Cigarette smoking, lipolysis and vascular disease

Lorimer, Andrew Ross (1975) Cigarette smoking, lipolysis and vascular disease. MD thesis, University of Glasgow.

Abstract

This thesis presents clinical and experimental studies relating to the effect of cigarette smoking on lipolysis in subjects with various types of vascular disease. The introduction reviews the evidence of the harmful effects of cigarette smoking and for its possible contribution to vascular disease through its action on lipid metabolism via the sympathetic adreno-medullary systems. The aims of the study are then outlined with respect to the effect of smoking varying numbers of cigarettes on levels of free fatty acids (FFA), ketone bodies (aceto-acetate and D hydroxybutyrate), glucose, insulin, cholesterol and triglyceride in subjects with either stable coronary heart disease (CFD) as manifest by angina or with peripheral vascular disease (PVD). The standard situation studied was serial venous sampling under controlled conditions before and after the smoking of two normal nicotine content cigarettes. Initial investigations indicated that a satisfactory steady state was achieved prior to smoking. Basal FFA values of the recent infarction group were consistently higher than those found in other subjects and suggested a possible residual "stress" situation. Following cigarette smoking the increments in FFA values were significantly higher in the recent infarction subjects. Changes in FFA were paralleled by increased ketone body levels. The findings indicated that the increased response to cigarette smoking was a feature of recent myocardial infarction rather than occurring in all types of clinical vascular disease. In no group was there any evidence to support the suggestion made by others that cigarette smoking might affect insulin, cholesterol or triglyceride levels. These variables remained unaltered. The subcutaneous injection of 0.01 ul of 1:10,000 adrenaline per kg bodyweight corresponded to the effect of cigarette smoking. Increased levels of FFA occurred in the post-infarction group again perhaps indicating an increased response to sympathetic or adrenomedullary activity. The effect of cigarette smoking was also examined in subjects classified according to their lipoprotein status (normal lipids, Type IT or Type IV hyperlipoproteinaemia). Overall percentage changes in FFA and ketone bodies were comparable in each group although the absolute changes in FFA were greater in Type IV subjects. Similar studies were done in subjects one year after myocardial infarction. The FFA and ketone body increases that developed were similar to those of control subjects and considerably less than those found 3 weeks after infarction. This suggested that the enhanced response to cigarette smoking is a temporary rather than a persistent finding. In addition, it was found that the increased FFA levels following smoking could be abolished by the prior administration of the beta-adrenoreceptor blocking agent propranolol. This effect could have important clinical implications for the long-term management of patients with CHD. Studies were also undertaken on the effect of smoking 6 normal cigarettes over 3 hours. The response in terms of FFA and ketone body increases (40% and 100% respectively) was similar in control subjects and those with angina or PVD. There was no evidence of an enhanced response among those subjects with vascular disease. There was, however, considerable variation among subjects in terms of blood glucose levels before and after smoking. The changes in glucose could not, however, be correlated with either changes in FFA or insulin levels. Measurement of individual fatty acid levels before and after smoking were done using the combination of thin layer and gas-liquid chromatography. There appeared to be a general increase in FFA levels after smoking rather than a change in only certain individual fatty acids. Nor did there appear to be any alteration in the fatty acid component of the triglyceride moiety. A series of investigations were done on glycerol kinetics in control subjects and those with vascular disease. The rate of removal of intravenously injected glycerol (50 ml of 10% glycerol) could be expressed as a single exponential with T1/2 values being similar in all groups studied. In addition, it was found that cigarette smoking following the administration of glycerol did not produce any alteration in the rate of removal from the bloodstream. An expected finding following glycerol infusion was an apparent rise in FFA levels, when measured by the Dole method. Detailed investigation by colorimetric and gas-liquid chromatographic methods indicated that in fact glycerol infusion resulted in a marked decrease in plasma FFA. It seems likely that infusion of glycerol results in the accumulation in the plasma of an acidic compound - as yet unknown - which is titrated by the Dole method as FFA.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Additional Information: Adviser: T DV Lawrie
• Keywords: Epidemiology, Medicine
• Date of Award: 1975
• Depositing User: Enlighten Team
• Unique ID: glathesis:1975-74035
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 23 Sep 2019 15:33
• Last Modified: 23 Sep 2019 15:33
• URI: https://theses.gla.ac.uk/id/eprint/74035