Electrocardiographic characterization of stress-induced myocardial infarction in atherosclerotic mice.
OBJECTIVE
We have previously shown that mental and hypoxic stress can trigger the development of myocardial infarction (MI) in atherosclerotic apoE(-/-) x LDLR(-/-) mice. The purpose of the present study was to characterize the interval between stress and MI and determine whether electrophysiological changes precede the precipitation of an infarct by assessing telemetry recordings of the electrocardiogram.


METHODS
Isoflurane anaesthetized apoE(-/-) x LDLR(-/-) (n = 16) and C57BL/6J (n = 8) mice were exposed to systemic hypoxia by reducing the inhaled oxygen concentration to 10% for 10 min. Mental stress was induced in eight conscious apoE(-/-) x LDLR(-/-) and eight C57BL/6J mice by blowing air into the cage. Physiological parameters were recorded every 30 min for 2-6 days by implanted transmitters.


RESULTS
During stress all mice developed transient ischaemic STU-area changes, which returned to normal at the end of stress. During the recovery phase (6 days) 50% (4/8) of the mentally stressed apoE(-/-) x LDLR(-/-) mice developed increased STU-area variability (P < 0.05) followed by dramatic STU-area elevations and spontaneous death at approximately 12-24 h. In hypoxia-exposed apoE(-/-) x LDLR(-/-) mice 56% (9/16) developed MI as determined by elevated serum levels of the infarction marker troponin T which correlated with increased variability in the STU-area (P < 0.05).


CONCLUSIONS
This is the first mouse model showing that increased STU-area variability is indicative of MI development in atherosclerotic mice following ischaemic stress. Furthermore, our findings suggest a two-phase pathway for the infarction development: an initial phase comprising a transient ischaemic response which triggers a delayed second phase of ischaemia and MI.
Hemdahl
A-L
AL
Center for Molecular Medicine L8:03 and Department of Medicine, Karolinska Institutet, Stockholm, Sweden. anne-louise.hemdahl@fyfa.ki.se
Caligiuri
G
G
Hansson
G K
GK
Thorén
P
P
D000818:Animals; D001161:Arteriosclerosis / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D003331:Coronary Vessels / Q000473:pathology; D004562:Electrocardiography / Q000379:methods; D006339:Heart Rate / Q000502:physiology; D000860:Hypoxia / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D013315:Stress, Psychological / Q000150:complications / Q000473:pathology / Q000503:physiopathology*