豚の慢性心不全モデルとして頻拍誘発性心筋

The overall goal of this surgical procedure is to induce dilated cardiomyopathy and provide a stable platform for studying pathophysiology of chronic heart failure including remodeling and excentric ventricular hypertrophy. This method can help to answer many questions in cardiovascular field such as heart failure progression involving the ventricular dilation and remodeling as well as discovery of novel therapeutic strategies in chronic heart disease. The main advantage of this technique is that it is a minimal invasive method that requires simple surgical techniques and can get results that are highly reproducible.

The implication of these techniques is to study pathophysiology and therapeutics of chronic heart disease since long term fast cardiac pacing induces dilated cardio myopathy and at the end of the protocol leads to biventricle dilation and general progression of heart failure. Have a healthy six months old domestic swine and after one day of fasting, initiated anesthesia by intramuscular administration of anesthetics. Insert canula into a marginal ear vein and secure by bandage.

Maintain the anesthesia by combination of suitable anesthetics and after oxygenation intubate with a cuffed endotracheal tube. Operate the mechanical ventilation by a closed loop automatic device, set to adaptive support ventilation to maintain adequate hemoglobin saturation and entitle CO2. Monitor all vital functions.

Attach the animal on the operation table in supine position, and before instrumentation administer wide spectrum antibiotics. When using radiation, wear appropriate protection. Shave the skin properly in the jugular and dorsal regions.

Using the ultrasound vascular probe, visualize the jugular vein and mark it's location on the skin. Locate the carotid artery too to prevent it's injury. Disinfect the skin and cover with a sterile surgical drape.

Prepare the necessary surgical material for pacemaker implantation and maintain a sterile environment throughout the procedure. Cut the skin above the jugular vein and form a shallow subcutaneous pocket, do not expose the large vessels. Use electric cauterization to stop possible minor bleeding.

From the bottom of performed pocket, insert a sheet into the jugular vein. Use the standard Seldinger technique to insert a peel away sheet. First introduce a softed guide wire through the 12G puncture needled.

Then over the guide wire insert a seven fringe plastic tearaway introducer sheet with dilator. Remove the sheet and fixate the active tip of the electrode to the myocardium. Under fluoroscopic guidance introducing the pacing lead and position it to the apex of the right ventricle.

There's the pacing parameters. The sensed ventricular signal and impedance must be stable. There's the pacing threshold.

Reposition the electrode until pacing parameters are optimal. Find location with optimal pacing parameters, then pull a rubber sleeve on the pacing lead and fix both together to the bottom of preformed jugular pocket by two non observable suture stitches. Consider the future possible growth of the animal.

Turn the animal over on its side and disinfect the wide skin region lateral to the backbone. Cover with sterile surgical drape with hole. Make sure the jugular pocket and lead remain sterile.

Cut the skin lateral to the backbone and form a deep spacious subcutaneous pocket. Use dell preparation and stop any possible bleeding. The pocket must be large enough to contain comfortably the pacemaker unit and any redundant lead.

Take a soft rubber extension tube from a sterile infusion set and cut off its both ends. Connect its one end to the tunneling tool and the other to the ventricular lead by pulling it onto it IS1 connector. Secure both connections by stitches.

Using the tunneling tool, perform a direct subcutaneous tunnel connecting the jugular and dorsal pockets. Draw the electrode through by pulling it dorsally. Remove both tunneling tool and extension tube.

Expose the ventricular lead from the dorsal pocket. Set up the implantable dual chamber heart pacemaker unit with Y connecting part. The Y connection allows a convergent connection of both pacemaker output to be joined and connected together to a single pacing lead.

This setting will provide a wide range of pacing frequencies. After connecting the pacing lead, fasten all the IS1 connection screws in the pacemaker header unit and Y lead connection. Hide the whole pacing system into the dorsal pocket.

There must be enough space to comfortably accommodate pacemaker unit and any redundant lead. Flush with disinfection and close both pockets. Use absorbable braided thread to suture fibrous tissue and non observable suture for skin adaptation.

Use tincture to scrub surgical site to prevent infection. Cover the surgical site for optimal healing and administer antibiotics repeatedly. To prevent post surgical pain, treat the animal with morphine and closely observe the animal.

Place the animal in a comfortable facility with free access to water and allow good recovery. After adequate resting period begin with the pacing protocol. Initially pace 200 beats per minute by setting to D00 mode and adjusting the rate AB delay.

Then increase the device to 220 beats per minute after one week, and to 240 beats per minute after two weeks. Verify daily the heart rate and pacing parameters including battery life. Specialized Veterinarian must ensure the animal's general health status and heart failure progression.

Adapt the protocol according to individual responses. Use echo cardiography to reveal structural and functional heart changes. After four to eight weeks of tachycardia, dilated cardiomyopathy is induced.

Left ventricle pressure and volume show dilation and impaired systolic function. Systolic blood pressure is reduced. Chest x-ray shows heart shadow dilation and systolic dysfunction is demonstrated by echo cardiography.

As we can see here, cardiac volume increases in tachycardia induced cardiomyopathy as demonstrated by higher heart to body rate ration, which is an indicator of cardiac hypertrophy. After training, the surgery can be done in 60 minutes if it is performed properly. During the pacing protocol, echo cardiography should be used for a noninvasive monitoring of the ventricular dysfunction and the progression of heart failure.

Then this animal model can be used for studying of new therapeutics like artificial supplementary supports. The development of this cardiomyopathy paved the way to studies in the field of chronic heart disease and can help to explore the pathophysiology of heart failure, it's adaptation mechanisms and the fact of new treatments. After watching this video you should have a good understanding of how to perform the lead introduction, pacemaker implantation and the pacing protocol to develop the tachycardia induced cardiomyopathy in swine.