There has been need for a convenient test of exercise tolerance in intermittent claudication. Such tests are necessary for appraisal of therapy and occasionally for diagnosis. In this respect, the need has been similar to that for quantitative measurement of exercise tolerance in angina pectoris. REVIEW OF LITERATURESeveral tests of exercise tolerance have been used in studies of intermittent
In earlier studies on intermittent claudication (1), we found that the exercise tolerance, as measured by the two-step test, remained constant when repeated at intervals on a single day. We then proceeded to a study of the effect of drugs used in the treatment of intermittent claudication. This paper, which reports the study, is concerned only with acute experiments done on a single day.The subjects varied in age from 49 to 77 years. Their intermittent claudication was caused by arteriosclerosis. Each drug was tested on ten patients, except aminophyllin, which was tested on twenty. A &dquo;blind&dquo; technique was used. In this technique, neither the patient nor the observer knows whether the drug or control substance is being tested. Written and sealed codes were drawn up in advance to record the order of administration of drugs tested. These codes were not examined until the experiments were completed. Half the experiments were done with the drug studied being given first and half with the control substance first. Before giving either medication or placebo, two to four measurements of exercise tolerance were made at fifteen minute intervals. We then gave substance § 1 (that is, either the drug or a placebo) and made four more measurements of exercise tolerance at fifteen minute intervals. We then gave substance # 2, which was also placebo or drug, and made four measurements. Altogether we made 10 or 12 measurements of exercise tolerance, 2 to 4 without medication, 4 after the drug being tested, and 4 after the control substance.Of course, it was not always possible to keep the patient unaware of the difference between drug and placebo. Ethyl alcohol given as whisky scarcely tasted the same as weak tea, the control substance. Methylene blue actually colored the patient blue. Niacin caused flushing of the face. Nitroglycerin occasionally caused headache. The tests were then made by a different observer than the one who gave the drug. Also, colored injections, such as methylene blue and cytochrome-C, were injected with the subject's arm screened from his eyes. In testing histidine and ascorbic acid, we made no control injections because of the long duration of the experiments. With that combination of drugs, we merely compared exercise tolerances before and after the injections.The effects of the following were studied: nitroglycerin, papaverin, ethyl alcohol, depropanex, niacin, histidine with ascorbic acid, paravertebral block, cytochrome-C, methylene blue and aminophyllin.
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