Effects of Subnormothermic Regulated Hepatic Reperfusion on Mitochondrial and Transcriptomic Profiles in a Porcine Model.

OBJECTIVE: We sought to investigate the biological effects of pre-reperfusion treatments of the liver after warm and cold ischemic injuries in a porcine donation after circulatory death model. SUMMARY OF BACKGROUND DATA: Donation after circulatory death represents a severe form of liver ischemia and reperfusion injury that has a profound impact on graft function after liver transplantation. METHODS: Twenty donor pig livers underwent 60 minutes of in situ warm ischemia after circulatory arrest and 120 minutes of cold static preservation prior to simulated transplantation using an ex vivo perfusion machine. Four reperfusion treatments were compared: Control-Normothermic (N), Control- Subnormothermic (S), regulated hepatic reperfusion (RHR)-N, and RHR-S (n = 5 each). The biochemical, metabolic, and transcriptomic profiles, as well as mitochondrial function were analyzed. RESULTS: Compared to the other groups, RHR-S treated group showed significantly lower post-reperfusion aspartate aminotransferase levels in the reperfusion effluent and histologic findings of hepatocyte viability and lesser degree of congestion and necrosis. RHR-S resulted in a significantly higher mitochondrial respiratory control index and calcium retention capacity. Transcriptomic profile analysis showed that treatment with RHR-S activated cell survival and viability, cellular homeostasis as well as other biological functions involved in tissue repair such as cytoskeleton or cytoplasm organization, cell migration, transcription, and microtubule dynamics. Furthermore, RHR-S inhibited organismal death, morbidity and mortality, necrosis, and apoptosis. CONCLUSION: Subnormothermic RHR mitigates IRI and preserves hepatic mitochondrial function after warm and cold hepatic ischemia. This organ resuscitative therapy may also trigger the activation of protective genes against IRI. Sub- normothermic RHR has potential applicability to clinical liver transplantation.

Calcium Chloride Requirement and Postreperfusion Rebound During Massive Transfusion in Liver Transplantation.

OBJECTIVES: The administration of citrated blood products during massive transfusion requires calcium salt administration to prevent citrate toxicity and to maintain ionized calcium values. The literature does not provide adequate guidance for the amount of calcium required during massive transfusions during liver transplantation. This study was conducted to provide guidance on calcium salt replacement during a massive transfusion in liver transplant patients, with a focus on the phase of transplantation during which citrate metabolism was minimal. DESIGN: An observational retrospective chart review. SETTING: An academic single-institution study of hospitalized patients. PARTICIPANTS: One hundred thirty-two patients after liver transplantation. INTERVENTIONS: The study authors observed documented measurements of ionized calcium and observed the ratio of calcium salts to citrated bank blood products in patients undergoing liver transplantation with complete data sets. They also observed the effect of continuous venovenous hemofiltration on the distribution of ionized calcium values. MEASUREMENTS AND MAIN RESULTS: Prereperfusion, an average of 1.09 g CaCl2/L of citrated blood was administered to maintain ionized calcium in the normal range. Postreperfusion, less CaCl2 was administered, and a rebound of ionized calcium occurred. Prereperfusion, continuous venovenous hemofiltration reduced the number of ionized calcium values outside of 2 standard deviations, meaning fewer values were critically low. CONCLUSIONS: With massive transfusions up to 67 liters (approximately 13 blood volumes), 1.09 g CaCl2/L citrated blood maintained ionized calcium in the normal range in the absence of citrate metabolism. This ratio may have value in empiric treatment when ionized calcium measurements are unavailable, and massive transfusion rates exceed metabolic capacity.

Heart Failure With Preserved Ejection Fraction: A Comprehensive Review and Update of Diagnosis, Pathophysiology, Treatment, and Perioperative Implications.

Almost three-quarters of all heart failure patients who are older than 65 have heart failure with preserved ejection fraction (HFpEF). The proportion and hospitalization rate of patients with HFpEF are increasing steadily relative to patients in whom heart failure occurs as result of reduced ejection fraction. The predominance of the HFpEF phenotype most likely is explained by the prevalence of medical conditions associated with an aging population. A multitude of age-related, medical, and lifestyle risk factors for HFpEF have been identified as potential causes for the sustained low-grade proinflammatory state that accelerates disease progression. Profound left ventricular (LV) systolic and diastolic stiffening, elevated LV filling pressures, reduced arterial compliance, left atrial hypertension, pulmonary venous congestion, and microvascular dysfunction characterize HFpEF, but pulmonary arterial hypertension, right ventricular dilation and dysfunction, and atrial fibrillation also frequently occur. These cardiovascular features make patients with HFpEF exquisitely sensitive to the development of hypotension in response to acute declines in LV preload or afterload that may occur during or after surgery. With the exception of symptom mitigation, lifestyle modifications, and rigorous control of comorbid conditions, few long-term treatment options exist for these unfortunate individuals. Patients with HFpEF present for surgery on a regular basis, and anesthesiologists need to be familiar with this heterogeneous and complex clinical syndrome to provide successful care. In this article, the authors review the diagnosis, pathophysiology, and treatment of HFpEF and also discuss its perioperative implications.

Characteristics associated with Publication of Randomized Controlled Trials in the Journal of Cardiothoracic and Vascular Anesthesia: A 15-Year Analysis, 2004-2018.

Randomized controlled trials (RCTs) provide important data to guide clinical decisions. Publication bias may limit the applicability of RCTs because many clinical investigators prefer to submit and journals more selectively accept studies with positive results. The authors tested the hypothesis that positive RCTs published in the Journal of Cardiothoracic and Vascular Anesthesia were more likely to be associated with factors known to predict publication of positive versus negative RCTs in other journals. This observational study was an internet analysis of all issues of Journal of Cardiothoracic and Vascular Anesthesia from 2004-2018. Each issue was searched to identify human RCTs. The numbers of centers and enrolled patients in each RCT were tabulated. The corresponding author determined the country of origin (United States v international). A trial was "positive" or "negative" based on rejection or confirmation of the null hypothesis, respectively, for the primary outcome variable or the majority of measured outcomes if a primary outcome was not identified. The presence or absence of a hypothesis, randomization methodology, sample size calculation, and blinded research design was recorded. Registration in a public database, Consolidated Statements of Reporting Trials (CONSORT) guideline compliance, and the source of funding also were determined. The number of citations for each RCT was determined by using Google Scholar; the citation rate was calculated as the ratio of the number of total citations and the duration in years since the trial's original publication. A total of 296 RCTs were identified, of which 58.8% reported positive results. Most RCTs were single center, relatively small, and international in origin. Total citations/RCT decreased over time, but citations/year did not. The percentage of RCTs that identified a randomization method, were registered, or followed CONSORT guidelines increased in a time-dependent manner. No differences in any factors associated with publication of RCTs were observed when positive and negative trials were compared. The Journal of Cardiothoracic and Vascular Anesthesia publishes more positive than negative RCTs, but factors that have been previously associated with RCT publication in other journals were similar between groups.

Advanced Age Attenuates Left Ventricular Filling Efficiency Quantified Using Vortex Formation Time: A Study of Octogenarians With Normal Left Ventricular Systolic Function Undergoing Coronary Artery Surgery.

OBJECTIVE: Blood flow across the mitral valve during early left ventricular (LV) filling produces a 3-dimensional rotational fluid body, known as a vortex ring, that enhances LV filling efficiency. Diastolic dysfunction is common in elderly patients, but the influence of advanced age on vortex formation is unknown. The authors tested the hypothesis that advanced age is associated with a reduction in LV filling efficiency quantified using vortex formation time (VFT) in octogenarians undergoing coronary artery bypass graft (CABG) surgery. DESIGN: Observational study. SETTING: Veterans Affairs medical center. PARTICIPANTS: After institutional review board approval, octogenarians (n = 7; 82 ± 2 year [mean ± standard deviation]; ejection fraction 56% ± 7%) without valve disease or atrial arrhythmias undergoing CABG were compared with a younger cohort (n = 7; 55 ± 6 year; ejection fraction 57% ± 7%) who were undergoing coronary revascularization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients were monitored using radial and pulmonary arterial catheters and transesophageal echocardiography. Peak early LV filling (E) and atrial systole (A) blood flow velocities and their corresponding velocity-time integrals were obtained using pulse-wave Doppler echocardiography to determine E/A, atrial filling fraction (ß), and E wave deceleration time. Pulse-wave Doppler also was used to measure pulmonary venous blood flow during systole and diastole. Mitral valve diameter (D) was calculated as the average of major and minor axis lengths obtained in the midesophageal LV bicommissural and long-axis transesophageal echocardiography imaging planes, respectively. VFT was calculated as 4 × (1 - ß) × SV/(πD3), where SV is the stroke volume measured using thermodilution. Systemic and pulmonary hemodynamics, LV diastolic function, and VFT were determined during steady-state conditions 30 minutes before cardiopulmonary bypass. A delayed relaxation pattern of LV filling (E/A 0.81 ± 0.16 v 1.29 ± 0.19, p = 0.00015; ß 0.44 ± 0.05 v 0.35 ± 0.03, p = 0.0008; E wave deceleration time 294 ± 58 v 166 ± 28 ms, p < 0.0001; ratio of peak pulmonary venous systolic and diastolic blood flow velocity 1.42 ± 0.23 v 1.14 ± 0.20, p = 0.0255) was observed in octogenarians compared with younger patients. Mitral valve diameter was similar between groups (2.7 ± 0.2 and 2.6 ± 0.2 cm, respectively, in octogenarians v younger patients, p = 0.299). VFT was reduced in octogenarians compared with younger patients (3.0 ± 0.9 v 4.5 ± 1.2; p = 0.0171). An inverse correlation between age and VFT was shown using linear regression analysis (VFT = -0.0627 × age + 8.24; r2 = 0.408; p = 0.0139). CONCLUSION: The results indicate that LV filling efficiency quantified using VFT is reduced in octogenarians compared with younger patients undergoing coronary artery bypass grafting.

Moderate Aortic Valvular Insufficiency Invalidates Vortex Formation Time as an Index of Left Ventricular Filling Efficiency in Patients With Severe Degenerative Calcific Aortic Stenosis Undergoing Aortic Valve Replacement.

OBJECTIVE: Transmitral blood flow produces a vortex ring (quantified using vortex formation time [VFT]) that enhances the efficiency of left ventricular (LV) filling. VFT is attenuated in LV hypertrophy resulting from aortic valve stenosis (AS) versus normal LV geometry. Many patients with AS also have aortic insufficiency (AI). The authors tested the hypothesis that moderate AI falsely elevates VFT by partially inhibiting mitral leaflet opening in patients with AS. DESIGN: Observational study. SETTING: Veterans Affairs medical center. PARTICIPANTS: Patients with AS in the presence or absence of moderate AI (n = 8 per group) undergoing aortic valve replacement (AVR) were studied after institutional review board approval. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Under general anesthesia, peak early LV filling (E) and atrial systole (A) blood flow velocities and their corresponding velocity-time integrals were obtained using pulse-wave Doppler transesophageal echocardiography (TEE) to determine E/A and atrial filling fraction (beta). Mitral valve diameter (D) was calculated as the average of major and minor axis lengths obtained in the midesophageal bicommissural (transcommissural anterior-lateral-posterior medial) and LV long-axis (anterior-posterior) TEE imaging planes, respectively. VFT was calculated as 4·(1-beta)·SV/πD(3), where SV = stroke volume measured using thermodilution. Hemodynamics, diastolic function, and VFT were determined during steady-state conditions before cardiopulmonary bypass. The severity of AS (mean and peak pressure gradients, peak transvalvular jet velocity, aortic valve area) and diastolic function (E/A, beta) were similar between groups. Moderate centrally directed AI was present in 8 patients with AS (ratio of regurgitant jet width to LV outflow tract diameter of 36±6%). Pulse pressure and mean pulmonary artery pressure were elevated in patients with versus without AI, but no other differences in hemodynamics were observed. Mitral valve minor and major axis lengths, diameter, and area were reduced in the presence versus the absence of AI. VFT was increased significantly (5.7±1.7 v 3.2±0.6; p = 0.00108) in patients with AS and AI compared with AS alone. CONCLUSION: Moderate AI falsely elevates VFT in patients with severe AS undergoing AVR by partially inhibiting mitral valve opening. VFT may be an unreliable index of LV filling efficiency with competitive diastolic flow into the LV.