These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Matrix metalloproteinase inhibitors attenuate endotoxemia induced cardiac dysfunction: a potential role for MMP-9.
    Author: Lalu MM, Gao CQ, Schulz R.
    Journal: Mol Cell Biochem; 2003 Sep; 251(1-2):61-6. PubMed ID: 14575305.
    Abstract:
    Enhanced cardiac generation of peroxynitrite contributes to septic cardiomyopathy. Since matrix metalloproteinases (MMPs) are activated in vitro by peroxynitrite, we hypothezised that MMPs may contribute to cardiac mechanical dysfunction in sepsis. Rats were injected (i.p.) with either lipopolysaccharide (LPS, 4 mg/kg) or vehicle. MMP inhibitors, either Ro 31-9790 (20 mg/kg), doxycycline (4 mg/kg), or vehicle were administered i.p. 30 min after LPS. At 6 h, when the symptoms of endotoxemia peak, hearts were excised and perfused as working hearts with Krebs-Henseleit buffer at 37 degrees C. Cardiac work (cardiac output x peak systolic pressure product) was measured. Perfusate and ventricle samples were analyzed by gelatin zymography to quantify MMP activity. Cardiac function was significantly depressed in LPS-treated rats compared to control rats (control: 55 +/- 4, LPS: 26 +/- 6 mmHg*mL*min(-1)). LPS also caused a loss of 72 kDa MMP-2 activity in the ventricles and the perfusate. Although MMP-9 activity was not detected in the ventricles, LPS resulted in an increase in perfusate 92 kDa MMP-9 activity. The MMP inhibitors significantly improved cardiac function of LPS-treated rats (Ro 31-9790: 38 +/- 3, doxycycline: 51 +/- 3 mmHg*mL*min(-1)), had no effect on the loss of MMP-2 activity, and significantly reduced the MMP-9 activity in the perfusate. These results demonstrate, for the first time, that LPS induced cardiac dysfunction is associated with a loss in ventricular MMP-2 activity and the release of MMP-9 from the heart. MMP inhibitors can significantly preserve cardiac mechanical function during septic shock.
    [Abstract] [Full Text] [Related] [New Search]