Congenital Heart Diseases in Swine

Transcription

1 Vet. Pathol. 19: (1982) Congenital Heart Diseases in Swine F. S. Hsu and S. J. Du Department of Veterinary Medicine, Animal Industry Research Institute, TSC, Chunan, Taiwan, and Department of Veterinary Pathology, Pig Research Institute of Taiwan, Chunan, Taiwan, R.O.C. Abstract. One hundred twenty-two congenital cardiac anomalies were diagnosed in 83 pigs (4.35%) during necropsies of 1906 pigs from one day to four years of age during an 1 1-month period. The incidence of cardiac malformation was highest at 29 to 56 days of age. Of the 83 pigs with cardiac anomalies, 47 (56%) were male and 36 (44%) were female, and of these, 15 (18%) were purebred and 68 (82%) were crossbred pigs. Of the 15 purebred pigs with cardiac malformation, there were seven Landrace pigs, four Large White pigs, three Duroc Jersey pigs, and one Yorkshire pig; whereas 94% of the 68 crossbred pigs were crossbred among Landrace, Duroc Jersey, and Large White. The 122 cardiac anomalies found in the 83 pigs were: dysplasia of the tricuspid valve in 42 pigs, atrial septal defect in 31 pigs, subaortic stenosis in 22 pigs, ventricular septal defect in nine pigs, persistent common atrioventricular canal in eight pigs, malformation of the moderator band in seven pigs, persistent vena cava in one pig, persistent truncus arteriosus in one pig, and pulmonary stenosis in one pig. The pathological features of the anomalies in swine were similar to those described in small animals and in man. The findings indicate that spontaneous porcine cardiac anomalies might provide models for cardiovascular investigators to study the etiology and pathogenesis of congenital heart diseases in man and other mammals. Congenital heart diseases have been studied extensively in man and small animals, but not in swine. Subaortic stenosis [6] and patent ductus arteriosus [ 111 are common in pigs. In one study, seven (14.6%) of 48 pigs that were stillborn or died within two weeks after birth were found to have congenital anomalies [20]. Eight cases (0.5%) of cardiac malformation (dysplasia of the tricuspid valve in six pigs and persistent common atrioventricular canal in two pigs) were recognized in necropsies of 1643 pigs 8 weeks to 3.5 years of age [23]. No pigs under 56 days of age were examined. This study describes cardiac anomalies found on necropsy of 1906 pigs examined in the Department of Veterinary Medicine, Animal Industry Research Institute, Taiwan Sugar Corporation, ROC. 616

2 Congenital Heart Diseases in Swine 611 Materials and Methods A total of 1906 pigs that died from disease were necropsied from 1 July 1978 to 30 April They were collected from a pig farm of the Animal Industry Research Institute, Taiwan Sugar Corporation, Chunan, Taiwan, Republic of China. The study farm produces 70,000 hogs for market annually. The pigs from one day to four years of age were purebred or crossbred. The crossbred pigs had two to four of the following breeds in their genetic background: Landrace, Duroc Jersey, Yorkshire, Large White, and Minnesota. At necropsy, the body weight of each carcass was recorded. The heart and 1.5 cm of the aorta and major arteries were removed and examined. The right ventricle was opened through the pulmonic valve (outflow tract) down to the apex. The left ventricle was opened from the apex through the aorta and inflow tract. The thickness of the ventricular wall was measured at the posterior left ventricular free wall, directly behind the midpoint of the posterior mitral valve leaflet; the ventricular septum was measured in the area of maximal thickness, usually about one-third to one-half the distance between the base of the aortic valve and the left ventricular apex, and the right ventricular wall was measured near the tricuspid valve annulus. In measuring ventricular wall thickness, we avoided the trabeculae or papillary muscles. The entire heart was fixed in neutral 10% formalin and weighed 24 hours after fixation. Specimens of myocardium were taken from the areas mentioned above, from lesions in the left ventricular outflow tract, and from atrioventricular valves and moderator bands. The specimens were embedded in paraffin, sectioned at 6 pm, and stained with hematoxylin and eosin (HE), Masson trichrome, and periodic acid-schiff. The 1906 necropsied pigs were divided into five groups based on age: birth to 28 days (suckling period), 29 to 56 days (nursing period), 57 to 110 days (growing period), 11 1 to 180 days (finishing period), and over 181 days (mature period). A statistical analysis was done on relative heart weight and ratio of the thickness of ventricular septa to left ventricular wall using a least significant difference procedure. Results Of the 1906 pigs examined during the 11-month period of study, 83 (4.35%) had congenital heart diseases. Age, sex, and breed distribution of the 83 affected pigs and the 1906 necropsied pigs is found in table I. The majority (70%) of the affected pigs were less than 110 days old. Of the 83 pigs with cardiac anomalies, 47 (56%) were male and 36 (44%) were female, and of these, 15 (18%) were purebred and 68 (82%) were crossbred pigs. The pigs with congenital anomalies were poorly developed and had dyspnea, lethargy, and anorexia. Often, these pigs died suddenly. The types and frequency of diagnosed congenital heart disease are given in table 11. Dysplasia of the tricuspid valve, diagnosed in 42 pigs, was the most common cardiac anomaly. Of the 42 pigs, 33 (79%) had single anomalies. These 33 pigs were from 18 days to 3.5 years of age, with most 29 to 56 days of age. Seventeen of the 33 affected pigs were males. In the 33 pigs with dysplasia of tricuspid valve, relative heart weight, mean thickness of ventricular free wall and septum, and ratio of ventricular septum to the thickness of the ventricular free wall did not differ significantly from those pigs with a normal heart.

3 678 Hsu and Du Age Under 28 days 29 to 56 days 57 to 110 days 111 to 180 days Over 180 days Sex Male Female Breed Table I. Age, sex, and breed distribution of 1906 pigs studied Pigs with Tota.I pigs congenital necrop sied (%) disease (%) Pure breed Landrace Large White Duroc Jersey Yorkshire Cross breed Cross breeds of Landrace, Duroc Jersey, and Large White o Table 11. Congenital cardiac malformations in 83 pigs* Number of Malformation abnormalities Dysplasia of the tricuspid valve Atrial septal defect Subaortic stenosis Ventricular septal defect Persistent common atrioventricular canal Malformation of moderator band Persistent cranial vena cava Persistent truncus arteriosus Pulmonary stenosis Total * A total of 1906 pigs were examined I 122 Percent o 1.o 1.o The morphological features (fig. 1) of the dysplasia of tricuspid valve included: irregular thickening of the leaflets; attachment of the deformed leaflets to the ventricular wall; absent or short, stout, fused chordae tendineae; abnormal insertion of the deformed lateral leaflet into the papillary muscle; hypertrophy of the papillary muscle; and enlargement of the right atrium and ventricle. Occasionally, the lateral leaflet was nodular and contained clefts and multiple small fenestrations. Additional cardiac anomalies in the affected pigs included five atrial septal defects and four ventricular septal defects.

4 Congenital Heart Diseases in Swine 619 Fig. 1: Right side of heart from 22-day-old pig with dysplasia of the tricuspid valve. Adhesion of anterior leaflet to fused moderator band (m) and papillary muscle (p); adhesion of the thickened septal leaflet (s) to the septum, and insertion of the lateral leaflet into the fused papillary muscle. Fig. 2 Right side of heart from 76-day-old pig with atrial septal defect (arrow). Fig. 3: Visceral organs from 76-day-old pig with atrial septal defect. Extensive dilatation of heart with severe passive congestion of liver. Fig. 4 Left side of heart from four-month-old pig with moderate subaortic stenosis. Fibrous ridge (arrow) encircling ventricular outflow tract. Atrial septal defect was diagnosed in 3 1 pigs, and 11 of these (35%) were single anomalies. These 1 1 pigs ranged from five to 223 days of age; six of them were males. The relative heart weight (8.27 f 5.73 gm/kg) in the 11 affected pigs was increased, but was not significantly different from pigs with a normal heart (table 111). The atrial septal defects varied in size from 3 to 9 mm and were found in the dorsal and middle portions of the interatrial septum (fig. 2). The heart was enlarged in all pigs and various degrees of passive congestion of visceral organs (fig. 3) were observed. The anomalies were accompanied by ventricular septal defect in seven pigs,

5 680 Hsu and Du Table 111. Relative heart weight and cardiac muscle thickness in normal and affected pigs Normal3 TD ASD SAS VSD A-V canal MMB PTA Relative Ventricular wallz Number heart thickness (mm) VS/LV2 weight' RV LV vs f 3.18" f 3.31" f 5.73" f 6.34b f 5.03b f 4.42b f 3.42" f f f f f f f f f f f f f f f f f f f f f 0.06" 1.09 f 0.08" 1.09 f 0.06" 1.07 f 0.13" 1.16 f O.lOb 1.07 f 0.11" 1.05 f 0.06" Comparison between normal and other heart anomalies: entries in the same column with different superscripts (" and b, are different at P <.01. Ratio of heart weight (gm) to body weight (kg). Thickness of right ventricular wall (RV), left ventricular wall (LV), ventricular septum (VS), and ratio of the thickness of VS to LV. From one day to four years of age. -+ = Standard error; TD = dysplasia of the tricuspid valve; ASD = atrial septal defect; SAS = subaortic stenosis; VSD = ventricular septal defect; A-V canal = persistent common atrioventricular canal; MMB = malformation of moderator band; PTA = persistent truncus arteriosus. persistent common atrioventricular canal in seven pigs, dysplasia of the tricuspid valve in four pigs, and subaortic stenosis in two pigs. Subaortic stenosis was diagnosed in 22 pigs, and 14 (70%) had single anomalies. The 14 affected pigs ranged from 30 days to 7.5 months of age. Nine of the 14 affected pigs were male. There was significant increase (P <.01) in relative heart weight in pigs with subaortic stenosis ( & 6.34 gm/kg), as compared with pigs with normal hearts (6.28 f 3.18 gm/kg) (table 111). The mean thickness of left ventricular wall (11.7 f 4.8 mm) and ventricular septum (12.4 & 5.1 mm) in the affected pigs were increased, but were not significantly different from normal pigs (table 111). Ratio of ventricular septum to left ventricular wall was 1.07 f The defect was characterized by the presence of a fibrous collar encircling the left ventricular outflow tract 0.5 to 1.5 cm below the aortic valve, with great variation in severity (fig. 4). In the eight pigs with severe lesions, the thickened endocardia1 collar or membrane extended from the base of the anterior leaflet of the mitral valve to the aortic valve. Constriction of the annulus and dilatation of the supra-valvular area were observed. In the six pigs with mild to moderate lesions, a narrow ring of white, fibrous endocardium extended partially around the left ventricular outflow tract. The ring primarily originated at the base of the anterior leaflet of the mitral valve and extended transversely across the interventricular septum for a variable distance. Of the 14 pigs with subaortic stenosis, seven pigs had left ventricular hypertrophy and four pigs had left ventricular dilatation, ten of the affected pigs had left atrial

6 Congenital Heart Diseases in Swine Fig. 5: Subaortic stenosis from same pig as fig. 4. Discrete membrane of fibrous tissue (me) on superficial endocardium in outflow tract. HE. Fig. 6 Photomicrograph of abnormal intramural coronary artery from pig with subaortic stenosis. Marked thickening of vessel wall with narrowing of lumen. HE. Fig. 7: Left side of heart from 25-day-old pig with ventricular septal defect. Fig. 8: Right side of heart from 56-day-old pig with persistent common atrioventricular canal of the transitional type with large defect (D) and cleft (arrow) at junction of septal and anterior leaflets of tricuspid valve. 8 hypertrophy, and three had both left and right ventricular hypertrophy. The heart wall of the remaining three pigs was of normal thickness. Microscopically, a well-developed subvalvular ring or membrane consisting of fibrous connective tissue and elongated fibroblastic cells, was present on the left ventricular outflow tract (fig. 5). Severe changes of the intramural coronary arteries (fig. 6) occurred in nine of the pigs with subaortic stenosis. These changes consisted of marked increase in vessel - size with a luminal narrowing, intimal fibromuscular proliferation, and disorganiza-

7 682 Hsu and Du Fig. 9 Abnormal heart (right) with malformed (thin. stringlike) moderator band (arrow) attached to deformed trabecule. Normal heart (left) for comparison. tion of the media. Occasionally, foci of myocardial necrosis with or without fibrosis were found, involving the left ventricular wall and ventricular septum. The anomaly was accompanied by vegetative endocarditis in four pigs, fibrous thickening of both mitral and tricuspid valves in two pigs, atrial septal defect in two pigs, ventricular septal defect in two pigs, and persistent common atrioventricular canal in three pigs. Ventricular septal defect was diagnosed in nine pigs from seven to 125 days of age. Six of the nine affected pigs were male. The relative heart weight in pigs with ventricular septal defect was 14.5 f 5.03 gm/kg (table 111), which is greater (P <.01) than in pigs with a normal heart (6.28 f 3.18 gm/kg). All these defects, varying from 3 to 10 mm, occurred in the membranous portion of the septum (fig. 7). Of the nine pigs with ventricular septal defect, two pigs had left ventricular hypertrophy, and three pigs had left ventricular dilatation. The remaining four pigs were normal on gross examination. Hypertrophy of the right ventricle was seen in five pigs. The abnormality was associated with atrial septal defect in seven pigs, with dysplasia of the tricuspid valve in five pigs, with subaortic stenosis in two pigs, and with vegetative endocarditis in two pigs. The mitral valves were normal on gross examination. Persistent common atrioventricular canal was diagnosed in eight pigs from 27 to 68 days of age. Two of the eight affected pigs were male. The relative heart weight was f 4.42 gm/kg (table 111), which was greater (P <.Ol) than in pigs with normal heart (6.28 f 3.18 gm/kg). The defects, varying from 6 mm to 20 mm, occurred in the lowermost portion of the atrial septum and the uppermost portion of the ventricular septum at the level of the coronary sinus. They were associated with malformation of the atrioventricular valves. This defect caused interatrial and interventricular communication among the four chambers of the heart (fig. 8).

8 Congenital Heart Diseases in Swine 683 Fig. 1 0 Right ventricle and great vessel from six-day-old pig with persistent truncus arteriousus (Tr). Of the eight anomalies, one was complete and seven were transitional. In the complete lesion, both the anterior mitral and septal tricuspid leaflets were cleft. The mitral valve was continuous with the tricuspid valve and was not attached to the upper edge of the ventricular septum, whereas in the transitional lesions, both the septal tricuspid and anterior mitral valves were cleft. The cleft valves were thickened and attached abnormally to the ventricular septum. Persistent atrioventricular canal was accompanied by: subaortic stenosis in the two pigs, pulmonary stenosis in one pig, vegetative endocarditis in one pig, and persistent left anterior vena cava in one pig. In the case of pulmonary stenosis, the pulmonary valve was dysplastic and markedly stenotic. The lesions resulted in marked supravalvular dilatation of the pulmonary artery. Malformation of the moderator band in the right ventricle was diagnosed in seven pigs. All were males from seven to 163 days of age. Five pigs were under two months of age, including two pigs which were seven days of age. The relative heart weight (7.28 f 3.42 gm/kg) in the seven affected pigs was greater, but not significantly different from that in the pigs with a normal heart (table 111). All 1906 pigs examined in this study had a muscular moderator band in the right ventricle of the heart (fig. 1, 9). It extended between the anterior papillary muscle of the ventricular septum and the lateral papillary muscle. The malformation of the moderator band of the seven affected pigs were all muscular, but the appearance varied. Three of the seven affected pigs had two stout, parallel bands, which extended from the lateral papillary muscle into the anterior papillary muscle of the ventricular septum. Fusing of the two abnormal bands at the mid portion was observed. Among the seven affected pigs, two had two to three branches on the band at the lateral papillary muscle end, one had a big cord-like

9 684 Hsu and Du band, and the remaining one had a normal-sized band, but it started at the lateral papillary muscle and extended to the ventricular trabeculae. Persistent truncus arteriosus was found in a six-day-old, female, Large White crossbred Landrace pig. The anomaly consisted of a gross ventricular septal defect, atrial septal defect, and biventricular origin of a single great vessel (31-mm circumference) (fig. 10). This anomaly was accompanied by persistent cranial vena cava. Discussion The data accumulated here show the incidence of congenital heart diseases in the necropsied pigs only, and the prevalence rate of the anomalies in the general population of swine remains unknown, since no live pigs were examined. The incidence of congenital heart disease found in this study (4.35%) was higher than one report (0.49%) [23], but lower than the results (14.6%) reported in a herd surveyed for a short period of time [20], whereas the prevalence rate of the defect in man [19], dogs [16], and cats [12], was 1%, 0.68%, and 0.17%, respectively. In this study, the congenital heart disease was found to be higher in the group of pigs 29 to 110 days of age than in pigs in other age groups. This might indicate that pigs with congenital heart disease commonly would die within this age period. Young children [8], dogs [4], and cats [12] less than one year of age with cardiac anomalies develop signs of acute heart failure. The prevalence of congenital heart disease is higher in purebred than in mixed dogs and is higher in certain breeds than in the general population [16]. The latter findings were not found in our study of swine. This may have been because too few purebred pigs were observed to permit any conclusions. From this study, it is not possible to determine whether the prenatal status of the sows contributed to the cardiac anomalies. It is thought that congenital disease in dogs and man results from single recessive genes or polygenic sets that have lesionspecific effects on cardiac development [5, 16, 171. Many types of congenital heart disease, such as dysplasia of the tricuspid valve, subaortic stenosis, atrial septal defect, ventricular septal defect, persistent common atrioventricular canal, persistent truncus arteriosus, persistent cranial vena cava, and pulmonary stenosis, which occur spontaneously in man [5, 191, dogs [17], and cats [12] were observed in pigs in this study, but some types, such as patent ductus arteriosus, tetralogy of Fallot, Ebsteins s malformation, and mitral insufficiency, which are common in man [5, 191 and small animals [12, 161, were not observed in pigs. Dysplasia of the tricuspid valve is the most important heart disease in swine and it occurred in the swine in this study with predominance at 29 to 56 days of age, while in dogs and cats, the predominance was at 5.4 and 6.7 months, respectively ~141. The changes of tricuspid valvular dysplasia observed in the 42 pigs in this study were very similar to those in man [ 11 and in small animals [ 141. The abnormalities differed from Ebstein s malformation by the absence of downward displacement of

10 Congenital Heart Diseases in Swine 685 the basal attachment of the leaflet [5]. This may result from a developmental arrest at some stage or incomplete development of the cardiac valve in fetal life [7]. The morphological alterations of subaortic stenosis in the pigs in this study were similar to those previously reported in man [5], dogs [15, 16, 181, pigs [6, 201, and cows [lo]. The etiology of subaortic stenosis in pigs is unknown. In man and dog, the anomaly usually is considered to be a congenital defect. Previous investigators [ 15, 181 think that discrete subaortic stenosis is inherited as a specific gene defect in Newfoundland dogs. Subaortic stenosis in man [5] and Newfoundland dogs [ 15, 181 often is complicated by infectious endocarditis. This also happens in pigs. Abnormalities of the intramural coronary arteries similar to those occurring in the ventricular septum of the pigs with subaortic stenosis also were observed in pigs with hypertrophic cardiomyopathy (Hsu, F.S., unpublished data). The morphological changes of ventricular septal defects in the membranous septum of the pigs in this study were similar to those reported in man [5], small animals [4, 12, 161, and cattle [2] with ventricular septal defect, whereas in sheep the defect was in the muscular septum [3]. The features of persistent common atrioventricular canal found in this study also were similar to those reported in man [5, 191 and small animals [12, 131. The etiology of persistent common atrioventricular canal is thought to be an embryologic malformation of the endocardial cushions. The hearts of 59 patients with persistent common atrioventricular canal malformations were examined and it was reported that the septum of atrioventricular malformation may arise as a result of reduced compression of the developing atria by surrounding structure during the embryonic stage [9]. It was reported that the complete and partial varieties of persistent common atrioventricular canal appear to represent different degrees of malformation in relation to the atrioventricular endocardial cushions, while transitional varieties present an intermediate degree of malformation [22]. Others indicated that a normal moderator band is present in the right ventricle in man, pigs, cattle, and dogs [21]. The development in pigs is exceedingly variable; it may be a long thread-like cord consisting almost entirely of Purkinje fibers, or it may be short and thick with a predominant amount of cardiac myofibers. The abnormalities of porcine persistent truncus arteriosus found in this study also were similar to those observed in man [5] and small animals [ 121. Enlargement of heart, passive congestion of visceral organs, ascites and hydropericardium consistently were observed in the cases of subaortic stenosis, atrial septal defect, ventricular septal defect and persistent common atrioventricular canal. The study also indicates that vegetative endocarditis commonly accompanied subaortic stenosis, ventricular septal defect, and persistent common atrioventricular canal. Seventy percent of the cases are related to streptococci. References 1 BECKER, A.E.; BECK, M.J.; EDWARDS, J.E.: Pathologic spectrum of dysplasia of the tricuspid valve. Arch Pathol 91: , 1971

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