Energy-wasteful total Ca²⁺handling underlies increased O₂cost of contractility in canine stunned heart

Abstract

Postischemic myocardial stunning halved left ventricular contractility [end-systolic maximum elastance (E(max))] and doubled the O(2) cost of E(max) in excised cross-circulated canine heart. We hypothesized that this increased O(2) cost derived from energy-wasteful myocardial Ca(2+) handling consisting of a decreased internal Ca(2+) recirculation, some futile Ca(2+) cycling, and a depressed Ca(2+) reactivity of E(max). We first calculated the internal Ca(2+) recirculation fraction (RF) from the exponential decay component of postextrasystolic potentiation. Stunning significantly accelerated the decay and decreased RF from 0.63 to 0. 43 on average. We then combined the decreased RF with the halved E(max) and its doubled O(2) cost and analyzed total Ca(2+) handling using our recently developed integrative method. We found a decreased total Ca(2+) transport and a considerable shift of the relation between futile Ca(2+) cycling and Ca(2+) reactivity in an energy-wasteful direction in the stunned heart. These changes in total Ca(2+) handling reasonably account for the doubled O(2) cost of E(max) in stunning, supporting the hypothesis.

Mechanoenergetics Characterizing Oxygen Wasting Effect of Caffeine in Canine Left Ventricle.

“…Either an increased Ca 2ϩ handling, an augmented Ca 2ϩ responsiveness of contractility or both will enhance E max generally [5,6,[26][27][28][29][30]. Either an increased futile Ca 2ϩ cycling, a suppressed Ca 2ϩ responsiveness or both may increase the O 2 cost of E max [26][27][28][29][30].…”

“…The slope (a) of the VO 2 -PVA relation represents the O 2 cost of PVA, and the VO 2 intercept (b) represents PVA-independent VO 2 . The VO 2 above basal metabolism is primarily for Ca 2ϩ handling in the E-C coupling [26][27][28][29][30]. The PVA-dependent VO 2 above b seems exclusively related to crossbridge cycling [5].…”

“…Even a single composite VO 2 -PVA line reflects the O 2 cost of E max [14]. This cost quantitates the energy wasting of the E-C coupling [5,6,[26][27][28][29][30].…”

Exponential Fitting of Postextrasystolic Potentiation May Underestimate the Cardiac Ca2+ Recirculation Fraction: A Theoretical Analysis

“…At these physiological beat intervals, RF increases as the beat interval shortens [17] in contrast to the constant RF independent of beat intervals longer than the period of full mechanical restitution [20,21,27,28]. At present, we are not interested in such relatively long beat intervals because we have to obtain RF at the shorter beat intervals we consistently observe in our cardiac mechanoenergetics experiments [7][8][9][10][11][12]22].…”

“…In fact, we previously reported that N increased to 1.2 after postischemic stunning and to 1.4 after ryanodine treatment in canine hearts [1,2,7,9,18]. At these N values, incorrectly underestimated RF values would yield an artifactually higher economy of Ca 2ϩ handling, leading to a serious misunderstanding of the pathophysiology of failing hearts.…”