The possession of a technique which permitted rapid estimations of cardiac output and which, demanding no intelligent cooperation, seemed especially suitable for use on ward patients, has permitted an extensive study on the action of common drugs on the heart and circulation in clinical conditions. This study contains about 450 estimations of cardiac output performed on 85 patients.Coincidentally with these estimations the action of drugs on pulse rate, on blood pressure, on respiratory rate and volume, and on metabolic rate was observed. Orthodiagrams and electrocardiograms were secured also. Therefore, certain parts of our study dealt with effects already well known.The results of such estimations have permitted the calculation of heart work, of peripheral resistance, of arteriovenous oxygen difference, and of the ratio of heart work to heart size, the latter a factor of decisive importance in our conception of cardiac stimulation and depression. Therefore our study demonstrates the effect of drugs on these functions also.Most of the drugs selected are commonly used in cases of cardiac and circulatory disease. We have studied the actions of digitalis, epinephrine, ephedrine, caffeine, theophylline, carbaminoylcholine, sodium nitrite, nitroglycerine, pitressin, quinidine, morphine and strychnine. We have studied the effects of drugs in those clinical conditions in which physicians are accustomed to employ them.But when suitable cases were not available the effects were studied in other conditions. Almost without exception our results support the general conceptions of drug action derived from animal experiments. PROCEDUREAll estimations were performed in the morning. The patients received no food after their evening meal and no water after midnight. They were taken from the ward in bed or in a wheel chair. An electrocardiogram and an orthodiagram were obtained first. Then the subjects lay down for at least 45 minutes. Duplicate estimations of cardiac output and metabolism were then made, together with repeated determinations of pulse rate, blood pressure, respiratory rate and volume.If the study concerned a rapidly acting drug, this was administered soon after the control estimations. The patient was watched until evidence of the drug's action became manifest objectively. Duplicate estimations of cardiac output and metabolism were then made, the purpose being to make these determinations at the height of action. Orthodiagrams and electrocardiograms were secured immediately afterward. Cardiac output was estimated by the method of Starr and Gamble (1), the analyses being performed by the katharometer method of Donal, Gamble and Shaw (2). Metabolism was estimated from samples of expired air drawn from a mixing bottle containing a fan.Respiratory volume was obtained by reading the spirometer at frequent intervals. Respiratory rate was counted repeatedly during the period of observations. It is well known that subjects breathing from a spirometer under 3 mm. H,O negative pressure, and through valves, tend to breathe...

In a previous communication the results of duplicate estimations of cardiac output on 50 persons, the majority hospital patients in the basal condition, have been ret)orted (1). The opportunity to extend this investigation rapidly was provided by the development, by Donal and Gamble, of a physical method for the estimation of ethyl iodide by means of its thermal conductivity in a katharometer (2). This improvement so increased the rapidity with which the cardiac output could be estimated, that about two hundred hospital cases, four hundred estimations of cardiac output, were added to the series with the expenditure of less time and effort than had been required to secure the results in the first fifty cases by the chemical technique. When the new series was combined with the old, over 200 cases were secured in which satisfactory estimations of basal cardiac output, metabolism, blood pressure, and pulse rate, had been made on resting patients 15 or more hours after the last meal; and in which orthodiagrams had been secured also. The analysis of these results forms the subject of this paper.As soon as results, secured by any cardiac output method, are examined a difficulty appears which can best be set forth by an example. The average cardiac output of 31 healthy persons is 2.9 liters per minute per 100 pounds, that of 8 cases of anemia 3.2 liters; should the difference be considered significant or not? An estimation of the validity of differences is based on knowledge of the relative accuracy of the methods involved. One may try to ascertain the accuracy of a cardiac output method, when applied to man, by the agreement of duplicate estimations, and by comparison of the results with those obtained by other methods, preferably based on different physiological principles. But it should be emphasized that cardiac output procedures have not attained the position of those methods the accuracy of which can be tested by estimation of known quantities. Therefore, we have fallen back on another way of approaching the problem and have estimated the significance of our differences by statistical procedures. 561

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