The presence of a dedicated cardiac surgical intensive care service impacts clinical outcomes in adult cardiac surgery patients.

BACKGROUND: Postoperative critical care management is an integral part of cardiac surgery that contributes directly to clinical outcomes. In the United States there remains considerable variability in the critical care infrastructure for cardiac surgical programs. There is little published data investigating the impact of a dedicated cardiac surgical intensive care service. METHODS: A retrospective study examining postoperative outcomes in cardiac surgical patients before and after the implementation of a dedicated cardiac surgical intensive care service at a single academic institution. An institutional Society of Thoracic Surgeons database was queried for study variables. Primary endpoints were the postoperative length of stay, intensive care unit length of stay, and mechanical ventilation time. Secondary endpoints included mortality, readmission rates, and postoperative complications. The effect on outcomes based on procedure type was also analyzed. RESULTS: A total of 1703 patients were included in this study-914 in the control group (before dedicated intensive care service) and 789 in the study group (after dedicated intensive care service). Baseline demographics were similar between groups. Length of stay, mechanical ventilation hours, and renal failure rate were significantly reduced in the study group. Coronary artery bypass grafting patients observed the greatest improvement in outcomes. CONCLUSIONS: Implementation of a dedicated cardiac surgical intensive care service leads to significant improvements in clinical outcomes. The greatest benefit is seen in patients undergoing coronary artery bypass, the most common cardiac surgical operation in the United States. Thus, developing a cardiac surgical intensive care service may be a worthwhile initiative for any cardiac surgical program.

Impact of troponin I level on coronary artery bypass grafting outcomes.

PURPOSE: The effect of preoperative cardiac troponin level on outcomes after coronary artery bypass grafting (CABG) is unclear. We investigated the impact of preoperative cardiac troponin I (cTnI) level as well as the time interval between maximum cTnI and surgery on CABG outcomes. METHODS: All patients who underwent isolated CABG at our institution between 2009 and 2016 and had preoperative cTnI level available were identified using our Society of Thoracic Surgeons registry. Receiver operating characteristic (ROC) analysis was performed to identify a cTnI threshold level. Subjects were divided into groups based on this value and outcomes compared. RESULTS: A total of 608 patients were included. ROC analysis identified 5.74 µg/dL as the threshold value associated with worse postoperative outcomes. Patients with peak cTnI >5.74 µg/dL underwent CABG approximately 1 day later, had twice the risk of adverse postoperative events, and had 2.8 day longer postoperative length of stay than those with peak cTnI ≤5.74 µg/dL. cTnI level was not associated with mortality or 30-day readmission. Time interval between peak cTnI and surgery did not affect outcomes. CONCLUSION: Elevated preoperative cTnI level beyond a certain threshold value is associated with adverse postoperative outcomes but is not a marker for increased mortality. Time from peak cTnI does not affect postoperative outcomes or mortality and may not need to be considered when deciding timing of CABG.

Identification of a common polymorphism in COQ8B acting as a modifier of thoracic aortic aneurysm severity.

Thoracic aortic aneurysm (TAA) predisposes to sudden, life-threatening aortic dissection. The factors that regulate interindividual variability in TAA severity are not well understood. Identifying a molecular basis for this variability has the potential to improve clinical risk stratification and advance mechanistic insight. We previously identified COQ8B, a gene important for biosynthesis of coenzyme Q, as a candidate genetic modifier of TAA severity. Here, we investigated the physiological role of COQ8B in human aortic smooth muscle cells (SMCs) and further tested its genetic association with TAA severity. We find COQ8B protein localizes to mitochondria in SMCs, and loss of mitochondrial COQ8B leads to increased oxidative stress, decreased mitochondrial respiration, and altered expression of SMC contractile genes. Oxidative stress and mitochondrial cristae defects were prevalent in the medial layer of human proximal aortic tissues in patients with TAA, and COQ8B expression was decreased in TAA SMCs compared with controls. A common single nucleotide polymorphism (SNP) rs3865452 in COQ8B (c.521A>G, p.H174R) was associated with decreased rate of aortic root dilation in young patients with TAA. In addition, the SNP was less frequent in a second cohort of early-onset thoracic aortic dissection cases compared with controls. COQ8B protein levels in aortic SMCs were increased in TAA patients homozygous for rs3865452 compared with those homozygous for the reference allele. Thus, COQ8B is important for aortic SMC metabolism, which is dysregulated in TAA, and rs3865452 may decrease TAA severity by increasing COQ8B level. Genotyping rs3865452 may be useful for clinical risk stratification and tailored aortopathy management.

Long-term results with cryopreserved arterial allografts (CPAs) in the treatment of graft or primary arterial infections.

OBJECTIVE: Our purpose was to evaluate our results with CPAs in patients with infected grafts or primary arterial infection with emphasis on long-term durability of these grafts. METHODS: To evaluate the long-term durability of CPAs, clinical outcomes were analyzed following their use for either graft or primary arterial infections at a single institution over a 9-y period (2000-2009). The 30-d mortality rate, 90-d mortality rate, and the cause of early mortality were determined in each case. Among those surviving 90 d, the grafts were evaluated for subsequent failure. RESULTS: From 2000 through 2009, 51 patients with either infected prosthetic grafts (35) or primary arterial infections (15) received CPAs. One patient had infection of a previously placed thoracic allograft. Forty-three graft infections involved either the thoracic or abdominal aorta. Eleven patients presented with fulminant sepsis with systemic inflammatory response syndrome (SIRS), seven of whom died postoperatively. Eight patients presented with aorto-enteric, esophageal, or bronchial fistulae with infected prosthetic grafts. The 30-d mortality rate was 25.5% (11 deaths) seven of which occurred in patients with SIRS. The 90-d mortality rate was 41.4%. There were 10 graft failures, seven occurring in patients with aorto-enteric or bronchial fistulae all of whom had recurrent hemorrhage. The other three graft failures were due to anastomotic hemorrhage in the early postoperative period. Among those surviving 90 d, the mean follow-up was 46.4 mo (range 1-112 mo). No aneurysmal degeneration of the CPAs was noted. Only one subsequent allograft graft failure was noted among those surviving more than 90 d. CONCLUSIONS: CPAs are a suitable option in dealing with cardiovascular infections. Patients with enteric or bronchial fistulae are a difficult group to treat perhaps because of ongoing contamination of the allograft. The operative mortalities are largely determined by patient comorbidities (SIRS). Subsequent degeneration or infection of the CPAs is rare.

An Emergent Nexus between Striae and Thoracic Aortic Dissection.

Current approaches to stratify the risk for disease progression in thoracic aortic aneurysm (TAA) lack precision, which hinders clinical decision making. Connective tissue phenotyping of children with TAA previously identified the association between skin striae and increased rate of aortic dilation. The objective of this study was to analyze associations between connective tissue abnormalities and clinical endpoints in adults with aortopathy. Participants with TAA or aortic dissection (TAD) and trileaflet aortic valve were enrolled from 2016 to 2019 in the setting of cardiothoracic surgical care. Data were ascertained by structured interviews with participants. The mean age among 241 cases was 61 ± 13 years. Eighty (33%) had history of TAD. While most participants lacked a formal syndromic diagnosis clinically, connective tissue abnormalities were identified in 113 (47%). This included 20% with abdominal hernia and 13% with skin striae in atypical location. In multivariate analysis, striae and hypertension were significantly associated with TAD. Striae were associated with younger age of TAD or prophylactic aortic surgery. Striae were more frequent in TAD cases than age- and sex-matched controls. Thus, systemic features of connective tissue dysfunction were prevalent in adults with aortopathy. The emerging nexus between striae and aortopathy severity creates opportunities for clinical stratification and basic research.

Outcomes of Surgical Coronary Revascularization Performed Before Solid Abdominal Organ Transplants.

BACKGROUND: Cardiac risk stratification and coronary angiography are routinely performed as part of kidney and liver transplant candidacy evaluation. There are limited data on the outcomes of surgical coronary revascularization in this patient population. This study investigated outcomes in patients with end- stage renal or hepatic disease who were undergoing coronary artery bypass grafting (CABG) to attain kidney or liver transplant candidacy. METHODS: This study was a retrospective analysis of all patients who underwent isolated CABG at our institution, Indiana University School of Medicine (Indianapolis, IN), between 2010 and 2016. Patients were divided into 2 cohorts: pretransplant (those undergoing surgery to attain renal or hepatic transplant candidacy) and nontransplant (all others). Baseline characteristics and postoperative outcomes were compared between the groups. RESULTS: A total of 1801 patients were included: 28 in the pretransplant group (n = 22, kidney; n = 7, liver) and 1773 in the nontransplant group. Major adverse postoperative outcomes were significantly greater in the pretransplant group compared with the nontransplant group: 30-day mortality (14.3% vs 2.8%; P = .009), neurologic events (17.9% vs 4.8%; P = .011), reintubation (21.4% vs 5.8%; P = .005), and total postoperative ventilation (5.2 hours vs 5.0 hours; P = .0124). The 1- and 5-year mortality in the pretransplant group was 17.9% and 53.6%, respectively. Of the pretransplant cohort, 3 patients (10.7%) underwent organ transplantation (all kidney) at a mean 436 days after CABG. No patients underwent liver transplantation. CONCLUSIONS: Outcomes after CABG in pre-kidney transplant and pre-liver transplant patients are poor. Despite surgical revascularization, most patients do not ultimately undergo organ transplantation. Revascularization strategies and optimal management in this high-risk population warrant further study.

Eleven-Year Experience Treating Blunt Thoracic Aortic Injury at a Tertiary Referral Center.

BACKGROUND: Blunt thoracic aortic injury treatment has evolved over the past decade particularly with respect to endovascular intervention options. We investigated the trends in blunt thoracic aortic injury management and outcomes over an 11-year span at the sole tertiary referral center in our state. METHODS: We retrospectively reviewed all patients who presented to our institution with blunt traumatic aortic injury between 2007 and 2017. Baseline demographics including aortic injury grade, injury severity score, and abbreviated injury scale were collected. Outcomes were compared by type and timing of treatment, which included either nonoperative management, endovascular repair, or open surgical repair. Bivariate and multivariable analyses were performed to examine treatment group differences and factors associated with 30-day mortality. RESULTS: In total, 229 patients were reviewed. The distribution of injury severity was grade 1 (30%), grade 2 (8%), grade 3 (30%), and grade 4 (31%). Overall, 27% of patients underwent endovascular repair, 29% open surgery, and 44% definitive nonoperative management. Over the study period, there was a dramatic decline in open surgery and a corresponding rise in endovascular treatment. Thirty-day mortality for the entire cohort was 22%. Mortality by treatment subgroup was 30% for nonoperative management, 8.2% for endovascular treatment, and 21% for open surgery. Delaying endovascular or open surgical treatment by at least 24 hours after admission was associated with significantly improved 30-day survival. CONCLUSIONS: Procedural intervention, whether endovascular or surgical, is associated with improved mortality compared with nonoperative treatment. Delayed intervention, particularly in the case of high-grade injuries, may allow for initial patient stabilization and improved outcomes.

Characteristics of second primary lung malignancy in patients with known breast cancer.

BACKGROUND: As breast cancer survival improves, the incidence of additional malignancies will likely rise. Identification of a lung nodule in a patient with known breast cancer poses a challenging diagnostic problem. This study outlines the management of such patients and identifies factors that correlate with survival. METHODS: From 1977 through 2002, 35 patients with known breast cancer were identified with an additional primary lung cancer. Data were collected from a retrospective chart review. Median and 2- year survival were determined by the Kaplan-Meier method and Cox regression analysis identified independent predictors of survival. RESULTS: Nineteen patients (54%) were asymptomatic at the time of diagnosis and had their lung cancer discovered during workup and/or follow-up of their breast cancer. The diagnosis of lung cancer was made by preoperative biopsy in 23 patients (82%). Nineteen patients (54%) were successfully treated with surgery. Mean follow-up was 2.3 years. Median survival for all patients was 1.8 years. Factors associated with a statistically significant improvement in survival included asymptomatic presentation of lung cancer (P = 0.003), absence of tobacco use (P = 0.021), and stage I lung cancer (P = 0.009). Multivariate analysis revealed that tobacco use (RR = 3.6, P = 0.047) and advanced stage of lung cancer (II-IV) at the time of diagnosis (RR = 2.2, P < 0.001) were independent predictors of decreased survival. CONCLUSION: The presentation of a lung nodule in patients with breast cancer warrants a comprehensive evaluation to differentiate between primary lung and metastatic breast cancers, as diagnosis and resection of an early stage lung cancer is associated with improved survival.

The Addition of Aortic Root Procedures During Elective Arch Surgery Does Not Confer Added Morbidity or Mortality.

BACKGROUND: During elective aortic arch replacement, the addition of an aortic root procedure has an unknown effect on morbidity and mortality. The purpose of this study is to determine the effect of adding an aortic root procedure to elective aortic surgery using the ARCH international database. METHODS: The ARCH Database was queried for all elective aortic arch replacements with and without aortic root replacement using moderate hypothermic circulatory arrest and antegrade cerebral perfusion from 2000 to 2015. Propensity score matching analysis was used to balance covariates, and a logistic regression model was created. RESULTS: A total of 1,169 patients were included for analysis, and 320 patients (27.4%) underwent an aortic root procedure. Patients undergoing root procedures were younger (69 versus 61 years), had less coronary artery disease (20% versus 32%), and had a higher incidence of Marfan's syndrome (4.2% versus 10.0%) (p < 0.001 for all). Concomitant coronary artery bypass grafting (26.6% versus 19.7%), total aortic arch replacement (41.6% versus 84.3%), and elephant trunk procedures (46% versus 17.2%) were performed more frequently in the nonroot cohort (p < 0.001 for all). Cardiopulmonary bypass and aortic cross-clamp times were significantly longer in the cohort of patients who underwent root procedures, whereas cerebral perfusion times were longer in the nonroot cohort (p < 0.001 for all). In both the propensity matched and nonmatched analyses, postoperative outcomes were not significantly different between patients who underwent root procedures and patients who did not (p > 0.05 for all outcomes). Multivariable logistic regression analyses showed no difference in mortality rates (odds ratio 0.62, 95% confidence interval: 0.9 to 1.34, p = 0.22) or in rates of permanent stroke (odds ratio 0.89, 95% confidence interval: 0.36 to 2.24, p = 0.81) between the root and nonroot cohorts. CONCLUSIONS: The addition of an aortic root procedure during elective aortic arch surgery lengthens cardiopulmonary bypass and aortic cross-clamp times but does not increase postoperative morbidity or mortality.

A 20-year multicenter analysis of dialysis-dependent patients who had aortic or mitral valve replacement: Implications for valve selection.

OBJECTIVE: Valve selection in dialysis-dependent patients can be difficult because long-term survival is diminished and bleeding risks during anticoagulation treatment are greater in patients with renal failure. In this study we analyzed long-term outcomes of dialysis-dependent patients who underwent valve replacement to help guide optimal prosthetic valve type selection. METHODS: Dialysis-dependent patients who underwent aortic and/or mitral valve replacement at 3 institutions over 20 years were examined. The primary outcome was long-term survival. A Cox regression model was used to estimate survival according to 5 ages, presence of diabetes, and/or heart failure symptoms. RESULTS: Four hundred twenty-three available patients were analyzed; 341 patients had biological and 82 had mechanical valves. Overall complication and 30-day mortality rates were similar between the groups. Thirty-day readmission rates for biological and mechanical groups were 15% (50/341) and 28% (23/82; P = .005). Five-year survival was 23% and 33% for the biological and mechanical groups, respectively. After adjusting for age, New York Heart Association (NYHA) class, and diabetes using a multivariable Cox regression model, survival was similar between groups (hazard ratio, 0.93; 95% confidence interval, 0.66-1.29; P = .8). A Cox regression model on the basis of age, diabetes, and heart failure, estimated that patients only 30 or 40 years old, with NYHA class I-II failure without diabetes had a >50% estimated 5-year survival (P < .001). CONCLUSIONS: Dialysis-dependent patients who underwent valve replacement surgery had poor long-term survival. Young patients without diabetes or NYHA III or IV symptoms might survive long enough to justify placement of a mechanical valve; however, a biological valve is suitable for most patients.

Repair of Thoracic and Thoracoabdominal Mycotic Aneurysms and Infected Aortic Grafts Using Allograft.

BACKGROUND: Mycotic aneurysm of the thoracic or thoracoabdominal aorta and infection of thoracic or thoracoabdominal aortic grafts are challenging problems with high mortality. In situ reconstruction with cryopreserved allograft (CPA) avoids placement of prosthetic material in an infected field and avoids suppressive antibiotics or autologous tissue coverage. METHODS: Fifty consecutive patients with infection of a thoracic or thoracoabdominal aortic graft or mycotic aneurysm underwent resection and replacement with CPA from 2006 to 2016. Intravenous antibiotics were continued postoperatively for 6 weeks. Long-term suppressive antibiotics were uncommonly used (8 patients). Follow-up imaging occurred at 6, 18, and 42 months postoperatively. Initial follow-up was 93% complete. RESULTS: Men comprised 64% of the cohort. The mean age was 63 ± 14 years. The procedures performed included reoperations in 37 patients; replacement of the aortic root, ascending aorta, or transverse arch in 19; replacement of the descending or thoracoabdominal aorta in 27; and extensive replacement of the ascending, arch, and descending or thoracoabdominal aorta in 4. Intraoperative cultures revealed most commonly Staphylococcus (24%), Enterococcus (12%), Candida (6%), and gram-negative rods (14%). Operative mortality was 8%, stroke was 4%, paralysis was 2%, hemodialysis was 6%, and respiratory failure requiring tracheostomy was 6%. Early reoperation for pseudoaneurysm of the CPA was necessary in 4 patients. One-, 2-, and 5-year survival was 84%, 76%, and 64%, respectively. CONCLUSIONS: Radical resection and in situ reconstruction with CPA avoids placing prosthetic material in an infected field and provides good early and midterm outcomes. However, early postoperative imaging is necessary given the risk of pseudoaneurysm formation.

Acute aortic syndrome.

Acute aortic syndrome (AAS) is a term used to describe a constellation of life-threatening aortic diseases that have similar presentation, but appear to have distinct demographic, clinical, pathological and survival characteristics. Many believe that the three major entities that comprise AAS: aortic dissection (AD), intramural hematoma (IMH) and penetrating aortic ulcer (PAU), make up a spectrum of aortic disease in which one entity may evolve into or coexist with another. Much of the confusion in accurately classifying an AAS is that they present with similar symptoms: typically acute onset of severe chest or back pain, and may have similar radiographic features, since the disease entities all involve injury or disruption of the medial layer of the aortic wall. The accurate diagnosis of an AAS is often made at operation. This manuscript will attempt to clarify the similarities and differences between AD, IMH and PAU of the ascending aorta and describe the challenges in distinguishing them from one another.

Polarized arrest with warm or cold adenosine/lidocaine blood cardioplegia is equivalent to hypothermic potassium blood cardioplegia.

BACKGROUND: Hypothermic depolarizing hyperkalemic (K + 20 mEq/L) blood cardioplegia is the "gold standard" in cardiac surgery. K + has been associated with deleterious consequences, eg, intracellular calcium overload. This study tested the hypothesis that elective arrest in a polarized state with adenosine (400 micromol/L via adenosine triphosphate-sensitive potassium channel opening) and the Na + channel blocker lidocaine (750 micromol/L) as the arresting agents in blood cardioplegia provides cardioprotection comparable to standard hypothermic K + -blood cardioplegia. METHODS: Anesthetized dogs were placed on cardiopulmonary bypass and assigned to 1 of 3 groups receiving antegrade cardioplegia delivered every 20 minutes for 1 hour of arrest: cold (10 degrees C) K + -blood cardioplegia (n = 6), cold (10 degrees C) adenosine/lidocaine blood cardioplegia (n = 6), or warm (37 degrees C) adenosine/lidocaine blood cardioplegia (n = 6). After an hour of arrest, cardiopulmonary bypass was discontinued, and reperfusion was continued for 120 minutes. RESULTS: Time to arrest was longer with cold and warm adenosine/lidocaine blood cardioplegia (175 +/- 19 seconds and 143 +/- 19 seconds, respectively) compared with K + -blood cardioplegia (27 +/- 2 seconds; P < .001). Postcardioplegia left ventricular systolic function (slope of the end-systolic pressure/dimension relationship) was comparable among the 3 groups (K + -blood cardioplegia, 15.2 +/- 2.1 mm Hg/mm; cold adenosine/lidocaine blood cardioplegia, 15.9 +/- 3.4 mm Hg/mm; warm adenosine/lidocaine blood cardioplegia, 14.1 +/- 2.8 mm Hg/mm; P = .90). Plasma creatine kinase activity in cold and warm adenosine/lidocaine blood cardioplegia was similar to that in K + -blood cardioplegia at 120 minutes of reperfusion (cold adenosine/lidocaine blood cardioplegia, 11.5 +/- 2.1 IU/g protein; warm adenosine/lidocaine blood cardioplegia, 10.1 +/- 0.9 IU/g protein; K + -blood cardioplegia, 7.6 +/- 0.8 IU/g protein; P = .17). Postcardioplegia coronary artery endothelial function was preserved in all groups. CONCLUSIONS: Intermittent polarized arrest with warm or cold adenosine/lidocaine blood cardioplegia provided the same degree of myocardial protection as intermittent hypothermic K + -blood cardioplegia in normal hearts.

Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion.

OBJECTIVE: We previously showed that brief intermittent ischemia applied during the onset of reperfusion (i.e., postconditioning) is cardioprotective in a canine model of ischemia-reperfusion. This study tested the hypothesis that the early minutes of reperfusion (R) during which postconditioning (Post-con) is applied are critical to its cardioprotection. METHODS: In anesthetized open-chest rats, the left coronary artery (LCA) was occluded for 30 min and reperfused for 3 h. All rats were randomly divided into six groups: Control (n=8): no intervention at R; Ischemic preconditioning (IPC) (n=8): the LCA was occluded for 5 min followed by 10 min of R before the index occlusion; Post-con 1 (n=8): after LCA occlusion, three cycles of 10 s R followed by 10 s LCA re-occlusion were applied during the first minute of R; Post-con 2 (n=8): Six cycles of 10 s R and 10 s re-occlusion were applied during the first 2 min of R; Delayed Post-con (n=8): the ligature was loosened for full reflow for the first minute of R, after which the three-cycle Post-con algorithm was applied; Sham (n=6): the surgical procedure was identical to other groups, but the LCA ligature was not ligated. RESULTS: Infarct size (TTC staining) was 23% smaller in Post-con 1 (40+/-2%*) than in Control (52+/-3%), confirmed by plasma creatine kinase activity (18+/-2* vs. 46+/-6 IU/g protein). There was no further reduction in infarct size with 6 cycles of Post-con (40+/-2.9%, p>0.05 vs. Post-con 1). Meanwhile, infarct size reduction was significantly greater in the IPC group (17+/-3%) than in Post-con1 (p<0.01). The plasma lipid peroxidation product malondialdehyde (MDA, microM/ml) was less after R in IPC and Post-con 1 (0.8+/-0.07* and 0.8+/-0.06*) vs. Control (1.21+/-0.08), consistent with a visual decrease in superoxide anion generation (dihydroethidium staining) in the AAR myocardium after 3 h of reperfusion. Neutrophil accumulation (myeloperoxidase activity, MPO, U/100 g tissue) in the AAR was less in IPC (1.4+/-0.3*) and Post-con 1 (2.5+/-0.3*) vs. Control (5.5+/-0.6). The reductions in infarct size, creatine kinase, MDA and DHE staining were lost with delayed Post-con, while MPO activity remained lower than in Control (3.2+/-0.4*). CONCLUSIONS: (1) Post-con at onset of R reduces myocardial injury; (2) cardioprotection may be mediated, in part, by inhibiting oxidant generation and oxidant mediated injury; (3) the first minute of R in the rat model is critical to cardioprotection by Post-con; and (4) cardioprotection by Post-con may be independent of neutrophil accumulation in AAR. *p<0.05 Post-con vs. Control.

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.

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.

Perfusion-assisted direct coronary artery bypass provides early reperfusion of ischemic myocardium and facilitates complete revascularization.

BACKGROUND: Perfusion-assisted direct coronary artery bypass (PADCAB) was developed to initiate early reperfusion of grafted coronary artery segments during off-pump operations to resolve episodes of myocardial ischemia and avoid its sequelae. This case series outlines intraoperative findings and clinical outcomes of our first year clinical experience with PADCAB. METHODS: From November 1999 to November 2000, 169 PADCAB and 358 off-pump coronary artery bypass procedures were performed at the Emory University Hospitals. The decision to use PADCAB was predicated on surgeon preference. Perfusion pressure and flow, amount of intracoronary nitroglycerin, and total perfusion time and volume were recorded at the time of operation. RESULTS: One off-pump coronary artery bypass patient required emergent conversion to cardiopulmonary bypass. Two PADCAB patients had ischemic ventricular arrhythmias during target vessel occlusion that resolved once active perfusion had begun. Perfusion pressure in PADCAB grafts was on average 44% higher than mean arterial pressure (p < 0.001). Nitroglycerin, infused locally by PADCAB, was used in 67 patients to resolve ischemic episodes and increase initial coronary flows. The mean number of diseased coronary territories and grafts placed was 2.8 +/- 0.5 and 3.4 +/- 0.7, respectively, in the PADCAB group, and 2.3 +/- 0.8 and 2.7 +/- 1.0, respectively, in the off-pump coronary artery bypass group (p < 0.001 for both comparisons). More PADCAB patients received lateral wall grafts than off-pump coronary artery bypass patients (83.4% vs 59.4%; p < 0.001). Hospital death and postoperative myocardial infarction were not different between groups. CONCLUSIONS: PADCAB can provide suprasystemic perfusion pressures and a means to add vasoactive drugs to target coronary vessels. PADCAB provides early reperfusion of ischemic myocardium and facilitates complete revascularization of severe multivessel coronary artery disease.

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 myosin light chain kinase provides prolonged attenuation of radial artery vasospasm.

OBJECTIVE: Current treatments for conduit vessel vasospasm are short-acting and do not inhibit all vasospastic stimuli. This study tests the hypothesis that irreversible inactivation of myosin light chain kinase provides sustained inhibition of arterial vasoconstriction stimulated by a spectrum of vasopressors. METHODS: Canine radial artery segments were soaked for 60 min in control buffer or buffer with wortmannin, an irreversible inhibitor of myosin light chain kinase. The vessels were then thoroughly washed and contractile responses were quantified in response to a spectrum of vasopressors at 2 and 48 h after treatment. After 48 h, selected vessels were examined for morphologic changes and development of apoptosis. RESULTS: Two hours after treatment, wortmannin-soaked vessels contracted significantly less than controls in response to norepinephrine (0.19+/-0.07 g vs. 7.22+/-0.37 g, P<0.001), serotonin (0.92+/-0.35 g vs. 9.64+/-0.67 g, P<0.001), thromboxane-mimetic U46619 (1.25+/-0.17 g vs. 10.99+/-0.50 g, P<0.001), and KCl (1.98+/-0.27 g vs.15.00+/-0.48 g, P<0.001). At 48 h, vasoconstriction remained significantly inhibited in wortmannin-treated vessels compared to control vessels in response to norepinephrine (2.36+/-0.17 vs. 6.95+/-0.47 g, P<0.001), serotonin (4.67+/-0.39 vs. 12.42+/-0.70 g, P<0.001), U46619 (5.42+/-0.34 vs. 9.29+/-0.74 g, P=0.008), and KCl (7.49+/-0.48 vs. 13.32+/-0.60 g, P<0.001). Histology of wortmannin-treated vessels revealed no overt smooth muscle or endothelial cell damage. TUNEL staining revealed a significantly greater proportion of apoptotic smooth muscle and endothelial cells in wortmannin-treated vessels as compared to controls. CONCLUSIONS: Disengaging the smooth muscle contractile apparatus by irreversibly binding myosin light chain kinase with wortmannin significantly attenuates radial artery vasoconstriction up to 48 h after brief treatment. This novel strategy may prevent vasospasm of arterial grafts from all causes for several postoperative days.