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Cardiac Output and Distribution of Blood Volume in Central and Peripheral Circulations in Hypertensive and Normotensive Man* MILOS ULRYCH, EDWARD D

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Cardiac Output and Distribution of Blood Volume in Central and Peripheral Circulations in Hypertensive and Normotensive Man* MILOS ULRYCH, EDWARD D Br Heart J: first published as 10.1136/hrt.31.5.570 on 1 September 1969. Downloaded from Brit. Heart J., 1969, 31, 570. Cardiac Output and Distribution of Blood Volume in Central and Peripheral Circulations in Hypertensive and Normotensive Man* MILOS ULRYCH, EDWARD D. FROHLICH, ROBERT C. TARAZI, HARRIET P. DUSTAN, AND IRVINE H. PAGE From the Research Division, Cleveland Clinic, Cleveland, Ohio, U.S.A. Most haemodynamic studies of arterial hyper- blood volume expansion since intravascular volume tension have been concerned with cardiac output was, if anything, decreased (Tarazi et al., 1969). and peripheral resistance (Page and McCubbin, The possibility remained that output might be 1965). Some, additionally, have investigated re- raised through a redistribution of intravascular gional distribution of blood flow and vascular volume from peripheral veins to the cardiopulmon- resistances, whereas only a few, dealing with circu- ary capacitance bed, even if total blood volume were lation in the extremities, were designed to provide diminished. The present study describes the rela- information about the venous segment of the circu- tions among cardiopulmonary blood volume, total lation (Wood, 1961; Caliva et al., 1963a, b). These blood volume, cardiac output, and arterial blood studies of the capacitance segment in hypertension pressure in normal subjects, in patients with dealt only with regional circulations; there has been essential hypertension, or with hypertension no report on the relationships of total blood volume accompanying renal arterial disease. This was to its distribution between the central and peripheral made possible by the recent development of circulations, to cardiac output, or to systemic arterial methods for determination of cardiopulmonary http://heart.bmj.com/ pressure in hypertensive patients. blood volume (Taylor et al., 1965; Levinson, In the absence of heart failure, the distribution of Pacifico, and Frank, 1966), which do not involve blood between peripheral and cardiopulmonary left atrial catheterization (Schlant et al., 1959; segments of the circulation should reflect the disten- Milnor, Jose, and McGaff, 1960; Dock et al., 1961; sibility and tone of peripheral and pulmonary Levinson, Frank, and Hellems, 1964; de Freitas et capacitance beds. Alterations of such factors may al., 1965). well underline the differences in cardiac output SUBJECTS AND METHODS found in different types of hypertension. Cardiac on September 29, 2021 by guest. Protected copyright. output has been shown to be high in mild, juvenile, The subjects in this study consisted of 19 individuals, and renovascular hypertension (Widimsky, Fej- 6 normotensive volunteers and 13 patients, 7 with farovi, and Fejfar, 1957; Finkielman, Worcel, and essential hypertension, and 6 with hypertension and Agrest, 1965; Bello, Sevy, and Harakal, 1965; renal arterial stenosis.* In all, cardiopulmonary blood Frohlich et al., 1965), but it is not known whether * The volunteers were for the most part aides and tech- this represents a developmental phase of hyper- nicians and their friends who came from various laboratories tension or a haemodynamic response to specific and were relatively familiar with some of the techniques used. One was a resident taking a year's training in medicine. To stimuli characterizing these types of hypertension. all, the study was explained and the procedure detailed; In regard to the latter consideration, our previous beyond a small fee paid for the time and inconvenience of the studies of renovascular hypertension had shown test, no promise was made and no pressure applied. Four that high cardiac output was not a reflection of of the 5 co-authors had their blood volumes measured with radio-iodinated human serum albumin; in 3, this was repeated more than once and associated with estimation of extracellular Received January 15, 1969. fluid volume with radiobromine. The radioactive doses used * Supported in part by grants from the National Institutes were well below permissible levels and were approved by the of Health. hospital isotope committee. 570 Br Heart J: first published as 10.1136/hrt.31.5.570 on 1 September 1969. Downloaded from Cardiopulmonary Blood Volume in Hypertension 571 volume and central venous pressure as well as cardiac peripheral resistance, by dividing mean arterial pressure output, heart rate, arterial blood pressure, and total by cardiac output; stroke volume, by dividing cardiac blood volume were obtained. None had cardiac de- output by heart rate; and peripheral blood volume, by compensation, severe nephrosclerosis, or apparent pri- subtracting cardiopulmonary from total blood volume. mary aldosteronism. Hypertensive patients therefore For purposes of comparison, cardiac output, cardio- were classified as World Health Organization stages I pulmonary, and total blood volumes were corrected for or II. Renal arteriography was performed in all patients ideal body surface area. permitting differentiation between essential and reno- Statistical evaluation of results was performed by vascular hypertension. standard techniques using the t-test and correlation All investigations were performed in a quiet laboratory coefficient methods (Croxton and Cowden, 1941). in the moming, with the subjects fasting and resting comfortably supine. Catheters were introduced into an RESULTS antecubital vein and brachial artery by the Seldinger Despite the small number of subjects, the results technique (1953), and advanced to the right atrium and were consistent with those obtained previously innominate artery or aortic arch, respectively, under this fluoroscopic control. As determined, cardiopulmonary (Frohlich et al., 1967) (Table). Therefore volume was not strictly limited to the heart and lungs sampling can be considered to be representative of but included a small part of the arterial system where our haemodynamic experience with normal subjects, circulation velocities should produce changes propor- and essential and renovascular hypertensive patients tionate to cardiac output. This introduced only a small (Frohlich et al., 1965, 1968). In brief, arterial blood systemic error by proportionately increasing absolute pressure and total peripheral resistance were raised values. in the hypertensive groups. Resistance was higher Cardiac output was determined in triplicate, at least, in essential than in renovascular hypertensives, and using indocyanine green dye (5 mg.) introduced into the cardiac output higher in renovascular than in venous or atrial catheter, and then flushed into the circu- essential hypertensives; total blood volumes were lation in less than a half second with 5 ml. saline. in renovascular Blood was withdrawn from the arterial catheter through decreased predominantly hyperten- a Gilford densitometer, using its constant rate pump sives. Cardiopulmonary blood volume in normo- with the speed set between 0 3 and 0-5 ml./sec. The tensive subjects and patients with essential and delay in the sampling system could be corrected using renovascular hypertension was 1 -12 L./173 m.2, the data of Milnor and Jose (1960), since the volume 1 16 L./1 73 m.2, and 1 27 L./1 73 m.2, respectively. and length of our catheters never exceeded theirs. Peripheral blood volume was significantly lower than Curves were inscribed on a fast response Texas Instru- normal in renovascular hypertensives (p <0 05); ment Rectiwriter recorder. Blood was reinfused im- there was no difference between these 7 essential mediately after the curve inscription thereby ensuring hypertensives and normal subjects. http://heart.bmj.com/ no blood loss during investigation. After each study, was a direct this system was calibrated with known dye concentra- For the entire group there correlation tions at the same pump speed used during output between cardiopulmonary blood volume and cardiac determinations. Curves were calculated using a modifi- output (r=0-617; p<0 005) and stroke volume cation (Ulrych, Widimsky, and Kasalicky, 1966) of the (r=0-661; p<O0005) (Fig. la and b). Similarly, principle first described by Cyvin (1950), which involves there was a direct correlation between the fraction integrating the first part of the curve at one-second of total blood volume in the heart and lungs and intervals, and calculating the area under the exponential cardiac output (r=0 774; p<0Q001) and stroke downslope by mathematical integration. Cardiopul- volume (r=0 679; p<0 005) (Fig. 2a and b). on September 29, 2021 by guest. Protected copyright. monary blood volume was the product of mean transit Because of the small numbers of studied, it time and blood flow per second and expressed as 1./1 .73 subjects M.2 Successive determinations of cardiac output was not possible to make valid correlations for each varied by only 7 per cent (average) in the same subject diagnostic group; however, the same relation (Frohlich et al., 1967). seemed to obtain. Arterial and venous pressures were measured using Statham P 23Db transducers and recorded on a Sanborn DISCUSSION direct-writing oscillograph. Heart rate was counted Cardiac output and stroke volume seem more from a continuously recorded electrocardiogram. dependent upon redistribution of intravascular Blood volume was estimated using radio-iodinated volume to the cardiopulmonary circulation than on human serum albumin, according to the technique of total blood volume. While both hypertensive Williams and Fine (1961), and expressed as ml./1 73 had diminished total blood their M.2 Haematocrit was measured in duplicate
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