Hegde, Bharati Krishna (2009-06). Remodeling of fiber and laminar architecture of rat heart septum in a transitional normal state between pressure overload hypertrophy and failure. Doctoral Dissertation.
Thesis
Congestive Heart Failure (CHF) is a major fatal disease today in the United States. The heart's function is a mechanical one. To diagnose and treat CHF effectively there is a need to understand at the microstructural level, the differences in the response of the myocardium to a change in its mechanical environment. Hence to assess growth and remodeling processes in the myocardium, the fiber and myolaminar structure of two groups of Dahl salt-sensitive rats were compared: low salt (LS) normal controls and a high salt (HS) group with hearts in "transitional eutrophy" defined by normal size and shape but in transition from pressure overload hypertrophy to dilated hypertrophy. To create the HS group with transitional eutrophy, we fed Dahl salt-sensitive rats, a sustained high salt diet from age 6 wks till sacrifice at age 11-13 wks. Such rats have a heart that transitions from too thick (pressure overload hypertrophy at about age 9 wks) to too thin (dilated hypertrophy at about age 15 wks to death) with a transitional period (age 11-13 wks) having normal size and shape. Fiber angles, sheet angles, number and thickness of sheets were measured in the septum at four transmural quarters (TQ1 to TQ4 with TQ1 being closest to LV and TQ4 closest to RV). A uniformity index was defined to characterize sheet angle dispersion. Upon comparison to LS controls, the HS group had normal size hearts with normal shape. However, there was a significant increase in the number of sheets, which corresponded with a significant decrease in the thickness of sheets in all quarters in HS group. Differences in fiber angles were significant in TQ1, TQ2, and TQ4 with fiber angles more positive in HS group. Differences in sheet angles and uniformity index were not significant. Despite having a normal size and shape, we found that hearts in a state of transitional eutrophy have a significantly different fiber and sheet morphology. The experimental data was used to develop a model that represents the path to failure that may be taken by the myolaminae when the heart is subjected to excessive pressure overload.
