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Blood Velocity and Endocarditis By SIAION RODBARD, Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 DESPITE the successful use of anitibioties in the treatment of infective endocarditis, the failure of therapy in perhaps onre third of the patients with this condition keeps it in the forefront as a major threat in heart disease.1 2 The increasing incidence of endocarditis following cardiac surgery has also provided an unexpected and disturbing feature of progress in cardiac management.3In addition to the practical problems of management of this disease a number of per plexing clinical and laboratory questions re main. Thus, the argument as to whether the locus of the infection requires previous trauma, inflammation, vascularization,6 or deformity7 remains undecided. The mechanisms in the progression of verrucae and uleerationis, the formationi of thrombi, the validity of spontaneous cures, and the tendency to recurrence, demand re-evaluationi. It is curious that extremnely large quantities of antibiotics are required to halt the growth of inifective agents at the valve, while a thousandth of these concentrations (calculated for extracellular body water) miay destroy the same organisms in other sites in the body or in vitro.Y2 The antibody titers for some of the antigens of the infecting organism mav have little or no inhibitory effect on the mnicrobial growth at the infected valve or artery.'3-1 5There can be little doubt that the circulation is seeded continually by organisms that are swept as emboli from a nidus to all the tissues of the body, with the production of local vascular occlusions; vet these pathogenic showers seldom produce local infections or abscesses. If some of these prob- M.D., Pn.D. lems could be resolved, it might become possible to approach the management of the disorder in a more adequate manner. Some of these questions have been re-exainiimed on the basis of findings of pathologic anatonlv and of studies of flow through specially prepared tubes. As a result, the point of view has been developed that the hydro-dvnamics of the blood stream in the region of a lesion can account for many of the special characteristics of the endocarditides. Theories of Infective Endocarditis The pathogenesis of infective endocarditis has been a favored topic of manv investigators. Primary points of departure have been that the lesion is engrafted most commonly at sites of edema. iniflaimmation, injury or vaseularization, thrombosis, or congenital anomalxv. Numerous workers have suggested that tibe hvdraulies of the blood stream played a key role in the pathogenesis of endocarditis. Particular emphasis has been given to the contact of the blood with the involved site, the volume of flow, the presence of eddies, or the force with which the apposing walls are com- pressed. 1. Contact with the Blood. The likelihood of involvement of a site has been considered byr Allen6 -18 to be proportional to the volume of blood in contact with the surface. lie tlhought that bacterial localization was favored by the impact of the blood streain against a fibroplastic deformity or a congenital anomalv. The atrial surfaces of the mitral valves and the ventricular surfaces of the aortic v-alves were believed to be in better contact with the blood than were other sites. The oreatest volume of blood, however, flows during ejeetion when the mitral leaflets are closed. the aortic leaflets are widely separated, and xv,hen, as a consequence, the quantity of blood im direct contact with the valves is minimal. Similarly. the mitral valves are widely open Froml the Puiblic Healtlh Resear chl TIustitute for Chlroniic Disease, State UVii-eirsitv of Ne\w York at Buffalo, New York. The Public Health Researeh Institute for Chronic Disease is supported in part by the New York State Department of Health. Aided by grant H-2271 from the National HIeart Institute, U. Se Public Health Service. 18 Circuiation, Volume XXVII. January 196.? BLOOD VELOCITY AND ENDOCARDITIS Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 during diastolic filling and the blood in contact with these leaflets must also be relatively small. 2. Increased Flow. An increased stroke output, as in aortic insufficiency or following the production of large peripheral arteriovenous fistulas or in chronic hypoxia, is known to enhance the tendency to endocarditis even in the absence of direct trauma to a valve. Highman and Altland"9 found proliferative changes on the mitral and aortic valves in young rats that were exposed repeatedly to simulated altitudes of 25,000 feet; such a situation can be expected to result in hypoxia and an increased cardiac output. Intravenous injection of bacteria resulted in infective endocarditis in some of these animals. The occasional failure of the combination of hypoxia and bacteremia was explained by these workers as due to trauma or other hydraulic factors. 3. Blood Currents. Swirling currents and increased pulse pressures in conditions such as patent ductus arteriosus may stretch and modify the vessel wall, with the production of intimal thickening on the wall opposite the entrance of the ductus. The infective process is considered to occur on the damaged surface.20 The buffetinog proeess, however, probably involves all segments of the tract while only a specific segment of the ductus becomes the seat of the endocarditic lesions. 4. Compression. Since the line of valve closure is compressed repetitively as the leaflets serve their normal function, endocarditis has been attributed to a compressive process, especially when a subendothelial inflammatory focus is present.2' Lepeschkin22 analyzed statisties of the incidence of endocarditis and showed it to occur in direct proportion to the pressures that act on a given valve. The highest pressures operate against the mitral valve while those acting on the aortic valve are somewhat less and the pressures on the valves of the right heart are lowest. Endocarditis occurs commonly, however, at sites that probably do not suffer compression, as at a ventricular septal defect or a patent ductus arteriosus. Further, the specific locus of the Cireulation, Volume XXVII, January 196S 19 lesions is always on the low pressure side of the valve, as discussed below. A Hydrodynamic Approach Recent studies of the effect of blood flow on the structure of vessels have indicated that certain aspects of the development and normal structure of the blood vessels, as well as their pathologic states, can be attributed to the response of the vascular connective tissues to the hydraulic forces of the blood stream.23 24 Thus, the strengthening of the arterial and venous walls by the accretion of ground substance, collagen, reticulin, and elastin, the genesis of valves, the progression of stenoses and ectasias, as well as other vascular changes, have been analyzed in terms of the potential interactions between the physical forces of the stream and the strains imposed on the tissues of the vessel wall. Evidence for the role of hydrodynamic forces in the genesis and maintenance of infective endocarditis is provided in a review of the pertinent literature, in studies on the effect of flow on the growth of bacteria, in chemical reactions in the walls of specially designed tubes, and in the deformative effects of a stream on a nonrigid wall. Present Concept Endocarditis appears only when a high pressure source (e.g., aorta) extrudes blood at critical velocities through a narrow orifice (patent ductus arteriosus) into a low pressure sink (pulmonary artery) (table 1, fig. 1). The velocity of the stream is a function of the pressure gradient from source to sink. If the orifice were wide, the large flow across it would quickly dissipate the gradient; however, when the orifice is narrow, the volume of the shunt will be small and a large pressure gradient and a high velocity will persist. As fluid enters an orifice, momentum causes the streamlines to continue to converge, with the result that the velocity is greatest a short distance beyond the anatomic constriction, at the vena contracta. This appears to be the consistent locus of the endocarditic process. It is at this point that hydrodynamic factors operate through two discrete mechanisms to 20*; R( MDBARD -educe the colntact of streamuborne materials wvitlh tlue vessel walls, i.e., bv thNe pattern of streamxYline flow and byr eductio iii the raue of vascular perfusion. The quanltity of nultritive and defensive inaterials passinog from the blood stream-t to the vascular lining depends in large part oii the conatact of stream-borne muaterials with the eiidothelituti and the rate of fliltration:of C. 1 t p)lasina eoinpolienits into tlle imtini.a. 'When the 0~~~~~ CCC~~~~~~~~~~~~~C t C;+@|5 .~~~~~~~~~~~~~~~~~°' + 9C i t 05= U X;_' ',C C " 0 Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 ~ t~ Ct- 5r I -I speed+to each j> i t> siiiootllly w-ith. rev- other, as occurs in miost norilal b lood vessels only the boulndarv lamniilacomties !71)100r 40;Uconitaet witlh the wvall. Thlis rlelatively slow XZ; ginto < t > -_ io, lll0sin0g layer briings only a ver. limiited quiami- w :t > C '> 5 lavers of tile streaiii imove _V V - - titv of streambornie iimaterials to the wall. Streamiilines passing through a niozzle conitinue to coanverer for a sliort distance bexvond the orifice because of uomnentumn: as a, result a small seetor of thIe vessel at the -venta colitracta have olily negligille conta(t vs itli tlhe matfterials of the streani. ); The lateral pressFure eolntribuLtes to the inu- vvill c: .rCL 2 ftritioi- of tlhe inormal vessel wall as well as to its remuarkable resistance to infection and -prbablv determiles certain aspects of its struclture. Thus the lligh pressure in arteries eolinpresses anid conidenises the tissu-es of the _-Z rlitilno layers alil Ttl y thdereby inihibit the rC O developumienit of the x asa vasortum in the intima anid inner miedia. At sites of highch locity, however, the pressure nmay be very low. even iii ani arterial system. rrlis is because the total onrergy of a h-ydraulic svstem is the ~~~~~~~~~~~~~~~~~~C) !_ 1 < sum of the lateral j)erfusiolnl1 pressure plus the energy imaniLfested in the x elocity of thie strean-i. Lateral pressure and perfusioni are ,m¢+.;i.axhitnalwhere flow is arrested since tIme entire hydratulic eimergv of the systeml distenlds the vessel ai-id perf uses its wall. With flow, solme of the hydraulie emiergy appears as > > >u -I umO ovemeut (kinletic energy) and the local perfalls. ft-Lfsion >= pressure . CZ7r; Q g }Wheim the distending- pressure oii a segi-i'ent of vessel wall- falls below aibient values | a localized suction xvill result and the fluiid p)erfusiimg this segmne1it of tIme arterial wall or x ! , -;4 > G f X-alve lininig mnay8T tno longer comne (lirectly frotm the hiood streain. Ilvstead. fluid from the mer4 C L itr -4- 4= 4- ~D0 V flS (Cl, 'rcu1atUi' X X V IL J( rf(eh 21 BLOOD VELOCITY AND ENDOCARDITIS SOURCE" VENA CONTRACTA/ Figure 1 Flow through a p,ermeable tube. A high pressure source (at left) drives fluid through an orifice into a low pressure sink. The curved arrows leaving the stream and entering the wall in the upstream segment represent the normal perfusion of the lining layer. Velocity is maximal and perfusing pressure is low immediately beyond the orifice where the momentum of the stream converges the streamlines to form a vena contracta. The low pressure in this segment results in reduced perfusion and may cause a retrograde flow from the deeper layers of the vessel into the flowing stream. Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 dia of adjacent segments of the wall where perfusion persists, will tend to pass retrograde and to re-enter the blood stream at the point of highest velocity (fig. 1). The intima at this site would thus be perfused with a fluid despoiled of its oxygen and nutrients and surcharged with accumulated metabolic end-products. Retrograde perfusion also may diminish the facility with which leukocytes, antibodies, and antibiotics can enter the site, and may contribute to the deformation of valve leaflets or vessel walls.23 27 This concept of retrograde flow is supported by catheterization data that demonstrate that the lateral pressure at a narrowing may fall to "zero " levels or lower. Studies on specially designed analogues also show that the interaction of the stream and the wall is minimal at the vena contracta.25 Certain effects of flow on lining materials in the walls of a tube have been demonstrated in studies of the effect of flow on bacterial deposition and growth. In these experiments, nebulized suspensions of Serratia marcescens were blown through tubes of agar (fig. 2). When the caliber of the agar tubes was uniform, a few random colonies appeared on the agar wall at the end of 16 hours of growth. Introduction of a nebulized suspension into the air stream flowing through a venturi-shaped agar tube resulted in a marked deposition on the downstream segment of the throat. Bacterial growth was so marked in this region as to Cirulation, Volume XXVII, January 1963 form a thick raised collar in the lumen. These results demonstrated that flow can determine the site of deposition and the rate of growth of bacteria on the walls of a tube. Similar hydrodynamic effects may contribute to the determination of the locus of deposition and growth of organisms in infective endocarditis. Sites of Clinical Endocarditis A number of situations can be cited as demonstrating that the lesion of endocarditis requires only a sufficient velocity in a given direction. For exanmple, in nonvalvular endocarditis and endarteritis, the process is consistently on only the downstream side of the orifice. Nonvalvular Endocarditis Coarctation. Endarteritis is associated quite frequently with coaretation of the aorta,28-31 the lesion being found on the lips of the stenosis immediately distal to the narrowing. When the orifice of the coaretation is oriented so that the stream is directed against the aortic wall, a satellite lesion may also develop beyond the coaretation. Fistula. Systemic arteriovenous fistulas are relatively vulnerable to infection.32 3 The artery leading to the fistula is commonly enlarged, consistent with the increased flow through it, and the pressure gradient across the fistula is high. Fistulas often exhibit small pedunculated vegetations (satellite lesions) on the adjacent vein wall.33 The development RODBARl) V1 a tricitlar Septal Defect. Endocarditis occurs in ventricular septal defects only wlheni the abnormal orifice is relatively small and a large pressure gradient persists. The lesions, appearing invariably on the right side of the eommnunication, may extend to the tricuspid valve. There is, however, little or no involvemnent of the left ventricular surfacee Valvular Endocarditis Figure 2 and bacterial deposition. In jection of an? Into the airstreamn pjassing from left to right th roagh ca venturi tu be re slt. in a m(ximal deposition immediatelyi beyoncd orifice. A collar of thick growth is seen consist entil at this point. Colonwis arranaged in streak lines ai-e also seen on the wall beyond this point. part of the supporting The vertical bars ar)'e *rStrrtch'I of the agar tube. F'lo Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 aw rosol containini-g bacter-ia a I. of nuiiierous collateral vessels adjacent to the fistuila makes it difficult to establish the exact .:1lynani relation-ships of the endarteritis. The (.cure, however, of this form of enidocarditis w-henl the hydraulic basis is elirninated bv surgery33 einphasizes the potential role of ioigh velocity flow in the inifective process. I)ictits Arteriosits. The ineidence of iiifece tive enidocarditis at patent ductus arteriosus is relatively high.37 40 In these, the vegetations are f ound alimost always in. t lie pulmonary arterv iiimmediately beyond the junction with the ductus, i.e.. at the site of the vena contracta and the miiaximnal stream -velocity. The aorta is seldom involv,ed by' these endocarditie processes. Endocarditis probablv occurs in. a ductus unIlxIywheni its diameter is small. The high veloeity of the jet stream-l produced by flow thlrouigl-h the small duetal orifice mnay also inv-olve a portion of the wall of the pulnionary arterv, The direetion. of flow of the shunit is inflicated by the faet that miultiple snmall enboli in th-e systemni ecircuit are relatively unlc-omrnmorn in patent ductus arteriosus, whereas nllibhi to the lun:gs oeeur commonly. The infective lesions discussed in the foregooing sections provide examples in whiech there ean be little doubt about the relationi of the direction of blood flow and the locationof the lesion. In involvement of the cardiac v,alves, the directioni of blood flow inivolved itn tl-he local infectioii is less certain. An anial vsis of the location of the valvular lesions, however, permits the suggestioon that, as with1 the abnorrmalities noted above, the infectioun appears on the dowv-nstreain side of an orifice through which a high pressure gradient extrudes a regurgitanit stream of blood at high velocities. This situation is observed most clearlv when a fenestration develops in a cardiae valve. Fenastration. Flow through aii aortic fenestration- probably does not occur during systole, Since the leaflets are blown aside by the stream; in diastole, flow through the fenestration is necessarilv from aorta to ventricle and a loud diastolic murnur and otlher sign-is of aortic valvular insufficieney mnav be present. Characteristie of clinical and animnal findings, a doughnut of inflamimatory mnaterial on the ventricular surface of the orifice attests to the regurgitant character of the flow; essentially similar patterns emerge when an aneurysnm of thie sinus of Valsalva ruptures into the right atrium or another low pressure sink.4'- 42 Pr( dilectioon for Incompetent Yalves. It is niot alwrays appreciated that the frequency of bacterial endocarditis is mueh higher in th e presenee of valvular incomupeteniee than in: stenosis. For example, 10 of 30 cases in one selected series of hospital cases of pure incoompetence were reported to have endocarditis.43 Cutler et al.44 have also noted that in rheumatie heart disease, baeterial. vegetationis (irrulatnov, Volxrne XX Vfi, January 1963 23 BLOOD VELOCITY AND ENDOCARDITIS generally are found on incompetent mitral and aortic valves, whereas pure acquired stenotic lesions are rarely sites of bacterial invasion. Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 Mitral and Tricuspid VaZves. Perhaps the most common site of endocarditis is on the mitral valves.45 Examination of such valves, especially in the acute process, reveals that the lesion is characteristically on the atrial surface adjacent to the line of closure. Considerable evidence may be cited to demonstrate that the process is associated with an insufficiency rather than a stenosis. Endocarditis occurs fairly commonly in valves that show no significant stenosis; especially is this so in patients after only a few episodes of rheumatic fever, long before stenotic processes become manifest. Indeed, infective endocarditis is not a common finding in patients with severe stenosis. The hydrodynamic process may thus be viewed as resulting from the high pressure source of the left ventricle, which drives blood at high velocities through the nearly closed, but insufficient valves, to the low pressure chamber of the left atrium. Satellite lesions on the left atrial wall support this point of view, as indicated below. The structure and alignment of the polypoid exerescences on the leaflets have been shown to extend in the direction of the left atrium as if they had been pulled in this retrograde direction by a regurgitant flow.46 Aortic Valves. The aortic valve is involved fairly commonly. In almost every instance, the infective process is situated on the ventricular surface of the leaflets in line with a high velocity regurgitant stream. Such lesions are seen particularly in bicuspid valves, the aortic insufficiency of syphilitic heart disease, and in rheumatic fever. In these instances, as well as in aortic valvular fenestration mentioned above, the dynamics may be explained as due to the extrusion of blood by the high pressure aortic source through the nearly closed but insufficient aortic valve to the low pressure sink of the relaxed left ventricle. Lesions in the Right Heart. In accord with the knowledge that the right ventricle norCirculation, Volume XXVII, January 196S mally develops only a low pressure,47 primary endocarditis of the tricuspid and pulmonic valves occurs relatively rarely.20' 48-50 Disease in some other part of the heart is usually present to account for abnormal pressure gradients. The pulmonary valve is rarely the site of bacterial endocarditis. Elevated right ventricular systolic pressures, however, as in patent ductus arteriosus, pulmonary emphysema, left ventricular failure, or congenital anomalies, may be sufficient to generate endocardial lesions on the ventricular surfaces of the pulmonic valves or the atrial surfaces of the tricuspid valve. Endocarditis of the tricuspid valve is associated with high right ventricular pressures secondary to pulmonic stenosis or pulmonary arterial hypertension. Satellite Lesions A high velocity stream can produce effects at a distance from the orifice, as noted in several sections above. Such a stream through an insufficient mitral valve may impinge upon and roughen an adjacent segment of atrium. producing a MacCallum patch. Similar involvement of adjacent areas is seen in aortic insufficiency where the primary lesion is on the ventricular surfaces of the aortic leaflets. The high velocity regurgitant flow, which streams in the direction of the chordae tendineae and their muscular attachments, may generate local mechanical disturbances that can open the way to rupture of these guy lines of the mitral valve leaflets (fig. 3). The rush of blood from an aortic insufficiency may also generate pseudovalvular formations.51 When the jet impinges on the wall of the aorta, a ductus, or the pulmonary artery, local aneurysms may become evident.24 Endocarditis in Previously Normal Structures Any distortion of a valve that permits insufficiency of the proper degree may serve as a nidus for infective endocarditis.52 5 Even when the valve is histologically normal, regurgitation because of high velocity flow can provide the mechanical basis for an infective process. Koletsky54 reported five cases of combined syphilitic heart disease and bacterial ,;;J4 )1'A I'd 2D H) Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 cardial infaretion with rupture of a papillary muscle. The valvular insufficieney that resulted from the abnorimal positiont of the ni: tral leaflet provided a basis for endocarditie in;volvement of the presumptivelv previously normal atrial surfaces of the mitral valves, Secondary Endocarditis. Somrie evidence in dicates that a primary infective endocarditis miav lead to involvement of a second site. This is documented in a number of eases of arteriivenous enidarteritis: infected fistuilas tenid to enilarge with time and the flow throulgl thli communication resuilts in an irnicreased strolwe outtput and cardiae dilatation'. stt-l An aortle diastolic murmu-lr, indicatinog valv fIar in sufficiency, may then appear in association Ax ith: involvement of the aoirtic valve, whichl mavI showv progression even after remova] of 4heb peripheral fistula.34-31 Surgical Approaches Figure 3 )epresentatiaon of the high reiocit, streams in. mnitr((l and aortic insuffieieneij ancn siteUs of endocardtitL iesion.. Arrow at left indiecates a h igh arteri!l p,ressure th(ut qene rates regcurgitcmt flow, from. r aortit to rentricle. The ena contracta and the endocarditic lesions appear at the reentricula r sturface of the ciortic vocles. The straom through the iiieonipetent caortic valcle mai produee lesionas on the rhordae tendineae of the aortic leaf of the mitrafl oalie. If the maitral caires caniot seat properlq71 during ventricular s/ystole, the reqitrgitant stream (arrow at riqht) irill pass to the sin k o f the left aftrium and endocarditis wicill tend to bethe atrial surfacie of the mitrl enrgrfted t n(-,ulocardiutm i;n line i'ithi the revale. The aal on conic urqrita nt str? m aij a shoir fibrous re tio n. etndocarditis; in one of these, the syphilitic as confined to the root of the aorta proeess w and the aeute bacterial endocarditis parexitlv superinmposed oni a was ap- normal aortic valve. Another instructive case, without prevrious pathology of the -valve, was reported bv Lehmann55 in a patient who suffered a nyo- Success in eliminating en darteritis asso eiated with systemic arteriovenous fistulas.3 together with improvements in anesthesia, the sulfonamnide drugs, and transfusions, opened the possibility 25 years ago that ligation of a duetus might affect the theni inenirable endarteritides. Early workers57 who attempted this approach feared that even if the ligation were successful, vegetations persisting in thle stumps of the duetus would continue to serv%e as a source of emboli and bacteremnia. After the first successful ligation of an uninfeeted patent ductus arteriosus by Gross and Hubbard,58 Touroff and Vesell59, 60 ligated the ductus in several eases of endoearditis and aehieved prompt recovery from the infection} AIore recently, surgical cure of endocarditis by means of open-heart surgery of a ventrienlar septal defect has been achievedc.1 The blood stream is freed of microorganisms immediatelv after closure of the defect, eveen though bacteria may persist in the lesion andl in contact with the blood. The prompt recovery of these patients and the absenee of recurrenee. emphasize the role of hydraulie factors iin the genesis aind persistence of en]doearditis. since congenital abnormalities of the vessel wall may be expected to persist despite occlusion of the abnormal openinga Circulation, Volume XXVI!.January 1196,7 BLOOD VELOCITY AND ENDOCARDITIS Postsurgical Endocarditis. While surgical technics have contributed to the treatment of endocarditis, they have also led to this infection in patients subjected to heart surgery.61-65 For example, surgically induced narrowing of the aorta, as at the site of placement of a Hufnagel valve, has been shown to be the seat of endarteritis.66 Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 The Absence of Endocarditis If anatomic abnormalities played a role in the pathogenesis of endocarditis, this condition might be expected to be as common at atrial septal defects and at larger ventricular septal defects or widely patent ductus arteriosus, as it is when the communications are small. Endocarditis, however, does not occur in congenital defects that have a cross section area large enough to abolish the pressure gradient. A survey of available data indicates that endocarditis is associated with shunts of relatively small volume. The relatively high incidence of endocarditis in patients with small ventricular septal defects contrasts sharply with the rarity of the disease when the defect is large. Such a conclusion can be drawn from the data of Wood,67 which attributed the causes of death in 53 necropsied cases of pulmonary hypertension with a shunt to the left (Eisenmenger's complex) to hemoptysis, cardiac failure, fibrillation, or surgical intervention. It is of particular interest that no mention is made of bacterial endocarditis in any of these cases. Berger et al.40 and others failed to note endocarditis in patients with Eisenmenger's complex. Dailey et al.68 have recently noted the absence of endocarditis in patent ductus arteriosus with reversed shunt. The reduction in pressure gradient between the two ventricles with its reduced tendeney to high velocity flow can account for the absence of endocarditis in such patients. This fact also challenges the direct pathogenic contribution of anatomic congenital abnormalities in the production of endocarditis. Atrial Septal Defect. Even though atrial septal defeet69' 70 is a most common congenital cardiac malformation, bacterial endocarditis rarely complicates it. This absence of endoCirctlation, Volume XXVII, January 1963 25 carditis may result because the thin-walled atria do not generate the high pressure gradient required for the development of the process. Further, the defect is usually quite large or multiple. Shunting of a large volume of blood through an atrial septal defect increases flow through other orifices and may thereby contribute to an increased susceptibility at another site. Thus, in a few cases of endocarditis that have been reported in patients with atrial septal defect, the infective process has involved the pulmonic, tricuspid, or mitral valves,'1 while the atrial defect itself was not infected. Aorta. Attention may be called to the absence of endocarditis in the aorta where high pressures and pulses abound. Even when the aortic and arterial walls are clearly damaged, as in severe atherosclerosis, these abnormal sites do not support endocarditic lesions. To date, no report has appeared of endarteritis at an aortic or arterial site subsequent to retrograde catheterization or arterial puncture. Veins. It is worthy of note that lesions like endocarditis do not occur in veins or their valves even though these often serve as the seats of inflammatory and thrombotic processes. The venous connection of an arteriovenous fistula may show involvement, but the presence of a high pressure gradient abrogates the normal characteristics of flow through veins. Reduced Cardiac Output. When the cardiac index is reduced, the tendency to endocarditis is diminished. Thus, many clinicians have commented that endocarditis is relatively uncommon in chronic heart failure, especially in mitral stenosis with atrial fibrillation. This may be another instance where a weakened heart or a reduced stroke output prevents the development of the high velocities necessary for the induction and persistence of the endocarditic process. On the other hand, endocarditis often precipitates acute failure by progressive damage to valves. The apparent absence of endocarditis in myxedema may also be noted.72 Spontaneous Heating. Prior to the advent of specific therapy, oeeasional spontaneous RODBARD -?. iz ,..dw Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 cUIrT's Of enidocarditis were reported. Eveir tlhouo1i somne of these may have represented diagnostic errors, others were probably true eases of infective endocarditis.j3, 74 Olesen and Fabricius,75 for example, described a patient with gonococcal endocarditis who continued to have pulmionary valvular regurgitation for 2-7 years, as indicated by clinical history and (atheterization data. Morhous76 has doeuInelite(l a case of endocarditis of a patenit duetus arteriosus that cleared spontaneouslv and in which the characteristic murmur disappeared. Spontaneous healing may result from 1losure of the orifice as a result of continued iHAtinial proliferation, with the elimination of the high velocity jet. The tenidenye to proglressive closure of stenotic lesions has been demoonstrated in experimental studies.2i More recentlyv catheterization data have beeome aivalable to indicate that smiall orifices, as i veitricular septal defects and patent ductus arteriosusn may close in the natural history o)f the condition.77 This belief is supported an(I I illistrated by the cures noted above that followed surgical occlusion of infected fistu las. It is also gradually becoming appreciated tlbat the static anatomic lesion exposed at autopsy whieh formis the basis for pathologi( liagnosis and classification of the ease, does hiot necessarily reflect the dynainically changinig picture of the lesioni. Tllus, orifices may increase in size relative to the chambers that tlhey connect,24 or they m-ay unidergo stenotic processes that mnay lead to physiologic or even2 anatomic closure."2 When progressive enlargenment of an orifice takes )lace, the augmented flow places an iinereased ]oad on the heart and this miay lead to .:ongestive failure. As the orifice is eii ltir-ed, however the hemodynamic conditions necessary for the persistenee of infective ei(docarditis mnay vanish and the process is 'eured " even though the cardiac failure mnay ensu'e. that drives blood at high velocities through a narrow orifice coaretation, ductus arteriosus ventricular septal defect, insufficient aortic or mitral valve) into a low pressure sink (pulnmonary artery, atrium). The high velocity of the streamii iminediately beyoond the orifice is associated with a marked drop in lateral pressure, and perfusion of the intimua of this segment of the vessel is reduced: this is also the characteristic site of the inlfective process. The inifrequeiney of peripheral niidatioin and abscess formation despite recnrrent bacteremia, and the rapid clearing after surgical correctioln of high velocitv jets, as in ligation of a patent ductus arteriosus, are in accord with the hvdrody namie concept. An analysis of the literature and experimental studies of the effects of flow on deforminable channels and onl bacterial growth anid chemical reactions are cited iin support of this concept. 1. 2. 3. 4. 5. 6. 7. 8. Summary and Conclusions Exainination of the problemr of inifective a hvdrodynamic point of view indicates that it is associated with a high p)eess-Lre source (aorta, left ventriele. etc. ti11docarditis from 9. 10. References MENDELSOIN, C. A., CARUE, A., KATZ, L. N., AND BRANS, W. A.: Long-term outlook for healed subacute bacterial endocarditis. J.A.M.A. 160: 437, 1956. FOGEL, R. I., SHOSHKES, -A.-, ANTD APPLEBAUM, 1. IL.: Bacterial endocarditis. Review of eases at New-ark Beth Israel Hospital between 1948. and 1938. J. Neveark Beth Israel Hospital 11 132, 1-960. DENTON, C., PAPPAs, E. G., UIRICCHIO, J. G.. GOLDBERG, H., AND LIKOFF, WA.: Bacterial endocarditis following surgery. Circulation 5: 525, 1957. BLUMENTHAL, S., GRIFFITHS, S. P., AND IORGAN, B. C.: Bacterial endocarditis in children with heart disease. Pediatrics 26: 993, 1960. HEINS, H. L., JR., AND LINDE, L. M.: Bacterial endocarditis after surgery for congenital heart disease. New England J. Med. 263: 65, 1960. GRoss, L.: The Blood Supply to the Heart. New York, Paul B. Hoeber, 1921. GRANT, R. T., WOOD, J. E., AND JONES, T. D.: Healed valve irregularities in relationi to subacute bacterial endocarditis. Heart 14: 247, 1928. MORGAN, W. L., AND BLAND, E. F.: Bacterial endoearditis in the antibiotic era with special reference to the later complications. Circulation 19: 753, 1959. JAWETZ, E.: The " tough case" of bacterial endocarditis. Circulation 20: 430, 1959. TuiTULTY, P. A.: The management of bacterial Ciretlatiovn. Volume XXVII, January 1962 2-7 BLOOD VELOCITY AND ENDOCARDITiS Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 endocarditis. Arch. Int. Med. 105: 126, 1960. 11. COHEN, S.: Staphylococcal infections of the heart. Circulation 20: 96, 1959. 12. KOENIG, M. G., AND KAYE, D.: Enterococcal endocarditis. Report of 19 cases with long-term follow-up data. New England J. Med. 264: 257, 1961. 13. ROSENOW, E. G.: Serologic specificity of streptococei having elective localizing power as isolated in various diseases of man. J. Infect. Dis. 45: 331, 1928. 14. HELD, I. W., AND LIEBERSON, A.: Pathogenesis of subacute bacterial endocarditis. Am. Heart J. 25: 478, 1943. 15. HAMBURGER, M., KAPLAN, S., AND WALKER, W. F.: Subacute bacterial endocarditis caused by penicillin-sensitive streptococei. J.A.M. A. 175: 554, 1961. 16. ALLEN, A. C.: Mechanism of localization of vegetations of endocarditis. Arch. Path. 27: 399, 1939. 17. ALLEN, A. C.: Nature of vegetations of bacterial endocarditis. Arch. Path. 27: 661, 1939. 18. ALLEN, A. C.: A case of bacterial endocarditis illustrating the mechanism of localization and the nature of vegetations. Am. Heart J. 21: 667, 1941. 19. HIGHMAN, B., AND ALTMAN, P. D.: Effects of altitude and cobalt, polycythemia, hypoxia, and cortisone on susceptibility of rats to endocarditis. Circulation Research 3: 351, 1955. 20. GILOHRIST, A. R., AND MERCER, W.: Infective endocarditis of the pulmonary artery. Lancet 2: 267, 1947. 21. HADPIELD, G., AND GARROD, L. P.: Recent Advances in Pathology. Ed. 5. Philadelphia Blakiston, 1947, p. 363. 22. LEPESCHKIN, E.: On the relation between the site of valvular involvement in endocarditis and blood pressure resting on the valve. Am. J. M. Sc. 224: 318, 1952. 23. RODBARD, S.: Vascular modifications induced by flow. Am. Heart J. 51: 926, 1956. 24. RODBARD, S.: Physics of blood flow. In Blood Vessels and Lymphatics. D. I. Abramson, Ed., New York, Academic Press, 1962, p. 31. 25. RODBARD, S., AND JOHNSON, A. C.: Deposition of flowborne materials on vessel walls. Circulation Research 11: 664, 1962. 26. RODBARD, S.: Physical factors in the progression of stenotic vascular lesions. Circulation 17: 410, 1958. 27. RODBARD, S.: Physical forces and the vascular lining. Ann. Int. Med. 50: 1339, 1959. 28. ABBOTT, M.: On the incidence of bacterial inflammatory processes in cardiovascular defects and on malformed semilunar cusps. Ann. Clin. Med. 4: 198, 1925. 29. STEINBERG, I., AND FINBY, N.: Congenital aneuCirculation, Volume XXVII, January 1963 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. rysm of the right aortic sinus associated] with coarctation of the aorta and subacute bacterial endocarditis. New England J. Med. 253: 549, 1955. MACKENZIE, G. M.: Coaretation of aorta withi staphylococcus albus aortitis. Am. J. M. Sc. 174: 87, 1927. POYNTON, F. J., AND SHELDON, W. P. H.: Coaretation of the aorta with ulcerative aortitis. Arch. Dis. Child. 3: 191, 1928. LIPTON, S., AND MILLER, H.: Streptococcus viridans septicemia. Subacute bacterial endarteritis of an arteriovenous aneurysm. J.A.M.A. 126: 766, 1944. HAMMAN, L., AND REINHOEP, W. F., JR.: Subacute streptococcus viridans septicemia cured by excision of an arteriovenous aneurysm of the external iliac artery and vein. Bull. Johns Hopkins Hosp. 57: 219, 1935. HECKLER, G. B., AND TIKELLIS, I. T.: Acquired arteriovenous fistula with subacute bacterial endocarditis and endarteritis. J.A.M.A. 150: 1301, 1952. GOWDRY, R. A., MARTIN, S. P., KERBY, G. P., AND SEALY, W. C.: Pathogenesis of valvular endocarditis. I. Production of acute cardiac valvular lesions by large arteriovenous shunt. II. Effects of arteriovenous shunt on removal of bacteria from blood stream. Arch. Surg. 65: 271, 1952. CURTIN, J. A., PETERSDORP, R. G., AND BENNETT, J. L., JR.: Acquired arteriovenous fistula complicated by pseudomonas aeruginosa endarteritis and endocarditis. Bull. Johns Hopkins Hosp. 101: 140, 1957. ABBOTT, M.: Atlas of Congenital Cardiac Disease. New York, American Heart Association, 1936. TERPLAN, K.: Mykotisches aneurysma des Stammes der Pulmonalarterie mit endocarditis des offenen Ductus Botalli bei einen Falls von Endocarditis lenta. Med. Klin. 20: 1331, 1924. KEYS, A., AND SHAPIRO, M. 5.: Patency of the ductus arteriosus in adults. Am. Heart J. 25: 158, 1943. BERGER, M., FERGUSON, C., AND IHENRY, J. C.: Patent ductus arteriosus in adult life. J. Pediatrics 56: 800, 1960. JICK, H., KASARJIAN, P. J., AND BARSKY, M.: Rupture of aneurysm of aortic sinus of Valsalva, associated with acute bacterial endocarditis. Circulation 19: 745, 1959. HALL, B., AND PICKARD, S. D.: Unsuspected rupture of aortic sinus aneurysm into the right atrium. Associated coaretation of aorta, bicuspid aortic valve, aortic stenosis, and bacterial endocarditis. Am. J. Cardiol. 3: 404, 1959. BRIGDEN, W., AND LEATHAM, A.: Mitral incompetence. Brit. Heart J. 15: 55, 1953. 28 I) Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 44. tUxrTEn, J..C, ONGeLrY I'. A., -i xxvWAC xi AN, 11., MTASSELL, B3. F., ANI) NADASS, A. S.: Bacterial enidocarditis in ehibirca xeiwiti hieart dIisease. Pediatrics 22: 706OC, 1958. 45. KERR, A., JR.: Subacute I3acteriial K"ndocarditis. Springfield, Illiniois, Cliarles C homias, 1-955. t6. LEWIS,-, T., AN-D GRANT, B,. T.: Observatioas relatinig to subacute inifeetix e enidocairditis. Heart, 10: 21, 1923. 47. IODB3ARD, S., BROWNx, FX. xAD l{ATZ, L. -N. The puhunonarv arte-ria-l pressure1(. A\mi. TTeart J. 38: 863, 1949. 4S. PitN . C., EDWARIDS, J. EL.,S f F C. IL.. X1)GEE ACr, J1. E. Bight sided bacterial, eridoCa-rdlitis arid endarteritis. A\ cliniical and pathi ologi-c study. Am. 3. MXed. 24: 98, 19-58. 49. KIRCeSTrax, R. L, ANDa SIDRAXNSKY, T1.: Mv cotic en-doca.rditis of the tricuspid v aixve due to aspergullis flavus. Arch. Path. 62: 1-03, 1956. 50. GELFE\MAN-\, R., AXXI) LEviNE, A.. .: Tire incidence of ac,ute anid sifbacute li.tcteriil andoca rditis al conlgenlital lieai7t; lisenl"e. Awl at .1 S. SC. 204: 324, 1942. 51. PAXLOWVSKT, I-T. : En lokardiaile Psetidokiappenbilduaiigen- des Iiiikeai Ventrikels bei- MNitraisteniose. -vi relioxi' Arc(h. pliatli. Anatif 33: 13,1960. 52. ACEVES, S., ErLInEL-, A., x.I) GoN-\ZXLT}PZ,M. Endoca rditi s bacteria.na desa rrollada sobrte aoititis sifilitica. A-rch. Ilast. Ca-rdiol. 'Mexico 27: 23 1, 1-957. NI WHITE, W3.IA LSIT, B. 3., CONN!--\ERTY, 11. AYD T). ID.: Coiigenital. subau,irtic Ateiosis wxitli detoriunitv of the a.or-ta(- valve. \Atm FlendrIT. 25: 837, 1943. 5-4. KowrTSKxY, S-.: Sy pfiilitic Cardioxvascular di-sea,se and bacterial eiidoearditis, A\ro. TTeart 1. 23: 208, 1942). I.1.T.: Subactute bacterial endoca-rditisof the mitral valv e previously rendered ineoati peteant by infairction of thje papilla.rv munsb anld shorteniing of the cliordae tenldineacw. Anni. 55. LEHMAIN-N, hit. 56i. le. 9: 1-58(7, 1935-36. 1IALLEIi~, C. AN., Li IsND TIMM, !.1 BZ. B., AX) Occurrence of eliilocarditis in vtalvular de.formiities in dlogs wiith- AV fistuti,,. Aaai. 8urg. 132: '5771, 1-950. 5)7. GCAYBIxEnL , A., STRIE.DER, J. \V., _ND BONLEI.H.: Ani attemipt to obliterate the pateni ductti-is :itrteriosus in a patient wNithi Subacute b)actericil. eiidocardlitis. Amii. Heart .1. 15: 62-11 -AT. B. 1-938. .58. (Gao-sS, B. E., AND 1-1B AnRxa. J1 P.: Sur-gical li-ga tiomi of a patenlt tliietiis arteriosus. Report oir fir-st successfuil ca-se. J.AM'\TA. 112: 7129, 1939. 5.Toifaoi i-, A.. S. WI.. AND VESEiLL, H.: Experieiwee iii the surgical tr-eatmienit of subacute sti-eptoc0Occus ridaris eii tinrteritis coalI)plicatiiig patenit dudaus arrterio,siss. J. Thoraciie Suirg. 10: 559, 1940, 60 lrot 110FF A.. S. AV.: Thte results~of smir BD gicaollI mienit of patencey of the ductuets nirteriosiis ecotti pdicated by subacute bacterial eiidlarteriti s \fitt Hear-t J. 25: 187-, 1943. 61l. RAY, J. H., BER-NTSTEIN1, S., EINTSTEIN, 1), XI FBIDDLEr, M.L: Sar-gical careo of Canliida Ath it,m endocaiditis u ith open-heart surgery. Neii Eng9" lanid J. MTNed. 264: 907, 1.961. 6-2. JOHNTsoN, A. C.: Bacterial end(ocarditis follouring toitral v n1xvilotouny. Canad. M. XA, T. 79: 997. 19 58. 63). TEITEL, M1., A.ND FLOEM AXN, A. L.: Post operatixve 64. 6-5. 66. 67. 65. 69. e-ndocardlitis due to pseudomonas. a eruginosat J.A.-M.A. 172: 3219, 1960. KELIer, J. V., X_ND THnoNrSoi-, N. B., Jr.. Ba terial enidocarditis comiplicating repair ofa ventricular septa]l defect. Nexw Eniglanid J1. fetd. 265: 12450, 1961. LORD, J. W., JR., xTAPARATO, A. M., TTiCKET., A., X-ND Doyiux, E. F.: Ead(ocal-rditis eomplicatiIlg open-heart sur-ger-v Circul'ation 23: 489, 1961. KLEINMAN, L. A.: Recurrenit endocarditiss anid niortitis wxith rupture of aorta. Report of a ease xxitlt death 4 years after insertiot-a of a Huifnagel xalve. J.A.MLA. 173: 38, 1960t. W"OOD, P.: The Eisenmienger syai-dronme or pu1. nionary livipertenisoion -x itfi rexversetd shunjt. Br it'. MT. J. 2: 701, 19158. 1)AILEY, F. 11., GEN-OVESE, P. 1)., AND BunEITux.E R. H.: Patentt (ductus arterios-us wxithi reversa-l of floxv iii adults. Anni. Thit. Mciid. 56: 865 , 1962). BIEDFORD, P). C., PAPP, C., XAID PARIKIXNSON, J.: Atrial septtal defect. Brit. [let ut .1. 2: 37 1941. 70. (GIFITuruS , S. P. Blacterial undi(ocarditis. atsocia,ted wixit -atrial septal diefect of tlhe ostiatt secarIduir tx -pe. Am. Heart J.. 61: 543, 1961l. 71. GEIGicER, A. .1., AX\Xi) AN-DERSONK, hi. C. LTAit cii bacher 's syiitron-e coaiplicated 1y-x c iteItt terial ciudocarditis. Report of a eise dli:tgilostl during life. Ami. hIeart J. 33: 2410, 1947'. 2. BRM X, D. A.: Cardiovascutlar comiplications of myxedema. J. L-aiicet 80: 3300, 1960. 7d. NIT_P PER,N. G., BLERCHELL, II1. -B., AN'D Ei)WA Ri)', JI. E. MTitral. insufficiencey in healed uriirecogniizedl bacteriacl en-doca rditis. P r-oe. Sta ff M-eet., MTayo Cliii. 31: 659, 19-56. 74. PRF,DE,MD (TLXAP P FR, Ai1., XXIDM)LR F S, GY. B.. I BA ., Eatdocarditis en used 1)v iiiie'rococe us pha rynlgis -dic is, recoxerl after treatmneit wxitli hiepairi-ii rind sulfapyridinie. Amn. Hleart J. 25: .547, 1943). a-. OLESENK, K. H1., ANID FABEICIUS, J.: PuAM1monarx-alvula r regurgitation daring 27' years a-fter~ geiiococen Il eritloca rditis. Case xxitli cntheteriLzti tioii dlata. Aiu. Herart J. 52: 791, 195-6. 7-6. MoaRHUos, E. J1.: Subacute bacterial eindocarditis of a pateuit daicturs ar-teriosuus, Virgini:i Medical MTonthlb 85: 565, 1958. NADAs, A. S. -Bacterial eiidocarditis in chiildrenixith h-eart disease. Pediatrics 22: 706, 1958, C'renTation, T"lur XX H!! rat oriy ti Blood Velocity and Endocarditis SIMON RODBARD Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017 Circulation. 1963;27:18-28 doi: 10.1161/01.CIR.27.1.18 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1963 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/27/1/18.citation Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. 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