Despite being considered one of the most pathogenic helminth infections of companion animals, members of macrocyclic lactone class are the only drugs available for the prevention of heartworm disease caused by Dirofilaria immitis. Alarmingly, heartworm prevention is at risk; several studies confirm the existence of macrocyclic lactone resistance in D. immitis populations across the United States.

To safeguard the long term prevention and control of this disease, the identification and development of novel anthelmintics is urgently needed. To identify novel, resistance-breaking drugs, it is highly desirable to:

Unfortunately, none of the three above statements can be answered sufficiently for D. immitis and most of our hypotheses derive from surrogate species and/or in vitro studies. Therefore, the present study aims to improve our fundamental understanding of the neuromuscular system of the canine heartworm by establishing new methods allowing the investigation of body wall and pharyngeal muscle responses and their modulation by anthelmintics. We found that the pharynx of adult D. immitis responds to both ivermectin and moxidectin with EC₅₀s in the low micromolar range. We also demonstrate that the somatic muscle cells have robust responses to 30 μM acetylcholine, levamisole, pyrantel and nicotine. This is important preliminary data, demonstrating the feasibility of electrophysiological studies in this important parasite.

尽管被认为是伴侣动物中最具致病性的蠕虫感染之一，但大环内酯类成员是唯一可用于预防犬恶丝虫引起的心丝虫病的药物。令人担忧的是，心丝虫预防处于危险之中。几项研究证实了美国各地D. immitis种群中存在大环内酯抗性。

为保障该病的长期防控，迫切需要新型驱虫药的鉴定和开发。为了识别新的、打破抗药性的药物，非常需要：

不幸的是，上述三个陈述都不能为D. immitis 提供充分的回答，我们的大多数假设都来自替代物种和/或体外研究。因此，本研究旨在通过建立允许研究体壁和咽部肌肉反应及其通过驱虫药调节的新方法，提高我们对犬心丝虫神经肌肉系统的基本了解。我们发现成年D. immitis的咽部对伊维菌素和莫昔克丁都有响应，EC ₅₀s 在低微摩尔范围内。我们还证明，体细胞对 30 μM 乙酰胆碱、左旋咪唑、吡喃妥和尼古丁有强烈的反应。这是重要的初步数据，证明了对这种重要寄生虫进行电生理研究的可行性。