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

Circulation Research
Elspeth B ElliottChristopher M Loughrey

Abstract

The extent to which sarcoplasmic reticulum Ca(2+)ATPase (SERCA) activity alone determines left ventricular (LV) pump function is unknown. To correlate SERCA activity with hemodynamic function of rabbit LV during thapsigargin perfusion. 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. The relationship between SERCA activity and LV f...Continue Reading

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Citations

Dec 24, 2015·Journal of Molecular and Cellular Cardiology·Christopher Kane, Cesare M Terracciano
Aug 16, 2012·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·David Hauton
Dec 12, 2012·Journal of Molecular and Cellular Cardiology·David EisnerAndrew Trafford
Jan 31, 2020·Circulation Research·David A EisnerDavid C Hutchings
Mar 11, 2020·Cardiovascular Research·Alexandra RiddellTamara P Martin
Sep 7, 2020·Cellular Signalling·Dylan O'TooleTamara P Martin

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