In other variables, studies conflict between showing convincing changes and convincing absence of change ( Table Table1 1). Moreover, the two studies that reported changes in SR Ca 2+ content indicated opposite directions of change ( Table Table1 1). For example, Ca 2+ transient amplitudes in HF cells are reported as significantly increased in more studies than decreased ( Table Table1 1).
10 However, the cellular data do not consistently fit this. The accepted paradigm is that reduced Ca 2+ transient amplitude contributes to reduced myocardial contractility. Standard statistical methodologies, if used instead, erroneously suggest that spark amplitude is significantly greater in HF and spark duration is reduced in HF.ĪAt physiological Ca 2+ (increased decay time at supraphysiological Ca 2+ of 5 mM). This means that a three-level hierarchical model is sometimes required for such measures. Spark analysis showed clustering, both within each cell and also within each rat, for morphological variables. For example, this would have led to the erroneous conclusion that time to 50% peak transient amplitude was significantly prolonged in HF.
This caused the common statistical approach to underestimate the standard error and report artificially small P values. The statistical tests found that there was significant hierarchical clustering. Data were analysed twice, once with the common statistical approach (assumption of independence) and once with hierarchical statistical methodologies designed to allow for any clustering. Ca 2+ transients were recorded in cells loaded with Fura-2AM and sparks were recorded in cells loaded with Fluo-4AM.
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