A Rho-kinase inhibitor improves cardiac function after 24-hour heart preservation

Mariko Kobayashi, Yoshihisa Tanoue, Masataka Eto, Hironori Baba, Satoshi Kimura, Shinichiro Oda, Kenichiro Taniguchi, Ryuji Tominaga

研究成果: ジャーナルへの寄稿記事

9 引用 (Scopus)

抄録

Objective: The Rho-kinase signaling pathway is associated with coronary vasculopathy and myocardial dysfunction after cardiac transplantation. This study evaluated whether using a Rho-kinase inhibitor during allograft storage could limit early endothelial dysfunction and improve myocardial performance after reperfusion. Methods: This experiment was performed with an isolated working rabbit heart model and a support rabbit. Donor hearts (control group, n = 8) were arrested with an extracellular type of cardioplegia, preserved with University of Wisconsin solution, and then immersed in University of Wisconsin solution for 24 hours (1°C). The Rho-kinase inhibitor (Rho-kinase inhibitor group, n = 8) was administrated in the cardioplegic solution, the preservation University of Wisconsin solution, and the storage University of Wisconsin solution. Left ventricular performance was evaluated from the modified Frank-Starling curve in the working mode. Coronary blood flow and donor heart rate were measured in Langendorff mode. Effective evaluation of the Rho-kinase inhibitor was inferred from phosphorylated myosin light chain. The expression of endothelial nitric oxide synthase mRNA was analyzed to assess endothelial function. Results: The Frank-Starling curve showed a significant left and upward shift in the Rho-kinase inhibitor group compared with the control group (P < .05). The coronary blood flow and heart rate in the Rho-kinase inhibitor group at 120 minutes was significantly higher than in the control group (P < .05). Phosphorylated myosin light chain was significantly suppressed in the Rho-kinase inhibitor group (P < .05). Endothelial nitric oxide synthase mRNA levels in the Rho-kinase inhibitor group increased 4-fold relative to those seen in the control group. Conclusions: Treatment with Rho-kinase inhibitor during allograft harvest and storage enhanced coronary blood flow and ventricular recovery through nitric oxide-dependent endothelial protection after reperfusion. Rho-kinase inhibitor could help prevent early myocardial dysfunction after transplantation.

元の言語英語
ページ(範囲)1586-1592
ページ数7
ジャーナルJournal of Thoracic and Cardiovascular Surgery
136
発行部数6
DOI
出版物ステータス出版済み - 12 1 2008

Fingerprint

rho-Associated Kinases
Starlings
Myosin Light Chains
Control Groups
Nitric Oxide Synthase Type III
Reperfusion
Allografts
Heart Rate
Rabbits
Induced Heart Arrest
Messenger RNA
Heart Transplantation
Blood Donors
Nitric Oxide
Transplantation
Tissue Donors

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

これを引用

A Rho-kinase inhibitor improves cardiac function after 24-hour heart preservation. / Kobayashi, Mariko; Tanoue, Yoshihisa; Eto, Masataka; Baba, Hironori; Kimura, Satoshi; Oda, Shinichiro; Taniguchi, Kenichiro; Tominaga, Ryuji.

:: Journal of Thoracic and Cardiovascular Surgery, 巻 136, 番号 6, 01.12.2008, p. 1586-1592.

研究成果: ジャーナルへの寄稿記事

Kobayashi, Mariko ; Tanoue, Yoshihisa ; Eto, Masataka ; Baba, Hironori ; Kimura, Satoshi ; Oda, Shinichiro ; Taniguchi, Kenichiro ; Tominaga, Ryuji. / A Rho-kinase inhibitor improves cardiac function after 24-hour heart preservation. :: Journal of Thoracic and Cardiovascular Surgery. 2008 ; 巻 136, 番号 6. pp. 1586-1592.
@article{81f3a05194884d5b9aa9470a03af83c4,
title = "A Rho-kinase inhibitor improves cardiac function after 24-hour heart preservation",
abstract = "Objective: The Rho-kinase signaling pathway is associated with coronary vasculopathy and myocardial dysfunction after cardiac transplantation. This study evaluated whether using a Rho-kinase inhibitor during allograft storage could limit early endothelial dysfunction and improve myocardial performance after reperfusion. Methods: This experiment was performed with an isolated working rabbit heart model and a support rabbit. Donor hearts (control group, n = 8) were arrested with an extracellular type of cardioplegia, preserved with University of Wisconsin solution, and then immersed in University of Wisconsin solution for 24 hours (1°C). The Rho-kinase inhibitor (Rho-kinase inhibitor group, n = 8) was administrated in the cardioplegic solution, the preservation University of Wisconsin solution, and the storage University of Wisconsin solution. Left ventricular performance was evaluated from the modified Frank-Starling curve in the working mode. Coronary blood flow and donor heart rate were measured in Langendorff mode. Effective evaluation of the Rho-kinase inhibitor was inferred from phosphorylated myosin light chain. The expression of endothelial nitric oxide synthase mRNA was analyzed to assess endothelial function. Results: The Frank-Starling curve showed a significant left and upward shift in the Rho-kinase inhibitor group compared with the control group (P < .05). The coronary blood flow and heart rate in the Rho-kinase inhibitor group at 120 minutes was significantly higher than in the control group (P < .05). Phosphorylated myosin light chain was significantly suppressed in the Rho-kinase inhibitor group (P < .05). Endothelial nitric oxide synthase mRNA levels in the Rho-kinase inhibitor group increased 4-fold relative to those seen in the control group. Conclusions: Treatment with Rho-kinase inhibitor during allograft harvest and storage enhanced coronary blood flow and ventricular recovery through nitric oxide-dependent endothelial protection after reperfusion. Rho-kinase inhibitor could help prevent early myocardial dysfunction after transplantation.",
author = "Mariko Kobayashi and Yoshihisa Tanoue and Masataka Eto and Hironori Baba and Satoshi Kimura and Shinichiro Oda and Kenichiro Taniguchi and Ryuji Tominaga",
year = "2008",
month = "12",
day = "1",
doi = "10.1016/j.jtcvs.2008.07.038",
language = "English",
volume = "136",
pages = "1586--1592",
journal = "Journal of Thoracic and Cardiovascular Surgery",
issn = "0022-5223",
publisher = "Mosby Inc.",
number = "6",

}

TY - JOUR

T1 - A Rho-kinase inhibitor improves cardiac function after 24-hour heart preservation

AU - Kobayashi, Mariko

AU - Tanoue, Yoshihisa

AU - Eto, Masataka

AU - Baba, Hironori

AU - Kimura, Satoshi

AU - Oda, Shinichiro

AU - Taniguchi, Kenichiro

AU - Tominaga, Ryuji

PY - 2008/12/1

Y1 - 2008/12/1

N2 - Objective: The Rho-kinase signaling pathway is associated with coronary vasculopathy and myocardial dysfunction after cardiac transplantation. This study evaluated whether using a Rho-kinase inhibitor during allograft storage could limit early endothelial dysfunction and improve myocardial performance after reperfusion. Methods: This experiment was performed with an isolated working rabbit heart model and a support rabbit. Donor hearts (control group, n = 8) were arrested with an extracellular type of cardioplegia, preserved with University of Wisconsin solution, and then immersed in University of Wisconsin solution for 24 hours (1°C). The Rho-kinase inhibitor (Rho-kinase inhibitor group, n = 8) was administrated in the cardioplegic solution, the preservation University of Wisconsin solution, and the storage University of Wisconsin solution. Left ventricular performance was evaluated from the modified Frank-Starling curve in the working mode. Coronary blood flow and donor heart rate were measured in Langendorff mode. Effective evaluation of the Rho-kinase inhibitor was inferred from phosphorylated myosin light chain. The expression of endothelial nitric oxide synthase mRNA was analyzed to assess endothelial function. Results: The Frank-Starling curve showed a significant left and upward shift in the Rho-kinase inhibitor group compared with the control group (P < .05). The coronary blood flow and heart rate in the Rho-kinase inhibitor group at 120 minutes was significantly higher than in the control group (P < .05). Phosphorylated myosin light chain was significantly suppressed in the Rho-kinase inhibitor group (P < .05). Endothelial nitric oxide synthase mRNA levels in the Rho-kinase inhibitor group increased 4-fold relative to those seen in the control group. Conclusions: Treatment with Rho-kinase inhibitor during allograft harvest and storage enhanced coronary blood flow and ventricular recovery through nitric oxide-dependent endothelial protection after reperfusion. Rho-kinase inhibitor could help prevent early myocardial dysfunction after transplantation.

AB - Objective: The Rho-kinase signaling pathway is associated with coronary vasculopathy and myocardial dysfunction after cardiac transplantation. This study evaluated whether using a Rho-kinase inhibitor during allograft storage could limit early endothelial dysfunction and improve myocardial performance after reperfusion. Methods: This experiment was performed with an isolated working rabbit heart model and a support rabbit. Donor hearts (control group, n = 8) were arrested with an extracellular type of cardioplegia, preserved with University of Wisconsin solution, and then immersed in University of Wisconsin solution for 24 hours (1°C). The Rho-kinase inhibitor (Rho-kinase inhibitor group, n = 8) was administrated in the cardioplegic solution, the preservation University of Wisconsin solution, and the storage University of Wisconsin solution. Left ventricular performance was evaluated from the modified Frank-Starling curve in the working mode. Coronary blood flow and donor heart rate were measured in Langendorff mode. Effective evaluation of the Rho-kinase inhibitor was inferred from phosphorylated myosin light chain. The expression of endothelial nitric oxide synthase mRNA was analyzed to assess endothelial function. Results: The Frank-Starling curve showed a significant left and upward shift in the Rho-kinase inhibitor group compared with the control group (P < .05). The coronary blood flow and heart rate in the Rho-kinase inhibitor group at 120 minutes was significantly higher than in the control group (P < .05). Phosphorylated myosin light chain was significantly suppressed in the Rho-kinase inhibitor group (P < .05). Endothelial nitric oxide synthase mRNA levels in the Rho-kinase inhibitor group increased 4-fold relative to those seen in the control group. Conclusions: Treatment with Rho-kinase inhibitor during allograft harvest and storage enhanced coronary blood flow and ventricular recovery through nitric oxide-dependent endothelial protection after reperfusion. Rho-kinase inhibitor could help prevent early myocardial dysfunction after transplantation.

UR - http://www.scopus.com/inward/record.url?scp=57949093352&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57949093352&partnerID=8YFLogxK

U2 - 10.1016/j.jtcvs.2008.07.038

DO - 10.1016/j.jtcvs.2008.07.038

M3 - Article

VL - 136

SP - 1586

EP - 1592

JO - Journal of Thoracic and Cardiovascular Surgery

JF - Journal of Thoracic and Cardiovascular Surgery

SN - 0022-5223

IS - 6

ER -