Isoprenaline increases the slopes of restitution trajectory in the conscious rabbit with ischemic heart failure |
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Authors: | Tomofumi Kimotsuki Noriko Niwa Martin N Hicks Michael Dunne Stuart M Cobbe Mari Alford Watanabe |
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Institution: | (1) Internal Medicine Department, St. Louis University School of Medicine, St. Louis, USA;(2) Developmental Biology Department, Washington University School of Medicine, St. Louis, USA;(3) Cardiology Department, Glasgow Royal Infirmary, Glasgow, UK;(4) Cardiology Division, Internal Medicine Department, St. Louis University Hospital, 3635 Vista Avenue at Grand Avenue, St. Louis, MO 63110-0250, USA;; |
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Abstract: | Roughly speaking, restitution is the dependence of recovery time of cardiac electrical activity on heart rate. Increased restitution
slope is theorized to be predictive of sudden death after heart injury such as from coronary artery occlusion (ischemia).
Adrenaline analogs are known to increase restitution slope in normal hearts, but their effects in failing hearts are unknown.
Twenty-six rabbits underwent coronary ligation (n = 15) or sham surgery (n = 11) and implantation of a lead in the heart for recording electrocardiograms. Eight weeks later, unanesthetized rabbits
were given 0.25–2.0 ml of 1 μmol/L isoprenaline intravenously, which increased heart rate. Heart rate was quantified by time
between QRS peaks (RR) and heart activity duration by R to T peak time (QTp). Ligated rabbits (n = 6) had lower ejection fraction than sham rabbits (n = 7, p < 0.0001) indicative of heart failure, but similar baseline RR (269 ± 15 vs 292 ± 23 ms, p = 0.07), QTp (104 ± 17 vs 91 ± 9 ms, p = 0.1), and isoprenaline-induced minimum RR (204 ± 11 vs 208 ± 6 ms, p = 0.4). The trajectory of QTp vs TQ plots displayed hysteresis and regions of negative slope. The slope of the positive slope
region was >1 in ligated rabbits (1.27 ± 0.66) and <1 in sham rabbits (0.35 ± 0.14, p = 0.004). The absolute value of the negative slope was greater in ligated rabbits (− 0.81 ± 0.52 vs − 0.35 ± 0.14, p = 0.04). Isoprenaline increased heart rate and slopes of restitution trajectory in failing hearts. The dynamics of restitution
trajectory may hold clues for sudden death in heart failure patients. |
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