Mechanical alternans and restitution in failing SHHF rat left ventricles.
We examined mechanical alternans and electromechanical restitution in normal and failing rat hearts. Alternans occurred at 5 Hz in failing versus 9 Hz in control hearts and was reversed by 300 nM isoproterenol, 6 mM extracellular Ca(2+), 300 nM -BAY K 8644, or 50 nM ryanodine. Restitution curves comprised phase I, which was completed before relaxation of the steady-state beat, and phase II, which occurred later. Phase I action potential area and developed pressure ratios were significantly reduced in the failing versus control hearts. Phase II was a monoexponential increase in relative developed pressure as the extrasystolic interval was increased. The plateau of phase II was significantly elevated in failing hearts. Thapsigargin (3 microM) plus ryanodine (200 nM) potentiated phase I to a significantly greater extent in control versus failing hearts and abolished phase II in both groups. The results suggest that both regulation of Ca(2+) influx across the sarcolemma and Ca(2+) release by the sarcoplasmic reticulum may contribute to altered excitation-contraction coupling in the failing spontaneously hypertensive heart failure prone rat heart.
Dumitrescu
Cristian
C
The Ohio State University Biophysics Program and Dorothy M. Davis Heart and Lung Research Institute, Columbus 43210, USA.
Narayan
Prakash
P
Efimov
Igor R
IR
Cheng
Yuanna
Y
Radin
M Judith
MJ
McCune
Sylvia A
SA
Altschuld
Ruth A
RA
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
D012433:Ryanodine; D019284:Thapsigargin; D007545:Isoproterenol; D002118:Calcium