Molecular and Cellular Biochemistry

, Volume 267, Issue 1–2, pp 47–58 | Cite as

Time course studies on the functional evaluation of experimental chronic myocardial infarction in rats

  • Panchatcharam Manikandan
  • Miriyala Sumitra
  • Mohammed Nayeem
  • Bhakthavatsalam Murali Manohar
  • Beema Lokanadam
  • Subbiah Vairamuthu
  • Samu Subramaniam
  • Rengarajulu Puvanakrishnan

Abstract

In vivo models of myocardial infarction induced by coronary artery ligation (CAL) in rats usually suffer from high early mortality and a low rate of induction. This study investigated the time course initiation of chronic myocardial infarction (CMI) in albino rats and the possibility of reducing early mortality rate due to myocardial infarction by modification of the surgical technique. CAL was carried out by passing the suture through the epicardial layer around the midway of the left anterior descending coronary artery including a small area of the myocardium to avoid mechanical damage to the heart geometry. In addition, the role of endothelin-1 (ET-1) in rat heart with congestive heart failure was critically assessed. Time course initiation experiments were designed by sacrificing the animals at different time intervals and by carrying out physiological, biochemical, histopathological, electron microscopical and immunohistochemical studies. Specific markers of myocardial injury, viz. cardiac troponin-T (cTnT), high sensitivity C-reactive protein, lactate dehydrogenase and fibrinogen were measured at different time points. Serum marker enzymes and activities of lysosomal hydrolases were found to be elevated on the eighth day post-ligation. Histopathological studies demonstrated focal areas showing fibrovascular tissue containing fibroblasts, collagenous ground substance and numerous small capillaries replacing cardiac muscle fibers. Transmission electron micrographs exhibited mitochondrial changes of well-developed irreversible cardiac injury, viz. swelling, disorganization of cristae, appearance of mitochondrial amorphous matrix densities, significant distortion of muscle fibers and distinct disruption of the intercalated discs. Immunoblotting studies confirmed the presence of alpha 2-macroglobulin which supported the inflammatory response. The severity of the CMI was inferred by the measurement of the level of ET-1 in plasma and left ventricle which was significantly higher in the CMI rats than in the sham-operated rats. Immunohistochemical studies at different time intervals showed that there was a significant immunoexpression of ET-1 on the eighth day post-ligation. This study conclusively showed that ligation of left anterior descending artery minimized mortality and ET-1 was expressed during CMI. (Mol Cell Biochem 267: 47–58, 2004)

coronary artery ligation endothelin lysosomal enzymes myocardial infarction transmission electron microscopy 

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Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Panchatcharam Manikandan
    • 1
  • Miriyala Sumitra
    • 1
  • Mohammed Nayeem
    • 2
  • Bhakthavatsalam Murali Manohar
    • 3
  • Beema Lokanadam
    • 4
  • Subbiah Vairamuthu
    • 4
  • Samu Subramaniam
    • 5
  • Rengarajulu Puvanakrishnan
    • 1
  1. 1.Department of BiotechnologyCentral Leather Research InstituteAdyarIndia
  2. 2.Alved PharmaFoods Pvt. Ltd.India
  3. 3.Department of PathologyMadras Veterinary CollegeVeperyIndia
  4. 4.Department of Biophysics and Electron MicroscopyCentral Leather Research InstituteAdyarIndia
  5. 5.Department of BiochemistryApollo HospitalsGreams LaneIndia

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