1998 Fiscal Year Annual Research Report

心筋スライス機械的無負荷収縮のメカノエナジェティックス

Research Project

Project/Area Number	09670053
Research Institution	Nara Medical University
Principal Investigator	高木都奈良県立医科大学, 医学部, 教授 (00033358)
Keywords	カルシウムイオン / 心筋 / スライス / 酸素消費 / メカノエナジェティクス / 2,3ブタンジオンモノオキシム / シクロピアゾン酸 / タプシガルギン
Research Abstract	心筋スライス機械的無負荷収縮のメカノエナジェティクスを評価する新たな実験方法:ラット心筋スライス法を用いて、以下の四点が明らかになった。第一に、測定系の最大[VO_2]検出感度は、0.2ml O_2・min^<-1>・100g LV^<-1>である。第二に、クロスブリッジ(CB)サイクリングの特異的抑制剤である5mM 2,3-butanedione monoxime(BDM)は刺激による無負荷収縮時のVO_2を低下させなかった。motilityをquiescent slicesの初回刺激により得られる大きさから76%抑制した。CBサイクリングに要するVO_2成分の低下は観察されなかったので無負荷収縮時にはCBサイクリングに要するVO_2は検出しうるまでには増大しないことが示唆された。第三に刺激頻度を1Hzから2Hzにした時、無負荷収縮時のVO_2から非刺激時のVO_2を差し引いたVO_2成分は頻度依存性を示した。これらの結果から、無負荷収縮時のVO_2は、基礎代謝(basal VO_2)と興奮-収縮連関に要するVO_2(E-C coupling VO_2)より構成され、たとえスライスのmotilityが低下してもその変化が検出されるほどはCBサイクリングに要するVO_2成分は含まれないと結論した。第四点目は、E-C coupling VO_2の構成成分を調べるため、筋小胞体(SB)Ca^<2+>ポンプの特異的抑制剤であるcyclopiazonic acid(CPA)またはthapsigargin(TG)による心筋スライスのbasal VO_2およびE-C couplig VO_2への効果を30℃で検討した。CPA 1-10μMおよびTG(0.1-1μM)は、basal VO_2には影響しなかったが、E-C coupling VO_2は、0.1-1μMTG又は1-10μM CPAでquiescent slicesの初回刺激により得られるE-C coupling VO_2 0.7ml O_2・min^<-1>・100g LV^<-1>からそれぞれ33%又は濃度依存性に28%および68%抑制した。そしてmotilityについては1μM TGでquiescent slicesの初回刺激により得られる大きさから63%、10μM CPAは81%抑制した。心筋スライスの機械的無負荷収縮時のVO_2のうちE-C couplingのCa^<2+> handlingに要するVO_2にはSR Ca^<2+> ATPaseが主として関与することが示唆された。

Research Products
(13 results)

All Other

All Publications (13 results)

[Publications] Shingo Yasuhara他4名: "Myocardial VO_2 of mechanically unloaded contraction of rat ventricular slices measured by a new approach" American Journal Physiology(Heart Circ.Physiol.). 270・39. H1063-H1070 (1996)
[Publications] Miyako Takaki他5名: "Sarcoplasmic reticulum Ca^<2+> pump blockade decreases O_2 use of unloaded contracting rat heart slices:thapsigargin and cyclopiazonic acid" Journal of Molecular and Cellular Cardiology. 30. 649-659 (1998)
[Publications] Miyako Takaki他4名: "Mechanoenergetics of rat left ventricules in in situ and excised blood-perfused hearts and in unloaded rat left ventricular slices" Heart and Vessels. Suppl.12. 100-102 (1997)
[Publications] Juichiro Shimizu他10名: "A new integrative method to quantify total Ca^<2+> handling and futile Ca^<2+> cycling in failing hearts" American Journal Physiology(Heart Circ.Physiol.). 275・44. H2325-H2333 (1998)
[Publications] Takeshi Mikane他9名: "Mechanism of constant contractile efficiency under cooling inotropy of myocardium:simulation" American Journal Physiology(Heart Circ.Physiol.). 273・42. H2891-H2898 (1997)
[Publications] Yoshiki Hata他9名: "Effects of thapsigargin and KCI on the O_2 use of the excised blood-perfused rat heart" Journal of Molecular and Cellular Cardiology. 30. 2137-2143 (1998)
[Publications] Miyako Takaki他8名: "Oxygen consumption and motility of mechanically unloaded myocardial slices" Mechanisms of work production and work absorption in muscle in Advances in Experimental Medicine and Biology. 453. 499-506 (1998)
[Publications] Junichi Araki他8名: "Ventricular pressure-volume area accounts for cardiac energy consumption of work production and absorption" Mechanisms of work production and work absorption in muscle in Advances in Experimental Medicine and Biology. 453. 491-498 (1998)
[Publications] Toshiki Hata他9名: "Ryanodine decreases internal Ca^<2+> recirculation fraction of the canine heart as studied by postextrasystollic transient alternans" Japanese Journal of Physiology. 47. 521-530 (1997)
[Publications] Yi Syuu他9名: "Effects of Ca^<2+> and epinephrine on Ca^<2+> recirculation fraction and total Ca^<2+> handling in canine left ventricles" Japanese Journal of Physiology. 48. 123-132 (1998)
[Publications] Wakako Fujii他5名: "Effects of intracoronary caffeine on left ventricular mechanoenergetics in Ca^<2+> overload failing rat hearts" Japanese Journal of Physiology. 48. 373-381 (1998)
[Publications] Yoshiki Hata他9名: "Linear O_2 use-pressure-volume area relation from curved end-systolic pressure-volume relation of the blood-perfused rat left ventricle" Japanese Journal of Physiology. 48. 197-204 (1998)
[Publications] Shinyu Lee他7名: "Effects of myosin isozyme shift on curvilinearity of the left ventricular end-systolic pressure-volume relation of in situ rat hearts" Japanese Journal of Physiology. 48. 445-455 (1998)

1998 Fiscal Year Annual Research Report

心筋スライス機械的無負荷収縮のメカノエナジェティックス

Principal Investigator

高木 都 奈良県立医科大学, 医学部, 教授 (00033358)

Research Products

[Publications] Shingo Yasuhara他4名: "Myocardial VO_2 of mechanically unloaded contraction of rat ventricular slices measured by a new approach" American Journal Physiology(Heart Circ.Physiol.). 270・39. H1063-H1070 (1996)

[Publications] Miyako Takaki他5名: "Sarcoplasmic reticulum Ca^<2+> pump blockade decreases O_2 use of unloaded contracting rat heart slices:thapsigargin and cyclopiazonic acid" Journal of Molecular and Cellular Cardiology. 30. 649-659 (1998)

[Publications] Miyako Takaki他4名: "Mechanoenergetics of rat left ventricules in in situ and excised blood-perfused hearts and in unloaded rat left ventricular slices" Heart and Vessels. Suppl.12. 100-102 (1997)

[Publications] Juichiro Shimizu他10名: "A new integrative method to quantify total Ca^<2+> handling and futile Ca^<2+> cycling in failing hearts" American Journal Physiology(Heart Circ.Physiol.). 275・44. H2325-H2333 (1998)

[Publications] Takeshi Mikane他9名: "Mechanism of constant contractile efficiency under cooling inotropy of myocardium:simulation" American Journal Physiology(Heart Circ.Physiol.). 273・42. H2891-H2898 (1997)

[Publications] Yoshiki Hata他9名: "Effects of thapsigargin and KCI on the O_2 use of the excised blood-perfused rat heart" Journal of Molecular and Cellular Cardiology. 30. 2137-2143 (1998)

[Publications] Miyako Takaki他8名: "Oxygen consumption and motility of mechanically unloaded myocardial slices" Mechanisms of work production and work absorption in muscle in Advances in Experimental Medicine and Biology. 453. 499-506 (1998)

[Publications] Junichi Araki他8名: "Ventricular pressure-volume area accounts for cardiac energy consumption of work production and absorption" Mechanisms of work production and work absorption in muscle in Advances in Experimental Medicine and Biology. 453. 491-498 (1998)

[Publications] Toshiki Hata他9名: "Ryanodine decreases internal Ca^<2+> recirculation fraction of the canine heart as studied by postextrasystollic transient alternans" Japanese Journal of Physiology. 47. 521-530 (1997)

[Publications] Yi Syuu他9名: "Effects of Ca^<2+> and epinephrine on Ca^<2+> recirculation fraction and total Ca^<2+> handling in canine left ventricles" Japanese Journal of Physiology. 48. 123-132 (1998)

[Publications] Wakako Fujii他5名: "Effects of intracoronary caffeine on left ventricular mechanoenergetics in Ca^<2+> overload failing rat hearts" Japanese Journal of Physiology. 48. 373-381 (1998)

[Publications] Yoshiki Hata他9名: "Linear O_2 use-pressure-volume area relation from curved end-systolic pressure-volume relation of the blood-perfused rat left ventricle" Japanese Journal of Physiology. 48. 197-204 (1998)

[Publications] Shinyu Lee他7名: "Effects of myosin isozyme shift on curvilinearity of the left ventricular end-systolic pressure-volume relation of in situ rat hearts" Japanese Journal of Physiology. 48. 445-455 (1998)

高木都奈良県立医科大学, 医学部, 教授 (00033358)