Preoperative risk factors in 10 418 patients with prior myocardial infarction and 5241 patients with prior unstable angina undergoing elective coronary artery bypass graft surgery.

BACKGROUND: The EuroSCORE associates coronary artery bypass graft (CABG) surgery with higher perioperative risk in the first 3 months after a myocardial infarction (MI). The optimal scheduling of CABG surgery after unstable angina (UA) is unknown. We investigated the preoperative predictors of adverse outcomes in patients undergoing CABG with prior MI or UA and investigated the importance of time interval between the cardiac event and CABG. METHODS: The Hospital Episode Statistics database (April 2006-March 2010) was analysed for elective admissions for CABG. Independent preoperative patient factors influencing length of stay, readmission rates, and mortality, were identified by logistic regression and presented as adjusted odds ratios (ORs). RESULTS: A total of 10 418 patients with prior MI (mortality 1.8%) and 5241 patients with prior UA (mortality 2.2%) were included in the respective cohorts. Multiple risk factors were identified in each population including liver disease and renal failure. The time interval from cardiac event (MI or UA) to elective CABG surgery did not influence perioperative outcomes when analysed as a continuous measure or using the arbitrary 3-month threshold [MI, OR 1.1 (0.78-1.57) and UA, OR 0.65 (0.39-1.09)]. CONCLUSIONS: Our hypothesis generating data suggest that the increased risk currently allocated in the EuroSCORE for an interval of 3 months between MI and CABG should be critically re-evaluated. Furthermore, prior MI should not be discounted as a risk factor if it is more than 3 months old.

Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.

BACKGROUND: The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary mechanism in the pathogenesis of postoperative myocardial infarction (PMI), a multifactorial disorder with significant inter-patient variability poorly predicted by clinical and procedural factors. We tested the hypothesis that candidate gene polymorphisms in inflammatory pathways contribute to risk of PMI after cardiac surgery. METHODS AND RESULTS: We genotyped 48 polymorphisms from 23 candidate genes in a prospective cohort of 434 patients undergoing elective cardiac surgery with CPB. PMI was defined as creatine kinase-MB isoenzyme level > or = 10x upper limit of normal at 24 hours postoperatively. A 2-step analysis strategy was used: marker selection, followed by model building. To minimize false-positive associations, we adjusted for multiple testing by permutation analysis, Bonferroni correction, and controlling the false discovery rate; 52 patients (12%) experienced PMI. After adjusting for multiple comparisons and clinical risk factors, 3 polymorphisms were found to be independent predictors of PMI (adjusted P<0.05; false discovery rate <10%). These gene variants encode the proinflammatory cytokine interleukin 6 (IL6 -572G>C; odds ratio [OR], 2.47), and 2 adhesion molecules: intercellular adhesion molecule-1 (ICAM1 Lys469Glu; OR, 1.88), and E-selectin (SELE 98G>T; OR, 0.16). The inclusion of genotypic information from these polymorphisms improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.764 versus 0.703). CONCLUSIONS: Functional genetic variants in cytokine and leukocyte-endothelial interaction pathways are independently associated with severity of myonecrosis after cardiac surgery. This may aid in preoperative identification of high-risk cardiac surgical patients and development of novel cardioprotective strategies.

Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i).

Cardiac G protein-coupled receptors that couple to Galpha(s) and stimulate cAMP formation (eg, beta-adrenergic, histamine, serotonin, and glucagon receptors) play a key role in cardiac inotropy. Recent studies in rodent cardiac myocytes and transfected cells have revealed that one of these receptors, the beta(2)-adrenergic receptor (AR), also couples to the inhibitory G protein Galpha(i) (activation of which inhibits cAMP formation). If beta(2)ARs could be shown to couple to Galpha(i) in the human heart, it would have important ramifications, because levels of Galpha(i) increase with age and in failing human heart. Therefore, we investigated whether beta(2)ARs in the human heart activate Galpha(i). By photoaffinity labeling human atrial membranes with [(32)P]azidoanilido-GTP, followed by immunoprecipitation with antibodies specific for Galpha(i), we found that Galpha(i) is activated by stimulation of beta(2)ARs but not of beta(1)ARs. In addition, we found that other Galpha(s)-coupled receptors also couple to Galpha(i), including histamine, serotonin, and glucagon. When coupling of these receptors to Galpha(i) is disrupted by pertussis toxin, their ability to stimulate adenylyl cyclase is enhanced. These data provide the first evidence that beta(2)AR and many other Galpha(s)-coupled receptors in human atrium also couple to Galpha(i) and that abolishing the coupling of these receptors to Galpha(i) increases the receptor-mediated adenylyl cyclase activity.

Effect of apolipoprotein E genotype on cerebral autoregulation during cardiopulmonary bypass.

BACKGROUND AND PURPOSE: The presence of the apolipoprotein E epsilon4 (apoE4) allele has been associated with cognitive decline after cardiac surgery. We compared autoregulation of cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO(2)), and arterial-venous oxygen content difference [C(A-V)O(2)], during cardiopulmonary bypass (CPB) in patients with and without the apoE4 allele to help define the mechanism of association with cognitive decline. METHODS: One hundred fifty-four patients underwent coronary artery bypass grafting with CPB, nonpulsatile flow, and alpha-stat management. CBF was measured by using (133)Xe washout methods. C(A-V)O(2), CMRO(2), and oxygen delivery were calculated. Pressure-flow autoregulation was tested by using 2 CBF measurements at stable hypothermia: the first at stable mean arterial pressure (MAP) and the second 15 minutes later, when MAP had increased or decreased >/=20%. Metabolism-flow autoregulation was tested by varying the temperature and measuring the coupling of CBF and CMRO(2). RESULTS: In patients with (n=41) or without (n=113) the apoE4 allele, there were no differences in CBF, CMRO(2), C(A-V)O(2), pressure-flow and metabolism-flow autoregulation corrected for age, gender, non-insulin-dependent diabetes, hemoglobin, CPB time, and temperature. CONCLUSIONS: We conclude that apoE genotype does not affect global CBF and oxygen delivery/extraction during CPB, which suggests that other mechanisms are responsible for the apoE isoform-related neurocognitive dysfunction seen in patients undergoing CPB.

Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery.

BACKGROUND AND PURPOSE: The importance of perioperative cognitive decline has long been debated. We recently demonstrated a significant correlation between perioperative cognitive decline and long-term cognitive dysfunction. Despite this association, some still question the importance of these changes in cognitive function to the quality of life of patients and their families. The purpose of our investigation was to determine the association between cognitive dysfunction and long-term quality of life after cardiac surgery. METHODS: After institutional review board approval and patient informed consent, 261 patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled and followed for 5 years. Cognitive function was measured with a battery of tests at baseline, discharge, and 6 weeks and 5 years postoperatively. Quality of life was assessed with well-validated, standardized assessments at the 5-year end point. RESULTS: Our results demonstrate significant correlations between cognitive function and quality of life in patients after cardiac surgery. Lower 5-year overall cognitive function scores were associated with lower general health and a less productive working status. Multivariable logistic and linear regression controlling for age, sex, education, and diabetes confirmed this strong association in the majority of areas of quality of life. CONCLUSIONS: Five years after cardiac surgery, there is a strong relationship between neurocognitive functioning and quality of life. This has important social and financial implications for preoperative evaluation and postoperative care of patients undergoing cardiac surgery.

Intraoperative physiologic variables and outcome in cardiac surgery: Part II. Neurologic outcome.

BACKGROUND: The impact of alterable physiologic variables on neurologic outcome after coronary artery bypass grafting procedures is unknown. The purpose of this study was to determine whether minimum intraoperative hematocrit, maximum glucose concentration, or mean arterial pressure during cardiopulmonary bypass influences risk-adjusted neurologic outcome after coronary artery bypass grafting. METHODS: Outcome data from 2,862 patients undergoing coronary artery bypass grafting were merged with intraoperative physiologic data. A preoperative stroke risk index was calculated for each patient. Variables found significant by univariate logistic regression were tested in a multivariable model to determine association with outcome. RESULTS: The incidence of stroke or coma in the study population was 1.3%. After controlling for stroke risk and bypass time, only an index of low mean arterial pressure during bypass retained a significant inverse association with outcome (p = 0.0304). CONCLUSIONS: This study found no evidence that glucose concentration or minimum hematocrit are associated with major adverse neurologic outcome. The association between lower pressure during bypass and decreased incidence of stroke or coma persisted in all risk groups. This points to mechanisms other than hypoperfusion as the primary cause of neurologic injury associated with cardiac surgery.

Cerebral emboli and serum S100beta during cardiac operations.

BACKGROUND: The glial protein S100beta has been used to estimate cerebral damage in a number of clinical settings. The purpose of this investigation was to determine the correlation between cerebral microemboli and S100beta levels during cardiac operations. METHODS: Transcranial Doppler ultrasonography was used to measure emboli in the right middle cerebral artery. Emboli counts (n = 111) were divided into five time periods: (1) incision to aortic cannulation; (2) aortic cannulation to cross-clamp onset; (3) cross-clamp onset to cross-clamp release; (4) cross-clamp release to decannulation; and (5) decannulation to chest closure. The level of S100beta (n = 156) was measured at baseline, at the end of cardiopulmonary bypass, then 150 and 270 minutes after cross-clamp release. RESULTS: The level of S100beta correlated with age, cardiopulmonary bypass time, cross-clamp time, and number of emboli at time period 2. Although cardiopulmonary bypass time was univariately associated with S100beta level, it became nonsignificant in a multivariable model that included age and cross-clamp time. CONCLUSIONS: The correlation of S100beta level with emboli measured during cannulation (time period 2) supports the hypothesis that cannulation is a high-risk time period for cerebral injury.

Cardiopulmonary bypass time does not affect cerebral blood flow.

BACKGROUND: A time-dependent decline in cerebral blood flow (CBF) has been reported in cardiac surgical patients despite stable pump flows and arterial carbon dioxide tension. Other studies have failed to support these hypothermic cardiopulmonary bypass (CPB) results, showing preservation of CBF during CPB. The purpose of the study was to define the influence of mildly hypothermic CPB duration on CBF. METHODS: Cerebral blood flow was measured using xenon-133 washout and alpha-stat blood gas management during nonpulsatile CPB. Cerebral blood flow measurements were made after the initiation of CPB and near the end of bypass during pump flows of 2.4 L.min-1.m-2. RESULTS: Fifty-two coronary artery bypass patients were studied. The average time between CBF measurements was 54 +/- 20 minutes (mean +/- standard deviation), with a range of 10 to 100 minutes. Temperature and arterial carbon dioxide tension were controlled: after the initiation of CPB, temperature was 35.5 degrees +/- 0.4 degree C and carbon dioxide tension was 37 +/- 2.8 mm Hg; whereas near the end of bypass temperature was 35.6 degrees +/- 0.5 degree C and carbon dioxide tension was 36 +/- 2.3 mm Hg. We found no correlation between CBF and time on CPB (p = 0.47; r = 0.101), in contrast to other studies suggesting that CPB duration may intrinsically affect CBF. CONCLUSIONS: Our experimental results include the following: (1) during mildly hypothermic bypass, CBF does not decrease in relation to time and (2) cerebral flow-metabolism coupling is intact at 35 degrees C.

Post-ischemic RSR13 amplifies the effect of dizocilpine on outcome from transient focal cerebral ischemia in the rat.

In a recent study of focal cerebral ischemia in rats, pre-ischemic administration of the synthetic allosteric hemoglobin modifier RSR13 (2-[4-[[3,5-dimethylanilino) carbonyl] methyl] phenoxy]-2-methylproprionic acid) reduced cerebral infarct size when combined with the NMDA receptor antagonist dizocilpine (MK-801) but not when given alone. We hypothesized that post-ischemic RSR13 administration would enhance neuroprotection afforded by NMDA receptor antagonism in a rat model of transient middle cerebral artery occlusion (MCAO). Fasted normothermic Wistar rats underwent 75 min of temporary MCAO. At onset of reperfusion, rats randomly received: (1) 0.9% NaCl (vehicle) i.v. alone (n=16); (2) 0.9% NaCl+dizocilpine (0.25 mg/kg) i.v. (n=16); or (3) RSR13 (150 mg/kg)+dizocilpine (0.25 mg/kg) i.v. (n=17). Seven days later, neurologic deficit and cerebral infarct size were determined. Dizocilpine alone compared to vehicle reduced mean+/-S.D. subcortical (52+/-24 mm(3) vs. 122+/-64 mm(3), P=0.003) and cortical (35+/-35 mm(3) vs. 125+/-72 mm(3), P=0.00074) infarct volumes. When compared to dizocilpine alone, the combination of RSR13+dizocilpine further reduced subcortical (37+/-14 mm(3) vs. 52+/-24 mm(3), P=0. 034) and cortical (8+/-19 mm(3) vs. 35+/-35 mm(3), P=0.018) infarct size. RSR13+dizocilpine improved neurologic scores vs. either dizocilpine alone (P=0.0014) or vehicle (P=10(-7)). The combination of NMDA receptor antagonism and a RSR13 mediated rightward shift of the oxy-hemoglobin dissociation curve improved outcome from MCAO. Because this occurred after reperfusion, our results suggest that the post-ischemic brain continues to suffer from hypoperfusion defects, which are amenable to therapy by enhanced O(2) delivery. The results also support the concept that neuroprotective strategies, which combine drugs with different mechanisms of action, may yield cumulative benefits.

Effects of RSR13, a synthetic allosteric modifier of hemoglobin, alone and in combination with dizocilpine, on outcome from transient focal cerebral ischemia in the rat.

This study examined the effect of a pharmacologically induced rightward shift in the partial pressure of oxygen at which 50% of hemoglobin is saturated (P50) on outcome from transient focal cerebral ischemia in the rat. Halothane anesthetized rats (n=20 per group) were given saline or a single 15-min infusion of 150 mg/kg RSR13 (2-[4-[[3,5-dimethylanilino) carbonyl]methyl]phenoxy]-2-methylproprionic acid) intravenously before or 30 min after onset of 75 min of middle cerebral artery filament occlusion (MCAO). Seven days later, severity of hemiparesis and cerebral infarct size were examined. RSR13 alone did not significantly improve outcome. Conscious normothermic rats (n=12 per group) were also given RSR13 (150 mg/kg) or 0.9% NaCl intravenously and subjected to 75 min of MCAO with 7 days of recovery. Again, RSR13 alone did not significantly reduce infarct size or improve neurologic score. A dose-response curve for dizocilpine (MK-801) was then constructed in conscious normothermic rats subjected to 75 min of MCAO. Dizocilpine (0.5 mg/kg i.v.) caused a 90% reduction in mean infarct size while 0.25 mg/kg reduced infarct size by 48%. Other rats were then subjected to 75 min of MCAO after being given dizocilpine (0.25 mg/kg i.v.; n=18) or RSR13 (150 mg/kg i.v. )+dizocilpine (0.25 mg/kg i.v.; n=15). RSR13+dizocilpine resulted in smaller cortical infarct volume (8+/-14 mm3 vs. 34+/-37 mm3, p<0.02) and total cerebral infarct volume (46+/-28 mm3 vs. 81+/-60 mm3, p<0. 05) compared to dizocilpine alone, respectively. We conclude that a pre-ischemic peak increase in P50 of approximately 25 mmHg alone is insufficient to reduce focal ischemic injury, but may be advantageous when used in conjunction with other neuroprotective agents.

Aortic dissection after angioplasty and stenting of an aortic coarctation: detection by intravascular ultrasonography but not transesophageal echocardiography.

In this case report, an iatrogenic dissection of the descending aorta occurred during balloon angioplasty and stenting of a recurrent coarctation. The dissection was not seen by transesophageal echocardiography, but intravascular ultrasonography, performed routinely during such procedures at this institution, identified the dissection and guided further therapeutic stent placement.

Persistent left superior vena cava and partial anomalous pulmonary venous connection: incidental diagnosis by transesophageal echocardiography during coronary artery bypass surgery.

Transesophageal echocardiography plays an important role in the intraoperative treatment of the heart surgery patient. Its utility in the description of both known and unexpected cardiac pathology is well established. We describe a patient with a previously undiagnosed partial anomalous pulmonary venous connection along with a persistent left superior vena cava scheduled for routine coronary artery bypass graft surgery (CABG).

Continuous jugular venous versus nasopharyngeal temperature monitoring during hypothermic cardiopulmonary bypass for cardiac surgery.

STUDY OBJECTIVE: To compare jugular venous to nasopharyngeal temperature during hypothermic cardiopulmonary bypass (CPB). DESIGN: Prospective observational study. SETTING: Tertiary care teaching hospital. PATIENTS: 5 ASA physical status IV patients (40 to 65 years of age) having cardiac surgery with hypothermic CPB. INTERVENTIONS, MEASUREMENTS AND MAIN RESULTS: Jugular venous and nasopharyngeal temperatures were recorded throughout the procedure with comparisons made during four time periods: pre-CPB, during CPB, during rewarming, and post-CPB. The patients underwent 85.8 +/- 45.8 minutes (mean +/- SD) of hypothermic CPB, cooling to 26.3 +/- 7.6 degrees C (nasopharyngeal) followed by rewarming at 0.35 +/- 0.1 degree C (nasopharyngeal)/min. There was a high degree of precision between the two temperature sites, but marked differences in bias. In particular, temperature bias was more pronounced during rewarming from CPB compared with other time periods (p < 0.05) where jugular venous temperature was greater than nasopharyngeal temperature by 3.4 degrees C. CONCLUSION: Nasopharyngeal temperature underestimates jugular venous temperature during rewarming from hypothermic CPB. As a result, the brain may be exposed to periods of hyperthermia, possibly increasing the risk of neurologic injury associated with CPB.