Life Cycle of the Heartworm
Circulating microfilaria are ingested by a mosquito when it bites a dog with mature female heartworms during a blood meal. The microfilaria develop into an infectious larval stage while within the mosquito.  They then migrate to the mosquito's mouth parts. Development in the mosquito is temperature dependent, requiring approximately two weeks of temperature at or above 80 degrees F. Below a threshold temperature of 57 degrees F, development cannot occur, and the cycle will be halted. As a result, transmission is limited to warm months, and duration of the transmission season varies geographically.

During a later blood meal on an appropriate host, the heartworm larvae will exit the mosquito's mouth, enter the bite wound, and penetrate local connective tissues. The heartworm larvae undertake extensive migration through the tissues beneath the skin, which continues for some 60-90 days until they molt and become immature adults. The immature adult heartworms migrate to the right side of the dog's heart within a few days of their final molt, presumably carried by the venous circulation.

Final maturation and mating occur in the pulmonary arteries. The adult worms live in the right side of the heart and pulmonary arteries, where they may survive for up to seven years. Production of microfilaria by fertilized female worms begins approximately six and a half months after infection. Microfilaria are then released into the circulation, for a mosquito to ingest during a subsequent blood meal.

Heartworm Diseases
Several diseases can result from heartworm infection. Of paramount concern is cardiopulmonary disease, where one finds narrowing and blocking of the pulmonary arteries. The distribution and severity of the damage depends on both the number and location of adult worms. If there is a high worm burden, worms may be found in the right atrium and ventricles, and the vena cava may be involved as well. Individuals with cardiopulmonary disease may show exercise intolerance, and this can lead to right-side heart failure. Heart failure in these individuals can be acute or gradual.

Caval syndrome is an acute disease due to large numbers of adult heartworms accumulating in the right atrium, tricuspid valve area, and posterior vena cava. Worms can literally pack these areas, increasing venous pressure in the liver, and causing damage. Liver dysfunction increases cholesterol content of the red blood cell membranes, resulting in red blood cell fragility. This leads to hemolysis, anemia, and hemoglobinuria and bilirubinemia. Common in younger individuals, from 3-5 years of age, clinical signs include an acute onset of weakness and anorexia, dyspnea, collapse, pale mucous membranes and/or jaundice, bilirubinemia, bilirubinuria, and hemoglobinuria. This is a clinical emergency!! Death can occur within 24-48 hours.

Occasionally, adult worms may go to sites other than the large veins and heart, and cause ectopic infection. If they go to the eye an individual may show conjunctival discharge, photophobia, or keratitis. Treatment is by surgical removal of the worm. If the worms migrate to the central nervous system, they are usually found in the arteries in the brain or the lateral ventricles. Signs vary, but may include convulsions, blindness, ataxia, excess salivation, prostration, and coma. Treatment is by surgical removal. Systemic arteries may also be involved in heartworm infection. The rear legs are most commonly affected. Cases usually present on an emergency basis, and surgical removal of the worms is the recommended treatment.

Heartworm Treatment
Drug treatment involves a three-pronged approach, in order to account for varying drug susceptibility and drug safety. First, the adults must be killed. There are two main classes of adulticides used.

Melarsomine dihydrochloride, "Immiticide", is a new arsenical adulticide which is given intramuscularly into the lumbar muscles. The standard protocol is two doses of the drug twenty-four hours apart, however there is a modified protocol where a single dose is given, followed by paired doses 4-6 weeks later. The latter regimen is especially useful in treating very sick dogs, or dogs with high worm burdens at risk of thromboembolic complications.

The other adulticide used is thiacetarsemide ('Caparsolate'), the predecessor to Immiticide. Caparsolate must be administered intravenously, and tissue sloughing can occur if the drug goes perivascularly. This drug is contraindicated when some liver and kidney diseases are present. With either of these drugs, if treatment with adulticides is successful, antigenemia and microfilaremia should be gone by sixteen weeks post-treatment.

Microfilaricidal Treatment
Microfilaricides are the next major type of drugs used when treating for heartworm. Ivermectin (Heartguard or Ivomec) has been used at fairly low doses. Although microfilaricides are usually not given until after recovery from any side effects due to the adulticide, not earlier than 3-4 weeks after this treatment had been administered. Milbemycin oxime (Interceptor) is an effective microfilaricide, and ivermectin given on an off-label basis will kill circulating microfilaria. Careful observation is required after an initial dose in order to treat potential systemic side effects.

Heartworm Prevention
Prophylaxis is the major component of heartworm chemotherapy for any animal that could potentially become infected. Three main drugs exist for this purpose. All dogs should be tested for microfilariae before medication begins, particularly when using Diethylcarbamazine (Filaribits), because dogs with circulating microfilaria may be killed if Diethylcarbamazine is administered.

Heartguard and Interceptor are completely effective in preventing adult maturation. Heartguard is administered orally. Interceptor is also administered orally, and acts as both a microfilaricide and a larvicide. Either of these drugs should be given once monthly by mouth from within one month following the onset of the transmission season to one month after transmission is considered unlikely. If a dose is missed, there is some afforded protection from residual amounts of drug remaining in the circulation. As a result, delayed administration may not lead to an adult infection.

Filaribits are given orally once per day, and are highly effective, but are only safe in dogs without circulating microfilaria. Missed doses are significant if the elapsed time is longer than 2 months. If the omission time is under six weeks, readministration should establish full protection in the dog again.