During acute myocardial ischemia, maintenance of an adequate cardiac output is critically dependent on the function of the remaining nonischemic myocardium. Thus, it is important to understand the factors which influence nonischemic area function. Although the major mechanical consequence of regional ischemia is the loss of effective contractile function by the ischemic zone, we recently have demonstrated that the ischemic zone also imposes a mechanical disadvantage on the nonischemic areas. A significant portion of the shortening by nonischemic areas is expended in stretching the ischemic zone during isovolumic systole, thereby reducing the amount of nonischemic area shortening during the ejection phase. The magnitude of this mechanical disadvantage is directly proportional to the amount of paradoxical isovolumic lengthening or bulge in the ischemic zone. The overall goal of this project is to more completely investigate the factors which influence the mechanical interaction between ischemic and nonischemic areas, and thus influence the magnitude of the mechanical disadvantage imposed by the ischemic zone. We will use open-chest anesthetized dogs and chronically instrumented conscious dogs to examine the consequences of acute myocardial ischemia on regional ventricular function. Regional function will be measured with midwall sonomicrometers implanted in the center of the ischemic zone and in several nonischemic areas. We will investigate the influence of ischemic zone size, alterations in loading conditions, and alterations in ventricular contractility on the magnitude of the mechanical interaction between ischemic and nonischemic areas. The time course of this interaction will be examined as the ischemic area undergoes infarction and healing with subsequent scar formation. The influence of an ischemic zone on diastolic function in nonischemic areas will be investigated by examining alterations in diastolic lengthening rates and the regional lengthening pattern in nonischemic areas. The studies will provide a rational basis for understanding the hemodynamic and mechanical consequences of acute myocardial infarction. The results from these studies can be used to guide therapy and the clinical management of patients with acute myocardial infarction so as to minimize the mechanical consequences of the ischemic zone and to increase the ability of the nonischemic area to maintain an adequate cardiac output for survival.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001731-05
Application #
3082106
Study Section
Special Emphasis Panel (SRC)
Project Start
1986-07-01
Project End
1991-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Gillebert, T C; Lew, W Y (1991) Influence of systolic pressure profile on rate of left ventricular pressure fall. Am J Physiol 261:H805-13
Villarreal, F J; Lew, W Y; Waldman, L K et al. (1991) Transmural myocardial deformation in the ischemic canine left ventricle. Circ Res 68:368-81
Villarreal, F J; Lew, W Y (1990) Finite strains in anterior and posterior wall of canine left ventricle. Am J Physiol 259:H1409-18
Hoit, B D; LeWinter, M; Lew, W Y (1990) Independent influence of left atrial pressure on regional peak lengthening rates. Am J Physiol 259:H480-7
Lew, W Y; Rasmussen, C M (1989) Influence of nonuniformity on rate of left ventricular pressure fall in the dog. Am J Physiol 256:H222-32
Gillebert, T C; Lew, W Y (1989) Nonuniformity and volume loading independently influence isovolumic relaxation rates. Am J Physiol 257:H1927-35
Lew, W Y (1988) Time-dependent increase in left ventricular contractility following acute volume loading in the dog. Circ Res 63:635-47
Villarreal, F J; Waldman, L K; Lew, W Y (1988) Technique for measuring regional two-dimensional finite strains in canine left ventricle. Circ Res 62:711-21
Lew, W Y (1987) Influence of ischemic zone size on nonischemic area function in the canine left ventricle. Am J Physiol 252:H990-7