treated animals up to 16 h after infusion revealed that lipid apheresis caused acute, marked reductions in plasma lipids. The pattern and extent of the plasma levels of cholesterol were different in the hypercholesterolemic animals when compared with normocholesterolemic animals, indicating that a readily extraplasma cholesterol pool in the hypercholesterolemic animals was rapidly mobilized into the plasma pool.(ABSTRACT TRUNCATED AT 250 WORDS)

TENS in refractory angina pectoris. Three case reports.

OBJECTIVE: To demonstrate the use of transcutaneous electrical nerve stimulation (TENS) in the treatment of refractory angina pectoris. CLINICAL FEATURES: Three cases are presented. Patient 1 was a 56-year-old man with a 20-year history of angina pectoris. Angiography revealed extensive stenoses of coronary arteries. He was deemed unsuitable for coronary bypass surgery due to significant distal coronary disease. Patient 2 was an 81-year-old woman with angina that responded poorly to increasing drug therapy: she also had extensive stenoses but was judged unsuitable for surgery. Patient 3 was a 69-year-old man who had previously undergone two coronary bypass procedures and presented with unstable rest angina. The patient was deemed unsuitable for a third coronary artery bypass operation due to distal disease and the small calibre of the intermediate artery. INTERVENTION AND OUTCOME: Each patient had TENS added to their treatment regimen (one hour twice a day for Patient 1; one hour three times a day for Patients 2 and 3). Patient 1 experienced a marked reduction in pain which lasted for over a year before symptoms of angina again worsened. Patient 2 has experienced no further pain of angina except on occasions when her TENS unit was not working or she neglected to use it as prescribed. Patient 3 had been free of angina from commencement of TENS therapy on review three months later. CONCLUSION: TENS may be useful in the treatment of angina pectoris which is refractory to medical therapy when the patient is not suitable for revascularisation procedures or revascularisation has failed. The mechanism of action is probably a combination of analgesia per se and inhibition of sympathetic nervous stimulation of the heart.

Comparison of the effects on lipoproteins and apolipoproteins of a diet high in monounsaturated fatty acids, enriched with avocado, and a high-carbohydrate diet.

A randomized trial was conducted to compare effects of a diet high in monounsaturated fatty acids, enriched with avocado (AE), and a high-complex-carbohydrate diet (AHA-III) on blood lipid concentrations. Fifteen females between 37 and 58 y of age were allocated either to AE followed by AHA-III, or vice versa. Each dietary phase lasted 3 wk. Both diets were found to lower total cholesterol compared with baseline values. AE was more effective, with an 8.2% decrease (P less than 0.05) whereas AHA-III was associated with a 4.9% decrease (NS). Low-density-lipoprotein cholesterol and apolipoprotein B decreased significantly on AE but not on AHA-III (P less than 0.05). The high-density-lipoprotein (HDL) concentration did not change on AE but decreased 13.9% on AHA-III (P less than 0.01). It is concluded that AE is more effective than is AHA-III in decreasing total cholesterol, and, unlike AHA-III, it does not decrease HDL concentrations.

Fatal envenomation by Chironex fleckeri, the north Australian box jellyfish: the continuing search for lethal mechanisms.

A child with severe envenomation by Chironex fleckeri presented in cardiac arrest at a hospital between 15 and 20 min after the sting was sustained. Resuscitation was not successful. Objective confirmation of C. fleckeri as the cause of death is described. Four metres of tentacle contact in this case represents the smallest-measured fatal C. fleckeri sting that has been recorded so far. The mechanism of this death was toxic and not allergic. The available clinical information suggests direct myocardial interference, but does not exclude a respiratory hypoxic element. A more widespread venom-induced functional disruption of the cell membrane is postulated, with a resultant dysfunction in several vital organ systems that were acting in concert. Early, vigorous and sustained resuscitation that is performed as a first-aid measure offers the best hope of prehospital survival after a massive C. fleckeri sting, which is the most explosive envenomation process that is presently known to humans. In-hospital resuscitation from unresponsive circulatory arrest should now involve intravenously-administered verapamil (or its equivalent) and additional box-jellyfish antivenom, while the patient is being monitored.