Format

Send to

Choose Destination
See comment in PubMed Commons below
Circ Res. 2012 Jun 8;110(12):1618-27. doi: 10.1161/CIRCRESAHA.111.262337. Epub 2012 May 3.

Isolated rabbit working heart function during progressive inhibition of myocardial SERCA activity.

Author information

1
Institute of Cardiovascular & Medical Sciences, West Medical Building, University of Glasgow, G12 8QQ, UK.

Abstract

RATIONALE:

The extent to which sarcoplasmic reticulum Ca(2+)ATPase (SERCA) activity alone determines left ventricular (LV) pump function is unknown.

OBJECTIVE:

To correlate SERCA activity with hemodynamic function of rabbit LV during thapsigargin perfusion.

METHODS AND RESULTS:

Isolated rabbit hearts were perfused in working heart configuration, and LV pump function was assessed using a pressure-volume catheter. Rapid and complete (>95%) inhibition of SERCA was associated with a moderate decrease in cardiac function (to 70%-85% of control). Further decrease in cardiac function to 50%-75% of control occurred over the next ≈ 30 minutes despite no detectable further inhibition of SERCA activity. Analysis of the 20 seconds prior to pump failure revealed a rapid decrease in end diastolic volume. Intermediate levels of SERCA function (≈ 50% of control) had only minor hemodynamic effects. Parallel experiments in field-stimulated isolated ventricular cardiomyocytes monitored intracellular Ca(2+) and cell shortening. On perfusion with thapsigargin, Ca(2+) transient amplitude and cell shortening fell to ≈ 70% of control followed by increased diastolic Ca(2+) concentration and diastolic cell shortening to achieve a new steady state.

CONCLUSIONS:

The relationship between SERCA activity and LV function in the rabbit is highly nonlinear. In the short term, only moderate effects on LV pump function were observed despite almost complete (>95%) reduction in SERCA activity. The terminal decline of function was associated with sudden sustained increase in diastolic tone comparable to the sustained contraction observed in isolated cardiomyocytes. Secondary increases of intracellular Ca(2+) and Na(+) following complete SERCA inhibition eventually limit contractile function and precipitate LV pump failure.

PMID:
22556337
DOI:
10.1161/CIRCRESAHA.111.262337
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center