TY - JOUR
T1 - Postextrasystolic mechanical restitution in closed-chest dogs
T2 - Effect of heart failure
AU - Prabhu, Sumanth D.
AU - Freeman, Gregory L.
PY - 1995/11/1
Y1 - 1995/11/1
N2 - Background: Postextrasystolic mechanical restitution (MR(PES)) is thought to be an expression of intracellular Ca2+ handling by cardiac sarcoplasmic reticulum (SR). Since congestive heart failure is characterized by abnormal intracellular Ca2+ homeostasis, we sought to delineate MR(PES) is behavior before and after the production of heart failure to obtain insights into the relation between altered mechanical performance and Ca2+ handling. Methods and Results: Ten dogs instrumented with left ventricular (LV) micromanometers and piezoelectric dimension crystals were studied under control conditions; 6 dogs also were studied after tachycardia heart failure (THF) produced by rapid LV pacing for 4 weeks. After priming at a basic cycle length of 375 ms, test pulses were delivered at fixed extrasystolic intervals (ESIs; 300, 375, or 450 ms) and graded postextrasystolic intervals (PESIs). Postextrasystolic mechanical response was assessed using single-beat elastance. MR(PES) curves were constructed by expressing normalized mechanical response as a function of the PESI. Control MR(PES) was a monoexponential function whose time constant (TC) and PESI-axis intercept (PESI0) increased significantly (P<.01) with increases in the antecedent ESI. THF significantly slowed MR(PES) kinetics at each antecedent ESI (P<.025), increased normalized maximal contractile response (CR(max), P<.01), and shortened PESI0 (P<.025). Increases in the TC and CR(max) were most pronounced with the smallest antecedent ESI (percent control postextrasystolic TC 363.7±60.5%, ESI of 300 ms versus 139.0±15.1%, ESI of 450 ms, P<.005; percent control CR(max) 128.6±4.9%, ESI of 300 ms versus 104.9±1.0%, ESI of 450 ms; P<.005). Conclusions: MR(PES) is much less dynamic in THF: The failing heart operates at lower levels of contractile performance after higher stimulation frequencies and cannot increase its speed of contractile recovery to compensate for higher heart rate. Prolongation of MR(PES) kinetics is consistent with depression of SR Ca2+ release mechanisms in THF and implicates this site in the loss of the capacity of the failing heart to maintain mechanical performance with tachycardia.
AB - Background: Postextrasystolic mechanical restitution (MR(PES)) is thought to be an expression of intracellular Ca2+ handling by cardiac sarcoplasmic reticulum (SR). Since congestive heart failure is characterized by abnormal intracellular Ca2+ homeostasis, we sought to delineate MR(PES) is behavior before and after the production of heart failure to obtain insights into the relation between altered mechanical performance and Ca2+ handling. Methods and Results: Ten dogs instrumented with left ventricular (LV) micromanometers and piezoelectric dimension crystals were studied under control conditions; 6 dogs also were studied after tachycardia heart failure (THF) produced by rapid LV pacing for 4 weeks. After priming at a basic cycle length of 375 ms, test pulses were delivered at fixed extrasystolic intervals (ESIs; 300, 375, or 450 ms) and graded postextrasystolic intervals (PESIs). Postextrasystolic mechanical response was assessed using single-beat elastance. MR(PES) curves were constructed by expressing normalized mechanical response as a function of the PESI. Control MR(PES) was a monoexponential function whose time constant (TC) and PESI-axis intercept (PESI0) increased significantly (P<.01) with increases in the antecedent ESI. THF significantly slowed MR(PES) kinetics at each antecedent ESI (P<.025), increased normalized maximal contractile response (CR(max), P<.01), and shortened PESI0 (P<.025). Increases in the TC and CR(max) were most pronounced with the smallest antecedent ESI (percent control postextrasystolic TC 363.7±60.5%, ESI of 300 ms versus 139.0±15.1%, ESI of 450 ms, P<.005; percent control CR(max) 128.6±4.9%, ESI of 300 ms versus 104.9±1.0%, ESI of 450 ms; P<.005). Conclusions: MR(PES) is much less dynamic in THF: The failing heart operates at lower levels of contractile performance after higher stimulation frequencies and cannot increase its speed of contractile recovery to compensate for higher heart rate. Prolongation of MR(PES) kinetics is consistent with depression of SR Ca2+ release mechanisms in THF and implicates this site in the loss of the capacity of the failing heart to maintain mechanical performance with tachycardia.
KW - contractility
KW - heart failure
KW - mechanics
KW - systole
KW - tachycardia
UR - http://www.scopus.com/inward/record.url?scp=0028868840&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.92.9.2652
DO - 10.1161/01.CIR.92.9.2652
M3 - Article
C2 - 7586369
AN - SCOPUS:0028868840
SN - 0009-7322
VL - 92
SP - 2652
EP - 2659
JO - Circulation
JF - Circulation
IS - 9
ER -