1. Flexible alligator forceps

The flexible alligator forceps is an instrument developed in 1986 for removal of heartworms from the pulmonary artery and right atrium with jugular venotomy [2]. These forceps can be used to remove almost all worms from the pulmonary arteries. Heartworm removal has been one of the best therapies for heartworm disease, and prevents pulmonary thromboembolism with dead worms. Alterations after heartworm removal have provided useful information about the pathophysiology of heartworm disease. Moreover, by use of the forceps, we can insert live and dead worms and worm-like strings into the pulmonary arteries via the jugular vein. Also from these procedures, we can gain pathophysiological data of heartworm disease.

2. Pathophysiology of heartworm disease

The pathophysiology of parasitic disease associates with their life cycles. The life cycle of the Dirofilaria immitis is as follows [6]. Adult worms living in the pulmonary arteries give birth to microfilariae. Microfilariae in circulation move to a mosquito at bite, and develop to infective third-stage larvae (L3) within the mosquito. L3s enter the host at bite, then migrate within the dog body, and enter the vascular system. Young adults move into the pulmonary arteries, wherein they mature. The life cycle is completed by female adults giving birth to microfilariae. It is very important to realize that adult worms die within several years [8]. In my lecture I hope to consider the pathophysiology of heartworm disease through the circulatory disturbance induced by parasitism of adult heartworms.

3. Pulmonary heartworm disease and caval syndrome

There are 2 major types of heartworm disease, pulmonary heartworm disease and caval syndrome. In the former type, dogs harbor live heartworms in their pulmonary arteries. In the caval syndrome, heartworms are observed in the tricuspid area. This presentation is about pulmonary heartworm disease, and I will talk about caval syndrome later.

4. Causes of pulmonary hypertension

Pulmonary hypertension is the most important circulatory disturbance in pulmonary heartworm disease [5]. Dogs with heartworm disease have dilated and tortuous pulmonary arteries on radiographs. Pulmonary arterial pressure is high. The following factors may be involved in the pulmonary hypertension in dogs with heartworm disease.

With live worms

1.  Presence of live heartworms in the pulmonary vessels. Live worms prevent pulmonary blood flow.

2.  Proliferation of pulmonary arterial endothelial lining.

With dead worms

1.  Pulmonary thromboembolism and hypoxemia

2.  Other lesions such as consolidations of the lung and pneumonia.

All of these factors contribute to pulmonary hypertension. Immediately after heartworm removal from the pulmonary arteries using the flexible alligator forceps [4], pulmonary arterial pressure was found to decrease. And then the pressure increased immediately after insertion of live worms into the pulmonary arteries using the forceps. Therefore, the presence of worms in the pulmonary arteries certainly contributes to pulmonary hypertension. After heartworm removal, the grade of pulmonary hypertension was associated more closely with pulmonary arterial pressure than the grade of proliferation of pulmonary arterial endothelial lining and other lesions [9]. If live worms are removed, the pulmonary arterial pressure will be reduced rapidly. And thromboembolisms will not be produced, because worms removed, of course, will never remain to die in the pulmonary arteries. Surgical removal of live heartworms, of course, improves the pulmonary circulation, and prevents the formation of thromboembolism following the death of worms.

5. Formation of thromboembolism in pulmonary arteries

In dogs without heartworm infection, the insertion of dead adult worms into the pulmonary arteries did not induce severe thromboembolisms and pulmonary hypertension. Besides, in dogs with infection, in which endothelial lining of pulmonary arteries proliferated severely, dead-worm insertion produced severe thromboembolism. Pulmonary arterial pressure increased in these dogs [1]. In dogs with heartworm infection, thromboemboli may be formed by an impossibly complex biological reaction, such as the interaction between endothelial cells and a foreign substance, but not by simple mechanical obstruction. Adulticidal treatment induces pulmonary thromboembolism. In dogs having severer proliferation of the intima in the pulmonary arteries and a heavy worm burden, the death of worms results in the formation of more severe thromboembolisms. However, no methods are yet available to diagnose the severity of endothelial proliferation and thromboembolism.

6. Treatments for pulmonary heartworm disease

Treatments for pulmonary heartworm disease include: 1) surgical heartworm removal using the flexible alligator forceps, 2) adulticidal treatment, and 3) symptomatic treatments without specific treatments for adult heartworms. Dogs with a very light worm burden and no clinical signs can receive adulticidal treatment. On the other hand, no treatment might be the best treatment. In dogs with a heavy worm burden, adulticidal treatment is dangerous, and surgical heartworm removal is selective. An adulticide can not be administered dogs showing the end-stage signs of heartworms disease: ascites, subcutaneous edema, and severe liver or renal failure. However, surgical heartworm removal can cure a half dog showing ascites [3]. We have no experience using an adulticide over 10 years, so we can not speak here about adulticidal treatment. Drs. Morini, Venco et al. [7] performed a very interesting investigation, comparing efficacies between the surgical and adulticidal treatments. As I mentioned earlier, the adulticidal treatment produces thromboembolisms including dead worms. Most dogs can supposedly tolerate adulticide treatment. But saying that a dog can endure it does not necessarily mean the treatment is safe. Actually, some dogs have died after treatment. Thus, we have to establish the dog-side standard for use of an adulticide for dogs with heartworm infection.

Recently, prophylaxis has spread widely among dogs bred in Japan, and dogs showing typical signs of heartworm disease have decreased. However, many dogs with heartworm infection are brought to us, and current knowledge of the disease is very important. Despite the fact that heartworm disease has been recognized from very early times, the pathophysiology of the disease remains unknown. For better treatment of the disease, a more definite elucidation of its pathophysiology is necessary.

References

1.  Hirano Y, Kitagawa H, Sasaki Y: J Vet Med Sci 54: 897-904, 1992.

2.  Ishihara K, Sasaki Y, Kitagawa H: Jpn J Vet Sci 48: 989-991, 1986.

3.  Kitagawa H, Kubota A, Yasuda K, Hirano Y, Sasaki, Y.: J Vet Med Sci 54: 751-756, 1992.

4.  Kitagawa H, Sasaki Y, Ishihara K, Hirano Y: Jpn J Vet Sci 52: 12111217, 1990.

5.  Knight DH: Adv Vet Sci Comp 21: 107-149, 1977.

6.  Kume S, Itagaki S: Brit Vet J 111: 16-24, 1955.

7.  Morini S, Venco L, Fagioli P, Genchi C. 235-240 Recent advances in heartworm disease: symposium '98. 1998.

8.  Ohishi I, Kobayashi S, Kume S. Jpn J Vet Med Assoc 33 (Suppl.): 250251, 1971 (in Japanese).

9.  Sasaki Y, Kitagawa H, Hirano Y: J Vet Med Sci 54: 739-744, 1992.