Details of the canine model were recently reported19 (link). Briefly, dogs (n=32) were subjected to left bundle radiofrequency ablation followed by 6-wks of atrial tachypacing (~200 bpm, dyssynchronous heart failure, DHF) or 3-wks atrial pacing (dyssynchrony) and then 3 weeks bi-ventricular pacing (LV lateral and RV antero-apical epiardium) at the same rapid rate (CRT). Sham DHF dogs (n=3) with both surgical ventricular leads placed but not utilized were also studied. Non-instrumented dogs (n=13) served as controls. Echo and tissue Doppler studies were performed at 3 and 6 weeks in conscious animals to assess LV dysynchrony19 (link), chamber dimensions, and ejection fraction.
At terminal study, dogs were anesthetized with pentobarbital, pacing suspended, and a micromanometer (Millar, Houston, TX) advanced to record LV pressures. The chest was opened, hearts rapidly harvested under cold cardioplegia and myocardium frozen for tissue analysis (endocardial and mid/epicardial segments from septum and LV lateral) or for myocyte isolation from anterior-septum and lateral walls. Details of these procedures have been reported20 (link),21 (link) and are also provided in supplemental online methods.
Eight additional animals were chronically instrumented with sonomicrometers to derive left ventricular volume (Sonometrics, WA) and micromanometer (Konigsberg, CA) to measure LV pressure, assigned to CRT or DHF groups, and LV function assessed in the conscious state at both 3 and 6 weeks to obtain paired invasive hemodynamic data.
At terminal study, dogs were anesthetized with pentobarbital, pacing suspended, and a micromanometer (Millar, Houston, TX) advanced to record LV pressures. The chest was opened, hearts rapidly harvested under cold cardioplegia and myocardium frozen for tissue analysis (endocardial and mid/epicardial segments from septum and LV lateral) or for myocyte isolation from anterior-septum and lateral walls. Details of these procedures have been reported20 (link),21 (link) and are also provided in supplemental online methods.
Eight additional animals were chronically instrumented with sonomicrometers to derive left ventricular volume (Sonometrics, WA) and micromanometer (Konigsberg, CA) to measure LV pressure, assigned to CRT or DHF groups, and LV function assessed in the conscious state at both 3 and 6 weeks to obtain paired invasive hemodynamic data.
