title: Consequences of regional inotropic stimulation of ischemic myocardium on regional myocardial blood flow and function in anesthetized swine.
abstract: Determination of the effect of inotropic stimulation on regionally ischemic and hypokinetic myocardium is complicated when intravenous administration of the inotropic agent also causes stimulation of nonischemic adjacent and distant regions, thereby altering global ventricular hemodynamics. To obviate such events, 16 anesthetized swine were studied during regional inotropic stimulation by infusion of dobutamine hydrochloride (2.5 +/- 1 microgram/min) into the cannulated left anterior descending coronary artery. Coronary inflow was controlled by a pump in an extracorporeal circuit. Two groups of swine with different degrees of ischemia were studied. In the first group of animals (n = 8), reduction in coronary inflow to produce a fall in coronary artery pressure (CAP) from 114 +/- 7 mm Hg to 62 +/- 2 mm Hg caused a decrease in percent systolic wall thickening (%WTh) from 34.6 +/- 8.1% to 25.4 +/- 5.8% (p less than 0.005). In the second group of animals (n = 8), CAP was decreased to 46 +/- 5 mm Hg (control: 115 +/- 8 mm Hg) and % WTh decreased from 34.1 +/- 16.4% to 10.4 +/- 6.9% (p less than 0.001). Subendocardial blood flow was reduced from 1.41 +/- 0.38 ml/min/g to 0.65 +/- 0.13 ml/min/g (group 1, p less than 0.001) and from 1.08 +/- 0.22 ml/min/g to 0.24 +/- 0.08 ml/min/g (group 2, p less than 0.001). Regional infusion of dobutamine caused asynchronous ventricular contraction with early systolic augmentation in wall thickening followed by late systolic thinning. Therefore, during hypoperfusion regional myocardial function assessed by %WTh remained unchanged (26.2 +/- 5.8%, p = NS) in group 1 and decreased significantly to 1.6 +/- 5.1% (p less than 0.041) in group 2. Subendocardial blood flow decreased to 0.44 +/- 0.15 ml/min/g in group 1 (p less than 0.005) and to 0.15 +/- 0.07 ml/min/g in group 2 (p less than 0.012). To account for the augmented early systolic thickening that occurred during asynchronous contraction, a myocardial work index was developed in which the sum of the instantaneous left ventricular pressure-wall thickness product was calculated for estimation of regional myocardial work. Increases in this work index were apparent with the addition of dobutamine at both levels of hypoperfusion. This significant enhancement in regional myocardial function in group 2 caused a significant increase of 16% (p less than 0.009) in overall left ventricular power during ejection. Thus, regional inotropic stimulation with dobutamine caused enhancement of maximum work of the ischemic myocardium in the steady state despite a further decrease in subendocardial blood flow.
authors.affiliation: Seaweed Canyon Laboratory, Department of Medicine, University of California, San Diego, La Jolla 92093.
authors.forename: R
authors.initials: R
authors.lastname: Schulz
authors.forename: S
authors.initials: S
authors.lastname: Miyazaki
authors.forename: M
authors.initials: M
authors.lastname: Miller
authors.forename: E
authors.initials: E
authors.lastname: Thaulow
authors.forename: G
authors.initials: G
authors.lastname: Heusch
authors.forename: J
authors.initials: J
authors.lastname: Ross
authors.forename: B D
authors.initials: BD
authors.lastname: Guth
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology*; D004280:Dobutamine / Q000494:pharmacology* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D013552:Swine
chemical_list: D004280:Dobutamine