Postoperative Myocardial Dysfunction Research Articles

Possibilities of predicting early postoperative complications after surgical correction in infants of the first year of life with ventricular septal defect

Objective. To study the echocardiographic (Echo-CG) indicators in infants of the first year of life with ventricular septal defect (VSD) in the early postoperative period after surgical correction of the defect.
 Materials and methods. Examination of 205 infants with VSD was carried out. Complex examination before the surgery, 6, 24 hours and the day 10th after the surgery was fulfilled.
 Results. In the early postoperative period, myocardial dysfunction (MD) was detected in 30.2 % of cases (n = 62). The patients were longer subjected to artificial lung ventilation (p = 0.04), had a longer period of staying in the intensive care unit (p = 0.002) and hospital (p = 0.004). The data, predicting the postoperative MD were revealed including VSD area index (OR 2.7; р = 0.00001), longitudinal deformation of the left ventricle (SLV; OR 2.69; р = 0.00001), longitudinal deformation of the free wall of the right ventricle (SRV; OR 1.04; р = 0.0001) and the average estimated pressure in the lung artery (OR 1.6; р = 0.0001).
 Conclusions. 1. After the surgery, MD was detected in 30.2 % of cases. 2. SLV and SRV in infants with MD demonstrate the aggravation of ventricular contractility earlier than traditional indicators of the systolic function. 3. Preoperative SLV «–» 12 %, SRV «–» 6 %, VSD area index 100,5 mm2/m2, average estimated pressure in the lung artery 38 mm Hg are independent predictors of complications accompanied by MD during the first day after the VSD closure. 4. Complications, connected with longer ALV, are associated with duration of staying in the intensive care unit and hospital.

The Perioperative Use of Levosimendan as a Means of Optimizing the Surgical Outcome in Patients with Severe Heart Insufficiency Undergoing Cardiac Surgery.

Postoperative myocardial dysfunction following cardiac surgery is a relatively common occurrence. Levosimendan, a calcium sensitizer and inotropic drug, has shown potential in improving outcomes for patients with low preoperative ejection fraction (EF) and myocardial dysfunction after cardiac surgery. This study aims to evaluate the efficacy of levosimendan in optimizing the surgical outcome for such patients. A retrospective analysis was conducted on 314 patients with preoperative severe heart failure who underwent cardiac surgery. Among them, 184 patients received perioperative adjunctive therapy with levosimendan, while a comparable group of 130 patients received conventional treatment. The use of levosimendan demonstrated several advantages in postoperative outcomes. It significantly improved short- and long-term survival rates after cardiac surgery, enhanced hemodynamic stability, reduced the requirement for inotropic support, and facilitated faster weaning from ventilator support. Patients who received levosimendan reported reduced angina and dyspnea symptoms, as well as fewer postoperative arrhythmias. Furthermore, levosimendan helped minimize myocardial injury inevitable after cardiac surgery. The levosimendan group also exhibited a notable reduction in hospital readmissions. This study provides evidence of several benefits associated with the perioperative use of levosimendan. However, further prospective randomized studies are warranted to standardize and comprehensively document the other perioperative therapies, in order to validate these findings and establish stronger conclusions.

Use of del Nido cardioplegia in adult cardiac surgery

In most adult cardiac surgery operations, the heart must be completely immobile and isolated from the blood. Therefore, the heart is stopped in diastole and a still operative site is obtained. Cardiac arrest results in ischemia-reperfusion injury. For these reasons, myocardial protection and the prevention of damages are required. Various cardioplegia solutions are used for this purpose. It can be said that cardioplegia is the gold standard method of myocardial protection in cardiac arrest. Nowadays, "Single-dose cardioplegia" applications are increasingly used, especially in minimally invasive cardiac surgery and basic coronary bypass procedures due to the advantages they provide, which include reduction of aortic cross-clamp time, prevention of frequent interruption of the procedure due to cardioplegia, and reduced postoperative myocardial dysfunction incidence. The two main solutions used in single dose cardioplegia applications are the Bretschneider solution and the del Nido extracellular cardioplegia solution. The del Nido cardioplegia solution (dNCS), which was originally developed for use in pediatric cardiac surgery, has recently increased its use in adult cardiac surgery due to straightforward application and long-term effectiveness. The del Nido cardioplegia reduces the aortic cross clamp duration, cardiopulmonary bypass time and required cardioplegia solution volume, and is a safer and superior cardioplegia solution and technique in terms of myocardial protection with regards to many organs and cardiac-biochemical parameters.

Elevated nuclear and mitochondrial cell-free deoxyribonucleic acid measurements are associated with death after infant cardiac surgery

ObjectivesMortality rates following pediatric cardiac surgery with cardiopulmonary bypass have declined over decades, but have plateaued in recent years. This is in part attributable to persistent issues with postoperative global inflammation and myocardial dysfunction, commonly manifested by systemic inflammatory response syndrome and low cardiac output syndrome, respectively. Quantified cell-free DNA (cfDNA), of nuclear or mitochondrial origin, has emerged as a biomarker for both inflammation and myocardial injury. Recent data suggest that nuclear cfDNA (ncfDNA) may quantify inflammation, whereas mitochondrial cfDNA (mcfDNA) may correlate with the degree of myocardial injury. We hypothesize that threshold levels of ncfDNA and mcfDNA can be established that are sensitive and specific for postoperative mortality mediated through independent pathways, and that association will be enhanced with combined analysis. MethodsProspective observational study of infants younger than age 1 year undergoing planned surgery with cardiopulmonary bypass. The study received institutional review board approval. Samples were drawn before skin incision, immediately after completion of cardiopulmonary bypass, and subsequently at predetermined intervals postoperatively. Association of early postoperative ncfDNA and mcfDNA levels with mortality were assessed by logistic regression with cut-points chosen by receiving operating characteristic curve exploration. ResultsData were available in 59 patients. Median age and weight were 122 days (interquartile range, 63-154 days) and 4.9 kg (interquartile range, 3.9-6.2 kg). Median STAT category was 3 (interquartile range, 1-4). The primary outcome of death was met in 3 out of 59 (5%). Combined analysis of ncfDNA and mcfDNA levels at 12 hours after the initiation of cardiopulmonary bypass with death at a threshold of 50 ng/mL ncfDNA and 17 copies/μL mcfDNA yielded 100% sensitivity and negative predictive value. The specificity (91%) and positive predictive value (38%) increased through combined analysis compared with univariate analysis. Combined analysis exhibited high specificity (93%) and negative predictive value (78%) for prolonged (>30 postoperative days) hospitalization. ConclusionsCombined analysis of early postoperative ncfDNA and mcfDNA can stratify risk of mortality and prolonged hospitalization following infant cardiac surgery. Evaluation of both ncfDNA and mcfDNA to identify states of generalized inflammation and myocardial injury may allow for targeted interventions and improved outcomes.

Utility of NT-proBNP as an objective marker of postoperative heart failure after coronary artery bypass surgery: a prospective observational study

BackgroundPostoperative heart failure (PHF) is the main cause for mortality after cardiac surgery but unbiased evaluation of PHF is difficult. We investigated the utility of postoperative NT-proBNP as an objective marker of PHF after coronary artery bypass surgery (CABG).MethodsProspective study on 382 patients undergoing isolated CABG for acute coronary syndrome. NT-proBNP was measured preoperatively, the first (POD1) and third postoperative morning (POD3). A blinded Endpoints Committee used prespecified criteria for PHF. Use of circulatory support was scrutinized.ResultsAfter adjusting for confounders PHF was associated with 1.46 times higher NT-proBNP on POD1 (p = 0.002), 1.54 times higher on POD3 (p < 0.0001). In severe PHF, NT-proBNP was 2.18 times higher on POD1 (p = 0.001) and 1.81 times higher on POD3 (p = 0.019). Postoperative change of NT-proBNP was independently associated with PHF (OR 5.12, 95% CI 1.86–14.10, p = 0.002). The use of inotropes and ICU resources increased with incremental quartiles of postoperative NT-proBNP.ConclusionsPostoperative NT-proBNP can serve as an objective marker of the severity of postoperative myocardial dysfunction. Due to overlap in individuals, NT-proBNP is useful mainly for comparisons at cohort level. As such, it provides a tool for study purposes when an unbiased assessment of prevention or treatment of PHF is desirable.Trial registrationClinicalTrials.gov Identifier: NCT00489827https://clinicaltrials.gov/ct2/show/NCT00489827?term=glutamics&draw=2&rank=1.

A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design

Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. Double-blind, placebo-controlled, multicenter randomized trial. Tertiary care hospitals. Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours. The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery.

Pulmonary Vasodilators in the Management of Low Cardiac Output Syndrome After Pediatric Cardiac Surgery

Pulmonary hypertension is among the causes of low cardiac output syndrome after neonatal and pediatric cardiac surgery. In the setting of transient postoperative myocardial dysfunction, even a moderate elevation of pulmonary pressure can result in heart dysfunction and circulatory collapse. Although, specific pharmacological manipulation of pulmonary vascular resistance is frequently required in the perioperative period, there is no widely standardized management. In this review, a systematic literature search of PubMed and MEDLINE databases using relevant terms was performed. All clinical trials and relevant manuscripts, along with important physiological, pharmacological, and evidence-based considerations involving the use of pulmonary vasodilators in the management of low cardiac output syndrome after cardiac surgery were reviewed. This article addresses the fifth of eight topics comprising the special issue entitled "Pharmacologic strategies with afterload reduction in low cardiac output syndrome after pediatric cardiac surgery".

Laryngeal clefts

Laryngeal clefts

A novel software program for detection of potential air emboli during cardiac surgery.

BackgroundRisks associated with air emboli introduced during cardiac surgery have been highlighted by reports of postoperative neuropsychological dysfunction, myocardial dysfunction, and mortality. Presently, there are no standard effective methods for quantifying potential emboli in the bloodstream during cardiac surgery. Our objective was to develop software that can automatically detect and quantify air bubbles within the ascending aorta and/or cardiac chambers during cardiac surgery in real time.FindingsWe created a software algorithm (“Detection of Emboli using Transesophageal Echocardiography for Counting, Total volume, and Size estimation”, or DETECTS™) to identify and measure potential emboli present during cardiac surgery using two-dimensional ultrasound. An in vitro experiment was used to validate the accuracy of DETECTS™ at identifying and measuring air emboli. An experimental rig was built to correlate the ultrasound images to high definition camera images of air bubbles created in water by an automatic bubbler system. There was a correlation between true bubble size and the size reported by DETECTS™ in our in vitro experiment (r = 0.76). We also tested DETECTS™ using TEE images obtained during cardiac surgery, and provide visualization of the software interface.ConclusionsWhile monitoring the heart during cardiac surgery using existing ultrasound technology and DETECTS™, the operative team can obtain real-time data on the number and volume of potential air emboli. This system will potentially allow de-airing techniques to be evaluated and improved upon. This could lead to reduced air in the cardiac chambers after cardiopulmonary bypass, possibly reducing the risk of neurological dysfunction following cardiac surgery.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-7120-13-3) contains supplementary material, which is available to authorized users.

Perioperative assessment of left ventricular function by 2D strain (speckle tracking) in pediatric cardiac surgery

Introduction Conventional echographic parameters are neither accurate nor reproducible to assess left ventricular function after cardiac surgery with cardiopulmonary bypass. The main objective of this study was to evaluate the feasibility and reproducibility of 2D strain during the peri-operative period. The second objective was to assess the post-operative evolution of 2D strain, particularly after an atrial septal defect closure. Methods 33 pediatric patients ( Results Mean age and weight were 4 years [2–6] and 15 kg [10–20]. Mean durations of cardiopulmonary bypass and aortic cross-clamp were 117 min [86–148] and 58 min [44–72]. The global post-operative feasibility of longitudinal, circumferential and radial strain was respectively 91%, 95% and 95%, similar to the feasibility of conventional parameters (97%). The intra- and inter-observer correlation coefficients were good for longitudinal strain (0.916, P P P P P = 0.002 and 0.559, P = 0.020). Early post-operative circumferential strain was correlated to the durations of aortic cross-clamp ( r = 0.603, P = 0.001), inotropic support ( r = 0.558, P = 0.004) and mechanical ventilation ( r = 0.580, P = 0.002). Circumferential strain significantly improved after an atrial septal defect closure (−19.86 [−22.73; −17.00] versus −14.95 [−17.79; −12.11], P = 0.028). Conclusion 2D strain is feasible and reproducible in the post-operative period. Further studies are needed to assess its interest in early diagnosis of post-operative myocardial dysfunction.

‘FREEDOM’ trial: Have the interventional cardiologists lost their freedom?

‘FREEDOM’ trial: Have the interventional cardiologists lost their freedom?

Reply to Bozok et al.

We thank Bozok and colleagues for their interest in our article [1, 2]. We would like to remind the readership that our report was a prospective randomized study of 345 consecutive AVR operations, comparing cold crystalloid cardioplegia with cold blood cardioplegia. The demographic data were similar in both groups, including the distribution of valve sizes. The main endpoint was hospital death and the secondary endpoints were low output syndrome, myocardial infarction, arrhythmias, duration of ventilatory support, stroke or minor neurological dysfunction, renal function, infections, blood transfusions and physical rehabilitation. No statistically significant differences were seen between the groups, also when comparing the patients with the longest ischaemic times. We do not think that more sophisticated tests of preoperative or postoperative myocardial dysfunction would have changed our conclusions. The absence of any differences in clinical variables or complications clearly indicated that none of the two cardioplegia techniques could be regarded as superior. In our material, there was a slight difference in the frequency of CABG as for the number of distal anastomoses (3.0 anastomoses versus 2.5 (P = 0.02) in favour of the crystalloid group). However, cardiopulmonary bypass times and crossclamp times turned out to be similar in both groups, and these intra-operative variables appear more relevant when comparing the effects of different techniques for myocardial protection.

Coronary Bypass Surgery: Protective Effects of Insulin or of Prevention of Hyperglycemia, or Both?

One of the major risks of coronary bypass surgery is the impact of transient ischemia-reperfusion of the myocardium inherent to the surgical technique, with or without the use of extracorporeal circulation. The ensuing reversible postoperative myocardial dysfunction, referred to as myocardial “stunning,” can have severe consequences because low cardiac output can evoke failure of other vital organs. Myocardial dysfunction necessitates pharmacological and/or mechanical support of the heart and prolongs the time in intensive care and the hospital. A metabolic strategy to protect the myocardium from the deleterious effects of ischemia and reperfusion that was suggested almost five decades ago by Dr. Sodi-Pallares is the infusion of glucose, insulin, and potassium (GIK) (1). The rationale behind this intervention was to provide the heart with an alternative metabolic substrate that requires less oxygen and to prevent arrhythmia in ischemic hearts. Indeed, the metabolic cocktail of GIK could fuel the heart with an energy-saving substrate while increasing myocardial oxygen efficiency. Shifting substrate utilization in the ischemic myocardium from predominantly free fatty acids to anaerobic glycolysis reduces oxygen consumption and can thereby protect the vulnerable (post)ischemic cardiomyocytes by optimizing the balance between oxygen supply and consumption. Increasing potassium flux into the cardiomyocytes could also reduce the risk of malignant arrhythmias. In addition to these metabolic effects of GIK, it was later shown that insulin is also a direct actor in the GIK cocktail. Via binding to the insulin receptor on cardiomyocytes and by triggering the insulin signaling cascade, intracellular survival pathways are activated that could mediate cardioprotection (2) and, in the ischemic myocardium, reduce the generation and accumulation of toxic free radicals. However, despite many studies in different experimental settings of myocardial ischemia and reperfusion, and despite valid insights into the underlying mechanisms, the definite role of GIK in clinical practice remains controversial even today, half a century after the introduction of the GIK concept by Sodi-Pallares (1, 3–5). Large clinical studies produced opposing outcomes, possibly due to variable study design and composition of GIK. Particularly GIK in high doses appeared to generate positive outcomes in randomized placebo-controlled studies of patients with acute myocardial infarction (4). But the more recent large trials (6, 7) did not confirm such a benefit of GIK therapy on cardiac mortality and morbidity. Since 2001, however, the focus of metabolic research in acute medicine shifted to the potential deleterious effects of hyperglycemia in stressed cells (8) and thereby reopened the field. The renewed interest was generated by our study of patients with critical illness treated in tertiary referral surgical intensive care (9). Sixty percent of these patients had been admitted to intensive care after complex or complicated cardiac surgery with high euroscores (9, 10). The study showed that titrating insulin infusion to prevent blood glucose exceeding the upper normal limit after the surgery and continuing during the entire stay in an intensive care unit substantially reduced morbidity and mortality, a benefit that was maintained at least up to 4 yr after surgery (10). A subsequent study confirmed the acute morbidity benefits in adult medical intensive care unit patients (11), and another extended the morbidity and mortality benefits to critically ill infants and children (12). Implementation studies also reported similar benefits (13, 14). In-depth analyses of the results suggested that the prevention of hyperglycemia, not the infusion of insulin per se, explained most of these benefits (15, 16). Studies in animal models of critical illness further unraveled this important

Cytokine Responses in Low-Risk Coronary Artery Bypass Surgery.

Inflammatory cytokines have been implicated in myocardial function, severe congestive heart failure and sepsis. The present study tested the hypothesis that cytokine levels are elevated after low-risk coronary artery bypass surgery (CABG), and that they may be associated with postoperative cardiac dysfunction. Twenty male patients undergoing elective CABG in cardiopulmonary bypass (CPB) were studied. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, and IL-10 were measured before anesthesia induction, 5 minutes after, and 1, 4, and 20 hours after reperfusion to the myocardium. Levels of the MB isoenzyme of creatine kinase (CK-MB) were measured postoperatively. Hemodynamic data were also recorded. Myocardial ischemia was followed by an increase in the plasma levels of IL-6, IL-8, and IL-10. The duration of IL-6 response lasted throughout the postoperative period studied. Plasma cytokine levels at 1 hour after reperfusion correlated with the maximum CK-MB value (IL-6, r = 0.587, p < 0.01; IL-8, r = 0.460, p < 0.05; IL-10, r = 0.570, p < 0.05). Higher plasma IL-6 and IL-8 levels after reperfusion tended to be linked with lower cardiac index. The present results confirm that the levels of inflammatory cytokines IL-6, IL-8, and IL-10 are elevated after CABG. Increased systemic pro-inflammatory cytokine levels were partially associated with postoperative myocardial dysfunction. </hea

Successful Repair of Multiple Muscular Ventricular Septal Defects Using a Unique Hybrid Procedure

The surgical management of multiple muscular ventricular septal defects (mVSDs) in the infant remains a challenging problem because of the presence of residual shunts and postoperative myocardial dysfunction. We present a case of successful repair of multiple mVSDs with a unique hybrid procedure combining both the perventricular closure and open surgical repair.

635 Cardiac Troponin I and Natriuretic Peptide Nt-Probnp in Children with Operated Congenital Cardiac Malformations

Background and aim: Cardiac troponin I (cTnI) and natriuretic peptide NT-proBNP are useful biomarkers in the evaluation of the sick heart. We aimed to detect a potential early postoperative myocardial disease in children with congenital cardiac malformations undergoing heart surgery. Methods: 24 patients aged between 6 months and 3 years with operated cyanogenic cardiac malformations and 17 control subjects were studied. cTnI was determined using an immunochemical method with detection by Immulite electrochemiluminescence (ECLIA); reference values < 0.2 ng/ml. Serum NT-proBNP levels were assessed by the ELISA immunoenzymatic method (Enzyme-linked Immunosorbent Assay) using a standardized kit containing monoclonal antibodies that recognize epitopes located in the NT-proBNP portion. Serum was taken from patients within 24 hours post-operation. Results: The mean cTnI value in patients with congenital heart diseases was 10.23 ng/ml, compared to those of the controls situated below the detection limit < 0.2 ng/ml. 50-fold higher cTnI values were found in patients compared to healthy subjects, suggesting myocardial injury. The mean value of NT-proBNP was 30.42 fmol/ml. There was a positive correlation between cTnI and NT-proBNP levels in patients with congenital cardiac malformations: cTnI tended to decrease with the increase in NT-proBNP. Conclusions: cTnI has increased values in the first 24 postoperative hours in children with congenital cardiac malformations. There is a positive correlation between cTnI and NT-proBNP values suggesting the association of an early postoperative myocardial dysfunction in children with heart surgery.

Transient mitochondrial permeability transition pore opening after neonatal cardioplegic arrest

Neonatal cardioplegic arrest is associated with apoptosis-related mitochondrial dysfunction, including Bax translocation to the mitochondria, mitochondrial permeabilization, cytochrome c release, and electron transport chain dysfunction. We sought to characterize the time course and mode of postcardioplegic mitochondrial membrane permeabilization and hypothesize that permeabilization is transient and mediated by the mitochondrial permeability transition pore. Isolated, perfused neonatal rabbit hearts underwent 60 minutes of warm crystalloid cardioplegic arrest followed by 120 minutes of reperfusion. Mitochondrial permeabilization was evaluated by means of infusion of 2-deoxy [(3)H] glucose and subsequent detection of entrapment in isolated mitochondrial fractions. Groups included preloading with 2-deoxy [(3)H] glucose followed by cardioplegia and reperfusion (CCP), cardioplegia and cyclosporin A (specific inhibitor of mitochondrial permeability transition pore opening; CCP+CsA) or HA14-1 (Bcl-2 inhibitor; CCP+HA), and noncardioplegia control hearts (non-CCP). Reconstitution of mitochondrial integrity was tested by means of delayed infusion of 2-deoxy [(3)H] glucose 30 minutes after reperfusion (P-CCP). Cardioplegic arrest was associated with mitochondrial permeability transition pore opening, Bax translocation, cytochrome c release, radical oxygen species production, and electron transport chain dysfunction. Inhibition of mitochondrial permeability transition pore opening by cyclosporin A ameliorated this response, whereas inhibition of Bcl-2 exacerbated these changes. Postreperfusion entrapment of 2-deoxy [(3)H] glucose was significantly reduced in comparison with that seen in CCP hearts, suggesting that closure of the mitochondrial permeability transition pore ensues within 30 minutes after reperfusion. Apoptosis-related mitochondrial dysfunction in postcardioplegic neonatal hearts is mediated by mitochondrial permeability transition pore opening, which is transient and associated with deficits in electron transport. Clinical strategies directed to minimize mitochondrial permeability transition pore opening are likely to improve postoperative myocardial dysfunction after neonatal cardiac surgery.

General anaesthesia for a patient with Williams–Beuren syndrome: is sevoflurane and ketamine contraindicated?

General anaesthesia for a patient with Williams–Beuren syndrome: is sevoflurane and ketamine contraindicated?

ECMO therapy for postcardiotomy failure via femoral cannulation in adults

Objective: Extracorporeal membrane oxygenation (ECMO) after cardiac surgery is an established therapy for postoperative severe myocardial dysfunction. The femoral cannulation is a simple approach for ECMO therapy. Therefore the femoral cannulation is performed for intraoperative implantation as well as postoperative implanation at the intensive care unit (ICU).

Cardiopulmonary Bypass with Cardioplegic Arrest Activates Protein Kinase C in the Human Myocardium

The protein kinase C (PKC) family consists of 12 isoforms, 6 of which have been found in human myocardium (PKC alpha, beta I/beta II, delta, epsilon, eta, and lambda/iota). These kinases function in regulation of contractility, ion channels, and in cellular protection or damage during ischemia-reperfusion injury. This study investigated the effects of controlled ischemia-reperfusion injury through cardioplegic arrest on PKC activity in patients undergoing cardiac surgery. Myocardium and skeletal muscle were harvested from patients before and after cardiopulmonary bypass and cardioplegic arrest. Total PKC (n=12) was isolated and specifically, the PKC delta (n=8) and PKC epsilon (n=8) isoforms were immunoprecipitated for use in functional kinase assays. Cellular fractions (n=4) were separated by differential ultracentrifugation and analyzed by Western blotting for membrane translocation (an indirect indicator of increased activity). Immunofluorescent staining for PKC delta and PKC epsilon was performed on myocardial sections. An in vitro assay of hypoxic cardioplegic arrest followed by reoxygenation was performed using isolated cardiomyocytes, and apoptosis was assessed. Cardioplegic arrest was associated with a 24.4% +/- 4.6% increase (p < 0.05) in total PKC activity, a 26.7% +/- 4.9% increase (p < 0.05) in PKC delta activity, and a 35.3% +/- 14% increase (p < 0.05) in PKC epsilon activity in myocardium. Cardioplegic arrest induced migration of PKC delta and epsilon to the z-line of the cardiomyocyte. Inhibition of PKC delta in the in vitro studies demonstrated a considerable reduction in apoptotic cells. PKC delta and epsilon have previously been shown to mediate and protect, respectively, from ischemia-reperfusion injury after myocardial ischemia. Demonstration of increases in their activity after cardioplegic arrest provides support for their possible role in myocardial function after cardiac surgery. Isoform-specific modulators may be of potential therapeutic value in treating postoperative myocardial dysfunction.