Achieving and Sustaining Zero: Preventing Surgical Site Infections After Isolated Coronary Artery Bypass With Saphenous Vein Harvest Site Through Implementation of a Staff-Driven Quality Improvement Process.

BACKGROUND: Surgical site infections (SSI) increase morbidity and mortality, hospital costs, length of stay, readmissions, and risk of litigation and may impact a facility's reputation. METHODS: Through implementation of a Six Sigma, interdisciplinary team process and the Contextual Model for change engaged all stakeholders. A total of 44 perioperative processes were evaluated, with 15 processes ultimately altered. Revisions involved identifying inconsistent implementation of procedures and standardizing processes, as well as utilizing new suture techniques and products including disposable electrocardiogram leads and pacing wires, antibiotic-coated sutures, and silver-impregnated midsternal dressings. RESULTS: In isolated coronary artery bypass grafting with donor-site procedures, an incidence of 3.74 per 100 procedures was reduced to 0.7 and ultimately to 0. No patients who underwent coronary artery bypass grafting developed a deep sternal wound infection in over 30 months and 590 procedures, resulting in an estimated cost savings of more than $600 000, from May 2012 through December 2014. CONCLUSIONS: A significant reduction in deep sternal wound infections was achieved by working at all levels of the organization through a multidisciplinary approach to create sustained change. Using real-time observations for current practices, areas for improvement were identified. By engaging frontline staff in the process, ownership of the outcomes and adherence to practice change were promoted. The result was a dramatic, rapid, and sustainable improvement in the prevention of deep sternal wound infection.

Impact of preoperative renal dysfunction on long-term survival for patients undergoing aortic valve replacement.

BACKGROUND: The impact of the degrees of renal dysfunction (RD) after aortic valve replacement (AVR) has not been well described. The purpose of this study was to compare patients undergoing AVR with a range of renal function from normal to dialysis-dependence. METHODS: A retrospective review of 2,408 patients undergoing AVR with or without coronary artery bypass graft surgery (CABG) from January 1996 to March 2009 was performed. Glomerular filtration rate (GFR) was estimated for patients using the Modification of Diet in Renal Disease formula. Multivariable logistic and Cox regression methods were used to determine the independent association of GFR with outcomes. Adjusted odds ratios were calculated for in-hospital outcomes, and Kaplan-Meier curves were created to estimate long-term survival. RESULTS: In all, 1,512 patients (62.8%) had isolated AVR, and 896 (37.2%) underwent AVR plus CABG. Preoperative RD was common among all patients: 1,148 of 2,408 (47.7%) with mild RD (GFR 60 to 90 mL·min(-1)·1.73 m(-2)), 644 of 2,408 (26.7%) moderate RD (GFR 30 to 59 mL·min(-1)·1.73 m(-2)), 59 of 2,408 (2.5%) severe RD (GFR 15 to 30 mL·min(-1)·1.73 m(-2)), and 114 (4.7%) with kidney failure (GFR<15) or requiring dialysis. In-hospital mortality generally rose with RD, from 2.9% for patients with no RD to 15.8% for patients with severe RD, and 17.3% for patients requiring dialysis. Patients with severe RD or preoperative dialysis were associated with significantly poorer outcomes. Adjusted long-term survival is progressively worse across levels of RD, as was postoperative length of stay (p<0.001). CONCLUSIONS: Preoperative RD is common among the AVR population and is associated with diminished long-term survival. The association between RD and worse outcomes after AVR surgery has significant clinical implications.

Long-term survival for patients with preoperative renal failure undergoing bioprosthetic or mechanical valve replacement.

BACKGROUND: The objective of this study was to assess short-term and long-term outcomes after valve replacement with biologic or mechanical prostheses in patients with preoperative end-stage renal disease on chronic dialysis. METHODS: A retrospective review of patients with end-stage renal disease undergoing valve replacement from January 1996 through March 2008 at Emory Healthcare Hospitals was performed. Outcomes were compared using χ(2) tests and 2-sample t tests. Adjusted long-term survival up to 10 years was assessed with Kaplan-Meier plots and compared between biologic and mechanical replacements using the Cox proportional hazards model. RESULTS: A total of 202 patients underwent 211 valve replacement operations. Patient age was 20 to 83 years (mean age, 54.8 ± 14.0); 115 of 211 (54.5%) were male. Operations included the following: 100 of 211 (47.4%) isolated aortic; 49 of 211 (23.2%) isolated mitral; 4 of 211 (1.9%) isolated tricuspid; and 58 of 211 (27.5%) combined replacements. Thirteen (6.2%) patients underwent reoperative valve replacements. Most patients received bioprosthetic valves (143 of 211, 67.8%), while 68 of 211 (32.2%) received mechanical valves. Concomitant coronary artery bypass was performed in 53 of 211 (25.1%) patients. Thirty-day mortality was in 42 of 211 patients (19.9%) and was not different between bioprosthetic and mechanical replacements. Overall 10-year survival was 18.1% for all patients and was not influenced by valve type implanted. CONCLUSIONS: For patients with end-stage renal disease treated with dialysis, valve replacement carries acceptable operative mortality. Long-term survival is similar among patients receiving bioprosthetic versus mechanical valve replacement. Careful risk assessment and choice of valve prosthesis should be performed prior to surgical intervention in this high-risk patient population.

Deep hypothermic circulatory arrest for repair of the brachiocephalic artery and aorta after a gunshot wound to the chest.

The incidence of penetrating trauma to the brachiocephalic artery and aortic arch is not known, because most patients die of hemorrhage before they receive adequate treatment. Furthermore, when torrential hemorrhage from penetrating trauma is present, the anatomy of the thoracic vasculature can present a challenge for gaining adequate exposure, achieving vascular control, and performing proper repair. We describe the case of a patient with a gunshot wound to the anterior chest; he was placed under cardiopulmonary bypass and deep hypothermic circulatory arrest while we performed a patch repair of the proximal brachiocephalic artery and aortic arch.

Racial disparity persists after on-pump and off-pump coronary artery bypass grafting.

BACKGROUND: Race has been shown to be an independent risk factor for operative mortality after coronary artery bypass grafting (CABG). This study sought to determine the extent to which race is a risk factor for adverse events, long-term mortality, and whether off-pump surgery (OPCAB) modifies that risk. METHODS AND RESULTS: The Society of Thoracic Surgeons Adult Cardiac Database at Emory Healthcare affiliated hospitals was queried for all primary isolated CABG records from 1997 to 2007. A propensity score was formulated to balance the patient groups with respect to treatment assignment (OPCAB or CABG on cardiopulmonary bypass). Multivariable logistic regression was used to assess the impact of black race and OPCAB on in-hospital outcomes (death, stroke, myocardial infarction, and their composite, major adverse cardiac events). Cox proportional hazards regression model and Kaplan-Meier curves determined whether black race affected long-term all-cause mortality. Interaction terms were constructed to test whether OPCAB surgery influences surgical results differently in black patients than in white patients. There were 12 874 consecutive CABG patients, including 2033 (15.8%) blacks and 10 841 (84.2%) whites. Survival at 3, 5, and 10 years for blacks (87.5%, 81.4%, 63.8%) was significantly lower than for whites (90.7%, 85.2%, 67.1%, P<0.001). Blacks (adjusted odds ratio, 0.77; 95% CI, 0.44 to 1.36) and whites (adjusted odds ratio, 0.72; 95% CI, 0.53 to 0.99) who had OPCAB had lower risk-adjusted odds of major adverse cardiac events than their racial counterparts who had CABG on cardiopulmonary bypass. CONCLUSIONS: Short- and long-term outcomes are significantly worse in black than in white patients undergoing primary isolated CABG. OPCAB does not narrow the disparity in outcomes between blacks and whites.

Aortic valve replacement for aortic stenosis in patients with left ventricular dysfunction.

BACKGROUND: The purpose of this study was to assess the impact of left ventricular dysfunction and other risk factors on short- and mid-term outcomes after aortic valve replacement for aortic stenosis. METHODS: From January 1, 2002, to December 31, 2007, 773 consecutive patients underwent primary aortic valve replacement for aortic stenosis at a single institution; concomitant coronary artery bypass graft surgery (CABG) was performed in 45.4% (351 of 773). Multivariable regression analysis was used to identify predictors of in-hospital mortality, with ejection fraction (EF) as the primary variable of interest. After discharge, survival status was determined using the Social Security Death Index. A Cox proportional hazards regression model was used to identify predictors of mid-term mortality. RESULTS: On univariable analysis, EF (odds ratio [OR] 0.979, 95% confidence interval [CI]: 0.960 to 0.999, p = 0.044) but not concomitant CABG emerged as a predictor of in-hospital mortality. However, on multivariable analysis, neither EF nor concomitant CABG was associated with increased in-hospital mortality. Multivariable predictors of in-hospital mortality included age, emergent status, and prolonged bypass time. On univariable analysis, mid-term mortality was associated with EF and concomitant CABG (OR 0.979, 95% CI: 0.966 to 0.991, p = 0.001, and OR 1.61, 95% CI: 1.11 to 2.36, p = 0.013, respectively). However, after multivariable adjustment, only EF was associated with mid-term mortality (adjusted OR 0.985, 95% CI: 0.970 to 1.00, p = 0.049). Other multivariable predictors of mid-term mortality included age, dialysis-dependent renal failure, previous stroke, and peripheral vascular disease. CONCLUSIONS: Left ventricular dysfunction, in addition to other patient comorbidities, may negatively impact survival after aortic valve replacement. Careful consideration of the cumulative effect of these multiple risk factors is necessary to optimize patient outcomes.

Successful cardiac transplantation in a patient with elevated pulmonary vascular resistance: a relative contraindication to transplantation.

Elevated pulmonary vascular resistance in a transplantation candidate should be viewed as potentially reversible, and there are several options for therapy. We describe a young patient with congenital restrictive cardiomyopathy and a markedly elevated pulmonary artery pressure. The patient underwent successful orthotopic heart transplantation after pharmacologic lowering of the pulmonary artery pressure with a new drug combination of milrinone and nesiritide. The length of therapy can be extended to 3 days to allow for determining the pulmonary vascular responsiveness.

Elevated preoperative hemoglobin A1c level is associated with reduced long-term survival after coronary artery bypass surgery.

BACKGROUND: The predictive role of hemoglobin A1c (HbA1c) on long-term outcomes after coronary artery bypass surgery has not been evaluated. METHODS: Preoperative HbA1c levels were obtained in 3,201 patients undergoing primary, elective coronary artery bypass surgery at Emory Healthcare Hospitals from January 2002 to December 2006 and entered prospectively into a computerized database. Long-term survival status was determined by cross-referencing patient records with the Social Security Death Index. Log-rank (unadjusted) and Cox proportional hazards regression models (adjusted) were employed to determine whether HbA1c and diabetes mellitus were independent risk factors for reduced long-term survival, adjusted for 29 covariates. Hazard ratios for each unit increase in continuous HbA1c were calculated. RESULTS: Patients with HbA1c of 7% or greater had lower unadjusted 5-year survival compared with patients with HbA1c less than 7% (p = 0.001). Similarly, patients with diabetes mellitus had lower unadjusted 5-year survival compared with patients without diabetes (p < 0.001). After multivariable adjustment, higher HbA1c (measured as a continuous variable) was associated with reduced long-term survival for each unit increase in HbA1c (hazard ratio 1.15, p < 0.001), but preoperative diagnosis of diabetes was not associated with reduced long-term survival after coronary artery bypass surgery (p = 0.41). Other multivariable predictors of reduced long-term survival included age, cerebrovascular disease, elevated serum creatinine, renal insufficiency, congestive heart failure, previous myocardial infarction, chronic lung disease, and peripheral vascular disease. CONCLUSIONS: Poor preoperative glycemic control, as measured by an elevated HbA1c, is associated with reduced long-term survival after coronary artery bypass surgery. Optimizing glucose control in these patients may improve long-term survival.

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.

Placement of a continuous-flow ventricular assist device in the failing ventricle of an adult patient with complex cyanotic congenital heart disease.

For patients with end-stage heart failure and contraindications to transplantation, insertion of a continuous-flow left ventricular assist device (LVAD) is an effective treatment strategy. We present a case of LVAD insertion in a 46-year-old man with cyanotic complex congenital heart disease and an extensive surgical history who presented with failure of his systemic ventricle. The insertion of an LVAD in our patient restored cardiac output and improved cyanosis and native ventricular function. As the number of patients with congenital heart defects surviving to adulthood increases, destination LVAD therapy may be increasingly considered as an alternative.

Biatrial primary cardiac paraganglioma: a rare finding.

The majority of primary cardiac tumors are benign; of these tumors, cardiac paragangliomas are among the rarest. We report a case of biatrial cardiac paraganglioma discovered during workup for palpitations and fatigue. The tumor involved the interatrial septum, with a lobulated portion protruding through the foramen ovale into the right atrium. The tumor was successfully excised, leading to uneventful recovery.

Intraoperative TandemHeart implantation as an adjunct to high-risk valve surgery.

Newer generations of assist devices for postcardiotomy support in patients with ventricular failure have eliminated bearings and incorporated suspended impellers, smaller cannulae and hardware, and simplified insertion techniques. We describe the use of a surgically implanted, percutaneous, continuous-flow centrifugal pump (the TandemHeart percutaneous ventricular assist device) as part of a planned, pre-emptive approach for postcardiotomy support in a patient with severe mitral regurgitation, moderate tricuspid regurgitation, and biventricular failure. To our knowledge, this report documents the 1st use of a percutaneous ventricular assist device as an elective support device in a patient undergoing high-risk mitral or tricuspid valve surgery.

Outcomes after off-pump reoperative coronary artery bypass grafting.

OBJECTIVE: : Application of off-pump techniques to reoperative coronary artery bypass (redo CABG) has been limited by technical difficulty and potential for embolism of atheromatous debris from diseased grafts, resulting in myocardial infarction and rapid hemodynamic deterioration. We compared outcomes after off-pump (OPCAB) and on-pump (ONCAB) in redo CABG. METHODS: : A retrospective chart review was performed for patients who underwent redo CABG at a single academic institution between January 1997 and December 2004. Outcomes were compared between groups based on intention to treat. Propensity scores were calculated for each patient using 23 preoperative risk factors. Logistic regression was applied for each end point as a function of group and propensity score. RESULTS: : A total of 771 consecutive patients had redo CABG (639 ONCAB and 132 OPCAB); 22 patients (16.7%) were converted from OPCAB to ONCAB for hemodynamic in stability, severe adhesions, or graft injury; 7 patients (1.1%) were converted from ONCAB to OPCAB for severe aortic calcification. Propensity-matched comparison of outcomes after OPCAB versus ONCAB for redo CABG showed that OPCAB was associated with a reduction in postoperative complications, transfusion, atrial fibrillation, and length of stay. OPCAB patients received fewer grafts with similar use of left internal mammary artery conduit; conversion from OPCAB to ONCAB did not reduce the benefit of OPCAB. CONCLUSIONS: : OPCAB can be safely and effectively applied to reoperative CABG in selected cases.

Intrathoracic gastrojejunostomy for gastric outlet obstruction after Ivor Lewis esophagogastrectomy.

Gastric outlet obstruction after esophagogastrectomy with a drainage procedure is unusual, but when encountered, its management can be formidable. A Rous-en-Y intrathoracic gastrojejunostomy was created in a 74-year-old woman 2 years after Ivor Lewis esophagogastrectomy for benign disease to treat severe gastric outlet obstruction at the native pylorus.

Reduction of infarct size and preservation of endothelial function by multidose intravenous adenosine during extended reperfusion.

It has been proposed that infarct extension is developed from the early to the late phase of reperfusion (R). This study compares the protective effect of single or multidose administration of adenosine (Ado) on infarct size during early and late phases of R by attenuating neutrophil (PMN) recruitment. Forty-one dogs underwent 60-min left anterior descending artery (LAD) ischemia followed by 6, 24, and 48 h of R, respectively. Infarct size (%) increased over 6 to 24 h (27 +/- 2 to 38 +/- 4; P < 0.05 24 h versus 6 h group), with a corresponding increase in creatine kinase activity. Transmural myocardial blood flow (mL/min/g) decreased from 6 to 24 h (0.47 +/- 0.02 to 0.29 +/- 0.02; P < 0.05 24 h versus 6 h group). PMN localization (mm(2) myocardium) in the perinecrotic tissue detected by immunohistochemistry with anti-CD18 antibody, and accumulation detected by myeloperoxidase (MPO, DeltaAbs/min/g) increased from 6 to 24 h (292 +/- 25 to 605 +/- 44; P < 0.05 24 h versus 6 h group; and 55 +/- 7 to 96 +/- 5; P < 0.05 24 h versus 6 h group), respectively. In in vitro analysis, PMN adherence (mm(2) endothelium) to postischemic LAD increased from 98 +/- 2 to 125 +/- 3 (P < 0.05 24 h versus 6 h group) and maximal LAD endothelium-dependent relaxation (%) impaired from 6 to 24 h (74 +/- 7 to 42 +/- 10; P < 0.05 24 h versus 6 h group). Intravenous Ado (140 microg/kg/min) for 2 h at R reduced infarct size (17 +/- 2; P < 0.05 Ado versus 6 h group), CD18 positive cells (130 +/- 10; P < 0.05 Ado versus 6 h group), MPO (14 +/- 3; P < 0.05 Ado versus 6 h group), PMN adherence (57 +/- 2; P < 0.05 Ado versus 6 h group), and augmented LAD vascular relaxation (102 +/- 5 versus 74 +/- 7; P < 0.05 Ado versus 6 h group). However, this protection by Ado was lost when R was extended to 24 h. Treatment with multiple infusion of Ado at 2, 6, 12, and 18 h R significantly preserved protective effects seen at 6 h R in the Ado group. Protection by multidose Ado was still preserved when R was extended to an additional 24 h. These data suggest that interventions aiming at permanently reducing R injury may thus need to be administered not only at early R, but also during late phase. A slow wave of PMN accumulation at late R may be involved in the extension of infarction and endothelial dysfunction.

Pretreatment with phenoxybenzamine attenuates the radial artery's vasoconstrictor response to alpha-adrenergic stimuli.

BACKGROUND: Although the radial artery bypass conduit has excellent intermediate-term patency, it has a proclivity to vasospasm. We tested the hypothesis that brief pretreatment of a radial artery graft with the irreversible adrenergic antagonist phenoxybenzamine attenuates the vasoconstrictor response to the vasopressors phenylephrine and norepinephrine compared with the currently used papaverine/lidocaine. METHODS: Segments of human radial artery grafts were obtained after a 30-minute intraoperative pretreatment with a solution containing 20 mL of heparinized blood, 0.4 mL of papaverine (30 mg/mL), and 1.6 mL of lidocaine (1%). The segments were transported to the laboratory and placed into a bath containing Krebs-Henseleit solution and 10, 100, or 1000 micromol/L phenoxybenzamine or vehicle. The segments were tested in organ chambers for contractile responses to increasing concentrations of phenylephrine and norepinephrine (0.5-15 micromol/L). RESULTS: Contractile responses to 15 micromol/L phenylephrine in control radial artery segments averaged 44.2% +/- 9.1% of the maximal contractile response to 30 mmol/L KCl. Papaverine/lidocaine modestly attenuated contraction to 15 micromol/L phenylephrine (32.1% +/- 5.9%; P =.22), but 1000 micromol/L phenoxybenzamine completely abolished radial artery contraction (-7.2% +/- 4.4%; P <.001). The effect of 10 and 100 micromol/L phenoxybenzamine on attenuating vasocontraction was intermediate between 1000 micromol/L phenoxybenzamine and papaverine/lidocaine. Responses to 15 micromol/L norepinephrine in control radial artery segments averaged 54.7% +/- 7.5% of maximal contraction to 30 mmol/L KCl. Papaverine/lidocaine modestly attenuated the contraction response of radial artery segments (35.6% +/- 5.1%; P =.04). In contrast, 1000 micromol/L phenoxybenzamine showed the greatest attenuation of norepinephrine-induced contraction (-10.5% +/- 2.0%; P <.001). CONCLUSIONS: A brief pretreatment of the human radial artery bypass conduit with 1000 micromol/L phenoxybenzamine completely attenuates the vasoconstrictor responses to the widely used vasopressors norepinephrine and phenylephrine. Papaverine/lidocaine alone did not block vasoconstriction to these alpha-adrenergic agonists.

Optimal dose and mode of delivery of Na+/H+ exchange-1 inhibitor are critical for reducing postsurgical ischemia-reperfusion injury.

BACKGROUND: In clinical trials, perioperative intravenous Na(+)/H(+) exchange isoform-1 (NHE1) inhibitors were only moderately effective in high-risk patients undergoing surgical reperfusion (GUARDIAN trial). However, effective myocardial concentrations of NHE1 inhibitor may not have been achieved by parenteral administration alone. We tested the hypothesis that increasing doses of NHE1 inhibitor EMD 87580 ((2-methyl-4,5-di-(methylsulfonyl)-benzoyl)-guanidine) delivered in blood cardioplegia (BCP) and by parenteral route at reperfusion reduce myocardial injury after surgical reperfusion of evolving infarction. METHODS: Twenty-six anesthetized dogs underwent 75 minutes of left anterior descending coronary artery occlusion, followed by cardiopulmonary bypass and 60 minutes of arrest with multidose 10 degrees C BCP. In the control group (n = 8), BCP was not supplemented. In the three EMD-BCP groups, BCP was supplemented with 10 micromol/L EMD 87580 (EMD-10, n = 5), 20 micromol/L EMD 87580 (EMD-20, n = 5), or 20 micromol/L EMD 87580 combined with an immediate reperfusion bolus (5 mg/kg intravenously) (EMD-20R, n = 8). The left anterior descending coronary artery occlusion was released just before the second infusion of BCP. Reperfusion continued for 120 minutes after discontinuation of cardiopulmonary bypass. RESULTS: Postischemic systolic and diastolic function in the area at risk was dyskinetic in all groups. Infarct size (percentage of area at risk) was not significantly reduced in the EMD-10 (26.2% +/- 3.6%) and EMD-20 (22.5% +/- 2.4%) groups versus control (30.7% +/- 2.4%); however, infarct size was significantly reduced in the EMD-20R group (16.1% +/- 2.8%, p = 0.003). Edema in the area at risk in the EMD-10 (81.1% +/- 0.5% water content), EMD-20 (81.7% +/- 0.3%), and EMD-20R (81.9% +/- 0.3%) groups was less than in controls (83.2% +/- 0.2%), (p < 0.056). Neutrophil accumulation (myeloperoxidase activity) in postischemic area-at-risk myocardium was less in the EMD-20R group versus the control group (5.3 +/- 0.7 versus 8.7 +/- 1.4 absorbance units x min(-1) x g(-1); p = 0.05), which suggests an attenuated postischemic inflammatory response. CONCLUSIONS: Optimal delivery of NHE1 inhibitor to the heart through combined cardioplegia and parenteral routes significantly attenuates myocardial injury after surgical reperfusion of regional ischemia. Timing, dose, and mode of delivery of NHE1 inhibitors are important to their efficacy.

Inhibition of myocardial apoptosis reduces infarct size and improves regional contractile dysfunction during reperfusion.

OBJECTIVE: Myocardial apoptosis is primarily triggered during reperfusion (R) through various mechanisms that may involve endonuclease to cleavage genomic DNA in the internucleosomal linker regions. However, the relative contribution of myocardial apoptosis to development of myocardial injury during R remains unknown. In the present study, we examined whether inhibition of apoptosis with aurintricarboxylic acid (ATA), an endonuclease inhibitor, during R reduces infarct size and improves regional contractile function. METHODS AND RESULTS: In two groups of chronically-instrumented dogs, 1 h of left anterior descending (LAD) coronary occlusion was followed by 24 h of R with infusion of saline (control, n=8) or ATA (1 mg/kg/h, n=8) into the left atrium starting 5 min before R and continuing for 2 h. ATA significantly reduced apoptotic cells (TUNEL staining) in the peri-necrotic myocardium (12+/-1%* vs. 36+/-4%), consistent with the absence of DNA laddering. To confirm inhibition of apoptosis with ATA, densitometrically, Bcl-2 (% of normal myocardium) was significantly increased vs. control (102+/-12* vs. 68+/-9) and Bax as well as the activated caspase-3 were significantly reduced vs. control (108+/-17* vs. 194+/-42 and -29+/-4* vs. 174+/-43, respectively). ATA significantly improved segmental shortening (3.3+/-1.2* vs. -1.8+/-0.7%) and segmental work (79.3+/-11.3* vs. 7.1+/-5.8 mmHg/mm) in area at risk myocardium, and reduced infarct size (TTC staining, 27+/-0.2* vs. 37+/-0.5%), confirmed by lower plasma creatine kinase activity. In addition, myocardial blood flow (0.9+/-0.1* vs. 0.4+/-0.1 ml/min/g) and endothelial-dependent maximal vascular relaxation (119+/-6* vs. 49+/-8%) were significantly improved. Myeloperoxidase activity in area at risk myocardium, a marker for neutrophil accumulation, was also significantly reduced (17+/-4* vs. 138+/-28 Delta Abs/min). CONCLUSIONS: These data suggest that the inhibition of apoptosis during R is associated with a reduction in infarction, improvement in regional contractile and vascular endothelial functions as well as augmentation in myocardial blood flow. *P<0.05 vs. control group.

Adenosine in myocardial protection in on-pump and off-pump cardiac surgery.

Adenosine is most well known for its potent vasodilation of the vasculature. However, it also promotes glycolysis, and activates potassium-sensitive adenosine triphosphate (K(ATP)) channels. Adenosine also strongly inhibits neutrophil function such as superoxide anion production, protease release, and adherence to coronary endothelial cells. Hence adenosine attenuates ischemic injury as well as neutrophil-mediated reperfusion injury. Adenosine has also been implicated in the cardioprotective phenomenon of ischemic preconditioning. Accordingly experimental evidence shows that adenosine reduces postischemic injury when administered before ischemia and at the onset of reperfusion. Clinical studies in cardiology and cardiac surgery show cardioprotective trends with adenosine treatment but the effects are not as dramatic as those reported by experimental studies.