Anomalous low susceptibility to ventricular fibrillation during infarct evolution in acutely-prepared pentobarbitone-anaesthetised rats Hugh Clements-Jewery & Michael J. Curtis. Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, Lambeth Palace Rd, London SE1 7EH.

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Following coronary artery ligation, conscious rats exhibit two distinct phases of ventricular fibrillation (VF), the first within 30 min of ischaemia onset (phase 1) and the second after 1.5 hours (phase 2) when the infarct is evolving. Phase 1 and phase 2 VF occur in 70-100% of control conscious animals (Curtis, 1998). The mechanisms of phase 2 VF are not well understood. Anaesthetised animal models are preferable to conscious for ethical reasons. Therefore we set up an anaesthetised rat model to explore mechanisms of phase 2 VF, based on a published method (Curtis et al., 1985).

Male Wistar rats (240-330g) were anaesthetised with i.p. pentobarbitone (60 mg kg^-1). Femoral arterial and venous cannulae were inserted for blood pressure recording and anaesthetic administration, respectively. The ECG was recorded using standard limb leads. Rats were ventilated at a rate of 54 strokes min^-1 and 10 ml kg^-1 stroke^-1 with oxygenated room air during chest opening. The heart was exposed by intercostal incision followed by rib retraction. A suture (Ethicon Prolene 4/0) was sewn under the left main coronary artery close to its origin, and the ends were threaded through a traction-type occluder that protruded from the chest. Ischaemia was induced by tightening the occluder.

Unexpectedly, VF was rare. Of 33 rats, none had phase 2 VF. In addition, only 5 rats had phase 1 VF. The presence or absence of phase 1 VF was unrelated to differences in occluded zone size (mean±SD 42±6% of ventricular weight in rats without VF vs 38±4% in rats with VF), 15 min blood K⁺ values (4.3±0.5 vs 4.3±0.3 mM), PO₂ (137±75 vs 87±28 mmHg), PCO₂ (29±7 vs 29±4 mmHg), and pH (7.46±0.07 vs 7.45±0.02; all p=NS). Retractor usage during ligature placement lowered blood pressure but since mean blood pressure during usage was similar in rats with or without VF (50±14 vs 45±3 mmHg respectively; p=NS), inadvertent preconditioning did not account for the absence of VF. However, during ischaemia, rats without VF had higher mean heart rates (458±37 vs 404±33 beats min^-1; p<0.05) and, as a trend, blood pressures (109±24 vs 87±14 mmHg) than those that had VF (15 min values shown). We investigated whether a supranormal heart rate could account for the low susceptibility to phase 1 and phase 2 VF. Further male Sprague-Dawley rats (250-390g; n=10 per group) were prepared as described. In the test group, heart rate was buffered to 400 beats min^-1 by stepwise anaesthetic (pentobarbitone) increments, whereas heart rate was not buffered in the control group. As a result heart rate was lower in the buffered group compared to controls (402±16 vs 446±19 beats min^-1 at 15 min and 396±44 vs 432±20 beats min^-1 at 180 min; p<0.05). However, this did not restore phase 1 VF (30% incidence vs 10% in controls; p=NS). In addition, only 20% of the buffered group developed phase 2 VF compared to 10% in controls (p=NS).

It remains unclear why a study-limiting, anomalous, low susceptibility to phase 1 and 2 VF may occur in acutely-prepared pentobarbitone-anaesthetised rats.

Curtis M.J., 1998. Cardiovascular Research, 39:194-215.
Curtis M.J. et al., 1985. Br. J. Pharmacol., 86: 663-70.