Development and characterization of a mouse in vitro model of ischaemia-induced ventricular fibrillation.
OBJECTIVE
We sought to generate a mouse Langendorff model of ischaemia-induced ventricular fibrillation (VF) that does not depend on triggers such as programmed electrical stimulation.


RESULTS
Hearts from male Tuck Ordinary mice were perfused with Krebs solution (modified to contain low-normal K(+), 3 mmol/L, and high Ca(2+), 2.4 mmol/L) containing different combinations of catecholamines (epinephrine 313 nmol/L plus norepinephrine 75 nmol/L) and/or angiotensin II (100 pmol/L) designed to mimic the in vivo milieu. VF was absent during 30 min regional ischaemia (and during 10 min reperfusion) in Krebs-perfused hearts. Catecholamines unmasked ischaemia-induced VF (50%; P < 0.05) and reperfusion-induced VF (50%; P < 0.05). Co-perfusion with angiotensin II did not facilitate VF. Supraventricular pacing (600 b.p.m.) stabilized pre-ischaemic sinus rhythm and partially mimicked the VF-unmasking effect of catecholamines. Arrhythmia susceptibility was greatest with supraventricular pacing plus catecholamines (57% VF during ischaemia and 71% during reperfusion).


CONCLUSIONS
For the first time, regional ischaemia-induced VF was consistently evoked in a mouse Langendorff preparation, unmasked by simple periphysiological manipulation of the perfusion conditions. The model is suitable for functional genomic studies.
Stables
Catherine L
CL
Cardiovascular Division, St Thomas' Hospital, King's College London, London SE1 7EH, UK.
Curtis
Michael J
MJ
D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects; D002395:Catecholamines / Q000008:administration & dosage; D004195:Disease Models, Animal; D004562:Electrocardiography; D006339:Heart Rate; D008297:Male; D051379:Mice; D017202:Myocardial Ischemia / Q000150:complications* / Q000503:physiopathology; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000503:physiopathology; D010477:Perfusion; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000503:physiopathology
D002395:Catecholamines; D000804:Angiotensin II