Anne-Marie Koop

68 from all eligible studies. Universal Desktop Ruler (Avpsoft) was used to derive data from graphs. In case of missing information, authors were contacted. If response was lacking, we approached the data as follows: when the SD was unknown, the SD was calculated when mean difference, (corrected) p-value and number of used subjects were available; in case of unknown SD of the control groups, we used the SD of the experimental group;if the exact n was unknown, the greatest number given was used for the calculation of the SD. Data synthesis Effect sizes, defined as Hedges’ g, with associated confidence interval of 95% were calculated, where after multiple separate random effects meta-analyses were performed using STATA 11. When the actual number of animals (n) used for a certain variable was unknown (i.e. not reported in the manuscript and not acquired after contacting the author), the smallest nmentioned by the authorswas used to calculate the Hedges’ g. Combined effect sizes of a particular variable were calculated for (1) the different models (shown by the grey squares) and (2) all studies describing the variable (shown by the black squares). Heterogeneity was assessed using Cochran’s Q-test and the I 2 quantity. In order to explore the sources of heterogeneity, meta- regression analyses were performed for duration and degree of pressure load if information was available for more than two groups. To perform meta-regression analysis of a variable with duration, actual duration of pressure load had to be given (i.e. variables were excluded frommeta-regression analysis if corresponding duration was defined as a time-interval (e.g. 2-6 weeks)). To be included for meta-regression analyses concerning the degree of pressure load, RV loading had to be measured as actual pressure rather than increase in hypertrophy. Unfortunately, meta-regression of cardiac or RV function was impossible due to lack of available data. In addition, differences between models were tested with unpaired t-test or one-way ANOVA with post-hoc Tukey’s correction. Since their different function in biological processes, gene expression (at mRNA level) and protein expression of studied variables were separately included in meta-analysis. In some studies, mitochondrial content was tested by different measurement techniques within the same animals. To avoid overrepresentation of included subjects, the results of only one (the superior) technique/definition was included for meta-analysis. We ranked the different definitions of mitochondrial content (which were used in the same animals) as follows: (1) ratio mitochondria to myofibrils, (2) mitochondrial yield, (3) citrate synthase activity, (4) citrate synthase at mRNA level, (5) whole tissue citrate synthase activity. However, all results (from all different techniques) are visually shown in the figures.