title: Chitosan hydrogels significantly limit left ventricular infarction and remodeling and preserve myocardial contractility.
abstract: BACKGROUND
  Left ventricular myocardial infarctions (MIs) consist of a central area of myocardial necrosis that is surrounded by areas of myocardial injury and ischemia. We hypothesized that chitosan hydrogels, when injected around the perimeter of MIs in rats, could decrease left ventricle (LV) wall stress by the Law of LaPlace, and therefore myocardial oxygen requirements, and prevent the ischemic and injured myocardium from becoming necrotic. In this manner, chitosan gels could limit LV infraction size and LV remodeling. Chitosan hydrogels are liquid at 25°C but gel at 37°C.
  
  
  METHODS
  Seventy Sprague-Dawley rats with ligation of the left coronary artery were treated with either Dulbecco's Modified Eagle Medium (DMEM) or chitosan hydrogel in DMEM, which was injected around the infarct perimeter. Echocardiograms were obtained before MI and at 2, 4, 8, 12, and 16 wk after MI. Hearts from randomly selected rats were harvested at baseline and at the time of echocardiography for determinations of LV infarct size, remodeling, and histopathology.
  
  
  RESULTS
  Infarct sizes as a percentage of the total ventricular myocardium in the DMEM group averaged 17% versus 14% in the chitosan group at 4 wk (P < 0.05), 18% versus 14% at 8 wk (P < 0.01), 19% versus 14% at 12 wk (P < 0.001), and 20% versus 14% at 16 wk (P < 0.001). Injection of chitosan into the infarctions produced LV wall thicknesses in the MI border zones that averaged 0.66 cm at 4 wk, which were greater than the LV wall thicknesses in the border zones of rats treated with DMEM, which averaged 0.33 cm (P < 0.01). Arteriole densities in the MI border zones were 160/mm(2) in the chitosan group but only 92/mm(2) in the DMEM rats (P < 0.01). The left ventricular end-diastolic diameters (LVEDs) in the rats averaged 0.73 cm before MI. After MI, LVED increased in the DMEM rats to 0.84 cm at 2 wk, then 0.89 cm at 4 wk, 0.89 cm at 8 wk, 0.89 m at 12 wk, and 0.87 cm at 16 wk. In contrast, LVED in the chitosan rats were on average 19% smaller in comparison with the DMEM rats (P < 0.05) and did not significantly change in comparison with their baseline LVEDs. Left ventricular ejection fraction (LVEF) in the rats averaged 83% before infarctions. In the infarction + DMEM group, the LVEFs significantly decreased after MI and averaged 59.7% at 2 wk, 52.5% at 4 wk, 46.1% at 8 wk, 52.4% at 12 wk, and 53.6% at 16 wk (P < 0.05). In the infarction + chitosan-treated rats, the LVEFs were greater and averaged 67.8% at 2 wk (P < 0.02), 68.9% (P < 0.02) at 4 wk, 69% (P < 0.003) at 8 wk, 65.2% at 12 wk (P < 0.05), and 67% at 16 wk (P < 0.05).
  
  
  CONCLUSIONS
  Chitosan gel can increase LV myocardial wall thickness, decrease infarct size and LV remodeling, and preserve LV contractility.
authors.affiliation: Department of Medicine, James A. Haley Hospital and the University of South Florida College of Medicine, Tampa, Florida; Department of Surgery, James A. Haley Hospital and the University of South Florida College of Medicine, Tampa, Florida. Electronic address: robert.henning@va.gov.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Henning
authors.affiliation: Department of Medicine, James A. Haley Hospital and the University of South Florida College of Medicine, Tampa, Florida; Department of Surgery, James A. Haley Hospital and the University of South Florida College of Medicine, Tampa, Florida.
authors.forename: Abraham
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Medicine, James A. Haley Hospital and the University of South Florida College of Medicine, Tampa, Florida; Department of Surgery, James A. Haley Hospital and the University of South Florida College of Medicine, Tampa, Florida.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Jimenez
mesh_terms: D000818:Animals; D048271:Chitosan / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D020100:Hydrogels / Q000494:pharmacology / Q000627:therapeutic use*; D007267:Injections / Q000379:methods; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D020100:Hydrogels; D048271:Chitosan
keywords: Apoptosis; Chitosan; Chitosan hydrogels; Ischemic cardiomyopathy; Left ventricular remodeling; Left ventricular wall stress; Myocardial infarction