Effect of left ventricular sphericity on the evolution of ventricular dysfunction in rats with diffuse isoproterenol-induced myocardial necrosis.
BACKGROUND
Previous studies in heart failure have suggested that increased left ventricular (LV) sphericity is a precursor to hemodynamic deterioration, although these studies have predominantly used models with segmental damage due to coronary vessel occlusion and have only made baseline assessments of LV function. The purpose of this study was to examine the relationship between LV geometry and hemodynamic compromise through time in heart failure due to graded, diffuse myocardial injury with a patent coronary circulation.


RESULTS
Rats received two injections of either 0, 85, 170, or 340 mg/kg isoproterenol. At 2, 6, and 16 weeks after injection, baseline hemodynamics, peak pressure-generating (aortic occlusion) and flow-generating (Tyrode's volume loading) capacities, and ventricular pressure-volume curves, dimensions, and histological scoring were measured. Increased LV sphericity preceded deterioration in baseline cardiac output, although it was the most powerful correlate of the dose-dependent decreases in peak cardiac output and ejection fraction. Time-dependent increases in pressure-generating capacity at a given volume were also due to compensatory increases in LV sphericity. The extent of right ventricular damage was also a strong correlate of peak flow-generating capacity.


CONCLUSIONS
This study demonstrates that isoproterenol-induced myocardial necrosis resulted in progressive hemodynamic dysfunction of the left ventricle which most closely correlated with alterations in LV geometry. Although increases in LV sphericity preceded decrements in baseline function, techniques that assessed peak LV function demonstrated that increased LV sphericity was directly correlated with decreased peak flow-generating capacity, underscoring the clinical importance of these geometric alterations.
Teerlink
J R
JR
Section of Cardiology, San Francisco Veterans Affairs Medical Center, California, USA.
Pfeffer
J M
JM
Pfeffer
M A
MA
D000318:Adrenergic beta-Agonists; D000704:Analysis of Variance; D000818:Animals; D002302:Cardiac Output; D009202:Cardiomyopathies / Q000139:chemically induced / Q000150:complications*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000473:pathology*; D006439:Hemodynamics; D007545:Isoproterenol; D008297:Male; D009336:Necrosis; D011312:Pressure; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D000318:Adrenergic beta-Agonists; D007545:Isoproterenol