Biomedical subjects

Juichiro Shimizu

Publications and source records attributed to Juichiro Shimizu.

23 records · Page 2Linked to original sources

PubMed2002

Electric currents applied during refractory period enhance contractility and systolic calcium in the ferret heart.

We investigated the mechanism of positive inotropism of electric currents applied during the absolute refractory period. Ten Langendorff-perfused ferret hearts were instrumented to measure isovolumic left ventricular pressure (LVP) and the aequorin luminescence. Biphasic square-wave electric currents (+/-20 mA, total duration 30 ms) were delivered between pairs of electrodes. Six hearts were perfused at different extracellular Ca(2+) concentrations ([Ca(2+)](o); 1, 2, 4, and 8 mM). These signals increased LVP from 50.0 +/- 9.4 to 70.1 +/- 14.7, from 67.5 +/- 11.0 to 79.0 +/- 15.6, from 79.3 +/- 21.0 to 87.1 +/- 22.8, and from 84.6 +/- 24.0 to 91.8 +/- 28.5 mmHg at the respective [Ca(2+)](o) (P < 0.05). Peak free intracellular [Ca(2+)] ([Ca(2+)](i)) increased from 0.52 +/- 0.13 to 1.37 +/- 0.23, from 0.76 +/- 0.23 to 1.73 +/- 0.14, from 1.10 +/- 0.24 to 2.05 +/- 0.33, and from 1.41 +/- 0.36 to 2.24 +/- 0.36 microM/ml, respectively (P < 0.001). With the use of 1 mg/l propranolol with 1 mM [Ca(2+)](o), LVP and [Ca(2+)](i) were increased significantly from 48.7 +/- 8.18 to 56.3 +/- 6.11 mmHg and from 0.61 +/- 0.11 to 1.17 +/- 0.20 microM, respectively (P < 0.05). In conclusion, positive inotropism of such electrical currents was due to increased peak [Ca(2+)](i) and Ca(2+) responsiveness of the myofilaments did not change significantly.

Adrenergic beta-Antagonists↗

PubMed2002

Temperature-dependent postextrasystolic potentiation and Ca(2+) recirculation fraction in canine hearts.

We have found that cardiac temperature proportionally changes O(2) cost of contractility, defined as O(2) consumption for myocardial total Ca(2+) handling normalized to contractility in terms of the end-systolic pressure-volume ratio (maximal elastance, E(max)), in the canine left ventricle (temperature sensitivity, Q(10) = 2). We have separately found that a decrease in the recirculation fraction (RF) of Ca(2+) within myocardial cells underlies an increased O(2) cost of E(max) in stunned hearts. We therefore hypothesized that a similar change in RF would underlie the Q(10) of O(2) cost of E(max). We tested this hypothesis by analyzing RF calculated from an exponential decay component of the transiently alternating postextrasystolic potentiation in the canine left ventricle. RF decreased from 0.7 to 0.5 as cardiac temperature increased from 33 to 38 degrees C with Q(10) of 0.5, reciprocal to that of O(2) cost of E(max). We conclude that Q(10) of ATP-consuming reactions involved in Ca(2+) handling and E(max) response to it could reasonably account for the reciprocal Q(10) of RF and O(2) cost of E(max).

Adenosine Triphosphate↗

PubMed2002

Load dependence of ventricular performance explained by model of calcium-myofilament interactions.

Although a simple concept of load-independent behavior of the intact heart evolved from early studies of isolated, intact blood-perfused hearts, more recent studies showed that, as in isolated muscle, the mode of contraction (isovolumic vs. ejection) impacts on end-systolic elastance. The purpose of the present study was to test whether a four-state model of myofilament interactions with length-dependent rate constants could explain the complex contractile behavior of the intact, ejecting heart. Studies were performed in isolated, blood-perfused canine hearts with intracellular calcium transients measured by macroinjected aequorin. Measured calcium transients were used as the driving function for the model, and length-dependent rate constants yielding the highest concordance between measured and model-predicted midwall stress at different isovolumic volumes were determined. These length-dependent rate constants successfully predicted contractile behavior on ejecting contractions. This, along with additional model analysis, suggests that length-dependent changes in calcium binding affinity may not be an important factor contributing to load-dependent contractile performance in the intact heart under physiological conditions.

Actin Cytoskeleton↗

PubMed2002

Cardiac contractility modulation by electric currents applied during the refractory period.

Inotropic effects of electric currents applied during the refractory period have been reported in cardiac muscle in vitro using voltage-clamp techniques. We investigated how electric currents modulate cardiac contractility in normal canine hearts in vivo. Six dogs were instrumented to measure regional segment length, ventricular volume (sonomicrometry), and ventricular pressure. Cardiac contractility modulating (CCM) electric currents (biphasic square pulses, amplitude +/-20 mA, total duration 30 ms) were delivered during the refractory period between pairs of electrodes placed on anterior and posterior walls. CCM significantly increased index of global contractility (E(es)) from 5.9 +/- 2.9 to 8.3 +/- 4.6 mmHg/ml with anterior CCM, from 5.3 +/- 1.8 to 8.9 +/- 4.0 mmHg/ml with posterior CCM, and from 6.1 +/- 2.6 to 11.0 +/- 7.0 mmHg/ml with combined CCM (P < 0.01, no significant change in volume axis intercept). End-systolic pressure-segment length relations showed contractility enhancement near CCM delivery sites, but not remotely. Relaxation was not influenced. CCM increased mean aortic pressure, but did not change peripheral resistance. Locally applied electrical currents enhanced global cardiac contractility via regional changes in myocardial contractility without impairing relaxation in situ.

Animals↗

PubMed2002

Frequency distribution, variance, and moving average of left ventricular rhythm and contractility during atrial fibrillation in dog.

Mean levels of left ventricular rhythm and contractility averaged over arrhythmic beats would characterize the average cardiac performance during atrial fibrillation (AF). However, no consensus exists on the minimal number of beats for their reliable mean values. We analyzed their basic statistics to find out such a minimal beat number in canine hearts. We produced AF by electrically stimulating the atrium and measured left ventricular arrhythmic beat interval (RR) and peak isovolumic pressure (LVP). From these, we calculated instantaneous heart rate (HR = 60,000/RR), contractility (E(max) = LVP/isovolumic volume above unstressed volume), and beat interval ratio (RR1/RR2). We found that all their frequency distributions during AF were variably nonnormal with skewness and kurtosis. Their means +/- standard deviations alone cannot represent their nonnormal distributions. A 90% reduction of variances of E(max) and RR1/RR2 required a moving average of 15 and 24, respectively, arrhythmic beats on the average, whereas that of RR and HR required 60 beats on the average. These results indicate that a statistical characterization of arrhythmic cardiodynamic variables facilitates better understanding of cardiac performance during AF.

Animals↗