Although the term CM was coined by Rosenbaum in 1981 [1
], the electrophysiological basis for T-wave memory and the mechanisms responsible for triggering CM have remained elusive. Identifying these mechanisms has important implications for the pathophysiology of common heart diseases involving CM [5
]. Guided by these considerations, we designed the non-thoracotomy CM model in which CM was precipitated by using endocardial pacing via internal jugular vein.
CM models can provide valuable insights into several areas. One is for use in analyzing mechanisms of CM. Another is that it offers the possibility of evaluating novel strategies for targeted prevention of CM. CM models can also be used to assess the effects of short-term and long-term CM on cardiac function. Recognition of these advantages has led to development of several CM models. Shvilkin et al. [4
] described a method inducing CM using epicardial pacing via thoracotomy in mongrel dogs. Approaching the heart through a thoracotomy at the fifth left intercostal space, epicardial pacing lead was attached to the inferolateral left ventricular wall. Then the lead was connected to a dual-chamber pacemaker affixed subcutaneously. The animal model of CM was frequently used in recent years[10
]. Some studies[10
] using the model have demonstrated that the transient outward potassium current (Ito
), epicardial mRNA levels of Kv4.3 (one of the molecular correlates of Ito
) and L-type Ca2+
) may be involved in the development and maintenance of cardiac memory. Nevertheless, the method inducing CM via thoracotomy had severe surgical trauma, may result in increasing dog mortality.
In the present study, our model minimized surgical trauma using endocardial pacing via internal jugular vein. In our model, just one dog died during the early part of the experience. Avoidance of thoracotomy should ultimately enhance survival. Moreover, we mimicked the use of pacemakers in humans. The method to induce CM in our model appears more similar to clinical situations in humans. Therefore, it may have an application in analyzing mechanisms of CM.
This canine model had a high success rate (11/12, 91.7%). After successful pacemaker implantation, all dogs in short-term and long-term CM groups develop the CM model. In our experience, the key points to develop the CM animal model are as follows: the operation of pacemaker implantation should be under fluoroscopy; right ventricular pacemaker lead insertion via internal jugular vein should be gentle, otherwise maybe result in cardiac perforation and tamponade.
In agreement with some previous studies [4
], we found that the appetite, behaviour, and activity status in all dogs did not change significantly over the course of the study, and there were no significant differences in the heart rate, blood pressure and echocardiographic parameters in the animals between before and after ventricular pacing in the short-term CM and long-term CM groups. Moreover, we demonstrated no significant pathologic changes with the light microscopy in the present study. The result was similar to that of previously reported studies [14
]. In addition, these studies [14
] also found that right ventricular pacing was associated with mismatching of perfusion and innervation with perfusion abnormalities of both the septum and free wall. However, other studies [16
] have identified ultrastructural changes induced by pacing. Karpawich et al. [16
] found that after the dogs with epicardial pacemaker lead placed near the right ventricular apex through a thoracotomy were paced for several months, myofibrillar disarray, and areas of dystrophic calcification dispersed throughout the left ventricular free wall on light microscopy. It is unclear whether the different findings by us reflect different pacing modes or pacing time or surgical method or other technical differences between our study and that of Karpawich et al.
In conclusion, a method of establishing a canine model of CM using endocardial pacing via internal jugular vein was successfully demonstrated and it proved to be simple, safe and effective. The ECGs characteristics of the model are in good accordance with those of CM in patients. The novel CM model described here can offer potentially important advantages over preexisting models.