Lars Orö

Plasma lipids and urinary excretion of catecholamines in man during experimentally induced emotional stress, and their modification by nicotinic acid

33 male volunteers were studied in the morning after fasting overnight. 11 (the control group) were allowed to sit comfortably for three consecutive 2-hr periods, no stressors or treatment being introduced. The remaining 22 were divided into two groups, each being exposed to standardized, emotional stressors during the second of the three 2-hr periods. The subjects in one of these groups were each given a total dose of 3 g of nicotinic acid during the first 3 hr of the experiment, whereas the other group received no treatment. Stress was accompanied and followed by increased levels of free fatty acids and triglycerides in arterial plasma, by an increase in catecholamine excretion, and a rise in heart rate and systolic and diastolic blood pressure. No such increases were seen in the control group. The stress-induced rise in free fatty acids was inhibited by nicotinic acid, and the triglyceride rise was turned into a fall. The stressor-induced increase in catecholamine excretion was not significantly affected by nicotinic acid, neither were the increases in heart rate and blood pressure. The hypothesis is discussed, from a qualitative as well as a quantitative viewpoint, that there is a direct relationship between the increased concentration of free fatty acids accompanying emotional stress in man and the eventual development of the stress hyperlipoproteinemia.

Effects of Hypolipidemic Regimes on Serum Lipoproteins

There is a rapid development in the area of serum lipid lowering regimes. Diets, drugs and other measures are used more and more frequently on more and more patients by more and more physicians. This increased use makes it mandatory that we know in detail the effects and the side-effects of these various regimes. One important aspect on the effects of the so called serum lipid lowering regimes is the effects on the different serum lipoprotein (LP) classes. Although it is well known that the serum lipids are bound to proteins and thus exist as LP in blood and that there are at least 3 major different LP classes we have surprisingly little knowledge about the effect of lipid lowering regimes on the concentration and composition of the LP classes. In fact it is not correct terminology to use expressions such as “lipid lowering drugs”, “cholesterol lowering drugs” or “triglyceride lowering drugs”. The correct terminology would be LP lowering drugs because it is not the serum cholesterol that is reduced by e.g. nicotinic acid but the concentration of the whole β (and also pre- β) lipoprotein molecules in serum (Carlson, 1969).

Circulatory and Metabolic Processes in Adipose Tissue in vivo

To permit the study in vivo of circulatory and metabolic processes in adipose tissue, a part of the dogs subcutaneous tissue was prepared with intact circulation and innervation. The preparation was found to be suitable for quantitative investigations on the nervous control of the blood flow and of the release of free fatty acids. We considered it to be of general interest to describe the method and some of its applications.

Clinical and metabolic effects of pentaerythritol tetranicotinate (perycit®) and a comparison with plain nicotinic acid☆

Abstract Perycit in a daily dose of 3 g lowers the cholesterol and triglyceride concentration in patients with different types of hyperlipidemia. Increasing the Perycitl ® dose up to 4.5 g causes a further decrease of the lipid levels. A comparison between Perycit ® and pure nicotinic acid showed that Perycit ® in doses up to 6 g is more effective in reducing elevated cholesterol levels. The reduction of the plasma triglyceride and cholesterol concentration is explained by a decrease of VLD triglyceride and cholesterol concentration. The cholesterol concentration also decreased in the LD fraction but increased in the HD fraction. The K 2 of the i.v. fat tolerance was not significantly influenced by the Perycit ® treatment in the material studied and changes of the triglyceride concentration were not related to changes in K 2 , suggesting that the mechanism of action of Perycit ® on the plasma lipids differs at least partly from that of pure nicotinic acid. As with nicotinic acid, elevated levels of transaminase and alkaline phosphatases were observed with Perycit ® but the increases were not related to the dose used or to the duration of the treatment. Perycit ® , in contrast to pure nicotinic acid, did not elevate the uric acid concentration in plasma.

Effects of oxandrolone on plasma lipoproteins and the intravenous fat tolerance in man

Abstract Twenty-five patients with hyperlipoproteinaemia have been treated with oxandrolone 7.5 mg/day for 3 months. Plasma triglycerides (TG) were reduced from 4.12 to 2.87 mmol/1, whereas plasma cholesterol was 310 mg/100 ml before and 303 mg/100 ml during treatment. Analyses of the lipoprotein classes revealed that the plasma TG effect was the result of a reduction of TG in very low density (VLD) and high density (HD) lipoproteins. No TG change was seen in low density (LD) lipoproteins. Cholesterol was significantly reduced in VLD and LD lipoproteins, but as there was a significant increase in HD lipoproteins no net effect could be seen. During treatment hypo-α-lipoproteinaemia appeared in almost 50% of the patients. In 10 patients where the oxandrolone dose was increased to 10 mg/day a slight further reduction of plasma TG was seen, but cholesterol remained unchanged. The intravenous fat tolerance was significantly increased during oxandrolone treatment, suggesting that an increased removal of plasma TG could at least partly explain the effects of oxandrolone. In 60% of the patients serum transaminases increased and in one patient this rise was so pronounced that the drug was withdrawn. No subjective side effects were noted and no other changes of the laboratory control tests were found. It was suggested that oxandrolone alone may be useful in the treatment of patients with hypertriglyceridaemia. In hyperlipidaemias where plasma cholesterol is also increased oxandrolone should be considered only in combination with other drugs that are more efficient in lowering plasma cholesterol.

EFFECT OF PROSTAGLANDIN E1 ON BLOOD PRESSURE, HEART RATE AND CONCENTRATION OF FREE FATTY ACIDS OF PLASMA IN MAN.

Summary Infusions of PGE1 to human subjects caused an increase in heart rate and in concentration of FFA and glycerol in plasma. When PGE1 was infused intravenously together with norepinephrine the nor-epinephrine induced increase in blood pressure was reduced and the bradycardia was abolished. The increase in concentration of FFA and glycerol in plasma caused by norepinephrine was, however, only slightly reduced by PGE1.

Dose-response study of the effect of ciprofibrate on serum lipoprotein concentrations in hyperlipoproteinaemia

The effect of ciprofibrate, 2[p-(2,2-dichlorocyclopropyl)-phenoxyl]-2-methyl propionic acid, in daily doses of 50, 100, and 200 mg was studied in 50 patients with hyperlipoproteinaemia (21 type IIA, 10 type IIB and 19 type IV). Ciprofibrate was convenient to take and was without subjective side effects. The greatest hypolipidaemic effects were reached for all lipoproteins with 200 mg daily. In type IIA and IIB, mean low density lipoprotein (LDL) cholesterol was normalized on the 200 mg dose. The effect was highly dependent on initial LDL cholesterol concentrations, decreases being observed above 4 mmol/l and increases below that concentration. Mean very low density lipoprotein (VLDL) triglyceride concentrations decreased on 200 mg per day by 48-59%. HDL cholesterol increased in all types of hyperlipoproteinaemia by 6-19%, the change being unrelated to changes in VLDL lipids. With a dosage of 200 mg daily the effects were maintained for the following period of 6 months. It is concluded from this study that it would be appropriate to start patients on 100 mg daily and then titrate their dose according to response. The optimal dosage for ciprofibrate seems to be 200 mg daily.

A note on the cardiovascular and metabolic effects of prostaglandin A1: Prostaglandin and related factors 61

Abstract Intravenous infusion of prostaglandin A 1 (PGA 1 , formerly PGE 1 -217) (9-keto-15-hydroxy prosta-10,13-dienoic acid) 0.056 or 0.20 μg/kg/min during 20 minutes, into anesthetized dogs lowered the blood pressure and increased the heart rate. Infusion of PGE 1 produced qualitatively similar cardiovascular effects as PGA 1 . However, the effects of PGA 1 on the cardiovascular system were usually quantitatively more pronounced than those produced by PGE 1 . No consitent changes in the plasma levels of FFA, glycerol or blood glucose were seen during administration of PGA 1 . Studies with rat adipose tissue in vitro showed that PGA 1 had less than 10 per cent of the lipolysis inhibiting activity of PGE 1 .

Clinical and metabolic effects of pentaerythritol tetranicotinate in combination with cholesolvin or clofibrate

Summary Combined treatment of hyperlipidaemia with the nicotinic acid derivative pentaerythritol tetranicotinate (Perycit ® ) and clofibrate or the clofibrate analogue cholesolvin has been used in 26 ambulant patients with different types of hyperlipidaemia (types IIa, IIb and IV). The treatment started with Perycit ® 1g × 3 daily followed by cholesolvin 1 g × 2 or vice versa. The two drugs were then given together in the same doses as before and finally clofibrate was substituted for cholesolvin. The two types of drugs, Perycit ® and cholesolvin or clofibrate respectively, were found to have additive synergistic effects on plasma cholesterol as well as on plasma triglyceride concentration. There was no difference between cholesolvin and clofibrate in this respect. The usual side effects like flush were seen with Perycit ® , but the combined treatment with Perycit ® and cholesolvin or clofibrate produced no additional adverse reactions.