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Oral clenbuterol may have deleterious effects on heart function in mice
Victor Chu, Jose M. Otero, Orlando Lopez, Ivo Amende,
and Thomas G. Hampton; Mouse Specifics, Inc., Boston, MA. USA.
Web Published: October 1, 2001
Abstract
Based on their anabolic properties, ß-adrenergic agonists such as clenbuterol have been used as muscle-specific growth-promoting agents. 1,2 The dual influences of clenbuterol on skelatal and cardiac muscle growth2-4 compelled us to screen its effects on the electrocardiogram (ECG) in mice. Accordingly, we non-invasively recorded ECGs in adult male AKR/J mice orally administered clenbuterol. Heart rate decreased ~18% after 3 days of clenbuterol administration (P<0.05). The QRS interval duration increased significantly. These observations may be suggestive of downregulation of ß-adrenergic receptors and the known hypertrophic effects of clenbuterol on cardiac muscle.
Methods
Figure 1.Heart rate
Figure 2.QRS interval duration
Male AKR/J mice (n=10, age 8 weeks) were obtained from The Jackson Laboratory. The ECGenie ECG screening system was used to record ECGs.5 Neither anesthetic nor surgery was required. After baseline recordings were performed, water bottles for 5 mice were replaced with bottles containing clenbuterol to provide effectively 1.5 mg/kg body weight/day.6 Recordings were repeated on the subsequent 3 days. Data were acquired at 2kHz for at least 2 seconds to provide equivalent continuous recordings of 20 to 30 beats. e-MOUSETM was used to interpret the signals.5
Results
Effects of Clenbuterol on Day 3.
Baseline (n=10)
Clenbuterol (n=5)
HR (bpm)
762 ± 17
631 ± 18*
PR (ms)
27.7 ± 0.8
29.4 ± 0.3
QRS (ms)
8.1 ± 0.2
9.5 ± 0.2*
QT (ms)
53.4 ± 2.1
68.2 ± 2.5*
QTc (ms)
59.9 ± 1.5
69.7 ± 1.6*
*P < 0.01 via Student's 2-tail unpaired
t-test.
Discussion
The ß2-adrenergic agonist clenbuterol is used by athletes because of its potent muscle anabolic and lipolytic actions.7 It has proved beneficial to mice with muscular dystrophy6,8, yet deleterious to excercise performance in rats7 and mice.9 Clenbuterol has also been shown to induce significant cardiac hypertrophy.3,4 We found that in young adult male AKR/J mice, oral administration of clenbuterol resulted in a significant decrease (~18%) in heart rate and a significant increase in the QRS interval duration. These observations may correlate to the decrease of ß2-receptors occurring with clenbuterol administration10 and extensive collagen infiltration in hypertrophied LV tissue resulting from clenbuterol treatment.7 These results are consistent with the previous findings that 3 days of isoproterenol administration to C57BL/6 mice resulted in decreased heart rate and significant cardiac hypertrophy.5 Our protocol provides a rapid means for non-invasively altering cardiac properties and monitoring these effects via the ECG.
References
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