[The influence of JNK inhibitor on hemodynamics after ischemia/reperfusion injury to the heart in rats].

Abstract

OBJECTIVE:

To investigate the effect and mechanism of JNK mitogen-activated protein kinases (JNK MAPKs) inhibitor SP 600125 on hemodynamics after ischemia/reperfusion (I/R) injury to heart in anesthetized rats.

METHODS:

Thirty-six healthy adult Sprague-Dawley (SD) rats were randomly divided into six groups (each n=6): sham operation (SO) group, I/R group, three JNK inhibitor groups (model groups) and ligustrazine hydrochloride (LH) group. In the SO group, a silk suture was passed underneath a main branch of the left coronary artery without tying. In the rest groups, the left coronary artery was occluded lasting for 30 minutes followed by reperfusion for 180 minutes. In the model groups, SP 600125 was intravenously administered 5 minutes before the end of the ischemia period, and continued during reperfusion period with a total dose of 4.7, 14.4 and 47.9 mg/kg respectively. Control animals received normal saline or LH 30 mg/kg in the same manner. The changes in hemodynamics, including heart rate (HR), mean blood pressure (MBP), maximal change rate of intraventricular pressure rise/down (+/-dp/dt max),left ventricular systolic pressure (LVSP), LVDP' [LVDP'=LVSP-left ventricular diastolic pressure (LVDP)], left ventricular end-diastolic pressure (LVEDP), were determined during I/R.

RESULTS:

There was no statistical difference in hemodynamics among the groups before occluding. The values of HR, MAP, +/-dp/dt max, LVSP, LVDP' in I/R group were significantly lower than those in SO group, and LVEDP was significantly higher. Compared with I/R group, +/-dp/dt max, LVSP, LVDP' in model groups and LH group were significantly higher (P<0.05 or P<0.01). There was no significant change in HR, MBP and LVEDP after the administration of JNK inhibitor or LH.

CONCLUSION:

Both JNK inhibitor and LH ameliorate cardiac systolic and diastolic dysfunction induced by I/R, without influence on MBP and HR in anesthetized rats.

• Authors: Hong-Jin Qian, Zhi-Liang Li, Bao-Ming Jiao, Jian-Sheng Zheng, Lei Su
• Journal: Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue (Zhongguo Wei Zhong Bing Ji Jiu Yi Xue) Vol. 20 Issue 12 Pg. 727-9 (Dec 2008) ISSN: 1003-0603 [Print] China
• PMID: 19111119 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracenes
• Protein Kinase Inhibitors
• Pyrazines
• pyrazolanthrone
• JNK Mitogen-Activated Protein Kinases
• tetramethylpyrazine

Topics

• Animals
• Anthracenes (pharmacology)
• Disease Models, Animal
• Hemodynamics (drug effects)
• JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors)
• Male
• Myocardial Reperfusion Injury (drug therapy, physiopathology)
• Protein Kinase Inhibitors (pharmacology)
• Pyrazines (pharmacology)
• Random Allocation
• Rats
• Rats, Sprague-Dawley