Biomedical subjects
Publications and source records attributed to Haruki Takemura.
Heartstring is a useful device. However, the device failure at the time of loading the seal into the delivery device is a troublesome issue. To avoid this problem, we invent a new method using 2 tourniquets made of 5 mm-wide woven Teflon tapes and plastic tubes. Using our method, the loading procedure became easier and more reliable.
Re-expression of fetal genes has been considered to underlie ionic remodeling in diseased heart. T-type Ca(2+) channels have been reported to be functionally expressed in embryonic hearts. In this review, we summarize developmental changes of T-type Ca(2+) channels in mouse ventricles from 9.5 days postcoitum (dpc) to adulthood, using patch clamp and quantitative PCR. In addition, we introduced T-type Ca(2+) channel expression in hypertrophied ventricles caused by myocardial infarction (MI) and aortic banding (AOB). Substantial T-type Ca(2+) channel current was recorded at both 9.5 and 18 dpc. The currents were inhibited by Ni(2+) at low concentrations. The current was not detectable in the adult stage. Ca(v)3.2 (alpha(1H)) mRNA is expressed dominantly at both 9.5 and 18 dpc. Ca(v)3.1 (alpha(1G)) increases from 9.5 to 18 dpc, but remains at low level compared with Ca(v)3.2. In contrast, Ca(v)3.1 is greater than Ca(v)3.2 at the adult stage. In MI, Ca(v)3.1 mRNA correlates negatively with brain natriuretic peptide (BNP) mRNA, whereas Ca(v)3.2 mRNA correlates positively with BNP mRNA. In AOB, these correlations are weak. We also analyzed the neuron-restrictive silencer factor (NRSF) in these hearts because it is the suppressor of transcription of the fetal cardiac gene program. The negative correlation between NRSF and BNP was stronger in MI than in AOB. Our findings show that Ca(v)3.2 underlies the functional T-type Ca(2+) channel in embryonic heart and suggest that NRSF may regulate Ca(v)3.2 expression in diseased hearts.
BACKGROUND: Embryonic hearts exhibit spontaneous electrical activity, which depends on Ca2+ influx through L-type Ca2+ channels. In this study the expression of the L-type Ca2+ channel alpha1 subunit gene in the developing mouse heart was investigated. METHODS AND RESULTS: Mouse cardiac ventricles 9.5 days post coitum (dpc), 18 dpc and adult were used. At 9.5 dpc the level of Cav1.3 mRNA was higher than that of Cav1.2 mRNA. With development, Cav1.2 mRNA increased and Cav1.3 mRNA decreased. Analysis of Cav1.3 splicing variants showed that Cav1.3(1b) mRNA was expressed at a higher density than Cav1.3(1a) mRNA. Cav1.3 protein was detected only at 9.5 dpc, whereas Cav1.2 protein was expressed from 9.5 dpc and its expression increased with development. L-type Ca2+ currents were prominent at 9.5 dpc. The Ca2+ current amplitude at 9.5 dpc was comparable to that at 18 dpc, and was larger in adults than at the embryonic stage. L-type Ca2+ current at 9.5 dpc was activated and/or inactivated at more negative membrane potentials than at 18 dpc or adult. L-type Ca2+ channels at 9.5 dpc were less sensitive to inhibition by nisoldipine than at adult. CONCLUSIONS: The Cav1.3 channel is functionally expressed in early embryonic mouse ventricular myocytes and potentially underlies ventricular automaticity.
T-type Ca2+ channels are implicated in cardiac automaticity, cell growth, and cardiovascular remodeling. Two voltage-gated Ca2+ subtypes (Ca(v)3.1 and Ca(v)3.2) have been cloned for the pore-forming alpha(1)-subunit of the T-type Ca2+ channel in cardiac muscle, but their differential roles remain to be clarified. The aim of this study was to elucidate the relative contribution of the two subtypes in the normal development of mouse hearts. A whole cell patch clamp was used to record ionic currents from ventricular myocytes isolated from mice of early (E9.5) and late embryonic days (E18) and from adult 10-wk-old mice. Large T-type Ca2+ current (I(Ca,T)) was observed at both E9.5 and E18, displaying similar voltage-dependence and kinetics of activation and inactivation. The current was inhibited by Ni2+ at relatively low concentrations (IC(50) 26-31 microM). I(Ca,T) was undetectable in adult myocytes. Quantitative PCR analysis revealed that Ca(v)3.2 mRNA is the predominant subtype encoding T-type Ca2+ channels at both E9.5 and E18. Ca(v)3.1 mRNA increased from E9.5 to E18, but remained low compared with Ca(v)3.2 mRNA during the whole embryonic period. In the adulthood, in contrast, Ca(v)3.1 mRNA is greater than Ca(v)3.2 mRNA. These results indicate that Ca(v)3.2 underlies the functional T-type Ca2+ channels in the embryonic murine heart, and there is a subtype switching of transcripts from Ca(v)3.2 to Ca(v)3.1 in the perinatal period.
BACKGROUND: The ionic basis of acquired QT prolongation and torsade de pointes (TdP) unrelated to drugs is not fully understood. METHODS AND RESULTS: We created a rabbit model with chronic complete atrioventricular block (AVB) (n=34), which showed prominent QT prolongation (by 120%), high incidence of spontaneous TdP (71%), and cardiac hypertrophy. Patch-clamp experiments were performed in left ventricular myocytes from 9 rabbits (8 with TdP, 1 without TdP) at approximately 21 days of AVB and from 8 sham-operated controls with sinus rhythm. Action potential duration was prolonged in AVB myocytes compared with control (+61% at 0.5 Hz, +21% at 3 Hz). Both rapidly and slowly activating components of the delayed rectifier K(+) current (I(Kr) and I(Ks)) in AVB myocytes were significantly smaller than in control by 50% and 55%, respectively. There was no significant difference in Ca(2+)-independent transient outward current (I(to1)). L-type Ca(2+) current (I(Ca,L)) in control and AVB myocytes was similar in peak amplitude, but the half voltage for activation was shifted to the negative direction (5.9 mV) in AVB myocytes. Voltage dependence of I(Ca,L) inactivation was not different in control and AVB myocytes. The inward rectifier K(+) current (I(K1)) significantly increased in AVB myocytes compared with control. CONCLUSIONS: In the rabbit, chronic AVB leads to prominent QT prolongation and high incidence of spontaneous TdP. Downregulation of both I(Kr) and I(Ks) in association with altered I(Ca,L) activation kinetics may underlie the arrhythmogenic ventricular remodeling.
There is not yet agreement about the optimal size of the prostheses in aortic and mitral valve replacement with Manouguian's technique. In this technique, the aortic prosthetic valve can be pushed upon the mitral prosthesis which may cause dysfunction of the aortic prosthetic valve. The aim of this study was to clarify the size of the prostheses needed to avoid dysfunction of the aortic prosthetic valve. Three patients underwent aortic and mitral valve replacement through this procedure. Two of them had active aortic and mitral valve endocarditis. Aortomitral continuity involved with abscesses could be approached and completely excised using this technique. All patients survived the operation, but 1 of them suffered aortic mechanical valve dysfunction for the reason stated. Anatomical analysis of the geometrical relation of the 2 prosthetic valves suggests that the mitral annulus should be enlarged less than 25 mm to avoid dysfunction of the aortic prosthetic valve.