1. Caval syndrome

In this type of heartworm disease, heartworms are observed in the tricuspid area. Worms move back and forth between the right atrium and right ventricle on an echocardiogram. Worms migrate from the pulmonary arteries, the primary habitat of heartworms, to the tricuspid area, where they induce severe circulatory disturbance and intravascular hemolysis. In typical cases, the sudden onset of so-called caval syndrome is associated with prostration, anemia, hemoglobinuria, jugular pulsation, and caval murmur. If the dog receives no adequate treatment, an acute disease course will result in death.

2. The cause of heartworm migration

We investigated the cause of heartworm migration from the pulmonary arteries to the right atrium. Heartworm migration has been observed at the shock after administration of a prophylactic to microfilaremic dogs [4,10], at the shock induced by administration of body fluid of adult worms [6], after administration of a beta blocker [5], after performing anesthesia [1], and after production of pulmonary arterial thromboembolisms [6]. In all these situations, the cardiac output decreases, indicating decreases in bloodstream flow volume and flow rate. Extremely heavy worm burden may constrict blood flow at the pulmonary arteries, and may induce heartworm migration from the pulmonary arteries to the right atrium. However, we have treated many dogs with heartworm caval syndrome having a small number of heartworms. Also in these dogs, we can find fresh thromboemboli including dead heartworms in the pulmonary arteries [7]. The death of adult worms brings about the release of body fluid from dead worms and the formation of thromboembolism at the pulmonary arteries. This induces a decrease in cardiac output, and triggers the migration of adult live heartworms in most natural cases with heartworm caval syndrome.

Recently, we observed dogs having a small number of heartworms in the tricuspid area and severe pulmonary hypertension. We call this type of disease chronic-type caval syndrome.

3. Circulatory disturbance in caval syndrome

Worms in the tricuspid area induce a tricuspid insufficiency (stenosis and regurgitation) which leads to a circulatory disturbance (acute right heart failure). It is confirmed by the fact that heartworm removal from the tricuspid valve area brings about disappearance of the characteristic caval murmur and amelioration of tricuspid valve function, while a circulatory disturbance is improved quickly after heartworm removal [7]. However, obvious signs of circulatory disturbance do not occur after cutting of the tricuspid valve leaflets and chordae in dogs with normal pulmonary arterial pressure. Besides, dogs with slight to moderate pulmonary hypertension develop signs of right heart failure such as ascites, subcutaneous edema, liver dysfunction and exercise intolerance, after the tricuspid valve leaflets and chordae are cut. The principal cause of circulatory disturbance is tricuspid insufficiency with worms, and pulmonary hypertension is another important cause of circulatory disturbance in dogs with caval syndrome.

4. Intravascular hemolysis

Hemoglobinuria is one of the characteristic signs in caval syndrome. It results from an increase in intravascular hemolysis. In dogs with heartworm disease, the low density lipoprotein involving a large amount of free cholesterol increases secondary to liver dysfunction. Based on this, cholesterol contents in erythrocyte membranes increase. This means increases in abnormal erythrocytes, such as spur cells and target cells. In these erythrocytes, the flexibility of erythrocyte membranes is reduced, and the resistance to mechanical force decreases (a predisposing factor easily destroyed) [2,9]. However, the intravascular hemolysis increases after insertion of combined silicone tubes into the tricuspid orifice in normal dogs without heartworm infection [8]. The predisposing factor of erythrocytes that can be easily destroyed is not the primary cause of an increase in intravascular hemolysis.

Dogs with caval syndrome reportedly do not have a circulating antierythrocyte antibody [1,2]. Intravascular hemolysis does not increase during incubation of normal erythrocytes from normal dogs in plasma of caval syndrome dogs. Therefore, immunological and chemical mechanisms are not involved in intravascular hemolysis, and a process of elimination has been considered to be the mechanical mechanism. The burr cells and small spherocytes observed in peripheral blood support the presentation of mechanical hemolysis in dogs with heartworm caval syndrome.

After surgical removal of heartworms from the tricuspid area, plasma hemoglobin concentrations decrease rapidly, whereas they increase after migration of heartworms from the pulmonary arteries to the tricuspid area [3]. Intravascular hemolysis increased after insertion of worm-like silicone tubes combined form into the tricuspid orifice [8]. These findings suggest the following hypothesis about intravascular hemolysis in dogs with caval syndrome. Heartworms at the tricuspid valve orifice cause stenosis and regurgitation of the tricuspid valve. The stenosis and regurgitation bring about abnormal bloodstream flow in the tricuspid area. The mechanical force of the abnormal bloodstream flow may then destroy erythrocytes predisposed to such a fate.

References

1.  Atwell RB, Buoro IBJ: Dirofilariasis, CRC Press, Boca Raton, 1988.

2.  Ishihara K, Kitagawa H, Ojima M, Yagata Y, Suganuma Y: Jpn J Vet Sci 40: 525-537, 1978.

3.  Kitagawa H, Sasaki Y, Ishihara K: Jpn J Vet Sci 48: 99-103, 1986.

4.  Kitagawa H, Sasaki Y, Ishihara K: Jpn J Vet Sci 48: 517-522, 1986.

5.  Kitagawa H, Ishihara K, Sasaki Y: Jpn J Vet Sci 49: 1081-1086, 1987.

6.  Kitagawa H, Sasaki Y, Ishihara K, Kawakami M: Jpn J Vet Sci 52: 591-599, 1990.

7.  Kitagawa H, Sasaki Y, Ishihara K, Kawakami M: Am J Vet Res 52: 126-132, 1991.

8.  Kitagawa H, Sasaki Y, Ishihara K, Kuwahara Y: Jpn J Vet Sci 52: 1029-1035, 1990.

9.  Kitagawa H, Sasaki Y, Mori M, Ishihara K: Jpn J Vet Sci 49: 285293, 1987.

10. Kitagawa H, Sasaki Y, Sukigara T, Ishihara K: Jpn J Vet Sci 49: 485-489, 1987.