Cardioprotection: A Review of Current Practice in Global Ischemia and Future Translational Perspective

The idea of protecting the heart from ischemic insult during heart surgery to allow elective cardiac arrest is as old as the idea of cardiac surgery itself. The current gold standard in clinical routine is a high potassium regimen added either to crystalloid or blood cardioplegic solutions inducing depolarized arrest. Ongoing patient demographic changes with increasingly older, comorbidly ill patients and increasing case complexity with increasingly structurally abnormal hearts as morphological correlate paired with evolutions in pediatric cardiac surgery allowing more complex procedures than ever beforeredefine requirements for cardioprotection. Many, in part adversarial, regimens to protect the myocardium from ischemic insults have entered clinical routine; however, functional recovery of the heart is still often impaired due to perfusion injury. Myocardial reperfusion damage is a key determinant of postoperative organ functional recovery, morbidity, and mortality in adult and pediatric patients. There is a discrepancy between what current protective strategies are capable of and what they are expected to do in a rapidly changing cardiac surgery community. An increased understanding of the molecular players of ischemia reperfusion injury offers potential seeds for new cardioprotective regimens and may further displace boundaries of what is technically feasible.

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Endothelial glycocalyx during early reperfusion in patients undergoing cardiac surgery

PLoS ONE ◽

10.1371/journal.pone.0251747 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0251747

Author(s):

Arie Passov ◽

Alexey Schramko ◽

Ulla-Stina Salminen ◽

Juha Aittomäki ◽

Sture Andersson ◽

...

Keyword(s):

Cardiac Surgery ◽

Heparan Sulfate ◽

Coronary Sinus ◽

Heart Surgery ◽

Coronary Circulation ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Open Heart Surgery ◽

Endothelial Glycocalyx ◽

Early Reperfusion

Background Experimental cardiac ischemia-reperfusion injury causes degradation of the glycocalyx and coronary washout of its components syndecan-1 and heparan sulfate. Systemic elevation of syndecan-1 and heparan sulfate is well described in cardiac surgery. Still, the events during immediate reperfusion after aortic declamping are unknown both in the systemic and in the coronary circulation. Methods In thirty patients undergoing aortic valve replacement, arterial concentrations of syndecan-1 and heparan sulfate were measured immediately before and at one, five and ten minutes after aortic declamping (reperfusion). Parallel blood samples were drawn from the coronary sinus to calculate trans-coronary gradients (coronary sinus–artery). Results Compared with immediately before aortic declamping, arterial syndecan-1 increased by 18% [253.8 (151.6–372.0) ng/ml vs. 299.1 (172.0–713.7) ng/ml, p < 0.001] but arterial heparan sulfate decreased by 14% [148.1 (135.7–161.7) ng/ml vs. 128.0 (119.0–138.2) ng/ml, p < 0.001] at one minute after aortic declamping. There was no coronary washout of syndecan-1 or heparan sulfate during reperfusion. On the contrary, trans-coronary sequestration of syndecan-1 occurred at five [-12.96 ng/ml (-36.38–5.15), p = 0.007] and at ten minutes [-12.37 ng/ml (-31.80–6.62), p = 0.049] after reperfusion. Conclusions Aortic declamping resulted in extracardiac syndecan-1 release and extracardiac heparan sulfate sequestration. Syndecan-1 was sequestered in the coronary circulation during early reperfusion. Glycocalyx has been shown to degrade during cardiac surgery. Besides degradation, glycocalyx has propensity for regeneration. The present results of syndecan-1 and heparan sulfate sequestration may reflect endogenous restoration of the damaged glycocalyx in open heart surgery.

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Markers of endothelial dysfunction after cardiac surgery: Soluble forms of vascular-1 and intercellular-1 adhesion molecules

Medicina ◽

10.3390/medicina45060056 ◽

2009 ◽

Vol 45 (6) ◽

pp. 434 ◽

Cited By ~ 12

Author(s):

Mindaugas Balčiūnas ◽

Loreta Bagdonaitė ◽

Robertas Samalavičius ◽

Alis Baublys

Keyword(s):

Cardiac Surgery ◽

Endothelial Dysfunction ◽

Reperfusion Injury ◽

Adhesion Molecules ◽

Heart Surgery ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Transplant Rejection ◽

Vascular Wall ◽

Tissue Ischemia

Endothelium forms an inner layer of vascular wall. It plays an important role in inflammatory process, regulation of vascular tone, and synthesis of thromboregulatory substances. Leukocyte and endothelium interactions during inflammation are regulated by different families of adhesion molecules. Increased levels of soluble forms of adhesion molecules have been detected in the circulating blood in conditions such as autoimmune diseases, transplant rejection, ischemia-reperfusion injury in addition to neutrophil- and endothelial membrane-bound forms reflecting the level of endothelial dysfunction. It is known that endothelial dysfunction is a risk factor for ischemic events such as stroke, myocardial infarction, unstable angina pectoris, ventricle fibrillation, necessity of revascularisation procedures, and death from cardiovascular reasons. Clinical studies showed that cardiac surgery has an impact on vascular endothelial function as well. The amount of endotheliumderived soluble forms of vascular-1 and intercellular-1 adhesion molecules increases after cardiopulmonary bypass suggesting endothelial dysfunction. However, further investigations are needed to be done to support the evidence that endothelial dysfunction proceeding heart surgery is one of the reasons of tissue ischemia-reperfusion injury.

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Pulmonary Protection During Cardiac Surgery: Systematic Literature Review

Asian Cardiovascular and Thoracic Annals ◽

10.1177/021849230801600617 ◽

2008 ◽

Vol 16 (6) ◽

pp. 503-507 ◽

Cited By ~ 16

Author(s):

Enisa MF Carvalho ◽

Edmo A Gabriel ◽

Tomas A Salerno

Keyword(s):

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Literature Review ◽

Heart Surgery ◽

Ischemia Reperfusion Injury ◽

Current Knowledge ◽

Ischemia Reperfusion ◽

Pulmonary Dysfunction ◽

Pulmonary Protection ◽

Postoperative Pulmonary Dysfunction

Ischemia-reperfusion injury occurs during heart surgery in which cardiopulmonary bypass is used. Current knowledge of the factors contributing to postoperative pulmonary dysfunction and the measures to avoid it are reviewed.

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Real-time monitoring of endogenous lipid peroxidation by exhaled ethylene in patients undergoing cardiac surgery

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00168.2014 ◽

2014 ◽

Vol 307 (7) ◽

pp. L509-L515 ◽

Cited By ~ 16

Author(s):

Simona M. Cristescu ◽

Rudolf Kiss ◽

Sacco te Lintel Hekkert ◽

Miles Dalby ◽

Frans J. M. Harren ◽

...

Keyword(s):

Lipid Peroxidation ◽

Cardiac Surgery ◽

Real Time ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Artery Bypass ◽

Organ Injury ◽

Real Time Monitoring ◽

Myocardial Ischemia And Reperfusion ◽

Endogenous Lipid

Pulmonary and systemic organ injury produced by oxidative stress including lipid peroxidation is a fundamental tenet of ischemia-reperfusion injury, inflammatory response to cardiac surgery, and cardiopulmonary bypass (CPB) but is not routinely measured in a surgically relevant time frame. To initiate a paradigm shift toward noninvasive and real-time monitoring of endogenous lipid peroxidation, we have explored pulmonary excretion and dynamism of exhaled breath ethylene during cardiac surgery to test the hypothesis that surgical technique and ischemia-reperfusion triggers lipid peroxidation. We have employed laser photoacoustic spectroscopy to measure real-time trace concentrations of ethylene from the patient breath and from the CPB machine. Patients undergoing aortic or mitral valve surgery-requiring CPB ( n = 15) or off-pump coronary artery bypass surgery (OPCAB) ( n = 7) were studied. Skin and tissue incision by diathermy caused striking (>30-fold) increases in exhaled ethylene resulting in elevated levels until CPB. Gaseous ethylene in the CPB circuit was raised upon the establishment of CPB (>10-fold) and decreased over time. Reperfusion of myocardium and lungs did not appear to enhance ethylene levels significantly. During OPCAB surgery, we have observed increased ethylene in 16 of 30 documented reperfusion events associated with coronary and aortic anastomoses. Therefore, novel real-time monitoring of endogenous lipid peroxidation in the intraoperative setting provides unparalleled detail of endogenous and surgery-triggered production of ethylene. Diathermy and unprotected regional myocardial ischemia and reperfusion are the most significant contributors to increased ethylene.

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516 NEW PROTECTIVE STRATEGIES AGAINST COLD ISCHEMIA-REPERFUSION INJURY IN STEATOTIC AND NON-STEATOTIC LIVERS USING TROPHIC FACTOR AS ADDITIVE TO UW SOLUTION: IS THERE A DIFFERENCE

Journal of Hepatology ◽

10.1016/s0168-8278(11)60518-7 ◽

2011 ◽

Vol 54 ◽

pp. S212

Author(s):

M.A. Zaouali ◽

S. Padrissa-Altês ◽

I. Alfany-Fernandez ◽

J. Roselló-Catafau

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Trophic Factor ◽

Cold Ischemia ◽

Uw Solution ◽

Protective Strategies

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Preoperative oral thyroid hormones to prevent euthyroid sick syndrome and attenuate myocardial ischemia-reperfusion injury after cardiac surgery with cardiopulmonary bypass in children

Medicine ◽

10.1097/md.0000000000012100 ◽

2018 ◽

Vol 97 (36) ◽

pp. e12100 ◽

Cited By ~ 7

Author(s):

Jia-Qiang Zhang ◽

Quan-Yong Yang ◽

Fu-Shan Xue ◽

Wei Zhang ◽

Gui-Zhen Yang ◽

...

Keyword(s):

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Myocardial Ischemia ◽

Thyroid Hormones ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Euthyroid Sick Syndrome ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

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Assessment of diaphragm dysfunction during cardiac rehabilitation after heart surgery: the role of ultrasound imaging

European Heart Journal ◽

10.1093/ehjci/ehaa946.3086 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

F Maranta ◽

V Rizza ◽

I Cartella ◽

S Pellegrino ◽

A Bonaccorso ◽

...

Keyword(s):

Cardiac Surgery ◽

Functional Recovery ◽

Heart Surgery ◽

Respiratory Cycle ◽

Invasive Technique ◽

Valve Repair ◽

Combined Surgery ◽

Diaphragm Dysfunction ◽

Diaphragm Function ◽

The Right

Abstract Background Diaphragm dysfunction is a frequent and underdiagnosed complication of cardiac surgery. It can cause dyspnoea, decreased exercise performance and, in more severe cases, respiratory failure. Ultrasonography (US) is a valuable, non-invasive technique for the assessment of diaphragm function. Only few trials have been conducted using US to evaluate diaphragm functional recovery after cardiovascular rehabilitation (CR). Purpose The aim of the study was to assess with US the incidence of diaphragm dysfunction after heart surgery and to define the impact of an inpatient CR programme on diaphragm functional recovery. Methods We performed a single-centre prospective cohort study, enrolling 185 patients hospitalized in our CR unit: 99 patients underwent mitral valve repair or replacement, 28 tricuspid valve repair or replacement, 53 aortic valve replacement, 30 coronary artery bypass grafting, 59 combined surgery and 14 other surgical procedures. Diaphragm US was performed at admission and after 10 rehabilitative sessions. We assess the following parameters on quiet breathing: excursion, time of inspiration, time of a respiratory cycle and contraction velocity (slope) in M-mode on the right anterior subcostal projections and thickening fraction (TF) in B-mode on the right intercostal projections. TF was defined as [(thickness at end inspiration–thickness at end expiration)/thickness at end expiration]. Results The median excursion at admission was 1.6 cm. Patients with excursion <2 cm (lower limit for the general population) were considered with diaphragm dysfunction. Following cardiac surgery, the incidence of diaphragm dysfunction was 70.8%. Patients with excursion <2 cm at admission gained an important benefit from CR, with a significant improvement in TF (p<0.001), excursion (p<0.001), time of inspiration (p<0.001), time of a respiratory cycle (p<0.001) and slope (p<0.001). Conversely, in patients with excursion ≥2 cm there was no significant improvement in slope (p=0.539) and excursion (p=0.179). At the final assessment, diaphragm function recovered in 50.5% of the patients, whilst 49.5% had a failure of recovery (excursion relative change between admission and discharge <33%). The multivariate analysis identified combined surgery (OR 3.08; 95% CI 1.59–5.99, p=0.001) and post-surgical pneumothorax (OR 3.05; 95% CI 1.23–7.55, p=0.036) as independent predictors of failure of diaphragm function recovery. Conclusions US might be a valuable tool for initial and follow-up assessment of patients after cardiac surgery. CR has been shown to be an effective strategy to improve diaphragm parameters in patients with post-surgical dysfunction. Patients undergoing combined surgery or developing post-surgical pneumothorax might benefit from a personalised rehabilitation programme to improve diaphragm function. Funding Acknowledgement Type of funding source: None

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Apelin-13 increases myocardial progenitor cells and improves repair postmyocardial infarction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00366.2012 ◽

2012 ◽

Vol 303 (5) ◽

pp. H605-H618 ◽

Cited By ~ 74

Author(s):

Lanfang Li ◽

Heng Zeng ◽

Jian-Xiong Chen

Keyword(s):

Progenitor Cells ◽

Functional Recovery ◽

Cardiac Fibrosis ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Coronary Artery Ligation ◽

Artery Ligation ◽

Beneficial Effects ◽

Postmyocardial Infarction ◽

Stromal Cell Derived Factor

Apelin is an endogenous ligand for the angiotensin-like 1 receptor (APJ) and has beneficial effects against myocardial ischemia-reperfusion injury. Little is known about the role of apelin in the homing of vascular progenitor cells (PCs) and cardiac functional recovery postmyocardial infarction (post-MI). The present study investigated whether apelin affects PC homing to the infarcted myocardium, thereby mediating repair and functional recovery post-MI. Mice were infarcted by coronary artery ligation, and apelin-13 (1 mg·kg−1·day−1) was injected for 3 days before MI and for 14 days post-MI. Homing of vascular PCs [CD133+/c-Kit+/Sca1+, CD133+/stromal cell-derived factor (SDF)-1α+, and CD133+/CXC chemokine receptor (CXCR)-4+] into the ischemic area was examined. Myocardial Akt, endothelial nitric oxide synthase (eNOS), VEGF, jagged1, notch3, SDF-1α, and CXCR-4 expression were assessed at 24 h and 14 days post-MI. Functional analyses were performed on day 14 post-MI. Mice that received apelin-13 treatment demonstrated upregulation of SDF-1α/CXCR-4 expression and dramatically increased the number of CD133+/c-Kit+/Sca1+, CD133+/SDF-1α+, and c-Kit+/CXCR-4+ cells in infarcted hearts. Apelin-13 also significantly increased Akt and eNOS phosphorylation and upregulated VEGF, jagged1, and notch3 expression in ischemic hearts. This was accompanied by a significant reduction of myocardial apoptosis. Furthermore, treatment with apelin-13 promoted myocardial angiogenesis and attenuated cardiac fibrosis and hypertrophy together with a significant improvement of cardiac function at 14 days post-MI. Apelin-13 increases angiogenesis and improves cardiac repair post-MI by a mechanism involving the upregulation of SDF-1α/CXCR-4 and homing of vascular PCs.

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