Tension cost and contractility changes Moreira CM et al. CLINICS 2012;67(5):489-496 Figure 1 - Effects of myocardial infarction (A), hypertension (B), diabetes (C), DOCA-salt-induced hypertension (D), and chronic L-NAME treatment (E) on the isometric force (g/mm2) in the rat papillary muscle. The results represent the mean ¡ SEM, and N indicates the number of experiments. *p,0.05 vs. control, Sham, NF, Salt, and DOCA (t-test or one-way ANOVA, repeated measurements). Because our results were consistent with the previously reported controversies, we attempted to identify a correla- tion between mechanical changes and biochemical changes. According to Rundell et al. (17), the relationship between myosin ATPase activity and developed force provides information about the energetic cost of tension. As shown in Figure 4, in which force is plotted against myosin ATPase activity (tension cost) observed in the L-NAME, DOCA-salt, diabetic, Wistar control, SHR and WKY groups, there was a positive correlation among these variables under both normal conditions (Figure 4A) and with the use of tetanic plateau force (Figure 4B). DISCUSSION Our results demonstrate that tension cost, the ratio of myosin ATPase activity to force, correlates mechanical and corresponding biochemical changes. The ratio shows that the contractile state of the myocardium in several condi- tions, such as post-myocardial infarction, DOCA-salt- induced hypertension, chronic L-NAME treatment, and streptozotocin-induced diabetes, is represented by a posi- tive correlation between tension developed and myosin ATPase activity. This characterizes the energetic cost of tension as an attempt to obtain a better mechanical advantage. The relationship between myosin ATPase activity and contraction velocity is well established (1). In the rat 492 myocardium, however, the activity and expression of myosin ATPase has been suggested to reflect myocardial force development (2-7). The three myosin isoforms are denoted as V1, V2, and V3. The V1 isoform (aa) possesses the highest ATP hydrolysis velocity of the three and composes the heavy chains. The isoform displaying the lowest velocity is V3 (bb); V2 (ab) is a mixed isoform with intermediate velocity (5,8,10). However, during adaptation to several pathophysiological conditions, Ca2+-handling mechanisms might prevent mechanical deficiencies before stable conditions are achieved. These various adaptive mechanisms explain why correlations between force devel- opment and the biochemical activity in cardiac muscle are still a matter of debate. We then performed experiments with several models that exhibit changes in myosin ATPase activity and force when conditions stabilize. Myocardial infarction is associated with adaptive changes that enable the heart to maintain an effective systolic performance (23). The infarcted chamber increases its volume and the end-diastolic pressure to maintain cardiac output. These changes are limited by the contractile capacity of the remaining myocardium and the energetic cost of the mechanical activity. Our results obtained 30 days after myocardial infarction show a reduction in isometric and tetanic tension. These findings and those regarding the area of infarction are similar to previous results from our laboratory (23-25). However, the mechanisms underlying this force reduction remain to be determined. Min et al. (26)