Submitted on September 5, 2007
Accepted on November 6, 2007
Susceptibility to Systolic Dysfunction in the Myocardium from Chronically Infarcted Spontaneously Hypertensive Rats
Gavin R Norton1, Demetri GA Veliotes1, Oleg Osadchii1, Angela J Woodiwiss2*, and D. Paul Thomas3
1 Physiology, University of the Witwatersrand, Johannesburg, South Africa
2 School of Physiology, University of the Witwatersrand, Johannesburg, Gauteng, South Africa
3 School of Physical & Health Education, University of Wyoming, Laramie, Wyoming, United States
* To whom correspondence should be addressed. E-mail: Angela.Woodiwiss{at}wits.ac.za.
We explored whether the hypertensive heart is susceptible to myocardial dysfunction in viable non-infarcted tissue post-myocardial infarction (MI), the potential mechanisms thereof, and the impact of these changes on pump function. Six-to-seven months after ligation of the left anterior descending coronary artery, left ventricular (LV) myocardial systolic function as assessed from % shortening of the non-infarcted lateral wall segmental length determined over a range of filling pressures (ultrasonic transducers placed in the lateral wall in anaesthetized, open-chest, ventilated rats) and % thickening of the posterior wall (echocardiography) was reduced in infarcted spontaneous hypertensive rats (SHR-MI) (p<0.05), but not in normotensive Wistar Kyoto (WKY-MI) animals as compared to corresponding controls (SHR-SHAM, WKY-SHAM). This change in regional myocardial function in SHR-MI, but not in WKY- MI, occurred despite a similar degree of LV dilatation (increased LV end-diastolic dimensions and volume intercept of the LV end-diastolic pressure-volume relation) in SHR-MI and WKY-MI rats and a lack of difference in LV relative wall thinning, LV wall stress, apoptosis (TUNEL) or necrosis (pathological score) between SHR-MI and WKY-MI rats. Although the change in regional myocardial function in the SHR-MI group was not associated with a greater reduction in baseline global LV chamber systolic function (endocardial fractional shortening-FSend and end-systolic elastance [LV Ees] determined in the absence of an adrenergic stimulus), in the presence of an isoproterenol challenge, non-infarct zone LV systolic myocardial dysfunction manifested in a significant reduction in LV Ees in SHR-MI compared to WKY-MI and SHR and WKY-Sham rats (p<0.04). In conclusion, these data suggest that with chronic MI, the hypertensive heart is susceptible to development of myocardial dysfunction, a change which cannot be attributed to excessive chamber dilatation, apoptosis or necrosis, but which in-turn, contributes toward a reduced cardiac adrenergic-inotropic reserve.
