Endothelium-dependent flow-induced dilation of canine femoral and saphenous arteries.

We have characterized the dilation response to increased blood flow in the canine femoral and saphenous arteries. An arterio-venous shunt was created and changes in arterial diameter measured by sonomicrometer crystals. Increasing shunt flow approximately 10-fold caused a 9% increase in femoral and 15% increase in saphenous artery diameter. The dilation response consisted of a transient decrease in diameter, followed by a rapid dilation and a slow return to control when flow was decreased. The increased diameter was not a result of decreased transmural pressure or alterations in pulse pressure. After removing the endothelial cells, the vessels did not dilate to increased flow or topical acetylcholine (10(-5) M), but responses to norepinephrine (10(-5) M) and sodium nitroprusside (10(-4) M) were unaltered. Indomethacin, theophylline or propranolol did not affect the flow-induced dilation. Quinacrine, an inhibitor of phospholipase A2, attenuated the dilation response in a dose-dependent manner. We conclude that increased blood flow affects endothelial cells, causing an active dilation of arterial smooth muscle.

Warm-up phenomenon in angina pectoris.

The warm-up phenomenon, in which the second of two successive exercise tests manifests less ischaemia than the first, was studied to find out whether it results from decreased myocardial oxygen consumption or from increased coronary-artery blood-flow during the second test. Patients performed an initial exercise test, then continued to exercise for 30 minutes after which they rested for 20 minutes. They then repeated the exercise test with a work load and duration identical to the first. 21 (95%) of 22 patients tested with a bicycle and 9 (75%) of 12 patients tested by a modified two-step test had less electrocardiographic evidence of ischaemia on the second test than on the first. Rate-pressure products at peak exercise suggested that the lessened ischaemia was not due to decreased mnyocardial oxygen consumption. Rather, the warm-up phenomenon seemed to result from increased coronary flow. It can be evoked in most patients who have an ischaemic response to exercise.

Effect of testosterone cypionate on postexercise ST segment depression.

A randomised double blind study was carried out with 50 men who had ST segment depression of 0.1 mV or more after a modified two-step exercise test. Rate and duration of exercise were the same for the last of each subject's several pretreatment tests as for his tests after 4 and 8 weeks of treatment with placebo or testosterone cypionate, 200 mg, intramuscularly weekly. The sum of ST segment depression in leads II, V4, V5, and V6 taken immediately, and 2, 4, and 6 minutes after exercise did not change significantly after 4 or 8 weeks of placebo treatment, but did decrease by 32 per cent (P less than 0.0001) and 51 per cent (P less than 0.0001) after 4 and 8 weeks, respectively, of testosterone cypionate treatment. The mechanism by which testosterone cypionate treatment results in lessened postexercise ST segment depression is not established.

Effect of oestrogens on postexercise electrocardiogram.

The effect of three oestrogens (including an oestrogen-progestogen combination) on the postexercise electrocardiogram was studied in 33 men and 18 women who earlier had shown ST segment abnormalities after exercise. When pretreatment exercise tests were compared with tests after two weeks of treatment, the postexercise ST segments which were abnormal before treatment became even more abnormal in 18 (90%) of 20 subjects treated with conjugated oestrogens 10 mg daily, in 16 (89%) of 18 subjects treated with stilboestrol 5 mg daily, and in 12 (92%) of 13 subjects treated with norethynodrel (9-85 mg) and mestranol (0-15 mg)1 daily. The ST segment abnormalities reverted to pretreatment appearance within 6 weeks of stopping oestrogens. When 10 subjects with normal near-maximal exercise tests were treated for 2 weeks with conjugated oestrogens 10 mg daily, the tests remained unchanged in 9. The hypothesis favoured to explain these findings is that of an oestrogen-induced increase in coronary artery smooth muscle tone. An increase in arterial tone would also account for the increased incidence of myocardial (and cerebral) infarction that has been reported among individuals treated with oestrogen, either alone or in combination with progestogen.