Disease transmission and life cycle
Over 60 mosquito species of the family Culicidae are known to transmit Dirofilaria immitis. When a mosquito, carrying infective L3, bites a dog and transmits the infection, the larvae grow, develop and migrate in the body over a period of several months to become sexually mature male and female worms. Adult heartworms live primarily in the pulmonary arteries of infected dogs. Seldom they are found in the right cardiac chamber and large adjacent vessels (cranial and caudal vena cava). Ectopic localizations (i.e. brain, eyes and aorta) can rarely occur.
Dirofilaria offspring, so-called microfilariae, can be detected in the peripheral blood (pre-patent period) about six to seven months after the infective larvae entered the dog during the blood meal of an infected mosquito. Male (10-15 cm in length) and female (25-30 cm in length) heartworms appear to possess a life span in dogs that averages up to five to seven years.
In experimentally induced infections with heartworms in dogs, the percentage of infective larvae developing to adults is high (40 to 90%). The percentage of experimentally infected dogs from which adult worms are isolated is virtually 100%. The number of worms infecting a dog can be very high, ranging from one to approximately 250.
Microfilaremia, the presence of heartworm offspring in the blood of infected dogs, is relatively common. However, not all heartworm infections result in microfilariae circulating in the blood. Infections not showing microfilaremia are known as occult heartworm infections and may be the result of a number of factors such as single sex heartworm infections, host immune responses affecting the presence of circulating offspring (microfilariae) and most significantly, the administration of heartworm preventives.
Lesions of the endothelial surface of pulmonary arteries are the first step in the pathogenesis of the disease. A few days after the heartworms have reached the caudal pulmonary arteries, endothelial cells become swollen with wide intercellular junctions and disoriented longitudinal axes, as response to the trauma.
Activated neutrophils adhere to the endothelial surface and enter the space between the lining endothelial cells. Furthermore, as linear areas of subendothelium are exposed, platelet adhesion and activation is greatly stimulated. The damaged arterial surface allows albumin, plasma fluid and blood cells to reach the perivascular space. After the endothelial changes, the initima thickens with fluid, leukocytes invade the wall and smooth muscle cells multiply within the tunica media and migrate toward the endovascular surface as response to growth factor release. In the end, villi are present on the internal arterial surface, appearing rough and velvety, and both the lumen and the compliance of the pulmonary arteries are reduced.
Lung disease occurs secondary to vascular changes. Fluid and protein leaking through the vessel walls of affected arteries produce edema in the parenchyma. Spontaneous death of single worms can cause thromboembolism and severe inflammatory reactions. Occlusion by either thromboembolism or villous proliferation results in a hypertensive pulmonary state and, as a consequence, in an increased afterload for the right ventricle which can induce a "cor pulmonale" and congestive heart failure in dogs. The right cardiac ventricle is involved in the disease not before the last stages.