Terumasa Morita

Ventricular contractility in atrial fibrillation is predictable by mechanical restitution and potentiation

We recently found that contractility ( E max) of an individual irregularly arrhythmic beat in electrically induced atrial fibrillation (AF) is reasonably predictable from the ratio of the preceding beat interval (RR1) to the beat interval immediately preceding RR1 (RR2) in the canine left ventricle. Moreover, the monotonically increasing relation between E max and the RR1-to-RR2 ratio (RR1/RR2) passed through or by the mean arrhythmic beat E max as well as the regular beat E max at RR1/RR2 = 1. We hypothesized that this E max-RR1/RR2 relation during irregular arrhythmia could be attributed to the basic characteristics of the mechanical restitution and potentiation. To test this, we adopted a known comprehensive equation describing the force restitution and potentiation as a function of two preceding beat intervals and simulated contractilities of irregular arrhythmic beats with randomized beat intervals on a computer. The simulated E max-RR1/RR2 relation reasonably resembled the one that we recently observed experimentally, supporting our hypothesis. We therefore conclude that the primary mechanism underlying the varying contractilities of irregular beats in AF is mechanical restitution and potentiation.We recently found that contractility (Emax) of an individual irregularly arrhythmic beat in electrically induced atrial fibrillation (AF) is reasonably predictable from the ratio of the preceding beat interval (RR1) to the beat interval immediately preceding RR1 (RR2) in the canine left ventricle. Moreover, the monotonically increasing relation between Emax and the RR1-to-RR2 ratio (RR1/RR2) passed through or by the mean arrhythmic beat Emax as well as the regular beat Emax at RR1/RR2 = 1. We hypothesized that this Emax-RR1/RR2 relation during irregular arrhythmia could be attributed to the basic characteristics of the mechanical restitution and potentiation. To test this, we adopted a known comprehensive equation describing the force restitution and potentiation as a function of two preceding beat intervals and simulated contractilities of irregular arrhythmic beats with randomized beat intervals on a computer. The simulated Emax-RR1/RR2 relation reasonably resembled the one that we recently observed experimentally, supporting our hypothesis. We therefore conclude that the primary mechanism underlying the varying contractilities of irregular beats in AF is mechanical restitution and potentiation.

Starling-effect-independent lusitropism index in canine left ventricle: logistic time constant.

The logistic time constant (&tgr;L) has been proposed as a better index of the rate of left ventricular (LV) relaxation or lusitropism than the conventional monoexponential time constant (&tgr;E). However, whether and how the Frank-Starling effect influences &tgr;L remains to be elucidated. We compared the effect of LV volume (LVV) loading on both logistic and monoexponential fittings. The isovolumic LV relaxation pressure curves from the maximum negative time derivative of pressure (-dP/dtmax) were analyzed at 3 different end-points at 4 LVVs of 10, 12, 14, and 16 mL in 8 excised, cross-circulated canine hearts. We found that the logistic fitting was superior to the monoexponential fitting at all LVVs and end-points. LVV loading did not affect &tgr;L but affected &tgr;E slightly. Although the advancing end-point increased both &tgr;L and &tgr;E, the increases were significantly smaller for &tgr;L than for &tgr;E at all LVVs. Moreover, the changes in both the amplitude constants and nonzero asymptotes with the advancing end-point were significantly smaller for the logistic fitting than for the monoexponential fitting. We conclude that &tgr;L served as a more reliable index of lusitropism that is independent of the change in LVV loading or the Frank-Starling effect.

Total Ca handling in canine mild Ca overload failing heart

SummaryWe analyzed total Ca handling of the left ventricle (LV) in the mildly failing heart preparation induced by a temporary intracoronary Ca overloading intervention in eight excised and cross-circulated canine hearts. This Ca intervention consisted of interruption of coronary blood perfusion by Ca-free oxygenated Tyrode perfusion for 10min followed by high-Ca (16 mmol/l) oxygenated Tyrode perfusion for 5 min. This intervention decreased the LV contractility index,Emax (end-systolic maximum elastance), by 40% after restoration of the blood cross-circulation. We expected a Ca overload or paradox failing heart resembling the postischemic stunned heart and being characterized by an increased O2 cost ofEmax. However, LV O2 consumption under mechanically unloading conditions decreased by 30% from control without increasing the O2 cost ofEmax. To obtain a mechanistic view of this failing heart, we investigated cardiac total Ca handling by our integrative analysis method. In this method, we obtained the internal Ca recirculation fraction (RF) from the decay beat constant of the postextrasystolic potentiation following each sporadic spontaneous extrasystole in these failing LVs. We combined the RF with the decreasedEmax and the unchanged O2 cost ofEmax in our recently developed formula of total Ca handling. We found that these failing LVs had a slightly but significantly increased RF accompanied by either a slightly increased futile Ca cycling or a slightly decreased Ca reactivity ofEmax, or both. Any of these three possible changes can account for the unchanged O2 cost ofEmax. This result indicates that the present mildly failing heart has not yet fallen into a typical Ca overload or paradox by the temporary Ca overloading intervention.