Faraz Kerendi

Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adenosine receptors.

AbstractObjectivesA series of brief coronary artery reperfusions and reocclusions applied during the early minutes of coronary artery reflow (“postconditioning”) attenuates reperfusion injury. However, it is not known whether brief ischemia–reperfusion applied to a distant organ at the onset of myocardial reperfusion (i.e. “remote postconditioning”, remote PostC) reduces infarct size in the reperfused myocardium. In an in vivo anesthetized rat model of myocardial infarction induced by coronary artery occlusion and reperfusion, this study tested the hypothesis that remote postC induced by a single 5 minute episode of renal artery (RA) occlusion and reperfusion applied immediately before the onset of coronary artery reperfusion protects the myocardium from reperfusion injury by mechanisms involving endogenous adenosine receptor activation.MethodsAll rats were subjected to a total of 30 minutes of left coronary artery occlusion (LCAO) and 3 hours of reperfusion. The rats were randomized to one of six groups: 1) Control: LCAO and reperfusion only with no other intervention; 2) Remote PostC: after 24 minutes of LCAO the RA was occluded for 5 minutes and released 1 min before coronary artery reperfusion; 3) Permanent RA occlusion: the RA was permanently occluded after 24 minutes LCAO continuing to the end of reperfusion; 4) Delayed Remote PostC: after 26 minutes LCAO the RA was occluded for 5 minutes, and its release was delayed until 1 min after coronary artery reperfusion; 5) CON + SPT: rats with LCAO and reperfusion received 10 mg/kg IV of the non–selective adenosine receptor antagonist 8–sulfophenyl theophylline [SPT] administered 5 minutes before coronary artery reperfusion; and 6) Remote PostC + SPT: after 24 minutes of LCAO the RA was occluded for 5 minutes and released 1 minute before coronary artery reperfusion in the presence of 10 mg/kg SPT given 5 min before coronary artery reperfusion.ResultsMyocardial infarct size (percentage necrosis/area at risk, mean ± SEM) was reduced by 50% in Remote PostC (25 ± 4%) compared to Control (49 ± 4%, p = 0.003), consistent with a reduction in plasma CK activity (44 ± 5 vs. 67 ± 6 U/ml, p = 0.023). In contrast, permanent RA occlusion before LCAO and reperfusion failed to reduce myocardial infarct size (47 ± 5%) vs Control. Delaying the release of the RA occlusion (delayed Remote PostC) abrogated the myocardial infarct reduction observed with Remote PostC (48 ± 6%). SPT alone had no effect on infarct size (47 ± 4% in CON + SPT vs. 49 ± 4% in CON); however, Remote PostC+SPT abrogated the myocardial infarct size reduction in Remote PostC (50 ± 3% in Remote PostC + SPT vs. 25 ± 4% in Remote PostC).ConclusionsRemote renal postconditioning applied immediately before the onset of coronary artery reperfusion provides potent myocardial infarct size reduction likely exerted during the first minutes of coronary artery reperfusion. This inter–organ remote postconditioning phenomenon is likely mediated in part by release of adenosine by the ischemic–reperfused kidney and subsequent activation of adenosine receptors.

Postconditioning--A new link in nature's armor against myocardial ischemia-reperfusion injury.

AbstractReperfusion injury is a complex process involving several cell types (endothelial cells, neutrophils, and cardiomyocytes), soluble proinflammatory mediators, oxidants, ionic and metabolic dyshomeostasis, and cellular and molecular signals. These participants in the pathobiology of reperfusion injury are not mutually exclusive. Some of these events take place during the very early moments of reperfusion, while others, seemingly triggered in part by the early events, are activated within a later timeframe. Postconditioning is a series of brief mechanical interruptions of reperfusion following a specific prescribed algorithm applied at the very onset of reperfusion. This algorithm lasts only from 1 to 3 minutes depending on species. Although associated with re–occlusion of the coronary artery or re–imposition of hypoxia in cell culture, the reference to ischemia has been dropped. Postconditioning has been observed to reduce infarct size and apoptosis as the “end games” in myocardial therapeutics; salvage of infarct size was similar to that achieved by the gold standard of protection, ischemic preconditioning. The cardioprotection was also associated with a reduction in: endothelial cell activation and dysfunction, tissue superoxide anion generation, neutrophil activation and accumulation in reperfused myocardium, microvascular injury, tissue edema, intracellular and mitochondrial calcium accumulation. Postconditioning sets in motion triggers and signals that are functionally related to reduced cell death. Adenosine has been implicated in the cardioprotection of postconditioning, as has e–NOS, nitric oxide and guanylyl cyclase, opening of KATP channels and closing of the mitochondrial permeability transition pore. Cardioprotection by postconditioning has also been associated with the activation of intracellular survival pathways such as ERK1/2 and PI3 kinase – Akt pathways. Other pathways have yet to be identified. Although many of the pathways involved in postconditioning have also been identified in ischemic preconditioning, some may not be involved in preconditioning (ERK1/2). The timing of action of these pathways and other mediators of protection in postconditioning differs from that of preconditioning. In contrast to preconditioning, which requires a foreknowledge of the ischemic event, postconditioning can be applied at the onset of reperfusion at the point of clinical service, i.e. angioplasty, cardiac surgery, transplantation.

Elevated preoperative hemoglobin A1c level is predictive of adverse events after coronary artery bypass surgery

OBJECTIVE Diabetes mellitus has been associated with an increased risk of adverse outcomes after coronary artery bypass grafting. Hemoglobin A1c is a reliable measure of long-term glucose control. It is unknown whether adequacy of diabetic control, measured by hemoglobin A1c, is a predictor of adverse outcomes after coronary artery bypass grafting. METHODS Of 3555 consecutive patients who underwent primary, elective coronary artery bypass grafting at a single academic center from April 1, 2002, to June 30, 2006, 3089 (86.9%) had preoperative hemoglobin A1c levels obtained and entered prospectively into a computerized database. All patients were treated with a perioperative intravenous insulin protocol. A multivariable logistic regression model was used to determine whether hemoglobin A1c, as a continuous variable, was associated with in-hospital mortality, renal failure, cerebrovascular accident, myocardial infarction, and deep sternal wound infection after coronary artery bypass grafting. Receiver operating characteristic curve analysis identified the hemoglobin A1c value that maximally discriminated outcome dichotomies. RESULTS In-hospital mortality for all patients was 1.0% (31/3089). An elevated hemoglobin A1c level predicted in-hospital mortality after coronary artery bypass grafting (odds ratio 1.40 per unit increase, P = .019). Receiver operating characteristic curve analysis revealed that hemoglobin A1c greater than 8.6% was associated with a 4-fold increase in mortality. For each unit increase in hemoglobin A1c, there was a significantly increased risk of myocardial infarction and deep sternal wound infection. By using receiver operating characteristic value thresholds, renal failure (threshold 6.7, odds ratio 2.1), cerebrovascular accident (threshold 7.6, odds ratio 2.24), and deep sternal wound infection (threshold 7.8, odds ratio 5.29) occurred more commonly in patients with elevated hemoglobin A1c. CONCLUSION Elevated hemoglobin A1c level was strongly associated with adverse events after coronary artery bypass grafting. Preoperative hemoglobin A1c testing may allow for more accurate risk stratification in patients undergoing coronary artery bypass grafting.

Selective antegrade cerebral perfusion via right axillary artery cannulation reduces morbidity and mortality after proximal aortic surgery

INTRODUCTION Selective antegrade cerebral perfusion is a well-described neuroprotective technique used in proximal aortic surgery. This study investigated whether selective antegrade cerebral perfusion is associated with improved outcomes in both emergency and elective settings compared with deep hypothermic circulatory arrest alone. METHODS Retrospective review was performed for all cases of proximal aortic surgery between January 2004 and May 2007. Of these 271 patients, 105 had emergency and 166 had elective operation. Selection bias was controlled using propensity scoring methods. Multivariable logistic regression analysis was used to model adverse outcomes as a function of selective antegrade cerebral perfusion, emergency status, and their interaction, adjusted for the propensity score. Adjusted odds ratios were formulated with 95% confidence intervals. RESULTS Operative mortality occurred in 12.1% (33/271) of patients: 8.8% (18/205) in patients with selective antegrade cerebral perfusion versus 22.7% (15/66) in those with deep hypothermic circulatory arrest alone (P = .003). Temporary neurologic dysfunction occurred in 5.9% (15/255) of patients: 4.5% (9/198) in selective antegrade cerebral perfusion versus 10.5% (6/57) in deep hypothermic circulatory arrest alone (P = .09). Stroke occurred in 4.3% (11/255) of patients with no difference between groups. In the elective setting, selective antegrade cerebral perfusion was associated with a significant decrease in operative mortality compared with deep hypothermic circulatory arrest alone. Overall, selective antegrade cerebral perfusion was associated with shorter intensive care unit and ventilator times and fewer renal and pulmonary complications. Significant multivariable predictors of operative mortality were emergency status, previous coronary surgery, and cardiopulmonary bypass time. CONCLUSIONS Use of selective antegrade cerebral perfusion confers a survival advantage during proximal aortic surgery that is most apparent in the elective setting. Improved resource utilization and fewer pulmonary and renal complications were observed in patients with selective antegrade cerebral perfusion.

Long-term inhibition of myocardial infarction by postconditioning during reperfusion.

AbstractCardioprotection with postconditioning has been well demonstrated after a short period of reperfusion. This study tested the hypothesis that postconditioning reduces infarct size, vascular dysfunction, and neutrophil accumulation after a long-term reperfusion. Canines undergoing 60 min left anterior descending artery (LAD) occlusion were divided into two control groups of either 3 h or 24 h of full reperfusion and two postconditioning groups with three 30 s cycles of reperfusion and re-occlusion applied at the onset of either 3 h or 24 h of reperfusion. Size of the area at risk (AAR) and collateral blood flow during ischemia were similar among groups. In controls, infarct size as percentage of the AAR (30 ± 3 vs. 39 ± 2* %) by TTC staining, superoxide anion generation from the post-ischemic coronary arteries by lucigenin-enhanced chemiluminescence [(89 ± 5 vs. 236 ± 27* relative light units (RLU/mg)], and neutrophil (PMN) accumulation by immunohistochemical staining in the AAR (52 ± 11 vs. 84 ± 14* cells/mm2 myocardium) significantly increased between 3 and 24 h of reperfusion. Postconditioning reduced infarct size (15 ± 4† and 27 ± 3.6† %), superoxide anion generation (24 ± 4† and 43 ± 11† RLU/mg), and PMN accumulation (19 ± 6† and 45 ± 8† cells/mm2 myocardium) in the 3 and 24 h reperfusion groups relative to time-matched controls. These data suggest that myocardial injury increases with duration of reperfusion; reduction in infarct size and attenuation in inflammatory responses with postconditioning persist after a prolonged reperfusion. * p < 0.05 24 vs. 3 h control; † p < 0.05 postconditioning vs. time-matched control.

[Postconditioning: a brief review].

ZusammenfassungDie Präkonditionierung ist die wirksamste Form der Kardioprotektion. Sie kann durch unterschiedliche Interventionen ausgelöst werden: kurze Ischämien, Pharmaka und volatile Anästhetika. Eine kurze Ischämie an einem anderen Organ—also nicht am Herzen selbst—kann ebenfalls zu einem Schutz des Herzens führen: heterotope Präkonditionierung. Nach jüngeren Befunden können auch kurze Ischämien während der Reperfusion nach einer andauernden Ischämie die postischämische Dysfunktion verbessern. Eine solche Postkonditionierung lässt sich ebenfalls durch eine kurze Ischämie an einem anderen Organ auslösen. Entsprechend wird dieses Phänomen als heterotope Postkonditionierung bezeichnet. Ziel dieser kurzen Übersichtsarbeit ist, Präkonditionierung und Postkonditionierung zunächst zu charakterisieren, mögliche Mechanismen zu nennen und auf die klinische Relevanz aufmerksam zu machen.AbstractPreconditioning is the most effective form of cardioprotection that can be induced via different interventions before a longer-lasting ischemia (= index ischemia). Preconditioning can be induced by short bouts of ischemia, several pharmaceuticals (e.g., adenosine), and volatile anesthetics. A brief ischemia of an organ other than the heart can likewise initiate protection of the heart, which has been called preconditioning at a distance or remote preconditioning. According to the more recent literature, short bouts of ischemia after an index ischemia can also initiate cardioprotection, e.g., improve postischemic dysfunction or reduce infarct size, which has been called postconditioning. Such a postconditioning can also be elicited at a distant organ, termed remote postconditioning. It is the aim of this short review to characterize preconditioning and in particular postconditioning, describe possible mechanisms, and call attention to the clinical relevance.

Perioperative Risks and Outcomes of Atrioventricular Valve Surgery in Conjunction With Fontan Procedure

BACKGROUND Long-term outcomes of staged single-ventricle palliation can be impaired by atrioventricular valve (AVV) regurgitation. Atrioventricular valve repair or replacement has been shown to improve late outcomes, but little data exist regarding the associated perioperative morbidity. This study aimed to evaluate the additional perioperative risks associated with single-ventricle AVV surgery. METHODS Two hundred thirty-six consecutive Fontan procedures were retrospectively reviewed. Group 1 (n = 21, with concomitant AVV repair [n = 19] or replacement [n = 2]) was compared with group 2 (n = 215, no AVV surgery) with regard to preoperative characteristics and perioperative outcomes. Atrioventricular valve regurgitation was graded as 1 (none or trivial) to 4 (severe). RESULTS Group 1 patients were older (4.3 +/- 3.7 versus 3.0 +/- 2.6 years; p = 0.04) and had longer cardiopulmonary bypass (118 +/- 38 versus 85 +/- 28 minutes; p < 0.001) and aortic cross-clamp times (33 +/- 32 versus 14 +/- 21 minutes; p < 0.001). There were no differences between groups regarding diagnosis, weight, hospital or intensive care unit length of stay, ventilator time, or 12-hour chest tube output. Postoperative complications were similar between groups, including bleeding (0 of 21 versus 8 of 215; p = 0.8), neurologic injury (1 of 21 versus 9 of 215; p = 0.7), arrhythmias (1 of 21 versus 24 of 215; p = 0.6), and operative mortality (0 of 21 versus 1 of 215; p = 0.1). Group 1 AVV regurgitation significantly decreased after surgery (3.0 +/- 0.9 preoperatively versus 1.7 +/- 0.9 postoperatively; p < 0.001). CONCLUSIONS Atrioventricular valve surgery has been shown to improve late outcomes for single-ventricle patients. This study demonstrates that AVV surgery performed with the Fontan procedure increased operative times, but did not significantly increase perioperative morbidity or mortality. This information supports appropriate utilization of AVV surgery for single-ventricle patients.

Off-pump coronary bypass surgery for high-risk patients: only in expert centers?

Purpose of review Off-pump coronary artery bypass (OPCAB) grafting has been increasingly adopted in an effort to prevent deleterious effects of cardiopulmonary bypass, including the associated inflammatory response, global myocardial ischemia and the risks of aortic manipulation. In many studies, the greatest benefit of OPCAB has been in high-risk patients. This review will summarize the recent literature examining outcomes of OPCAB versus on-pump coronary artery bypass in high-risk subgroups, and will examine the safety of routine application of OPCAB in these patients. Recent findings Prospective randomized trials have shown that in comparison to on-pump coronary artery bypass, OPCAB reduces perioperative morbidity, but have failed to show a mortality benefit, owing to small sample sizes. However, numerous large retrospective series and meta-analyses have demonstrated a reduction in risk-adjusted mortality and morbidity with respect to the following outcomes: stroke, pulmonary function, renal function, atrial fibrillation, need for early reoperation, blood transfusion requirements, length of ICU and hospital stay, and hospital costs. An even greater benefit has been seen in the following high-risk patients: those with acute myocardial infarction, left ventricular dysfunction, previous history of stroke, renal insufficiency, women, elderly patients, and those undergoing reoperations. Summary Risk-adjusted outcomes are superior after OPCAB versus on-pump coronary artery bypass for mortality and numerous morbidity endpoints. This benefit is most easily demonstrated in high-risk patient populations.

Self-perceived video-assisted thoracic surgery lobectomy proficiency by recent graduates of North American thoracic residencies

Minimally invasive surgical techniques offer several advantages over traditional open procedures, yet the pathway to minimally invasive proficiency can be difficult to navigate. As a part of an effort of the Joint Council of Thoracic Surgical Education to increase access to this skill set in the general thoracic community, recent graduates of thoracic residencies were surveyed to determine the self-reported achievement of video-assisted thoracic surgery (VATS) lobectomy proficiency and the merits of various educational opportunities. The objective of this study was to estimate the comfort level of recent graduates with the minimally invasive approach, as this demographic not only reflects the current status of training, but represents the future of the specialty. Surgeons graduating North American thoracic residencies between 2006 and 2008 identifying themselves as practitioners of general thoracic surgery were surveyed. A total of 271 surgeons completed training between 2006 and 2008 and indicated general thoracic to be a part of their practice (84 dedicated thoracic and 187 mixed). One hundred and forty-six surgeons completed the survey (54%) including 74 of 84 (88%) dedicated thoracic surgeons. Overall, 58% of recent graduates who perform general thoracic procedures consider themselves proficient in VATS lobectomies (86% of dedicated thoracic surgeons and 28% of surgeons with a mixed practice, P < 0.0001). Of surgeons considering themselves to be proficient at VATS lobectomies, 66% felt thoracic residency was critical or very important to achieving proficiency. Fellowships after completing board residency, animal labs, and follow-up VATS courses put on by experts were much less consistently beneficial. The vast majority of the 25 dedicated general thoracic surgeons who graduate each year consider themselves proficient in VATS lobectomies, largely due to training in their thoracic residencies. On the other hand, the minority of surgeons performing general thoracic procedures as a part of a mixed practice consider themselves proficient in VATS lobectomies. Further study is warranted to enhance the VATS lobectomy experience of mixed practice surgeons particularly during their thoracic residencies.

Early Results of Valve-Sparing Aortic Root Replacement in High-Risk Clinical Scenarios

BACKGROUND The feasibility of valve-sparing aortic root procedures (David) in certain high-risk situations has been questioned. We sought to determine the safety of the David procedure in the following high-risk subgroups: acute type A dissection, severe aortic insufficiency (AI), and reoperations. METHODS From 2005 through 2007, 110 root replacements were performed for the above criteria: 73 root replacements with a composite valve-conduit (Bentall) and 37 David procedures. The reimplantation technique was used in all 37 David patients, with 7 requiring aortic cusp repair. RESULTS There were no significant differences in preoperative or intraoperative variables between the groups, with the exception of cross-clamp time, which was longer for David patients. There was a slight, but nonsignificant increase in mortality among Bentall patients (8.2% [6 of 73]) compared with David patients (5.4% [2 of 37], p = 0.59]. There were no differences with respect to postoperative stroke, renal failure, or respiratory failure. Predischarge echocardiogram in the surviving 35 David patients demonstrated no AI in 25 patients and trace/mild AI in 10. Freedom from AVR at a mean follow-up of 8.8 months (range, 1 to 40) was 94.3% (33 of 35). One patient required AVR because of endocarditis at 9 months, and 1 had severe AI 13 months postoperatively. CONCLUSIONS Valve-sparing aortic root replacement can be performed safely in the setting of acute dissection, severe AI, and reoperations with acceptable early results. Long-term follow-up is needed to determine the durability of repair in these high-risk groups.