Effect of Respiration on Venous Return and Stroke Volume in Cardiac Tamponade

Transcription

1 Effect of Respraton on Venous Return and Stroke Volume n Cardac Tamponade MECHANSM OF PULSUS PARADOX US By Warren G. Guntheroth, M.D., Beverly C. Morgan, M.D., and Gay L. Mullns, B.S. Wth the Techncal Assstance of George A. McGough and Donald G. Breazea/e ABSTRACT n 40 lghtly anesthetzed dogs, 5 to 30 days after surgcal preparaton, flow was measured smultaneously n the venae cavae, pulmonary artery, pulmonary ven, and aorta wth ultrasonc flowmeters. ntrapleural and percardal pressures were measured va slastc cannulas. Pulmonary ven dameter was montored by mnature mutual nductance cols. n the restng anmal wth snus arrhythma, nspraton ncreased heart rate and flow n the vena cava, and to a lesser extent, n the pulmonary ven. Left ventrcular stroke volume (LVSV) vared drectly wth the rght ventrcular stroke volume (RVSV) n dogs wth slow heart rates. Cardac tamponade nvarably caused tachycarda and a marked decrease n cardac output, arteral pressure, pulse pressure, and stroke volume; venous pressure and dameter ncreased. Percardal pressure, although markedly elevated, fell wth nspraton parallelng the fall n ntrapleural pressure. Flow n the pulmonary ven rose or remaned constant wth nspraton. Pulmonary ven dameter frequently ncreased wth nspraton durng tamponade, but only after the pulmonary artejy dameter ncreased wth the nspratory surge. LVSV dd not declne sharply wth nspraton, and actually ncreased wthn 2 beats of the ncrease n RVSV. The sum of LVSV plus RVSV ncreased markedly wth nspraton, contradctng the concept of fxed ntrapercardal volume. Almost all of the changes of pulsus paradoxus reflect the normal respratory effects on the RVSV, delayed by transt through the pulmonary bed and exaggerated by the small LVSV n a vasoconstrcted state. ADDTONAL KEY WORDS determnants of stroke volume percardal effuson cardac output percardal pressure pulmonary ven flow snus arrhythma ultrasonc flow studes vena cava flow respratory effect on blood pressure dog The mechansm of normal varaton n blood pressure wth respraton must be understood n order to understand the mecha- From the Dvson of Pedatrc Cardology, Department of Pedatrcs, Unversty of Washngton School of Medcne, Seattle, Washngton. Ths work was supported by U. S. Publc Health Servce Grants HE and HE-0758 from the Natonal Heart nsttute. Dr. Morgan s recpent of U. S. Publc Health Servce Research Career Program Award HE Ths paper was presented n part at the Scentfc Sessons, Amercan Heart Assocaton, October 22, 966, n New York. Accepted for publcaton February 20, 967. nsm of pulsus paradoxus, an exaggerated fall n systolc blood pressure wth nspraton found n cardac tamponade. However, there are two major obstacles to a complete knowledge of ether the normal state or the abnormal state of cardac tamponade. Frst, the large number of varables whch nfluence the blood pressure make t dffcult to measure these smultaneously n a preparaton that s physologcal. Secondly, the nterrelatonshps of these varables are nconstant n dfferent states n any gven anmal, and between anmals there s even more varaton n the determnants of systolc blood pressure. Crculaton Rnt*rcb, Vol. XX, Apnl

2 382 GUNTHEROTH, MORGAN, MULLNS We have prevously reported the varatons n percardal pressure wth respraton and heart beat n the normal, and n tamponade (). We found that changes n percardal pressure followed pleural pressure closely, effectvely rulng out Dock's (2) theory that percardal pressure rses durng nspraton wth tamponade, due to tracton on the percardum. Our fndngs are also dffcult to reconcle wth the theory of Katz and Gauchat (3), who nferred that the nspratory drop n pleural pressure was not transmtted to the percardum and left heart chambers. Katz and Gauchat concluded that the ncreased capacty of the pulmonary vens wth nspraton, n the face of an unchanged dstendng pressure for the left atrum and ventrcle, caused a transent poolng of blood n the pulmonary vens. Ths concept has been challenged by Dornhorst, Howard, and Leathart (4) and by Lange and Tsagars (5). Recently, Lange and others (6) have suggested that pulsus paradoxus s a smple reflecton of events of the rght heart delayed by transt through the pulmonary crculaton. Dornhorst and hs assocates (7) accept ths for the normal, but attrbute a domnant role n pulsus paradoxus to competton by the rght ventrcle for a fxed, total dastolc volume, resultng n a reducton of left ventrcular fllng wth nspraton. Shabeta and co-workers (8) also favor ths theory. n normal dogs at rest, wth slow respratory rate, slow heart rate and snus arrhythma, we found that the best predctor of left ventrcular stroke volume (LVSV) was the duraton of the precedng fllng nterval (9). The nspratory surge was transmtted from the rght heart n to 2 beats, but had less effect on left ventrcular stroke volume than dd the dastolc nterval. However, wth tachycarda or smply absence of snus arrhythma, the best predctor of LVSV became the rght ventrcular stroke volume of the precedng or 2 beats. We also showed that the pulmonary ven flow dd not regularly fall durng nspraton, but rose n more than one-half of our experments (0). We are now reportng our studes of the venous return and stroke volume of the two ventrcles n ntact dogs wth cardac tamponade to elucdate the mechansm of pulsus paradoxus. Materal and Methods Forty dogs weghng 7 to 30 kg were subjected to left thoracotomy wth aseptc technque under pentobarbtal anesthesa (30 mg/kg). The percardal sac was entered and ultrasonc flow transducers were mplanted at the base of the aorta and pulmonary artery. A specal slastc catheter was sutured nto the percardal sac () and the percardal sac was tghtly closed. Addtonal flow probes were placed on the superor or nferor vena cava near the rght atral juncton and on a lobar pulmonary ven outsde the percardal sac; from 2 to 4 flow transducers were mplanted n each anmal. n 5 of the anmals, a par of mnature mutual nductance cols (, 2) were sutured onto another pulmonary ven and onto a lobar artery to record dmenson changes. A flat, slastc balloon, 20 X 25 mm, was placed n the pleural space. The percardal sac was rrgated wth salne contanng hydrocortsone on the day of operaton and daly for 3 days thereafter; ntegrty of the percardal sac was confrmed by recovery of rrgatng flud. Data were obtaned from these dogs 5 days to 6 weeks postoperatvely; the dogs were under lght general anesthesa (morphne to.5 mg/ ' kg and pentobarbtal 0 to 5 mg/kg) and were breathng spontaneously. The followng 6 varables were measured n the course of the 40 experments: electrocardogram, ntrathoracc pressure, percardal pressure, vena caval pressure, rght ventrcular pressure, left ventrcular pressure, arteral pressure, pulmonary ven pressure, superor vena caval flow, nferor vena caval flow, pulmonary artery flow, pulmonary ven flow, aortc root flow, descendng thoracc aortc flow, and pulmonary artery and ven dameters. Not all varables were recorded n each anmal; some experments were desgned to elucdate a partcular aspect of the problem, and n some anmals, ncomplete data was a result of chewed wres and other vcsstudes of chronc anmal studes. Arteral and venous pressures were measured by catheterzng approprate vessels, and n 3 dogs, left ventrcular pressure was measured by retrograde aortc catheterzaton. A sngle lmb lead ECG was recorded n most anmals. Pressures were recorded by means of Statham P23Db, P23bb, and Sanborn 276 transducers wth zero level at the md-rght atrum. Flow records were not calbrated, snce our nterest was CnmUUon Rumrcb, Vol. XX, Aprl 967

3 MECHANSM OF PULSUS PARADOXUS 383 n relatve changes rather than absolute values. Zero level for venous flows was determned by ntravenous admnstraton of acetylcholne n dosage suffcent to produce transent cardac arrest. All anmals appeared to be n good health at the tme of study, and at autopsy the percardum appeared normal. Tamponade was produced by nfuson of 00 to 330 ml of sterle salne at 37 to 38 C nto the percardal sac. Nne anmals had satsfactory smultaneous records of flow at the aortc and pulmonc roots n the normal state and durng cardac tamponade. The stroke volumes for the rght and left ventrcles were determned by planmetry, and the mean values for these two varables were equalzed and the correcton factor, f any, appled to all of the ndvdual values. The amplfcaton was not changed durng the procedure, so that the values durng tamponade could be compared wth the normal values. These values, and data on pressure and nterval, were entered on punch cards and computatons were performed at the Unversty of Washngton Computer Center on the BM "Plot " from XTAB Programs was used for generatng scattergrams, and the BMD03R program was used to calculate the usual descrptve statstcs n addton jto regresson coeffcents, correlaton coeffcents, partal correlaton coeffcents, and multple correlaton coeffcents (3). The data from the control state and tamponade were analyzed separately and as a pooled group. Results Although several general changes n crculatory functon occurred n all nstances wth tamponade, there was consderable varablty from one anmal to another. Pulsus paradoxus was not nvarably produced by tamponade, but was present n 70$ of the anmals. Pulsus alternans occurred n almost 20& However, n all anmals wth tamponade, there was a marked tachycarda and a decrease n cardac output, mean blood pressure, pulse pressure, and stroke volume. The venous pressure, the dameter of the pulmonary ven, and the percardal pressure were elevated, although the nspratory drop n the percardal pressure was unchanged (). The voltage of the lmb lead electrocardogram X F. J. Massey. XTAB computer programs for bomedcal data processng, modfed by R. A. Kronmal and S. R. Yarhell, 966. CrctUten Rnurcb, Vol. XX, Aprl 967 was reduced by over 50%, but there were no S-T segment or T-wave changes. Flow patterns n the vena cava and pulmonary ven wth respraton were not apprecably dfferent n tamponade than n the normal. nspraton n both the normal and n tamponade ncreased the caval flow by only 20% n these chronc anmal preparatons, much less than the 50 to 60% fgure found by Shabeta et al. (8) n acute experments. Although the pulmonary ven dameter frequently ncreased durng nspraton, t usually ncreased or more beats after the augmented rght ventrcular stroke volume (RVSV) and ncreased dameter of the pulmonary artery. Flow n the pulmonary ven ncreased smultaneously wth or shortly after the ncrease n ven dameter (Fg. ). An mportant relatonshp observed n over one-half the experments was a smultaneous ncrease n RVSV and caval flow wth nspraton. The ncreased capacty of the thoracc cage wth nspraton appeared to favor an ncrease n RVSV even before the venous return was augmented. n the remanng experments, RVSV ncreased beat after the ncrease n caval flow. The declne n LVSV and arteral systolc pressure wth nspraton was rarely abrupt, appearng rather as a contnued, gradual declne from the precedng peak flow (Fg. 2). The cycle of rsng and fallng stroke volume of the left ventrcle was to 2 beats delayed from the cycle of the RVSV. A "smoothng functon" of the pulmonary vascular bed has been descrbed whch reduces the varance n LVSV compared to the varance of RVSV (4). We ndeed found a greater varance n RVSV n both normal and n cardac tamponade, but n only sx of nne experments subjected to statstcal analyss. The average of the standard devatons of nne experments for the LVSV was % and 3% for the RVSV n the control state, and 27% and 3% respectvely durng tamponade. n absolute terms, the varance for LVSV was greater n tamponade than n normal for only three of nne experments, whereas the varance expressed as a percentage of the mean stroke volume was greater n tamponade

4 j 384 GUNTHEROTH, MORGAN, MULLNS NTKATMOHA ~" JTJT- r " 3 _l -».->~t-t- rtt -\- SSUKE mm mmh J- - /l ^. yr A«TE«Y PtESSUlt (mmhj).ttt H Tl hn - NTAHOHACC ntttsuu - ~p j t! T / Sx. TT-T " jv_'y P =T -W-r J rul-mona«y ATETl OlAMCTU SJ nr J ' r *" «^ rulmonahy VEN DtAMETtt f a NAlY VE -J MKrHaEft.^sHB'^'affgK! ekjv.! 'tseflhttsl'.'m^vss.c^ rl: P -FJ,. M.. " 'M "J n J _ ll M V *> PUMONAKY AtrtUAl ROW 0 (^ / > - A V V A DCSCENDNC HOACC AO«HC R.OW P CLCCTDOCAtOtOOCAM 4-4 TFT ft -f r f -/ t h; FGURE T M J f* «v T p ' ' - ^k X - /! J- ' ± r Records from a normal anmal. n ths anmal, the percardum was not entered and the aortc flow probe s on the descendng thoracc aorta. Wth nspraton, the systolc pressure n the pulmonary artery decreased by 6 to 7 mm Hg, but the ntrathoracc pressure fell 8 to 9 mm Hg, producng a net ncrease n the dstendng pressure, reflected by a prompt ncrease n the pulmonary artery dameter. One beat later, the pulmonary ven dameter has ncreased n dmenson. The pulmonary ven flow ncreased slowly wth nspraton, peakng n late nspraton or early expraton. The major flow pdse n the pulmonary ven occurred n early ventrcular dastole. n sx of nne. Ths reflects prncpally the marked reducton n stroke volume unformly found wth cardac tamponade. Ths ncrease n devaton n relaton to a smaller mean stroke volume accounts for the exaggerated varaton n systolc blood pressure wth respraton. The varaton n systolc pressure was more than doubled; n the normal state standard devaton was ± 42 of the average 30- AOTK ROW FffcOlAL ATUAL «tt5su«(mmhg) FGURE 2 TAMPONADE Record durng cardac tamponade. The percardal pressure was consderably elevated, but the change wth nspraton was the same as that n the ntrathoracc pressure. The percardal pressure rose rapdly durng dastole and there was marked regurgtaton n the vena cava wth atral systole. The aortc flow pattern lagged 2 beats behnd the pulmonc. The left ventrcular stroke volume shown here was only 35% of the control value, but there was no sharp declne n the LVSV wth nspraton. The systolc pressure vared by 20 mm Hg. systolc pressure and ± 0$ durng tamponade. From the output of the BMD03R program, we ranked the measured varables as predctors of LVSV and aortc systolc pressure. The three statstcs used to rank each varable were the correlaton coeffcent, the partal correlaton coeffcent, and the proporton of total explaned varance. An example of the analyss for LVSV from anmal s CrcmUthn Rt rcb, Vol. XX, Aprl 967

5 MECHANSM OF PULSUS PARADOXUS 385 gven n Table. The correlaton between these varables and LVSV ranged wdely from anmal to anmal. Even when addtonal ndependent varables were used, the multple correlaton coeffcent was not necessarly mproved. Table 2 s from an experment n a dfferent anmal n whch left ventrcular fllng pressure (left ventrcular dastolc percardal pressure, LV PP) was measured n addton to the varables lsted n Table. Although LV PP n md-dastole was the most successful predctor of LVSV, the multple correlaton coeffcent was less than n the prevous analyss n Table. Of addtonal nterest s the lack of predctablty of LVSV from end-dastolc LV PP n ths experment, although n other experments, ths predctor was more successful. n the nne control experments, n order of ther performance, ntrathoracc pressure, precedng dastolc nterval, and precedng aortc dastolc pressure were the three best predctors of LVSV, excludng left ventrcle percardal pressure whch was measured n only two of the nne. Durng tamponade, the rght ventrcular stroke volume of the precedng beat (RVSV, -) was the best predctor of LVSV, followed closely by RVSV (-2) and ntrathoracc pressure. For aortc systolc pressure n the control anmal and n tamponade, left ventrcular peak ejecton velocty was the major determnant n every anmal, followed by ntrathoracc pressure, precedng aortc dastolc pressure, and precedng dastolc nterval. f Dornhorst's theory s correct (4), that durng nspraton left ventrcular fllng s reduced because of competton by ncreased rght ventrcular fllng for a fxed ntrapercardal volume, the sum of LVSV plus RVSV should be relatvely unvaryng. Fgure 3 s a Cal-Comp plot of the stroke volumes and ther sums durng tamponade, ndcatng that the sums of LVSV and RVSV ncrease as TABLE Data from Dog C-39 Durng Cardac Tamponade Regresson coeffcent ntrathoracc pressure Precedng dastolc nterval Precedng aortc dastolc pressure RVSV, (-)* RVSV, (-2) Correlaton coeffcent Partal correl. coeffcent Proporton of varance added Dependent varable, left ventrcular stroke volume. Multple correlaton coeffcent, * = dentfyng the beat precedng the beat analyzed, de th beat. Smlarly, 2 s the RVSV for the second beat precedng the th beat. TABLE 2 Data from Dog G-40 Durng Cardac Tamponade Regresson coeffcent ntrathoracc pressure Precedng dastolc nterval Precedng aortc dastolc pressure LV percardal p., md-dastolc LV percardal p., end-dastolc RVSV, RVSV, Correlaton coeffcent Partal correl. coeffcent Proporton of varance adde Dependent varable, left ventrcular stroke volume. Multple correlaton coeffcent,.975. CrcuUso* Rurcb, Vol. XX, Aprl 967

6 386 GUNTHEROTH, MORGAN, MULLNS O LEFT VENTRCULflR STROKE VOLUME RGHT VENTRCULflR STROKE VOLUME LEFT»RGH VENTRCULflR STROKE VOLUME BEAT NUMBER FGURE 3 A Cal-Comp plot from data from an anmal wth cardac tamponade. The stroke volumes of the rght and left ventrcle and the sums of the 2 stroke volumes are plotted for 39 successve beats. The ordnate represents the readng of planmeter, not mlllters of blood. Gray bars ndcate the duraton of nspraton. n ths anmal, the LVSV lags the RVSV by only beat. Durng nspraton the sum of flvsv plus LVSV ncreases to over 200% of the sum durng expraton, n contrast to the predcton by Dornhorst (4) that the ntrapercardal volume s relatvely fxed. much as 00% durng nspraton. Addtonal evdence aganst the concept of a fxed ntrapercardal volume s found n the hghly sgnfcant correlaton coeffcents between the sums of the stroke volumes and the ntrathoracc pressure n both the normal and tamponade. The ntrathoracc pressure s consstently the best predctor of the sum of stroke volumes. Dscusson The cyclcal events of the cardopulmonary system wth respraton whch we observed n our normal, ntact dogs were n substantal agreement wth prevous reports. The major dfference was the pronounced effect of snus arrhythma whch was present n the great majorty of our anmals at rest (9). Wth snus arrhythma, the precedng dastolc nterval becomes the most mportant determnant of left ventrcular stroke volume and may obscure the effects of the nspratory enhancement of venous return from the venae cavae. Wth nspraton n a subject at rest there s an ncreased heart rate; the dmnshed dastolc nterval results n less complete ventrcular fllng and a relatve decrease n stroke volume. On the other hand, the systolc pressure n the aorta may actually rse n some subjects because the shortened dastole permts less runoff from the aorta, causng a hgher dastolc pressure (Fg. 4). Wth expraton, heart rate slows and there s ncreased ventrcular fllng tme. However, Crculton Ru rcb, Vol. XX, Aprl 967

7 MECHANSM OF PULSUS PARADOX US 387 s. PHCAJtOlAL PRBSUW (mmhg). \ ; ; t t j ; j. V-Aj^^^v nl>*"* "\ -wf *r [ ' j"' u*^ v ~^, : M*!, rr. '!,. - f r 4:. - s t '"f L,. -._, _,. " t t -, ' ; ' T~.... CAXOTD A«r«AL ftessum ( mm Hg) FGURE 4 MCOnd Records from a healthy anmal wth snus arrhythma. Note covarance of the stroke volumes of rght and left ventrcles. The systolc pressure n ths anmal actually rses wth nspraton despte a declne n left ventrcular stroke volume due to cardoacceleraton, wth resultng shortenng of fllng nterval and aortc runoff tme. A full nspraton occurs twce n ths record, ndcated by a substantal fall n percardal pressure. Wth longer ntervals between beats occurrng n early expraton, caval flow and to a lesser extent, the pulmonary ven flow ceases and the followng atral systole produces a large, regurgtant pulse. there s obvously a lmt to ventrcular fllng, causng a curvlnear relatonshp between the nterval and stroke volume, prevously reported by Hoffman and co-workers (5). However, the relatonshp s reasonably lnear for the frst sec of fllng tme, and the lnear correlaton coeffcent was qute hgh wth snus arrhythma. Fgure 4 shows the recprocal nature of caval flow and percardal pressure wth a long dastole, wth levelng off of both after approxmately sec. The varatons n systolc pressure wth respraton are nfluenced by almost all the determnants of LVSV. n addton to LVSV, there are several factors whch nfluence the aortc systolc pressure n both the normal and n tamponade. Varaton n ntrathoracc pressure wll be drectly transmtted to the aorta (6). The precedng dastolc nterval wll nfluence the runoff tme as well as the left ventrcular fllng perod. Ths wll determne the dstenson of the aorta, and ts da- Crculaton Rutmrcb, Vol. XX, Aprl 967

8 388 GUNTHEROTH, MORGAN, MULLNS 5 N TRA THORACC PRESSURE! (mmhg) J '' -'- L -L-. \ 4-,'!.. PEHCARDAL PRESSURE (mmhg) ' '! ' ' 0) -r- ^ J, j ] c '! l t '.., SUPEROR VENA CAVAL FLOW j T ' : ' U ft «* ; 'll ; PULMONARY ARTERAL FLOW» ]» w ^ W T,» - HDTjlLlJrLr--:: 7 FEMORAL ARTERAL PRESSURE (mmhg) FGURE 5 Ths record begns mmedately after dscontnuaton of forced hyperventlaton wth a Palmer resprator. There s no respratory movement untl the end of the record (the marks occur at -sec ntervals). Note Traube oscllatons at 6/mn of heart rate, blood pressure, caval flow, and pulmonary artery flow. These perodc changes n the absence of respratory actvty ndcate a neural contrbuton to varatons n nterval, and through nterval changes, consderable varaton n pulmonary artery flow and arteral blood pressure. stolc pressure, whch also has a consstently hgh correlaton wth the systolc pressure. Cyclcal changes n perpheral resstance and n heart rate emanatng from the central nervous system may be major factors n systolc pressure fluctuatons. Fgure 5 was obtaned after a perod of forced hyperventlaton wth a Palmer resprator. The resprator was then turned off, and there was a perod of apnea, accompaned by blood pressure oscllatons unassocated wth even slght respratory movements. These are frequently referred to as Traube waves, and are ascrbed to spllover from the respratory center to the cardovascular center (7). Wth cardac tamponade, there s nvarably tachycarda, and very lttle varaton n dastolc nterval. The fluctuatons n left ventrcular stroke volume n tamponade then are largely correlated wth events of the rght ventrcle or 2 beats pror to a gven LVSV. n ths context, t s nstructve to revew the experments of Katz and Gauchat relatve to ther conclusons that nspraton caused a reducton n venous return to the left atrum and a fall n LVSV (3). They found n dogs wth open chest, that pnchng the nferor vena cava resulted n a change n the perpheral arteral pulse after 3 or 4 beats, whereas obstructng the pulmonary vens produced Crculaton Rtsmrcb, VoL XX, Aprl 967

9 MECHANSM OF PULSUS PARADOXUS 389 arteral changes n the frst or second beat thereafter. They concluded that the event whch condtoned arteral pulse changes wth respraton must be pulmonary ven "poolng." However, they dd not comment on ther observaton that clampng the pulmonary artery nvolved the same delay as clampng the pulmonary ven. Ther observatons are then n agreement wth our correlaton of LVSV wth RVSV of the precedng frst or second beats. n addton, our measurements ndcate that the pulmonary ven flow s relatvely constant or ncreases wth nspraton, beat after pulmonary artery flow ncreases. These observatons are also consstent wth the results of Shabeta et al. (8), who found that marked varatons n systemc blood pressure dd not occur wth cardac tamponade f the rght heart was bypassed and the pulmonary artery nflow was held constant. Shabeta and co-workers (8) agreed wth Dornhorst and hs assocates (4) that successful competton of rght ventrcular fllng for a fxed ntrapercardal volume was a major cause of reducton of LVSV, resultng n pulsus paradoxus. We dd not usually fnd an abrupt reducton n left ventrcular stroke volume wth nspraton smultaneous wth augmentaton of the RVSV, nor dd we fnd that the ntrapercardal volume was fxed. On the contrary, the sum of RVSV plus LVSV ncreased consderably wth nspraton durng tamponade, and ths sum was hghly correlated wth ntrathoracc pressure. Shabeta offered as evdence for hs hypothess that the transpercardal pressure rose durng nspraton;.e., that the percardal pressure fell less than the pleural pressure. We found that the peak-to-peak changes of percardal pressure wth nspraton were no less than the pleural pressure changes (). These contradctory fndngs may be due to the fact that Shabeta was dealng wth acute experments, n whch the chest had just been closed, before the cardopulmonary system had returned to a normal state. n addton, the term "transpercardal" pressure requres defnton n relaton to the cardac cycle (7). Crculaton Rtsurcb, Vol. XX, Aprl 967 As s evdent from Fgure 2, the ncrease n pressure n the percardum durng tamponade s much more rapd n dastole than n the normal, and the nstant at whch one measures the transpercardal pressure wll permt varatons of more than 50$ (). n concluson, n the normal, restng anmal wd snus arrhydma, nspraton produces cardoacceleraton, ncreased flow n the vena cava, and to a lesser extent, ncreased flow n the pulmonary ven. When t s not fxed, the fllng nterval s the sngle best predctor of the left ventrcular stroke volume. n cardac tamponade, there s tachycarda; the nspratory surge nto the pulmonary artery s the domnant event, and ts appearance n the left ventrcular output or 2 beats later accounts for most of the changes of pulsus paradoxus. The respratory varatons of stroke volume durng tamponade are unchanged from the normal n absolute terms but are ncreased when expressed as a percentage of the respectve means. The exaggerated respratory varatons n blood pressure durng tamponade are a result of normal fluctuaton of a markedly reduced stroke volume n a vasoconstrcted state. Acknowledgment Several ndvduals partcpated n some of the studes and have co-authored papers wth us on other aspects of the problem, partcularly Dr. Francs Abel, now at ndana Unversty, and Dr. Davd Dllard, who developed the operatve technques. Dr. Rchard Kronmal of our Department of Preventve Medcne generously provded access to the computer technques employed n ths report and advce n the choce of programs and n nterpretaton of the output Dr. Allen Scher was partcularly helpful through many dscussons and suggestons durng the course of the experments and preparaton of the manuscrpt. References. MORGAN, B. C, GUNTHEROTH, W. G., AND DLLARD, D. H.: Relatonshp of percardal to pleural pressure durng quet respraton and cardac tamponade. Crculaton Res. 6: 493, DOCK, W.: nspratory tracton on the percardum. Arch. nternal Med. 08: 837, KATZ, L. N., AND GAUCHAT, H. W.: Observatons on pulsus paradoxus (wth specal reference to percardal effusons). Arch. nternal Med. 33: 37, 924.

10 390 nnn, MORGAN, MULLNS 4. DORNHORST, A., HOWARD, P., AND LEATHART, G. C: Pulsus paradoxus. Lancet : 746, LANCE, R. L., AND TSACARS, T. J.: Tme course of factors causng exaggerated respratory varaton of arteral blood pressure. J. Lab. Gn. Med. 63: 43, LANCE, R. L., BOTTCELL, J. T., TSACARS, T. J., WALKER, J. A., GAN, M., AND BUSTA- MANTE, R. A.: Dagnostc sgns n compressve cardac dsorders: constrctve percardts, percardal effuson, and tamponade. Crculaton 33: 763, DORNHORST, A. C., HOWARD, P., AND LEATHART, G. L.: Respratory varatons n blood pressure. Crculaton 6: 553, SHABETA, R., FOWLER, N. O., FEXTON, J. C, AND MASANCKAY, M.: Pulsus paradoxus. J. Cln. nvest. 44: 882, MORCAN, B. C, ABEL, F. L., MULLJNS, G. L., AND GUNTHEROTH, W. G.: Flow patterns n cavae, pulmonary artery, pulmonary ven, and aorta n ntact dogs. Am. J. Physol. 20: 903, MORCAN, B. C, DLLARD, D. H., AND CUNTHER- OTH, W. G.: Effect of cardac and respratory cycle on pulmonary ven flow, pressure, and dameter. J. Appl. Physol. 2: 276, GUNTHEROTH, W. G., AND MULLNS, G. L.: Lver and spleen as venous reservors. Am. J. Physol. 204: 35, TAFUR, E., AND GUNTHEROTH, W. G.: Smultaneous pressure, flow and dameter of the vena cava wth frght and exercse. Crculaton Res. 9: 42, DXON, W. J. (ED.) : BMD. Bomedcal Computer Programs. U.C.L.A. Health Scences Computng Faclty, 965, p LAUSON, H. D., BLOOMFELD, R. A., AND COUR- NAND, A.: nfluence of the respraton on the crculaton n man. Am. J. Med. : 35, HOFFMAN, J.. E., Guz, A., CHARLER, A. A., AND WDLCKEN, D. E. L.: Stroke volume n conscous dogs; effect of respraton, posture, and vascular occluson. ]. Appl. Physol. 20: 865, HAMRLTON, W. F., WOODBURY, R. A., AND HARPER, H. T.: Physologc relatonshps between ntrathoracc, ntraspnal and arteral pressures. J. Am. Med. Assoc. 07: 853, HOLT, J. P., RHODE, E. A., AND KNES, H.: Percardal and ventrcular pressure. Crculaton Res. 8: 7, 960. CrcmUtm, Ruarcb, Vol. XX, Aprl 967