Imbalance between tissue inhibitor of metalloproteinase 1 and matrix metalloproteinase 9 after cardiopulmonary resuscitation

Abstract Aims This study aimed to determine whether ( a ) there was an imbalance between matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) after cardiopulmonary resuscitation (CPR) in a canine model of prolonged ventricular fibrillation (VF); ( b ) with the duration of VF, the degree of the imbalance would be greater; and ( c ) there was a relationship between the level of MMP-9 or TIMP-1 and the cardiac function. Methods and Results Ventricular fibrillation was electrically induced in 24 dogs. The animals were randomly divided into 3 groups (sham control, n = 8; 8-minute VF, n = 8; 12-minute VF, n = 8). Echocardiographic measurement and hemodynamic variables were recorded before VF and after return of spontaneous circulation. Tissue inhibitor of metalloproteinase 1 (TIMP-1) and MMP-9 were analyzed by Western blot and immunohistochemistry. Compared with sham controls, dogs under VF and CPR showed significantly decreased level of TIMP-1 ( P < .001), and with the duration of VF, the level of TIMP-1 declined ( P < .01). The level of MMP-9 did not achieve statistical significance in the 3 groups ( P > .05); however, they were higher in VF and longer duration VF groups. The ratios of TIMP-1/MMP-9 were lower in VF groups ( P < .05). There was a negative correlation between TIMP-1 and left atrium dimension and left ventricular diastolic dimensions ( r = −0.83 and r = −0.96, respectively; P < .01) and a positive correlation between TIMP-1 and left ventricular ejection fraction ( r = 0.85; P < .01). Conclusions There was an imbalance between TIMP-1 and MMP-9 after CPR. It may partly contribute to the postresuscitation cardiac dysfunction.