Mechanism of mechanical alternans in ischemia-reperfusion: role of deficient relaxation of the strong twitch.
We tested the hypothesis that impaired and incomplete relaxation of the strong twitch of mechanical alternans causes the peak force deficit (PFD) of the weak twitch and that, by decreasing the relaxation deficit (RD) of the strong twitch, dobutamine would diminish the PFD. We studied isometric twitches of the in situ blood-perfused canine papillary muscle (n = 8). To produce mechanical alternans, we paced the heart at 110-155 beats/min and decreased mean coronary perfusion pressure (MCPP) stepwise to produce ischemia and then increased it to produce reperfusion. We measured the RD and PFD and fit each curve of isometric force [F(t)] with the relation F(t) = F0 + C(t/A)Be1-(t/A)B, where F0 is force at twitch onset, to obtain the parameters A, B, and C. B is a dimensionless index of myocardial relaxation; it decreases with impaired (delayed) relaxation. At each MCPP, we averaged B for the strong and weak twitches. The PFD showed a positive correlation with the RD. At each MCPP, mean B was lower for the strong twitch than for the weak twitch, indicating impaired relaxation of the strong twitch. Dobutamine increased B from 1.83 +/- 0.14 to 2.12 +/- 0.16 (P = 0.00002) in the strong twitch and decreased B from 4.15 +/- 2.42 to 2.19 +/- 0.18 (P = 0.05) in the weak twitch. Dobutamine thus equalized the relaxation of the strong and weak twitches. Consequently it decreased the RD from 2.57 +/- 2.14 to 0.16 +/- 0.24 g (P = 0.01) and the PFD from 5.50 +/- 3.67 to 1.04 +/- 1.15 g (P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Nwasokwa
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Division of Cardiology, Harris Chasanoff Heart Institute, Long Island Jewish Medical Center, New Hyde Park, New York 11042, USA.
D000818:Animals; D003326:Coronary Circulation; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D010210:Papillary Muscles / Q000187:drug effects / Q000503:physiopathology*; D010477:Perfusion; D011312:Pressure
D004280:Dobutamine