changes in heart failure Flashcards
IK1 in HF
DEcreased: reduced IK1 channel density
=> AP prolongation, increased autoamticity
what happens in overexpression of IK1?
acceleration and stabilisation of fibrillary rotors => shortens APD and cardiac wavelength => stabilises reentrant actiivty
what does pharmacological reduction of IK1 do?
suppresses the dominant frequency of mother rotor that underlies arrrhythmias in structurally normal hearts =>promotes triggers, enhances automaticity
delayed rectifiers in KF
Iks and Ikr are Decreased => prolonged APD
leads to EADs, conduction block and thus reentry
molecular mechanisms of downregulation are controversial
discrepant findings of HERG (Ikr) and KvLQT1 (IKs) expression => discrepancies highligh ion channel function as being dependent on several factors which go beyon the absolute quantities of channel subunit expression: i.e. post - translational modification, changes in protein assembly, trafficking, membrane insertion, degradation - all can modulate channel behaviour
IKATP in HF
INCREASED => shortens ADP, increases conduction block
If in HF
DEcreased in SAN, INcreased in the ventricles
Increases automaticity
Na/K-atpase in HF
DEcreased => prolongs ADP, increases reverese NCX activity (Ca influx)
Generally Na amounts in HF
are INcreased, which drives reverse NCX causing Ca overload and DADs
Ito in HF
functionally DOWNregulated => shortens APD
overall APD in HF
is prolonged
ICa-L in HF
depends on the stage of HF:
ICa-L INCREASED in mild-moderate HF but DEcreased if mroe advanced
The response of ICa-L to Beta-AR stimulation is attenuated in HF, also rate-dependent potentiation is slowed, there is increased uncoupling, the inactivation is slowed
===> prolongs APD
ICa-T
INcreased => electrical heterogeneity
INCX
INCREASED => DADs
INHE
increased in ischaemia and reperfusion injury
SERCA2a
DECRREASED => decreased contractility decreased relaxation increqased APD increased phosphorylation