Katra RP, Oya T, Hoeker GS, Laurita KR. Ryanodine receptor dysfunction and triggered activity in the heart. Am J Physiol Heart Circ Physiol 292: H2144 -H2151, 2007. First published December 22, 2006; doi:10.1152/ajpheart.00924.2006.-Arrhythmogenesis has been increasingly linked to cardiac ryanodine receptor (RyR) dysfunction. However, the mechanistic relationship between abnormal RyR function and arrhythmogenesis in the heart is not clear. We hypothesize that, under abnormal RyR conditions, triggered activity will be caused by spontaneous calcium release (SCR) events that depend on transmural heterogeneities of calcium handling. We performed highresolution optical mapping of intracellular calcium and transmembrane potential in the canine left ventricular wedge preparation (n ϭ 28). Rapid pacing was used to initiate triggered activity under normal and abnormal RyR conditions induced by FKBP12.6 dissociation and -adrenergic stimulation (20 -150 M rapamycin, 0.2 M isoproterenol). Under abnormal RyR conditions, almost all preparations experienced SCRs and triggered activity, in contrast to control, rapamycin, or isoproterenol conditions alone. Furthermore, under abnormal RyR conditions, complex arrhythmias (monomorphic and polymorphic tachycardia) were commonly observed. After washout of rapamycin and isoproterenol, no triggered activity was observed. Surprisingly, triggered activity and SCRs occurred preferentially near the epicardium but not the endocardium (P Ͻ 0.01). Interestingly, the occurrence of triggered activity and SCR events could not be explained by cytoplasmic calcium levels, but rather by fast calcium reuptake kinetics. These data suggest that, under abnormal RyR conditions, triggered activity is caused by multiple SCR events that depend on the faster calcium reuptake kinetics near the epicardium. Furthermore, multiple regions of SCR may be a mechanism for multifocal arrhythmias associated with RyR dysfunction. spontaneous calcium release; sudden death; arrhythmia mechanisms ARRHYTHMIAS CAUSED BY ABNORMAL impulse formation (i.e., triggered activity) have been associated with (33, 34) and without (5, 9, 16, 27) structural heart disease. In addition, recent evidence suggests that such arrhythmias can be caused by spontaneous calcium release (SCR) from the sarcoplasmic reticulum (SR). SCR events may be a result of cardiac ryanodine receptor (RyR) dysfunction such as that associated with mutations in the human cardiac RyR channel (37), heart failure (25, 40), and/or alterations in the RyR (30) and accessory proteins (e.g., FKBP12.6) (45, 49); however, the underlying mechanisms are controversial. FKBP12.6 is an accessory protein to the tetrameric RyR channel with 4:1 stoichiometry that stabilizes the RyR in the closed/open state and prevents aberrant activation during diastole. Dissociation of the FKBP12.6 molecule is believed to cause RyR channels to gate independently and alter individual RyR channel gating kinetics, rendering the channel prone to SCR events (28). Alternatively, SCR associated with abn...
of active or passive recovery on performance and muscle oxygenation during short-duration intermittent exercise. Japan J. Phys. Educ. Hlth. Sport Sci. 58: 463 471, December, 2013 AbstractPurpose: Recovery condition is classiˆed into two major categories during short-duration (<6 s) intermittent sprint exercise: active recovery (AR) and passive recovery (PR). Performance in passive trials is superior to active trials during short-duration intermittent sprint exercise. The eŠect of AR intensity on performance during short-duration intermittent sprint exercise remains unclear. The purpose of this study was to compare the eŠect of recovery conditions (active vs. passive) and exercise intensity of the recovery period on performance, as well as muscle oxygenation during short-duration intermittent exercise. Methods: Ten subjects performed a graded test and ten 5 s maximal sprints with 25 s of PR or AR between sprints on a cycle ergometer. Exercise intensity of AR was adjusted to 15 (AR15), 25 (AR25), or 40 (AR40) of maximal oxygen uptake ( _VO 2 max), and these were randomly assigned. Peak power and percentage decrement in power were determined during the intermittent sprint exercise. Oxyhemoglobin (O 2 Hb) and deoxyhemoglobin were also measured using near-infrared spectroscopy. Results: Peak power values were signiˆcantly higher with PR than with AR40 (P<0.05). The percentage of peak power decrement was signiˆcantly lower with PR than with AR40 (8.4±2.9 vs. 10.9± 3.6, P<0.05). O 2 Hb variation was signiˆcantly higher with PR than with AR40 (27.9±9.6 vs. 20.6 ±6.0, P<0.05). Conclusion: AR40 is associated with reduced sprint performance and lower muscular reoxygenation. Performance with AR is not inferior compared with PR if AR is less than 25 of _VO 2 max during shortduration intermittent exercise.
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