Pharmacological conditioning aims to protect the heart from myocardial ischemia-reperfusion injury (IRI). Despite extensive research in this area, today, a significant gap remains between experimental findings and clinical practice. This review provides an update on recent developments in pharmacological conditioning in the experimental setting and summarizes the clinical evidence of these cardioprotective strategies in the perioperative setting. We start describing the crucial cellular processes during ischemia and reperfusion that drive acute IRI through changes in critical compounds (∆G_ATP, Na⁺, Ca²⁺, pH, glycogen, succinate, glucose-6-phosphate, mitoHKII, acylcarnitines, BH₄, and NAD⁺). These compounds all precipitate common end-effector mechanisms of IRI, such as reactive oxygen species (ROS) generation, Ca²⁺ overload, and mitochondrial permeability transition pore opening (mPTP). We further discuss novel promising interventions targeting these processes, with emphasis on cardiomyocytes and the endothelium. The limited translatability from basic research to clinical practice is likely due to the lack of comorbidities, comedications, and peri-operative treatments in preclinical animal models, employing only monotherapy/monointervention, and the use of no-flow (always in preclinical models) versus low-flow ischemia (often in humans). Future research should focus on improved matching between preclinical models and clinical reality, and on aligning multitarget therapy with optimized dosing and timing towards the human condition.

The adverse impact of common diseases like diabetes mellitus and acute hyperglycemia on morbidity and mortality from myocardial infarction (MI) has been well documented over the past years of research. In the clinical setting, the relationship between blood glucose and mortality appears linear, with amplifying risk associated with increasing blood glucose levels. Further, this seems to be independent of a diagnosis of diabetes. In the experimental setting, various comorbidities seem to impact ischemic and pharmacological conditioning strategies, protecting the heart against ischemia and reperfusion injury. In this translational experimental approach from bedside to bench, we set out to determine whether acute and/or prolonged hyperglycemia have an influence on the protective effect of transferred human RIPC-plasma and, therefore, might obstruct translation into the clinical setting. Control and RIPC plasma of young healthy men were transferred to isolated hearts of young male Wistar rats in vitro. Plasma was administered before global ischemia under either short hyperglycemic (HGs Con, HGs RIPC) conditions, prolonged hyperglycemia (HGl Con, HGl RIPC), or under normoglycemia (Con, RIPC). Infarct sizes were determined by TTC staining. Control hearts showed an infarct size of 55 ± 7%. Preconditioning with transferred RIPC plasma under normoglycemia significantly reduced infarct size to 25 ± 4% (p < 0.05 vs. Con). Under acute hyperglycemia, control hearts showed an infarct size of 63 ± 5%. Applying RIPC plasma under short hyperglycemic conditions led to a significant infarct size reduction of 41 ± 4% (p < 0.05 vs. HGs Con). However, the cardioprotective effect of RIPC plasma under normoglycemia was significantly stronger compared with acute hyperglycemic conditions (RIPC vs. HGs RIPC; p < 0.05). Prolonged hyperglycemia (HGl RIPC) completely abolished the cardioprotective effect of RIPC plasma (infarct size 60 ± 7%; p < 0.05 vs. HGl Con; HGl Con 59 ± 5%).

Background: Pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is performed using phases of deep hypothermic circulatory arrest (DHCA). DHCA has been discussed as a risk factor for cardiac surgery-associated acute kidney injury (AKI). The study analyzes the influence of the duration of DHCA on the incidence of postoperative AKI in patients undergoing PEA. Methods: This retrospective single-center cohort study included adult CTEPH patients who underwent PEA. The main exposure was DHCA at 18–20 °C core temperature. Primary endpoint was postoperative AKI defined by the KDIGO serum creatinine criteria. Secondary endpoints included severe postoperative AKI, major adverse cardiovascular events and mortality. Univariate and multivariate logistic regression models were performed for risk factor analysis. Results: Four hundred and eighty-three patients were included (mean age 61 ± 13 years). The incidence of postoperative AKI was 50%. Multivariate analysis showed no association between DHCA and AKI. Postoperative AKI was independently associated with chronic kidney disease (OR = 1.76, 95% CI = 1.05–2.95), age (OR = 1.02, 95% CI = 1.00–1.03), cardiopulmonary bypass (CPB) time (OR = 1.01, 95% CI = 1.01–1.02) and vasoactive-inotropic score (VIS) (OR = 1.05, 95% CI = 1.01–1.10). Patients with preoperative diuretics had a lower risk for postoperative AKI (OR = 0.44, 95% CI = 0.29–0.66). MACE were more frequent in patients with postoperative AKI (28.4% vs. 14.2%, p < 0.001), whereas 30-day and 1-year mortality did not differ. Conclusions: Results from this study indicate no influence of DHCA duration on occurrence of postoperative AKI. Risk factors identified for postoperative AKI were chronic kidney disease, age, CPB duration and VIS.