EXPERIMENTAL GALLOP RHYTHM IN SHEEP WITH GOUSIEKTE: CORRELATION OF CHANGES IN AMPLITUDE WITH HAEMODYNAMIC PARAMETERS

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1 Onderstepoort J. vet. Res., 55, (1988) XPRIMTAL GALLOP RHYTHM I SHP WITH GOUSIKT: CORRLATIO OF CHAGS I AMPLITUD WITH HAMODYAMIC PARAMTRS P. J. PRTORIUso>,J. M. VAROOY< 1 >,J. C. J. VARYSSil andj. P. MIAAR< 2 > ABSTRACT PRTORIUS, P. J., VA ROOY, J. M., VA RYSS, J. C. J. & MIAAR, J. P., xperimental gallop rhythm in sheep with Gousiekte: orrelation of hanges in amplitude with haemodynami parameters. Onderstepoort Journal of Veterinary Researh, 55, (1988) To investigate the orrelation of haemodynami parameters with the intensity of the gallop sound (S 3 ), use was made of right heart atheterization with a Swn-Ganz atheter to measure the pulmonary and right atrial pressures. The ardia output was determined with the thermodilution method. A radioardiogram was obtained after a bolus injetion of tehnetium pertehnetate. The ardiopulmonary flow-index was obtained from the simultaneous reordings of the radioardiogram and an eletroardiogram. With the haemodynami parameters, heart sounds were reorded simultaneously and externally with a mirophone. ight Merino sheep were dosed with dried Pahystigma pygmaeum (Shltr) Robyns plant material through rumen fistulas until the linial symptoms of heart failure suh as gallop sounds, systoli murmurs and haemodynarni symptoms as well as inreases in end diastoli pressure and dereases in stroke volume, appeared. After the appearane of the symptoms the sheep were treated symptomatially to delay the development of the ardiomyopathy. The hanges in haemodynami parameters before and after treatment were used and orrelated with the intensity of the gallop sounds on a 6 point riterium sale. The results in brief show that, for gallop sound intensities between and 6 on the riterium sale, most of the haemodynami parameters orrelate with the intensity of the gallop sounds, exept the ardia output, ardiopulmonary blood volume and the systemi and pulmonary vasular resistanes. The haemodynami parameters orrelate better with the intensities of the gallop rhythm between and 3. It is evident from this study that the model of heart failure in sheep is useful to study heart sounds and may also be valuable in the study of the genesis of the gallop sound. ITRODUCTIO Ventriular gallop sounds despite remarkable avanes in the understanng of ardia physiology, are still a muh debated subjet. Beause of the onspiuousness of abnormal heart sounds, the linial orrelation and physiologial meaning are important. A review of the literature on gallop sounds revealed that the physiologial and linial aspets of gallop sounds are omplex and still to a great extent unknown (Van de Werf, Minten, Carmeliet, De Geest & Kesteloot, 1984; Shaver, Reddy, Alvares & Salemi, 1987; Ozawa, Smith & Craige, 1983 a and b). Although gallop sounds are an indiator of ardia failure, the relation between haemodynami parameters, pathologial hanges and gallop sounds are not lear. Funtional and strutural aspets of the ventriular wall, hanges in blood flow, hanges in pre- and afterload, even in mehanial effets as a ause of ardia movement may play a role in the development of pathologial and physiologial (S3) sounds. It is important to develop and ev.aluate e::perimental models for investigating hypothesis regardmg gallop sounds. In this study ardia failure was evoked experimentally in sheep, and haemodynami hanges were manipulated and orrelated with gallop sounds. The usefulness of this anintal model as well as the relation between haemodynami parameters and the intensity and nature ofthe gallop sounds, were investigated. MATRIALS AD MTHODS The experimental proedures for this study onsisted of induing a ardiomyopathy (gousiekte) after dosing sheep daily through ruminal fistulas with 9-13 gmlkg body mass dried Pahystigma pygmaeum (Shltr) Robyns plant material (Theiler, Du Toit & Mithell, (I) Department of Physiology, Pothefstroom University for CH, Pothefstroom, Republi of South Afria <Z> Animal and Dairy Siene Researh Institute, Private Bag X2, Irene, Republi of South Afria Reeived 5 September 198&--ditor 1923). The method of induing experimental ardia failure in sheep is desribed in previous publiations (Pretorius & Terblane, 1967; Pretorius, Terblanhe, Van der Walt & Van Ryssen, 1973; Vander Walt, Van Rooyen, Cilliers, Van Ryssen & Van Aarde, 1981; Kellerman, Coetzer & aude, 1988). From these results the following were onluded: This experimental ardia failure is a typial ongestive heart failure haraterized by ardia dilation, systoli murmurs, typial haemodynami symptoms suh as inreases in end diastoli pressure and dereases in stroke volume (SV) and the development of gallop sounds. About 2 weeks before the experimental proedures started, 8 adult Merino sheep were anaesthetised with pentobarbital sodium and subutaneous arterial loops were surgially made from the arotid arteries and fistulas were implanted in the rumens ofthe sheep. The sheep were dosed for 7 to 28 days with plant material until the gallop rhythm appeared. The sheep were then treated symptomatially and use was made of siliv inotropi agents, suh as dobutamine hydrohlonde, m doses of,497-15,92 JLg/kg!min with a mean d?se of 8,?1 g(kg!min and vasodilators, suh as sodium mtroprusstde, m doses of,67-l,44 JLg/kg!min with a mean dose of 1,6 JLg/kg!min. In some ases furosemide3, was injeted intravenously in ombination with sodium nitroprusside in doses of 2 or 4 mg. The sheep were treated with the drugs to delay the development of the ardiomyopathy and to ensure that all sheep would show gallop rhythms. All the haemodynami reordings were made n unanaesthetised anintals after they were suspended m a normal upright position in a anvas radle. The heart sounds were reorded with a mirophone 4 and amplifier on a hart reorder. The mirophone was positioned and the sensitivity and filter hosen to reord the different omponents of the first (S 1 ) and seond (S 2 ) 1 "Dobutrex", li Lilly (SA) Pty Ltd 1 " Hypoten' ', Covan Pharmaeutials Rosslyn, RSA 3 "Lasix", Hoehst Pharmaeutials, RSA 4 lema MT

2 XPRIMTAL GALLOP RHYTHM I SHP WITH GOUSIKT heart sounds. The amplitudes of the gallop sounds were measured and quantified aording to a 6 point riterium sale in the following manner: o gallop (S 3 or S 4 ) 5 visible 1 Unertain, very small amplitude, intermittent 2 Very small amplitude, smaller than S 2, onstant 3 Small amplitude (same order as S 2 ), learly visible 4 Medium amplitude 5 Amplitude nearly the amplitude of S 1 6 Amplitude greater than sl In all the experiments a 7F-11 em Swan-Ganz double lumen thermodilution atheter was positioned in the pulmonary artery after perutaneous jugular vein atheterization. Cardia output (CO) was determined by using the thermodilution tehnique with a ardia output omputer. 6 The ardiopulmonary flow-index (CPFI) whih is the quotient of the ardiopulmonary transit time and the period of the heart beat, was determined from the simultaneous reording of a radioardiogram and an CG (Van der Walt et al., 1981 ). The radioardiogram was obtained after the injetion of a bolus of,74 GBq-,185 GBq 99m-Tehnetium pertehnetate through the proximal opening of the Swan-Ganz atheter. The ardiopulmonary blood volume (CPBV) was alulated as the produt of the CPFI and the stroke volume (SV) (Van der Walt et al., 1981) whih was determind with thermodilution. The distending pulmonary pressure (DPP) was alulated from the mean pulmonary arterial pressure (PAP) and the pulmonary apillary wedge pressure (PCWP) by averaging the 2 pressures, (PAP + PCWP)/2. The mean arterial pressure (MAP) was determined through the arterial loop with a 21 needle. The systemi (SVR) and pulmonary (PVR) vasular resistanes, as well as the left ventriular stroke work (LVSW), were alulated from the haemodynami parameters whih were measured diretly. The results obtained after treatment were analysed with a BMDP-8-D-analysis programme (Dixon, 1983) to 6, 'i3 5,.., 4,. 2.., 3, 2, o--o PCWP..._.opp L>----,::, CPBV -RAP o---o CPFI FIG. I The relationship of pulmonary apillary wedge pressure (PCWP), distending pulmonary pressure (DPP), ardiopulmonary blood volume (CPBV), right atrial pressure (RAP) and the ardiopulmonary flow index (CPFI) with the intensity of the gallop rhythm ' s. sound is seen as a low intensity low frequeny vibration with probably an atrial systoli origin. S 4 sounds are found in sheep with heart failure with low heart rates. With higher heart rates S 3 and S 4 an summate 6 dwards model 952A show the orrelation between haemodynarni parameters and the gallop rhythm. A BMDP 9R (analysis of variane programme) (Dixon, 1983) was also used on the data to show whih haemodynarni parameters orrelate 1,8 PVR I,6 'i3.., 1,4 I,2. 1, 2..,,8,6,4 --svr o----o LVSW, FIG. 2 Th.: relationship of the pulmonary vasular (PVR) systemi vasular resistane (SVR) and left ventriular stroke work (L VSW) with the intensity of the gallop rhythm 2, o--o SV I,9 --MAP Cr o I,8.HR : I,7 Q) I,6 I,5 1,4. 1,3 I,2 2.., 1,1 1,,9,8,7,6, FIG. 3 The relationship of the stroke volume (SV), mean arterial pressure (MAP), ardia output (CO) and heart rate (HR) with the intensity of the gallop rhythm 2, o--o Pdp --Psp :.., I,8 er----e. PAP I,6. 1,4 2 Q) I,2 1,, FIG. 4 The relationship of the pulmonary diastoli (Pdp), pulmonary systoli (Psp) and mean pulmonary artery pressure (PAP) with the intensity of the gallop rhythm 222

3 -r- Vl > I I -l >.. > Vl I I r-..,. ' ' ;:2; I I r- '..,. > Ill.. u.. 1..,. ;> Cl l..,. r- ' r-.. a:.. > Vl "' $ ' I I :::!: : u I. I 1 \ ' :X: r- \ "'..,.... j., ::;.!:! I IS 9 = = 8 8.!2 ';:l.!! u u!::: I q "'..,. :q "' I I - I I I :.!! = I 8.!2.!! u P. J. PRfORIUS,J. M. VAROOY,J. C.J. VARYSS &J.P. MIAAR best with the gallop rhythm. Aording to Pearson's8rodut, moment orrelation oeffiient, values above,32 show signifiant orrelations of 95 % between the gallop rhythm and the haemodynami parameters. RsULTS After the development of the ardiomyopathy in 8 sheep the intensity of the gallop sound, whih is a linial symptom of the disease in the later stage of heart failure, was orrelated with haemodynarni parameters obtained after right heart atheterization. The results show that ertain haemodynarni onditions have an influene on the intensity of the gallop rhythm. From Fig. 1 it is lear that an inrease in right atrial pressure (RAP) has a diret relationship with the intensity of the gallop rhythm up to 4 on the riterium sale. The RAP starts dereasing with an inrease in intensity above 4. The dereases in RAP an probably be related to the treatment of the sheep whih started at that stage. The CPFI, PCWP, DPP and the CPBV also show relationships with the intensity of the gallop rhythm. In Fig. 2 it is indiated that with a derease in the L VSW and SVR the intensity of the gallop rhythm inreased. With an inrease in PVR the intensity of the gallop also inreased to 3 on the riterium sale. In Fig. 3 it is indiated that with a derease in the CO, MAP and the SV as a result of the development of heart failure, the intensity of the gallop rhythm inreased up to 6 on the riterium sale. With an inrease in HR as a result of ompensation, the intensity also inreases. From Fig. 4 it is evident that the intensity of the gallop rhythm inreased with an inrease in the pulmonary pressures. The pulmonary pressures inreased probably as a result of ongestion of the lungs. The above figures indiate orrelations between the haemodynarni parameters measured and the intensity of the gallop rhythm. From statistial analysis of the haemodynarni data and the intensity of the allop rhythm it is evident from Table 1 a that for intensities of the gallop rhythm between and 6 the HR (,68, P<,5), LVSW (-,58, P<,5) RAP (,55, P<,5), PCWP (,53, P<,5), SV (-,5, P<,5), DPP (,49, P<,5), Psp (,47, P<,5), MAP (-,47, P<,5), PAP (,46, P<,5), Pdp (,45, P<,5) and the CPFI (,37, P<,5) show signifiant orrelations with the gallop rhythm. The CO, CPBV, SVR and the PVR did not show any orrelation with the gallop rhythm for intensities between and 6. It is evident from Table 1b for intensities between and 3 that the LVSW (-,71, P<,5), HR (,69, P<,5), RAP (,67, P<,5), MAP (-,66, P<,5), DPP (,65, P<,5), PCWP (,64, P<,5), SV (-,61, P<,5), PAP (,58, P<,5), Pdp (,57, P<,5), Psp (,56, P<,5), CPFI (,49, P<,5) and the CPBV (,42, P<,5) orrelate signifiantly with the gallop rhythm. For intensities between and 3 there is no signifiant orrelation between the CO, SVR and the PVR with the gallop rhythm. For gallop rhythm intensities between 4 and 6 there is no orrelation between most of the parameters and the gallop rhythm, although the PCWP (,4, P<,5), DPP (,51, P<,5) and the SVR (,43, P<,5) show signifiant orrelations with the gallop rhythm. DISCUSSIO The aim of this study was to show orrelations between the intensity of the pathologial S 3 sound and 223

4 XPRIMTAL GALLOP RHYTHM I SHP WITH GOUSIKT hanges in haemodynami parameters as well as to determine whih parameters are predisposing to S 3 Correlations between haemodynami parameters and the intensity of the gallop sound an be expeted beause there was a delay in the development of the ardiomyopathy as a result of the symptomati treatment of the sheep. In this way the experimental model may resemble human heart failure more losely. For intensities between and 3 on the riterium sale it is evident that the L VSW orrelates best with the intensity of the gallop sound. The good orrelation between the heart rate and the intensity of the gallop sound is also expeted, beause the heart rate, although seondary to heart failure is a sign of ompensation. The CPFI, whih an be obtained noninvasively, without right heart atheterization, also show signifiant orrelations with the intensity of the gallop sound exept for intensities between 4 and 6 on the riterium sale. One would expet that beause at the higher intensities, treatment had already been used to delay the development of the ardiomyopathy. Aording to Van der Walt et al. (1981), the CPFI is sensitive to evaluate treatment of heart failure, and at that stage the derease in CPFI beause of the treatment, will result in no orrelation with the intensity of the gallop sound. The signifiant orrelation of the filling pressures with the gallop rhythm at higher intensities is expeted beause at that stage the heart beomes very dilated and ongested, whih impedes the normal filling of the heart. Table 1 shows that the orrelation values of intensities between and 3 are muh higher than the other intensities, therefore the haemodynami parameters orrelate better with the intensities of the gallop rhythm between and 3. The ombination of parametres (Table 2) show, that the HR, PCWP, DPP, PAP, Psp and the SV give the best desription of the gallop rhythm with intensities between Oand6. TABL 2 Correlation of a ombination of parameters with the gallop rhythm with intensity between and 6. Heart rate (HR) in beats/min; pulmonary apillary wedge pressure (PCWP), distending pulmonary pressure (DPP), mean pulmonary artery (PAP) and pulmonary systoli pressure (Psp) in kpa; stroke volume (SV) in mc Haemodynmni parameter Regression oeffiient Standard deviation Relative on- tribution to R 2 =,59898 HR 2,157,7824,8467 PCWP 2,3745,925,7412 DPP -2,6288 1,12,6339 PAP -5,242 2,3145,5632 Psp 5,5529 2,723,4642 sv -1,556,8365,3855 Intereption onstant for regression oeffiient -,1233 The above-mentioned haemodynami parameters desribe 59 % (R 2 ;:::,599) of the information of the gallop rhythm. From Table 3 it is evident that for intensities from to 3, the HR, Psp, RAP, SV and the CPBV desribe the gallop rhythm best. These parameters desribe 73 % (R 2 =,73) of the information of the gallop rhythm. Although it was not the aim of this study to investigate the mehanism of the prodution of the gallop sound, it is possible to speulate on the genesis of the gallop sound. Considering die possible explanations for the TABL 3 Correlation of a ombination of parameters with the gallop rhythm with intensity between and 3. Heart rate (HR) in beats/min; pulmonary systoli pressure (Psp), right atrial pressure (RAP) in kpa; stroke volume (SV) and ardiopulmonary blood volume (CPBV) in mc Haemodynami parameter Regression oeffiient Standard deviation Relative on- tribution to R 2 =,73 HR 1,9898,6147,9431 Psp -1,5851,5674,724 RAP,2573,19,5848 sv -1,11747,4934,4617 CPBV,5195,282,354 Intereption onstant for regression oeffiient -,2658 genesis and ause of the 3rd heart sound the following hypothesis emerged from a study of the literature: 1. Abnormal rapid ventriular filling 2. Vibrations aused by diret impat of the heart against the thorax wall 3. Strething of the mitral valve apparatus beause of ardia dilation 4. Change in ventriular wall motion beause of strutural or funtional hanges Although this study yields no diret evidene against or in favour of the above hypothesis, the results obtained in 2 sheep where 3 me of blood was withdrawn in an attempt to relieve the ongestion, show, however, that the filling pressures dereased in both sheep. The intensity of the gallop sound dereased from 6 to 1 in 1 sheep and from 5 to 2 on the riterium sale in the other sheep. It is further evident from our results that with the smaller pressure gradient (high filling pressure and lesser elevated PAP) for flow to the left ventrile, that the flow to the left ventrile is impeded, and this fator, inluding the hanges in ventriular wall motion as a ause of strutural or funtional hanges in wall properties as a result of the development of the ardiomyopathy, are in favour of the theory proposed by Van de Werf et al. (1981), that the left ventriular wall is the major ardia struture whih is set into vibration during deeleration of flow and ausing the S 3 heart sound. The hypothesis that gallop sounds are produed as a result of hanges in the equilibrium between ventriular wall harateristis (strutural and funtional) and filling fators (preload, venous return) is hereby proposed for the genesis of gallop sounds. The measurement of the amplitudes of the gallop sounds and the quantitative presentation of the intensities to a 6 point riterium sale will be valuable in determining the prognosis of at least experimental animals suffering from heart failure, beause no animals with gallop sound intensities of 5 or 6 survived. This dilation ardiomyopathy, as indued after dosing sheep through rumen fistulas with dried plant material from the Rubiaeae family, resulted in gallop sounds assoiated with heart failure. This experimental model of heart failure in sheep, is useful however, to study heart sounds as well as the progression of pathologial S 3 sounds. Beause the same fators are probably responsible for the genesis of pathologial and physiologial s3 sounds, this model may be valuable in the study of the genesis of the gallop sound. In brief, this study shows that ertain haemodynami parameters orrelate with the intensity of the gallop 224

5 P.I. PRrORIUS,I. M. VAROOY,I. C. I. VARYSS &I. P. MIAAR sound and some of these haemodynami fators predispose S 3, espeially in the low intensity range before any treatment has ommened. RFRCS DIXO, W. I. ed., BMDP statistial software. Berkeley: University of California Press. 88 pp. KLLRMA, T. S., COTZR,I. A. W. & AUD, T. W., Plant poisonings and myotoxioses of livestok in Southern Afria. Cape Town: Ox.ford University Press. 243 pp. OZAWA, Y., SMITH, D. & CRAIG,., 1983 a. Origin of the third heart sound. I. Studies in dogs. Cirulation, 67 (2), OZAWA, Y., SMITH. D. & CRAIG,., 1983 b. Origin of the third heart sound. II. Studies in human subjets. Cirulation, 67 (2) PRTORJUS, P. J. & TRBLACH, M., A preliminary study on the symptomatology and ardiodynamis of gousiekte in sheep and goats. Journal of the South Afrian Veterinary and Medial Assoiation, 38 (1), PRTORIUS, P. J., TRBLACH, M., VADR WALT, I. D. & VA RYSS, I. C. J., Cardia failure in ruminants aused by gousiekte. Cardiomyopathies, 2, SHAVR, I. A., RDDY, P. S., ALVARS, R. F. & SALRI, R., Genesis of the physiologi third heart sound. Amerian Journal of on-invasive Cardiology, l, THILR, A., DU TOIT, P. I. & MITCHLL, D. T., Gousiekte in sheep. Reports of the Division of Veterinary duation and Researh of the Department of Agriultural Tehnial Servies of South Afria, 911, VA D WRF, F., MIT, I., CARMLIT, P., D GST, H. & KsTLOOT, H., The genesis of the third and fourth heart sounds. A pressure flow study in dogs. Journal of Clinial Investigation, 73, VADR WALT, I. I., VA ROOY, I. M., CILLIRS, G. D., VA RYSS, I. C. J. & VA AARD, M.., Ratio of ardiopulmonary blood volume to stroke volume as an index. of ardia funtion in animals and in man. Cardiovasular Researh, 15 (1),