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Molecular and Cellular Biochemistry

, Volume 304, Issue 1–2, pp 79–91 | Cite as

Therapeutic drugs during healing after myocardial infarction modify infarct collagens and ventricular distensibility at elevated pressures

  • Bodh I. Jugdutt
  • Halliday Idikio
  • Richard R. E. Uwiera
Article

Abstract

We investigated whether therapeutic drugs given during healing following acute myocardial infarction (AMI) modify infarct collagens and left ventricular (LV) distensibility. We treated dogs with drugs from major classes (i.e., indomethacin, ibuprofen, captopril, enalapril, verapamil, amlodipine, propranolol, isosorbide dinitrate [ISDN] and digoxin) between day 2 and 6 weeks and measured hemodynamics, LV remodeling and function during healing over 6 weeks after transmural anterior AMI, and regional collagens, LV distensibility under increasing pressure, rupture threshold (RT), and topography at 6 weeks. Relative to sham, AMI controls showed infarct zone (IZ) expansion and thinning, 9.3-fold increase in IZ collagen, LV dilation and dysfunction, and no change in distensibility and RT. Relative to controls, indomethacin as well as enalapril, captopril and amlodipine decreased IZ collagen. Infarct expansion was attenuated by ibuprofen, captopril, amlodipine and ISDN but augmented by indomethacin. Infarct thinning was prevented by captopril, amlodipine and ISDN but enhanced by indomethacin. Importantly, indomethacin and enalapril enhanced LV distensibility and lowered RT. Distensibility correlated positively with IZ type III collagen and negatively with type I/III collagen ratio and pyridinoline cross-links whereas RT correlated positively with IZ type I collagen. Systolic volume and ejection fraction deteriorated with indomethacin but were improved or preserved with other therapies. The results demonstrate that different therapeutic drugs may produce different effects on IZ collagens during healing post-AMI: drugs that attenuate or adversely alter IZ collagens also enhance LV distensibility, augment adverse remodeling and lower RT, suggesting that testing for these effects post-AMI is warranted.

Keywords

Healing post myocardial infarction Collagen remodeling Ventricular distensibility Rupture threshold NSAIDs ACE inhibitors Beta-adrenergic blocker Calcium-channel blockers Nitrate Digoxin 

Notes

Acknowledgements

Grants to B. Jugdutt from the Canadian Institutes of Health Research and Canadian Heart and Stroke Foundation, Ottawa, ON supported this work. It was presented in part at the Heart Failure Society of America Annual Meeting, September 2006, Seattle, WA. We thank technicians for assistance with data collection and Catherine Jugdutt with manuscript preparation.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Bodh I. Jugdutt
    • 1
  • Halliday Idikio
    • 2
  • Richard R. E. Uwiera
    • 3
  1. 1.2C2 Walter MacKenzie Health Sciences Centre, Division of Cardiology, Department of Medicine and Cardiovascular Research GroupUniversity of AlbertaEdmontonCanada
  2. 2.Department of Pathology and Laboratory MedicineUniversity of AlbertaEdmontonCanada
  3. 3.Health Sciences Laboratory Animal Services, Faculty of MedicineUniversity of AlbertaEdmontonCanada

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