Mechanisms Underlying the Increase in Force and Ca2+ Transient That Follow Stretch of Cardiac Muscle A Possible Explanation of the Anrep Effect

TLDR: The data indicate that the second force phase and the increase in [Ca(2+)](i) transient after stretch result from activation of the Na(+)/H(+) exchanger (NHE) increasing [Na(+)] (i) and leading to a secondary increase in [/Ca( 2+](i), which reflects an autocrine-paracrine mechanism.

Abstract: —Myocardial stretch produces an increase in developed force (DF) that occurs in two phases: the first (rapidly occurring) is generally attributed to an increase in myofilament calcium responsiveness and the second (gradually developing) to an increase in [Ca2+]i. Rat ventricular trabeculae were stretched from ≈88% to ≈98% of Lmax, and the second force phase was analyzed. Intracellular pH, [Na+]i, and Ca2+ transients were measured by epifluorescence with BCECF-AM, SBFI-AM, and fura-2, respectively. After stretch, DF increased by 1.94±0.2 g/mm2 (P<0.01, n=4), with the second phase accounting for 28±2% of the total increase (P<0.001, n=4). During this phase, SBFI340/380 ratio increased from 0.73±0.01 to 0.76±0.01 (P<0.05, n=5) with an estimated [Na+]i rise of ≈6 mmol/L. [Ca2+]i transient, expressed as fura-2340/380 ratio, increased by 9.2±3.6% (P<0.05, n=5). The increase in [Na+]i was blocked by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA). The second phase in force and the increases in [Na+]i and [Ca2+]...