Mechanical properties of the myocardium at end diastole have been thought to be dominated by passive material properties rather than by active sarcomere cross-bridge interactions. This study tested the hypothesis that residual cross-bridges significantly contribute to end-diastolic mechanics in vivo and that changes in end-diastolic cross-bridge interaction parallel concurrent changes in systolic cross-bridge interaction. Open-chest anesthetized pigs were treated with intracoronary verapamil (n = 7) or 2,3-butanedione monoxime (BDM; n = 8). Regional left ventricular external work and end-diastolic pressure (EDP) versus end-diastolic segment length (EDL) relations were determined in the treated and untreated regions of each heart. Both agents reduced external work of treated regions to 31-38% of baseline and concurrently shifted EDP versus EDL relations to the right (i.e., greater EDL at a given EDP) by an average of 5% (P < 0.05). During washout of the drugs, EDP versus EDL returned to baseline in parallel with recovery of external work. Sarcomere length, measured by transmission electron microscopy in BDM-treated and untreated regions of the same hearts after diastolic arrest and perfusion fixation, was 8% greater in BDM-treated regions (P < 0.01). We concluded that residual diastolic cross-bridges significantly and reversibly influence end-diastolic mechanics in vivo. Alterations of end-diastolic and systolic cross-bridge interactions occur in parallel.
Keywordsdiastole; ventricular function; calcium channel blockers; di-acetyl analogs and derivatives; sarcomeres Cross-bridge cycling triggered by the presence of cytosolic calcium is the basis for force generation in muscle. In systole, the cross-bridge cycling rate and force generation increase in relation to the magnitude of the cytosolic calcium transient and the sensitivity of myofibrillar regulatory proteins to calcium (8). In diastole, there is an active reuptake of calcium into the sarcoplasmic reticulum; however, a low level of calcium-activated crossbridge cycling and active tension development may persist at end diastole (17). Thus, whereas end-diastolic ventricular pressure-dimension relations are generally considered to reflect the underlying passive material properties of cardiac muscle (13), it is possible that changes in calcium availability or myofilament calcium sensitivity influence these relations. This concept is supported by a study (5) in isolated spontaneously beating cardiac myocytes demonstrating that cell length continues to increase throughout diastole. It is also supported by studies (12,19) Recent data from our laboratory support such a prediction. In a porcine model of acute myocardial ischemia and reperfusion resulting in systolic dysfunction (stunning), we observed increased end-diastolic segment length (EDL) at low EDP in vivo and increased diastolic sarcomere length after in situ perfusion fixation at low LV cavity pressure (15). These increases in end-diastolic muscle length and diastolic sarcomere length occurred in ...