SHORTENING VERSUS ISOMETRIC CONTRACTIONS IN ISOLATED HUMAN FAILING AND NONFAILING LEFT-VENTRICULAR MYOCARDIUM - DEPENDENCY OF EXTERNAL WORKAND FORCE ON MUSCLE LENGTH, HEART-RATE AND INOTROPIC STIMULATION

For reasons of simplicity, studies on isolated human myocardium have b een conducted using exclusively isometric contractions, although posit ive inotropic interventions may differently influence force developmen t, extent of shortening and myocardial work performance. We investigat ed human left ventricular failing and non-failing preparations compari ng isometric versus isotonic, i.e., shortening contractions. Results: (1) When muscle length is increased from 90% to 100% l(max), peak deve loped force increases by 36% and 43% (p < 0.05) in non-failing and fai ling human left ventricular myocardium, respectively. Maximum performe d work increases similarly in non-failing but decreases in failing myo cardium. It can be shown that this discrepancy is due to significantly higher resting tension and does not present an insufficient intrinsic shortening capacity in failing myocardium. (2) When stimulation rate is increased from 0.5 to 2.0 Hz, isometric force increases significant ly by 59% in non-failing and decreases by 27% in failing myocardium, w hereas maximum performed work increases by 98% and decreases by 46%, r espectively. (3) Pharmacological positive inotropic interventions by 7 .2 mM calcium (n = 9), 3 x 10(-8) M isoproterenol (n = 7), 3 x 10(-8) M ouabain (n = 5), and 10(-5) M EMD 57033 (n = 3) equally increased fo rce development and extent of shortening: When the fractional effect o n shortening (y) was correlated to the fractional effect on force (x), the following linear regression equation was obtained: y = 0.91x + 0. 26 (r = 0.86; p < 0.001). Conclusions: The data presented are of clini cal and pharmacological importance: (1) The Frank-Starling mechanism i s demonstrated to be existent in the failing human myocardium regardin g both isometric force developed and maximum work performed. (2) Both force-frequency relations and - to a greater extent - work-frequency r elations are reversed in failing human myocardium. (3) Independent of the pharmacological mode of action, positive inotropic compounds incre ase developed isometric force to the same extent as isotonic shortenin g and therefore potentiate maximum performed work. (C) 1998 Elsevier S cience B.V.