Effects of diltiazem on suppression and regression of experimental atherosclerosis

The effects of diltiazem (a calcium antagonist) on the suppression and regression of atherosclerosis were studied. Thirty-one rabbits were fed a 1% cholesterol (atherogenic) diet together with saline (n = 22) or diltiazem (n = 9) injections. After 10 weeks, seven rabbits that received saline and nine rabbits that received diltiazem were killed. The remaining 15 saline-treated rabbits were then put on a standard (regression) diet for the next 15 weeks with saline (n = 7) or diltiazem (n = 8) injections. Sixteen rabbits given a standard diet were used as controls. At 5 and 10 weeks, the plasma LDL cholesterol level in rabbits on the atherogenic diet with diltiazem was significantly lower than in those on the atherogenic diet with saline. The aortic total cholesterol, esterified cholesterol and calcium contents were also significantly lower in rabbits on the atherogenic diet with diltiazem. After 25 weeks (15 weeks on the regression diet), the differences in aortic total cholesterol and calcium contents between the two groups on the regression diet were not significant; however, the aortic esterified cholesterol content was significantly lower in the regression diet with diltiazem. The results suggest that diltiazem has a favourable effect both on regression and on suppression of atherosclerosis.     

Effects of stimulation and suppression of cell-mediated immunity on experimental cryptococcosis.

A model of cryptococcosis was developed using intraperitoneal infections of guinea pigs. This model shared characteristics with cryptococcosis in humans and was used to study the effects of immunosuppression and immunostimulation on cryptococcosis. Female guniea pigs survived longer than males; perphaps this was related to a greater capacity of their monocytes to kill cryptococci. A brief course of cortisone shortened survival of females and resulted in depressed immune and inflammatory responses, which persisted long after cortisone was stopped. Stimulation of the immune response by treatment with cryptococci in Freund complete adjuvant improved survival in males. Preliminary studies indicated the usefulness of this model for the study of other potential immunostimulants, including immune lymphocytes, transfer factor prepared from immune lymphocytes, and levamisole. Overall, long-term survivors appeared to clear disseminated cryptococci from extraperitoneal sites including brain, rather than prevent dissemination of cryptococci from the peritoneal cavity. The quantity of the inflammatory response in infectious foci, rather than the ability of individual leukocytes to kill crytococci, may have determined the outcome of most infections.     

Dietary restriction and regression of atherosclerosis

Summary Rabbits were fed a cholesterol-enriched diet to render them atheromatous. After 3 months on this diet they were switched to a low-lipid stock diet. Some animals were killed at this point, while the rest were divided into (a) a group allowed to eat ad-libitum and (b) a restricted group allowed to eat half by weight of what the ad-libitum group consumed. Most animals were killed at 9 months (i.e. after 6 months' regression). The group allowed the restricted diet showed a 27% weight loss, but their serum cholesterol fell slightly more slowly than that of the ad-libitum animals. Likewise, atherosclerosis was slightly worse in the restricted than in the ad-libitum group. The results do not support the view that severe dietary restriction causes atherosclerosis to regress.     

硝苯啶、硫氮(艹卓)酮对兔实验性动脉粥样硬化症的影响

硝苯啶和硫氮(艹桌)酮不明显影响血清脂蛋白组分水平,但均显著抑制家兔主动脉动脉粥样硬化形成,降低血浆过氧化脂质、血栓烷和主动脉内中膜胆固醇、磷脂及钙含量,升高血浆6-酮-PGF_(1α),使,TXB_2/6-酮-PGF_(1α)趋于平衡。说明钙在血栓烷-前列环素代谢中起重要作用。     

Effects of meprobamate on plasma lipids, lipoproteins, and experimental atherosclerosis

The effects of the tranquilizer meprobamate (Equanil) on plasma lipids, lipoproteins, and atherogenesis in cockerels fed an atherogenic diet have been investigated. Gross gradings (visually assessed blindly) of the atherosclerosis of the thoracic and abdominal aortas of the meprobamate-treated plain mash were significantly more severe than the untreated plain mash controls. There were no significant differences in the gradings of thoracic and abdominal aortic lesions in the atherogenic groups, whether treated with meprobamate or not. Microscopic examination of the coronary arteries of birds on the atherogenic regimen treated with meprobamate revealed that these birds had atherosclerosis similar to the atherogenic diet group.     

Effects of ethanol on lipids and atherosclerosis.

Moderate alcohol consumption is associated with an increase in plasma high density lipoprotein (HDL) cholesterol concentration and a decrease in low density lipoprotein (LDL) cholesterol concentration. Changes in the concentration and composition of lipoproteins are estimated to account for more than half of alcohol's protective effect for coronary heart disease. Alcohol intake also affects plasma proteins involved in lipoprotein metabolism: cholesteryl ester transfer protein, phospholipid transfer protein, lecithin:cholesterol acyltransferase, lipoprotein lipase, hepatic lipase, and phospholipases. In addition, alcohol intake may result in acetaldehyde modification of apolipoproteins. Furthermore, "abnormal" lipids, phosphatidylethanol and fatty acid ethyl esters are formed in the presence of ethanol and are associated with lipoproteins in plasma. Ethanol and ethanol-induced modifications of lipids may modulate the effects of lipoproteins on the cells in the arterial wall. The molecular mechanisms involved in these processes are complex, requiring further study to better understand the specific effects of ethanol in the pathogenesis of atherosclerosis. This review discusses the effects of ethanol on lipoproteins and lipoprotein metabolism, as well as the novel effects of lipoproteins on vascular wall cells.     

Studies on the progression and regression of coronary and peripheral atherosclerosis in the cynomolgus monkey. I. Effects of dipyridamole and aspirin.

The morphological and biochemical changes in the arteries of the cynomolgus monkey were investigated during the induction and regression of atherosclerosis. During the feeding of an atherogenic diet containing 2% cholesterol and 10% butter for 5 months, the animals developed fibro-fatty plaques which involved the coronary and peripheral arteries and caused significant luminal narrowing of these vessels. The induced aortic lesions contained increased amounts of free and esterified cholesterol, collagen, elastin, and calcium. These changes were associated with an elevation of plasma cholesterol and an increased net influx of plasma cholesterol and LDL into the aorta. Dipyridamole (10 mg/kg) and aspirin (50 mg/kg) had no effect on the arterial uptake of plasma LDL and cholesterol and did not protect against atherosclerosis in any of the vessels examined.During the regression period (low cholesterol diet) of 12 months duration, the induced lesions became more fibrotic and calcified while the cellularity and lipid content of the same lesions decreased. As a result of these changes there were no significant decreases in the atherosclerotic narrowing of the coronary and peripheral vessels. The net influx of plasma LDL and cholesterol into the aorta returned to normal during the regression period. This finding together with the slow rate of aortic cholesterol equilibration suggests that the retention of cholesterol in the regressed aortic lesions is due to a defect in cholesterol transport rather than to an abnormality in intimal permeability. The addition of dipyridamole and aspirin to the regression diet did not alter the course of the atherosclerosis.     

Koch''s postulates and experimental atherosclerosis

Koch's postulates contributed substantially to the evolution of scientific knowledge of infectious diseases, but are inapplicable to chronic non-infectious, degenerative diseases such as atherosclerosis. In experimental atherogenesis compliance with appropriately modified postulates is essential to preclude spurious causes from consideration. The crux of such postulates is that the experimental procedure must reproduce the disease and its complications and their pathogenesis and experimental conditions must be analogous to those prevailing in man. Since atherosclerosis is not species specific to man and consists of multiple lesions, which develop independently of one another but can ultimately coalesce, reproduction of the disease in a localized segment of a blood vessel in susceptible animals under conditions similar to those prevailing in man would comply with the spirit of Koch's postulates.     

Dietary fat and experimental atherosclerosis

This paper reviews studies relating to the effects of fat unsaturation and fatty acid composition on the development of experimental atherosclerosis in rabbits. The results derived from the feeding of various fats are similar whether one feeds cholesterol or an atherogenic, cholesterol-free semipurified diet. In general, the severity of atherosclerosis is inversely related to the level of fat unsaturation. Two exceptions are cocoa butter which is much less atherogenic than expected, most probably due to its high content of stearic acid, and peanut oil, while relatively unsaturated, is surprisingly atherogenic for rats, rabbits and monkeys. This latter effect is not related to the level (6%) of long-chain saturated fatty acids (arachidic, behenic, lignoceric) present in peanut oil, but rather to its triglyceride structure. Randomization of peanut oil, which modifies its triglyceride structure, significantly reduces its atherogenicity.     

Effects of organic Ca antagonist, diltiazem, on neuromuscular transmission.

The effects of the organic "Ca antagonist" diltiazem on the frog neuromuscular junction was investigated. The addition of diltiazem to the bath solution increased the frequency of spontaneous miniature endplate potentials (MEPPs) and quantal content. The amplitude of the endplate current (EPC) recorded from a d-tubocurarine-blocked endplate was significantly decreased by diltiazem (20-200 microM). However, the amplitude of miniature endplate current (MEPC) was relatively unchanged by diltiazem. The same degree of decrease in the decay time constant was observed in both EPC and MEPC. ACh potentials induced by repetitive iontophoresis were depressed gradually by low concentrations of diltiazem (2, 5 microM), suggesting enhanced desensitization. Using a patch-clamp method, the effects of diltiazem on ACh-activated single current in chick cultured myotubes were examined. The addition of diltiazem to the bath solution shortened the mean open time in a dose-dependent manner between 10 and 50 microM. The voltage-dependence of mean open time disappeared in the presence of diltiazem, with little change in the channel conductance. The present experiments suggest that diltiazem acts on the ACh-activated channel as an open channel blocker.     

输精管结扎对实验性动脉粥样硬化的影响

输精管结扎术后7和9个月家兔各10只,随机分为输精管结扎基础饲料(V-S)组和输精管结扎胆固醇(V-Ch)组,同种雄兔20只随机分为对照基础饲料(C-S)组和对照胆固醇(C-Ch)组。实验结果表明,V-S组血脂、脂质过氧化物含量与C-S组比较无差异,主动脉和冠动脉均无脂质斑块形成。在持续高脂负荷后,V-Ch组总脂、β-脂蛋白水平显著地高于C-Ch组,但是主动脉、冠动脉的病变面积和程度则无差异。这可能与V-Ch组血清脂质过氧化物含量与C-Ch组比较无增高有关,也可能与V-Ch组虽有抗精子抗体产生,但无循环免疫复合物形成有关。     

Early endothelial changes in experimental primate atherosclerosis.

Aortic tissues of cholesterol-fed African green monkeys were studied by light and electron microscopy. The sampled areas were either grossly normal, or showed minute grayish white translucent or yellowish white intimal elevations. Samples of topographically corresponding areas from animals on normal diet served as controls. By light microscopy, the intimal elevations were either pure fatty dots or a combination of fatty dots and focal intimal edema. The most conspicuous ultrastructural findings in the experimental animals were a marked increase in the number of Weibel-Palade bodies, and figures suggestive of release of their content into the vascular lumen. Invaginations or pseudochannels of varying depth as well as intracytoplasmic lipid inclusions were also observed in the experimental series. These findings suggest that Weibel-Palade bodies may play a role in the initial stages of atherosclerotic lesions, and that transendothelial transport may take place via transendothelial channels.