What is the clinical evidence from this study?

Study design: Other. Population: Right ventricular hypertrophy (n=16). Intervention: Pulmonary artery banding vs. Sham operation. Primary outcome: Time from peak tension to 50% relaxation.

December 4, 2017Open Access

Length-Dependent Prolongation of Force Relaxation Is Unaltered by Delay of Intracellular Calcium Decline in Early-Stage Rabbit Right Ventricular Hypertrophy

Key Result

In early-stage rabbit right ventricular hypertrophy, the time from peak tension to 50% relaxation is not significantly altered despite a significantly prolonged intracellular calcium transient decline.

Structured PICO

Does pulmonary artery banding alter the time for calcium decline and force relaxation in early-stage right ventricular hypertrophy in rabbits?

Population

16 young male New Zealand white rabbits subjected to pulmonary artery banding or sham operation and followed for 10 weeks to study right ventricular hypertrophy.

Intervention

Pulmonary artery banding procedure followed by 10 weeks of recovery to induce right ventricular hypertrophy.

Comparator

Sham-operated animals treated and handled identically, with the sole omission of placing the band around the pulmonary artery.

Outcome

Time from peak tension to 50% relaxation and time for intracellular calcium decline in isolated right ventricular trabeculae.surrogate

In early-stage right ventricular hypertrophy, the rate of force relaxation is not directly related to calcium transient decline, suggesting myofilaments predominantly determine the rate of relaxation.

Limitations

The degree of hypertrophy was slightly less than in previous experiments due to the younger age of the rabbits and the size of the band used.
It was not possible to obtain an in vivo Kd for the calcium indicator bis-fura-2 due to leakage and photobleaching during the experiments.
Myofilament protein phosphorylation status could not be determined because the calcium-binding fluorescent indicator calibration protocol required permeabilizing the muscle membrane at the end of the experiment.

Abstract

Chronic pressure overload can result in ventricular hypertrophy and eventually diastolic dysfunction. In normal myocardium, the time from peak tension to 50% relaxation of isolated cardiac myocardium is not directly determined by the time for calcium decline. This study aims to determine whether the time for calcium decline is altered with a change in preload in early-stage hypertrophied myocardium, and whether this change in time for calcium decline alters the rate of relaxation of the myocardium. Young New Zealand white rabbits underwent a pulmonary artery banding procedure and were euthanized 10 weeks later. Twitch contractions and calibrated bis-fura-2 calcium transients were measured in isolated thin right ventricular trabeculae at optimal length and with the muscle taut. Systolic calcium, calcium transient amplitude, and time from peak tension to 50% relaxation all increased with an increase in preload for both hypertrophied and sham groups. Time for intracellular calcium decline increased both with an increase in preload and an increase in extracellular calcium concentration in hypertrophied myocardium but not in sham, while time from peak tension to 50% relaxation did not significantly change between groups under either condition. Also, time for intracellular calcium decline generally decreased with an increase in extracellular calcium for both hypertrophied and sham groups, while time from peak tension to 50% relaxation generally did not significantly change in either group. Combined, these results indicate that the mild hypertrophy significantly changes calcium handling, but does not impact on the rate of force relaxation. This implies that the rate-limiting step in force relaxation is not directly related to calcium transient decline.

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