Vasoconstrictor peptides and cold intolerance in patients with stable angina pectoris.

BACKGROUND: The exact mechanism that explains the phenomenon of cold intolerance in patients with angina remains controversial. Although the response to the effects of a cold environment has been examined in these patients, their response to cold air inhalation has produced conflicting results. In addition, the possible role of vasoactive peptides in the pathophysiology has not been explored. OBJECTIVES: The aims of this study were to examine the response of patients with stable angina to the effects of cold air inhalation during exercise testing, and to investigate the possible role played by the vasoconstrictor peptides endothelin-1 (ET-1) and angiotensin-II (AT-II) in the pathophysiology. METHODS: In a randomised order, 12 men with stable angina, whose medication had been stopped, underwent two separate symptom limited treadmill exercise tests. At one visit the patients exercised while breathing room air and at the other visit they exercised while breathing cold air from a specially adapted freezer. Serial peripheral venous blood samples were taken for ET-1 and AT-II estimations during each visit. RESULTS: Cold air inhalation resulted in a significant reduction in the mean time to angina (232.7 (20.4) s v 274.1 (26.9) s, P = 0.04) and the mean total exercise time (299.5 (27.0) s v 350.3 (23.9) s, P = 0.008), but no significant change in the time to 1 mm ST depression (223.3 (29.0) s v 241.3 (29.2) s, P = 0.25). There was no significant difference between the rate-pressure products at the onset of angina (P = 0.13) and the time to 1 mm ST depression (P = 0.85), but at peak exercise the rate-pressure product was significantly lower in patients breathing cold air as opposed to room air (P = 0.049). There was an equivalent significant decrease in ET-1 concentrations at peak exercise compared with that at rest at both visits (room air 5.0 (0.7) pmol/l v 4.3 (0.7) pmol/l, P = 0.03; cold air 4.4 (0.6) pmol/l v 3.8 (0.5) pmol/l, P = 0.02). There was a significant increase in AT-II concentrations 10 min after peak exercise in patients breathing room air (39.2 (6.1) pmol/l v 32.1 (4.8) pmol/l, P = 0.01) which was not repeated during cold air inhalation (36.6 (3.4) pmol/l v 28.3 (3.4) pmol/l, P = 0.07). CONCLUSIONS: Cold air inhalation in patients with stable angina results in an earlier onset of angina and a reduction in exercise capacity. Both peripheral and central reflex mechanisms appear to contribute to the phenomenon of cold intolerance. Peripheral ET-1 and AT-II do not appear to play a significant role in the pathophysiology.

Free-radical activity after primary coronary angioplasty in acute myocardial infarction.

Free-radical activity in coronary venous outflow was assessed before and after reperfusion in nine patients with acute infarction who had undergone successful recanalization of the infarct-related artery by primary coronary angioplasty. Free-radical activity was measured in serum samples from coronary venous outflow over a timed period of 24 hours by using (1) the percentage molar ratio (PMR) of the diene conjugate 9,11-linoleic acid, and (2) malonaldehyde concentration. Preangioplasty PMR means lay within the normal range, but showed a marked increase soon after successful recanalization. Relative to baseline, the changes over time reached statistical significance between 2 and 60 minutes. No statistically significant changes in malonaldehyde occurred over the study period. We conclude that successful recanalization of the infarct artery is associated with significantly elevated free-radical activity, as measured by the PMR of conjugated diene, in coronary venous outflow. Such patients may be at risk from free radical mediated reperfusion injury.

Interference by thimerosal in cholesterol estimation by the CHOD-PAP method.

We report that interference with the cholesterol assay using the cholesterol oxidase: p-aminophenazone method which is observed during lipoprotein preparation, is caused by the anti-bacterial agent thimerosol used in the preparation. We suggest that an alternative anti-bacterial agent should be used in these circumstances.

Loss of A-apoprotein immunoreactivity during high-density lipoprotein separation.

By use of an electroimmunoassay, concentrations of A-apoproteins were estimated in serum and in corresponding apoprotein fractions isolated by ultracentrifugation. These values were compared with high-density lipoprotein concentrations determined by analytical ultracentrifugation. Concentrations of A-apoproteins estimated in serum were considerably higher than in isolated high-density lipoprotein fractions. These discrepancies could not be accounted for entirely by material losses into other fractions during ultracentrifugal fractionation. No comparable differences in apoprotein-B concentrations were observed during the ultracentrifugal separation of low-density lipoprotein. Concentrations of A-apoproteins estimated in the residual serum after precipitation of low-density lipoproteins by heparin and manganous ions were also lower than in the corresponding whole sera. The discrepancies persisted after treatment of serum and isolated fractions with tetramethylurea, urea (9 mol/l), and by heating at 52 degrees C for 3 hours. It is considered that separation by ultracentrifugation induces subtle alterations in the surface structure of the lipoprotein species which give rise to changes in immunoreactivity.

Selective precipitation of very low density lipoproteins from fasting sera by heparin and manganese ions.

Complete and discrete precipitation of very low density lipoproteins (VLDL) from fasting sera required heating at 40 degrees C for 60 min in the presence of 0.05 M manganous ions and heparin in a concentration dependent upon the VLDL content. The minimum polyanion concentration, employed with VLDL contents less than 1.0 g/l, was 85 mg/l; an increment of 5 mg/l was required for each 1.0 g/l increase in VLDL content. The products isolated by this procedure had electrophoretic, immunochemical and ultracentrifugal characteristics skin to those of native VLDL and were slightly contaminated with albumin. The reaction conditions did not affect adversely the subsequent precipitation of low density lipoproteins.