Force production in rat ventricular trabeculae: the response to stretch and a rest interval

Abstract

The increase in inotropy of the heart with stretch is well established: less well known is its biphasic nature. Stretching cardiac muscle produces an immediate increase in force (immediate response) which, if the stretch is sustained, is followed by a slower progressive increase, known as the "slow force response" (SFR). Right ventricular trabeculae were isolated from Wistar rat (200-300g) hearts, mounted in a muscle chamber and attached to a force transducer. Trabeculae were electrically stimulated to contract at 0.2Hz, and subjected to incremental increases in length to investigate the immediate force response, and to find optimal length (Lo). Trabeculae were stretched from 50% of Lo to 100% Lo, and held at this length for 5 minutes to investigate the SFR. The stretch responses were investigated for control and during exposure to pharmacological agents: 500μM indomethacin, a blocker of prostaglandin synthesis, and 1μM isoproterenol, a selective β-adrenergic agonist. Both indomethacin (P= 0.007, n=7) and isoproterenol (P=0.00008 n=7) were found to inhibit the SFR, while the immediate response to stretch was not affected by indomethacin (paired repeated measures ANOVA: P= 0.0825 , n=10), or isoproterenol (paired repeated measures ANOVA: P= 0.0425 , n=10). The second part of this study investigated the mechanisms underlying rest potentiation, a phenomenon in animals with a high dependence on sarcoplasmic reticulum (SR) Ca2+ for contraction, where the stress immediately following a rest interval (~30s) becomes potentiated. 3mM caffeine, a promoter of SR Ca2+ leakage inhibited rest potentiation (122± 6%, n=3) following 30 s of rest (99 ± 2%, P=0.05, n=3). Rest potentiation displayed stimulation frequency-dependence, with a greater increase in stress following a 30 s rest at higher frequencies (2 Hz > 0.2 Hz) (paired repeated measures ANOVA: P= <0.0001, n=3). 1mM isoproterenol inhibited rest potentiation following 30 s of rest (P= 0.03, n=8) while indomethacin had no effect (P = 0.3, n=8).