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Hemodynamic Consequences of the Injection of Radiopaque Material By G. C. FRIESINGER, M.D., JOCHEN SCHAFFER, M.D., J. MICHAEL CRILEY, M.D., ROBERT A. GAERTNER, M.D., AND RICHARD S. Ross, M.D. Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017 terials in-to the left heart and aorta in man can be quite different from those following rightsided injection and have not been well documented." We have observed significant and consistent changes in a variety of hemodynamic parameters as a consequence of the injection of radiopaque materials into the left atrium, left ventricle and aorta in patients undergoing diagnostic cineangiocardiography.'2 These clinical observations, supplemented by related animal experiments, form the subject of the current report. ANGIOCARDIOGRAPHY and cineangiocardiography are employed with increasing frequency for the diagnosis of cardiovascular diseases. These commonplace technics of cardiovascular radiology depend upon the rapid injection of radiopaque materials into the heart or central circulation. A wide variety of substances are in use, but all are hypertonic and some are considerably more viscous than blood. A variety of studies are available to indicate that the hemodynamic effects can be related to chemical structure, -3 but as newer and safer agents have become available it seems clear that the pharmacodynamic effects are related most importantly to the hypertonicity of these compounds. The effects of the injection of oontrast media can therefore be considered to be the effects of hypertonicity on the circulation, and the study of these effects assumes considerable practical importance. Numerous reports are available that deal with the effects of hypertonic (and radiopaque) materials injected into the right heart and pulmonary circulation in animals,4-10 but comparable systematic studies in man are not available. The hemodynamic consequences associated with the injection of radiopaque ma- Materials and Methods The records of 101 patients undergoing cineangiographic studies have been analyzed. Al] patients were studied by technics previously described.13-15 The electrocardiogram and intracardiac pressures were recorded before and after the injection of radiopaque material in every case. Left atrial pressure was recorded for at least 15 minutes after left atrial injections of contrast material in 28 patients, and after left ventricular or aortic injections, or both, in 21 patients. The other patients had less prolonged or less systematic observation. Sodium and methylglucamine diatrizoate (75 per cent or 90 per cent Hypaque) was the radiopaque material injected into all patients. The dose was 30 to 50 ml., depending upon body weight, heart size, and site of injection. Sodium and methylglucamine diatrizoate (90 per cent) contains 30 per cent sodium salt and 60 per cent methylglucamine salt with edathamil calciumdisodium 1:10,000, and the pH is adjusted to between 6.5 and 7.5. At body temperature, the 90 per cent solution has a viscosity approximately four times that of water and an osmolality 10 times that of blood. The 75 per cent solution is made up of 25 per cent sodium and 50 per cent methlyglucamine salts. No qualitative or obvious quantitative difference in reactions to the two concentrations was noted, and hence no distinction was made between the two in the analysis of results. The Hypaque was injected by a power syringe at a pressure of 8 to 10 Kg./cm.2 and delivered From the Departments of Medicine, Surgery, and Radiology, The Johns Hopkins University School of Medicine and The Johns Hopkins Hospital, Baltimore, Maryland. Supported by Research Grant HE-05584 CV from the National Heart Institute, U. S. Public Health Service, and by Clinical Center Grant FR-35 from the Division of General Medical Sciences. This work done during Dr. Friesinger's tenure as U. S. Public Health Service Research Fellow (1960- 62). Presented in part to the Federation of American Societies for Experimental Biology, Atlantic City, April 1962. 730 Circulation, Volumse XXXI, May 1965 T3 1 RADIOPAQUE MATERIAL7 mm 3025 20- 5t 10U) 0 '4 ; ma mn P _ -- p "I 7r I - Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017 Figure 1 Left atrial pressure records obtained before and(c at 25 seconds, 6 minuttecs, anid 14 nintintcs oifter inijection of radiopaq tic contrast material into the left atriumiii. ihcb electrocardiogrtant anid phonocardlogranm have also beere recorded. All paramneters of thie left atrial pressure pulse increasedl after thfe injietion witl the miost promninent increase in thie uv" icave. T'7he hieart rcate is relativelyl unchanged (Ilurinig the period of observation. IbIis tracing tas obtained fr'ont1 a patient wvith puire miiitr'al stenosis. in 1.5 to 3 seconds. Pressure imeasuremenits were made xvith a p23A Statham strain-gage. Cardiac ouitpult was measured with indocyanine green anid the indicator-dilution currves were iniscribed withi a Gilford 103 JR (lenisitometer aind a Harvard with- delawal pump. Cardiac ouitpuit calculations wvere per-formed as described by Hamilton.1" Results Observations in Patients Undergoing Cineangiography Left Atrial Pressuire A typical record of left atrial pr-essure prior to and after the injection of radiopaque material into the left atritum of a patient with mitral stenosis is shown iu figure 1. The left atrial mean pressuire ofteui increased by 100 per cent or more. The increase began Within 30 seconds after the injection and persisted for as long as 1O minuites. The "v" wave regularly increased more thani the "a" xvave. Figure 2 shoxv s that there is nio evident relationship betxveen the resting left atrial pressture and the inicrease resultinig from the injection. Figuire 3 shoxvs the average pressu-res and time sequence of changes in 28 patients. Similar left atrial pressure changes were recorded after injections inlto the aortic root as vell as in patients with niormal mitral valves (although the changes xvere of lesser magni- tu-ide). Citzulaiion, Vol/iue XX\I, ALa 19(65 Left Ven1tricuilar J)iastolic Pressnine Left ventricuilar end-diastolic pressure was measured in 21 patieits before anid after in.jection of Hypaquie into the left ventricle or ao-rtic root, anid the restults are shoxvn in figure 4. In all patients, the left ventricuilar enddiastolic pressure increased but there xvas great variability in the magnitude of the inmm Hg 50 45 40 35 .'A 30 ,,* , lip 25 _' ,", i0t 5 .I * ,Io 0 jp,. 20 15 ,I . -°i~ ,. 'fp - t= c- -js, -f C- C- i- Q o o . 00--, -- LAMP under 15mmHg v LAMP above lSrn15mmHg sobservatons otter Hypaque injections irito LA in 2Spaternts with rnitral disease 0 2 3 4 5 minutes Figure 2 Left cttrial mean pressure (LAMAIP) int 25 patients mvitli mitral valve dlisease befor e anid after injections of IIypaquce into the left a1triumw11 Ottfthe time scale, 0 is tite Otiontettt of itjictiont. 732 FRIESINGER ET AL. Hg HEARTRATE 140 130. 120 110 - I 0 100 90 80 70 60 50 01 28 Patients 0 heartrate ** v-wove 0 0 a-wave * v LA mean pressure LA diastolic pressure A mm Hg 45 40 35 30. 25 20. 5 0 5 peripheral ort. pressure A A . I /, I ' ,,, Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017 e sixty SECONDS 2 3 4 5 6 7 8 9 10 MINUTES II 12 13 14 15 Figure 3 Mean values for peripheral artery pressure, heart rate, and left atrial pressure from 28 patients with mitral valve disease who had pre-injection measurements recorded and serial measurements (at 1 or 2 minute intervals) for 12 to 15 minutes after injection of Hypaque into the left atrium. maximal LVEDP mm Hg riseafter Hypaque ir 21 patients 45 40 crease, which may be explained by the lack of homogeneity of the patient population with regard to type and severity of heart disease present. 40 Left Atrial-Left Ventricular Pressure Gradient 35 = 30 25 20 15 ; 10I i_ * . 0 1 2 3 4 5 minutes Figure 4 Left ventricular end-diastolic pressure (LVEDP) before and at designated times after injection of Hypaque into left ventricle or aortic root in 21 patients. 0 on time scale indicates instant of injection. In 21 patients with mitral valve disease, simultaneous left atrial-left ventricular pressures were obtained before and after the injection of Hypaque. An increase in diastolic gradient always resulted. Figure 5a illustrates the pressure tracing from a patient with pure mitral stenosis (on the basis of clinical, cineangiographic, and operative findings). Figure 5b was obtained from a patient who has primarily mitral regurgitation (on the basis of clinical and cineangiographic findings). The left atrial pulse contour is similar in the two patients following the injection although the pre-injection pulse oontours are very different and the mitral valve lesions are dissimilar. Cardiac Output In six patients, cardiac output was meas- Circulation, Volume XXXI, May 1965 SIW-w 1R-mls l z_ RADIOPAQUE MATERIAL BEFORE M .: ROM l l S . ECO AFTER ROM .IV - mmH -5o- -30- - A:v o-. -O Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017 BEFORE R O Ml I733 V~~~~~~~~~ AFTER ROM ECG mmHg -30_.R -20_ .k 111-Vt It v LAfi ,j-.A I 4 I> A, .N -10- Li I LV i~~~~-0 Figure 5 Simiullltaineouis left atrial and left venitricular pressures im7lmedliately beforec andcl after inijectionI of Ilypaque into the left atritum. A., upper. Tracings from a patient with pure mitral stenosis. Thl'ere is elevation of left venitricular end-diastolic pressure, increase in gradient, atnd marked inrcrease int "v' waves. The heart rate is niot changed. Postinijection tracitng was obtainied 3 mitiniutes after 40 ml. of IHypaque in1to the left atrium. B., lower. T'racings obtained before anid 5 minuites after the injection of 40 ml. of Hypaque into left atrium of a patient wcho blad prumarily mitral regu4rgitation. "V" twave again has markedly increased icithi slightly increased gradient. Heart rate has slowedl. uired with indocyanine green before and within 10 minutes after injections of Hypaque into the left heart. Cardiac output increased in each case; the average increase was 21 per cent. It was appreciated that indocyanine green may not be measured accurately in the presence of radiopaque material, but any error introduced by optical inlterference of the material would result in an underestimate of the cardiac output.' I Circulation, Volume XXXI, May 1965 Peripheral Artery Pressure The changes in arterial pressure are illustrated in figure 3. During the first minute after injection of Hypaque into the left heart, a drop in peripheral artery pressure of 20 to 30 per cent occurred. This hypotension was accompanied by a transient increase in heart rate of 10 to 15 per cent. Both arterial pressure and heart rate returned to control values within 3 or 4 minutes after the injection. FRIESINGER ET AL. 734 Hematocrit Determinations Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017 In 11 patients, serial hematocrit determinations were made. The initial blood sample was taken within the first minute after injection of Hypaque and serial measurements were continued for a period of 10 to 15 minutes. All samples were obtained from the free flow of an indwelling arterial needle. A marked and sudden fall in hematocrit level occurred immediately after the injection, with return to control values in 10 to 15 minutes (fig. 6). No gross hemolysis was detected in the plasma, and spectrophotometric analysis with correction for the interfering effects of radiopaque material indicated that hemolysis was absern or present only to a minimal degree. Supplementary Observations in Dogs and in Vitro Studies To supplement the observations made during cineangiography 24 mongrel dogs were studied with a variety of preparations. Observations were made with use of hypertonic solutions of siodium chloride and glucose, but in general Hypaque was used, since the primary objective was a better understanding of conditions that prevailed in patients undergoing cineangiography. The systematic study of the effects of solutions of varying hyperdrop in hematocrnt after injection of Hypaque in 11 patients %tHct y 100 0 0.~~~ 0 90Q :VPF 80 i V + " t i i. 0 70 1 0 1 2 3 4 5 6 7 minutes 8 9 10 11 Figure 6 Serial hematocrit determinations in 11 patients who had injections of Hypaque into the left atrium, left ventricle, and aortic root. Control hematocrit level is taken as 100 per cent. tonicity was not attempted here. As hematocrit and spectrophotometric changes in the blood occur with the injections of hypertonic solution, and these alterations can influence the flow measurements, it is important to emnphasize that similar flow changes were recorded whether dye-dilution, rotameter, or electromagnetic flow meter was utilized for the cardiac output determination. Hematocrit Valiue In 14 dogs, serial hematocrit determinations after injection of 50 per cent glucose showed changes similar to those resulting from injections of Hypaque. Hematocrit changes occurring after a regional injection of the material were also studied. The femoral artery was most frequently used as the site of injection and samples were withdrawn from the accompanying vein. The drop in hematocrit level in the first minute after injection wvas extreme, usually more than 50 per cent, sometimes as much as 70 to 80 per cent of the control value. The effect of hypertonic solutions on the hematocrit level was studied in vitro by adding solutions to blood in a beaker. The addition of a volume of Hypaque equal to 2 per cent of the volume of blood in the beaker resulted in a 10 per cent reduction in the hematocrit level. Therefore, the drop observed in vivo was at least in part the result of shrinkage of red blood cells due to the loss of red cell water (fig. 7). Shrinkage and deformation of red cells could be observed by light microscopy after the addition of radiopaque material. Observations on the Effects of Hypaque on the Coronary Circulation In five dogs, left coronary blood flow, left ventricular diastolic (or left atrial) and peripheral artery pressures, myocardial contractile force, and multiple electrocardiographic leads were recorded during the intracoronary injection of S to 2 ml. of radiopaque or other hypertonic media. The changes are illustrated in figure 8. There was an initial marked drop in coronary blood flow, which may be a-ttributed to the high viscosity of Hypaque Circ?nlatioz, Vuoltme XXXI, May 1965 RADIOPAQUE MATERIAI7 -i J3 HUMAN BLOOD (in vitro) % of Control Hct 100 0 S A 099%NoCI 5%NoCI 90%Hypaque 95 90 85 100 101 102 103 104 % of Control Volume Figure 7 Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017 An in vitiro study ncleiontistiratintig tlhat the early fall iii 1eieoiatoct'it mtutlst be nIne to loss of red cell water. A (quantity of wchole b0lood in a beaiker- hlad its volumwlle inicreadse by the addition of radiopaqute mnaterial in the a(mlountts inidicateld annl serial hbemnatocrit valties tere determnined, e.g., wchent 4 nil,. of 90 per cent Hypay(ne Lucre aclddcnl to 100 ndl. whole blood tihe hct,iiatocrit of thle sotiuttuin was oirily 85 per (cTit of thlc control valne (40 and 34, rcspectively). or may be dtue to the agglutinationl of red l)lood cells and transient mechanical l)lockage of the coronary vascuilar l)ed, and suibsequient- ly a marked prolonged increase in coronaixl)lood flow. \Iyocardial conitractile force anti peripheral arterv blood pressture fell transiently, while there was a ininmal elevation of left ventricular end-diastolic or left atrial pressures. Striking changes in the electrocardiogram have been observed following the injectionii of I-Iypaq(e into the coronary arteries. These may be stummarized by stating that the T-wave vector moves away from the milass of myocardiunm 1eing perfused by the hypertoniic' medIiuim. Isotonic soluitioni also causes T-xxwave chaniges wheni inijected into the coronary arteries, butt these are less macrked acnd more transient. In txvo aniimals in which the left coronary artery wxas cannuilated and supplied Nxxith blood from a perftusion bottle, the changes resuilting from left heart injections of radiopaque material were inot significantly altered. Hence, inijection of Hypaquie into the coronary arteries does not produce changes simnilar- to those occutirrinig with iinjections into the left heart chambers anid, excluding the coronai-ry circuilation, does not motdify the effects of left heart inijections. 901% I cc (LCA) Hypoque .Do#28 Figure 8 Tracing obtaiiiicel ni/c'n I nl. of 90 )er cent IHypaque ways iijectecl inito the left coronary artery of a (log whose artery hladc l)Cen canttnlatedI withl a Gregg canr nula and flotw Imeasuired wiillh arotaiuter. Myocaindial conltr'actile for'ce (top), femlor-al artcry 1pressure (middle), and left atrinl p)rcssure (bottom) in anlndition to left coronary a rte-ry flowc atre shown. Siitmltancetos o electroc'iZ'(ardiographic moitor-ing1 (not Slimterl) sholced profond T-tLeave chan1ges th7at )crsisted for o2 t 3 mintces of tcr thin injectioni. (Circlation, Volume X/X,X Slin 1965 736 F1IIESINGER ET AL. "Artificial" Mitral Stenosis By the technique of Davila,18 an umbilical tal)e xvas passed around the AV ring and a left ventricular-left atrial diastolic gradient vas produced to simulate mitral stenosis in four dogs. These animals shoved the same pressure and flow changes as seen in patients. In addition, contractile force was measured vith a strain-gatuge arch placed on the veintricle. Although contractile force was decreased by the injection of Hypaque, the decrease was small (less than 25 per cent) and transienit (iusually not longer than 10 to 12 seconds). An example of the pressure changes produced in these dogs is illustrated in figuire 9. Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017 Comparison of Right- and Left-Sided Injections In animals, sequential injections of Hypaqtue and other hypertonic media into the right and left side of the circulationi xvere possible. In Control mnmHg / six animals, it was demonstrated that 1 ml./Kg. of Hypaque into the right side of the circulation usually produiced outpult inicreases and pressure alterations similar to changes described with left-side injections of the same quantity of the material. However, injections of larger quantities into the right side of the cireulation (uip to 3 ml./Kg.) produiced very different results. Again, peripheral artery pressture fell but pulmonary artery pressure rose sharply, cardiac output fell markedly and cardiac arrhythmias frequtently occuirred. After several injections of these volumes of flypaquie, tachyplhylaxis developed, which likely vas due to the hypervolemia created.'9 Hence, a number of studies were performed with use of hypertonic saline (18 per cent) xvhich produced identical effects as the Hypaque but with lesser voluimes of injectate required. Figuire 10 is a record from an animal LA INJECTION 90% HYPAQUE lOcc 2 seconds 3 seconds 23 seconds % 50 seconds '** fA, v --------- .4 (. , 2501o00 ~ ~ V 20LV 15I LA go. t I Figure 9 Serial excerpts from a continuous tracing fromtia dog teitl "mitrcal steniosis" created acutely by passing umbilical tape about AV ring. Time designations are seconds after injection. Peripheral artery pressure, left ventrictlar diastolic and left atrial pressure are shown. Cardiac output was 1.6 L./min. at time of control pressure tracing antd teas 2.2 L./min. 1 mrinute after injection. Note large "a" wave prior to injection and elevation of all aspects of left atrial pressure pulse injectionis. There is a marked drop in femoral artery pressuire with beginning recovery at 50 seconds after injection, when left ventrictular-left atrial diastolic pressure gradient is mutch increased over control. Note that the left ventricular end-diastolic pressure (lid not significantly elevate in this instance and heart ralte is relatively con1stant throughou1t. (The left ventricular-left atrial and femoral artery pressuires are on different amplification, anld separate calibration scale.s are shown at left mnargin of figure.) (irculation, Volumne XXY,J Mlay 1965 RADIOPAQUE MATERIAIL7 737 1 mmhig 14mt of 09"/,NaCt NaCI 18l1 .z& DA 180/. NCt, into LA Into LA i t¶M PA4f 50- 0 FA mmNHg 160- mi/ruin Aortic Flow (mean) 5000- mi/min Aortic Flow (phasic) Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017 60- ecods-- s 13.7kg Figure 10 Sequential in jections of 0t9 011(I 18 petr cett NaCI icitli incasucmrients of pulmonarty aoItcry piessure", feinrot-al artery pressure, (lorttci mneant atI( phasic flowl (luit/i electoiroll-netic flonc probe ab0otit aootie root). Note iniinial atid transicet (1litliIges cit/i (0.9) per ('en! NaCl. 1/lic flowc inl(reasc produced by t/hc intjection of lie1r'toic .solntioiis ill-t tow/c 1(:lft ofthiim is coniid(tI-bly less thian tli(it uisuially prodiwted. in xw hich sequential injectionls of hypertonic saline were made into the righit anid left heart. A control injection of isotoniic saline is also shown. With larger volumeis of hypertonic saline (1 m1. Kg.) injected directly into the ptilmonary artery, peripheral artery pressure and flox sometimes fell to zero and the animal died. The immediate drop in peripheral artery pressrire (and rise in pulmonary artery pressuire) xith right-sided injections must be duie to mechanical blockage of the pulmonary vaseilar bed by clumping of red cells as posttulated by Read241 and noted by Wolcott's group. 1- Discussion It xxas the recognition of the change in left atrial pressure (most pronounced in patients with mitral stenosis) after injection of radiopaquie material that stimulated this investigation. An inicrease in cardiac ouitptut is chiefly responsible for the changes, but a rise in left ventricular enid-diastolic pressure also contributes, and the elastic properties of the left atritum must play a role.21 2 Circultrion, Volume XXXI, May 1965 It is important to niote that there is no evidence to indicate that an increase in the severity of mitral regurgitatioi or the developm-enit of this lesion is responsible for the changes in puilse contour. MXlany of the patients witli "pure mitral stenosis" showing the increase in the "v xwave have beenr operated iponlland no mitral insuifficiency has been founiid; in others, mitral regurgitationi has not becni seeni duiring left vxentricular angiograms. Stuidies in dogs xxith suirgically produced "mitral steniosis" confirm the fact that iincreases in stroke output accouint for the increase in the "v" wx ave since mitral insufficiency cannot occuir in this preparation. Hence, it is clear that the v'-wxxave inicrease is duie to increased atrial filling as a resuilt of the increase in cardiac ouitput. The simutltaneous left atrial anid left veiltricular pressirecs obtained in patients after inijection of Hypaque inito the left atrium, vllich shoxx that the left xventricular end-diastolic pressuire rises, "v" wave inicreases, and mitr al diastolic gradienit becormes greater, 738 Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017 emphasize the potential inaccuracy of methods that attempt to evaluate the functional status of the mitral valve by analysis of left atrial pulse contour alone. This point has been emphasized by Nixon.24 The decrease in peripheral artery pressure after left-sided injection is the result of peripheral vascular dilatation, and, when considered with the increase in cardiac output, indicates that a marked fall in peripheral vascular resistance has occurred. The increase in cardiac output is achieved by an increase in stroke output, since tachycardia does not occur. This "relative bradycardia" in face of an increased output and decreased peripheral vascular resistance is difficult to explain. The effect of the vagus nerve can probably be excluded as all patients have received atropine prior to the study, and, in dogs, sectioning of the vagi did not alter the heart rate response. In the dog experiments, the vagolytic effect of barbiturate anesthesia may account for the failure of rate to increase after vagotomy.25 It is also possible that some direct effects of radiopaque material on the myocardium or on the neural effector organs within the heart may account for this peculiar rate response. The profound and sudden drop in hematocrit level must be chiefly due to shrinkage of red cells, but its persistence may be attributed to an increase in plasma volume due to imbibition of extravascular fluid.26 Shrinkage of red cells should be an'ticipated when they are placed in solutions 3 to 4 times the osmolality of blood,27 and shrinkage was directly demonstrated by the in vitro studies. Hemolysis was not detected in these studies and therefore did not contribute to the decrease in hematocrit level. The absence of hemolysis is important from another point of view in that some of the peripheral effects of Hypaque might be explained by the liberation of potent vasodilatory agents known to be present in red cells. The absence of hemolysis on spectrophotometric examination makes this unlikely, although minute amounts of hemolysis can be responsible for market hemodynamic changes.28-30 It seemed possible that some of the hemo- FRIESINGER ET AL. dynamic changes could be the result of a high-pressure rapid injection, since the existence of pressor receptors in the left heart chambers31 has been postulated. The failure of injections of isotonic saline in dogs to elicit significant hemodynamic changes rules out the mechanical effect of injections as an important contributor to the reaction. Our observations on the effects of injection of Hypaque directly into the coronary circulation, which agree with those of others,32 33 and the observation that exclusion of the coronary circulation does not alter the reaction make it evident that entry of the material into the coronary circulation is not necessary for the changes reported here. The many observations by other investigators,34-39 as well as measurements in this study, indicate that a wide number of hypertonic agents will dilate the peripheral vascular bed. It must be this action of the Hypaque that is primarily responsible for the reactions following left heart injections we have recorded. Pressures and flow changes are readily accounted for as a consequence of this dilatation. Other actions occur and modify the outcome, among them the peculiar heart rate response and direct myocardial and possible neural effects of radiopaque material speculated upon earlier. The effects of the injection of hypertonic media into the right side of the heart can be different in many important ways from the effects observed after left-sided injection. As previously mentioned, the changes with the right-sided injections are more variable than those resulting from left-sided injections and must be dependent on the amount as well as the hypertonicity of the solutions delivered. After right-sided injections, pressures rise in the pulmonary artery and throughout the right heart, systemic pressure falls, and cardiac output falls; bradyeardia and ectopic beats regularly occur. Numerous animal experiments4' 20 have led to the suggestion that blockage of the pulmonary vascular bed by aggregated red blood cells can be the explanation for the events that follow rightsided injection. The hematocrit changes demCirculation, Volume XXXI, May 1965 RADIOPAQUE MATERIAL Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017 onstrated in the current investigation are in keeping with the hypothesis that sludging and clumping of the red cells are occurring, but indicate that the flow and pressor responses to this phenomenon are quite different in the systemic and pulmonary circulations. In the presence of pulmonary hypertension and increased pulmonary vascular resistance, these differences between right- and left-sided injections may be especially important when considering the "toxic effects" of contrast material. The changes resulting from the injection of hypertonic radiopaque material into the central circulation in man are widespread and dramatic. Awareness of these factors is important in the interpretations of data obtained after angiography as well as in explaining and avoiding untoward effects of radiopaque material. Contrast media have become safer in recent years, but hypertonicity will almost certainly remain as a property of these agents, and hence the effects described in this report will continue to occur with such agents. The relative safety of the injection of Hypaque into the heart or central circulation is illustrated by the fact that more than 500 patients were studied by cineangiography during the period when the data for this report were accumulating, and no deaths occurred although many patients had two or three injections. Significant reactions were few and chiefly limited to transient periods of mild hypotension or arrhythmia. Summary The hemodynamic changes resulting from injection of radiopaque material into the left heart in a series of patients undergong cineangiographic studies have been reported. The hypertonicity of radiopaque materials appears to be responsible for much of the observed reaction. The mechanism whereby hypertonic solutions produce the observed physiologic changes remains unknown. Changes observed in patients could be reproduced in experimental animals. The combined experimental and clinical data show that left atrial pressure increases, left atrial pulse contour alters, stroke output increases, Circulation, Volume XXXI, May 1965 739 heart rate is much unchanged, peripheral artery pressure falls, hematocrit level falls, and myocardial contractile force decreases mildly and transiently. The difference between the physiologic effects of injecting hypertonic media into the right and left sides of the circulation is discussed. Because the pressure changes are easy to monitor and parallel the other features of the hemodynamic reaction, it is good to wait until pressures have returned to the pre-angiographic level before proceeding with the injection of more radiopaque material. This usually requires 15 minutes. References 1. HOPPE, J. 0.: Some pharmacological aspects of 2. 3. 4. 5. 6. 7. radiopaque compounds. Ann. New York Acad. Sc. 78: 727, 1959. MOE, R. A., AND CRAVER, B. 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