Impact of Reperfusion Calcium and pH on the Resuscitation of Hearts Donated After Circulatory Death

Controlled Reperfusion Strategies Improve Cardiac Hemodynamic Recovery after Warm Global Ischemia in an Isolated, Working Rat Heart Model of Donation after Circulatory Death (DCD)

“…Taken together, conditions in several previous reports are likely to generate a more severe ischemia than in our study, which may lead to conditions that are more damaging, but put hearts in a position to benefit from mildly acidic reperfusion. Moreover, combined conditions such as a hypocalcemic, acidic solution (White et al, 2016) might be more effective in improving post-ischemic recovery than a normocalcemic, acidic solution, as used in our study.…”

“…Mildly acid reperfusion is believed to act by delaying the restoration of physiological pH (Inserte et al, 2008, 2011), thereby prolonging the low-pH–induced inhibition of mPTP opening while reducing intracellular calcium overload and hypercontracture in the first minutes of reperfusion. Discrepant cardioprotective effects for mildly acidic reperfusion between previous studies (Inserte et al, 2008; Duan et al, 2011; Inserte et al, 2011; Penna et al, 2013; White et al, 2016) and ours are unlikely to be explained by differences in the acidic reperfusion conditions (previous studies used pH ranging from 6.4 to 6.8 for 2–3 min, while we used pH 6.8 for 3 min), but may be explained by differences in experimental conditions, as several previous studies used longer ischemic periods [30–40 min vs. 27 min in our study; (Inserte et al, 2008, 2011; Duan et al, 2011; Penna et al, 2013)] and/or higher buffer calcium concentrations 1.4–1.8 mM (Inserte et al, 2008, 2011; Duan et al, 2011) or lower (0.22 mmol/L) (White et al, 2016) vs. 1.25 mM in our study. Taken together, conditions in several previous reports are likely to generate a more severe ischemia than in our study, which may lead to conditions that are more damaging, but put hearts in a position to benefit from mildly acidic reperfusion.…”

“…Although it has been reported to improve hemodynamic recovery (Inserte et al, 2008, 2011; Duan et al, 2011; Penna et al, 2013; White et al, 2016), infarct size (Inserte et al, 2008; Penna et al, 2013), ATP levels (Inserte et al, 2008), and to decrease cyt c release and mitochondrial swelling (Duan et al, 2011) and markers of cell death (Inserte et al, 2008; Duan et al, 2011), we did not observe hemodynamic benefits, nor did we see a difference, compared to controls, in necrosis parameters. Although we measured higher oxygen consumption at 10 min reperfusion, we did not see other differences in metabolic recovery.…”

“…Therefore, we decided to test the effects of no O 2 for 2 min in our model for its clinical practicality. Several acidic reperfusion strategies have also been tested, using with ranges of pH from 6.6 to 6.8 (Inserte et al, 2008, 2011; Duan et al, 2011; Penna et al, 2013; White et al, 2016); we decided to use a mildly acidic strategy, starting at pH 6.8 and then increasing with stepwise increments of 0.2 pH units per min to reach 7.4 after 3 min, as preliminary tests with lower pH levels and rapid normalization led to worse recovery compared with controls (data not shown).…”

Enhanced myocardial protection in cardiac donation after circulatory death using Intralipid® postconditioning in a porcine model

“…5 We have previously shown that controlled initial reperfusion of the DCD heart can result in optimization of functional recovery compared with standard recovery techniques. 6,7 These studies focused on the initial reperfusion period of the donor heart, without subsequent further intervention during EVHP. Nevertheless, pharmacologic postconditioning, which is known to enhance innate endogenous protective cellular mechanisms within the myocardium resulting in improved recovery after IR injury, has not been well explored in the DCD context.…”