Yusheng Bao

Tight Glycemic Control in Diabetic Coronary Artery Bypass Graft Patients Improves Perioperative Outcomes and Decreases Recurrent Ischemic Events

Background—This study sought to determine whether tight glycemic control with a modified glucose-insulin-potassium (GIK) solution in diabetic coronary artery bypass graft (CABG) patients would improve perioperative outcomes. Methods and Results—One hundred forty-one diabetic patients undergoing CABG were prospectively randomized to tight glycemic control (serum glucose, 125 to 200 mg/dL) with GIK or standard therapy (serum glucose <250 mg/dL) using intermittent subcutaneous insulin beginning before anesthesia and continuing for 12 hours after surgery. GIK patients had lower serum glucose levels (138±4 versus 260±6 mg/dL; P <0.0001), a lower incidence of atrial fibrillation (16.6% versus 42%; P =0.0017), and a shorter postoperative length of stay (6.5±0.1 versus 9.2±0.3 days; P =0.003). GIK patients also showed a survival advantage over the initial 2 years after surgery (P =0.04) and decreased episodes of recurrent ischemia (5% versus 19%; P =0.01) and developed fewer recurrent wound infections (1% versus 10%, P =0.03). Conclusions—Tight glycemic control with GIK in diabetic CABG patients improves perioperative outcomes, enhances survival, and decreases the incidence of ischemic events and wound complications.

Glucose-insulin-potassium solutions improve outcomes in diabetics who have coronary artery operations

BACKGROUND This study was undertaken to determine whether glucose-insulin-potassium (GIK) would improve myocardial performance and limit morbidity after coronary artery bypass grafting in diabetic patients. METHODS Forty consecutive coronary artery bypass grafting patients with medically treated diabetes mellitus were prospectively randomly assigned to either a GIK group (n = 20; 500 mL D5W + 80 U regular insulin + 40 mEq KCl 30 mL/hour) or a no-GIK group (n = 20; D5W at 30 mL/hour). The GIK was begun at anesthetic induction and continued for 12 hours postoperatively. RESULTS Patients treated with GIK had higher postoperative cardiac indices (2.88 +/- 0.50 versus 2.20 +/- 0.39 L/minute per square meter; p < 0.0001), lower inotrope scores (0.40 +/- 0.68 versus 1.25 +/- 1.44; p = 0.05), less weight gain (5.80 +/- 3.76 versus 13.85 +/- 6.52 pounds; p < 0.0001), and had shorter times of ventilator support (8.35 +/- 2.60 versus 13.45 +/- 7.33 hours; p = 0.0128). They had a significantly lower prevalence of atrial fibrillation (15% versus 60%; p = 0.003), and shorter hospital stays (6.70 +/- 1.52 versus 10.15 +/- 6.62 days; p = 0.02). CONCLUSIONS Substrate enhancement with GIK in diabetic patients improved myocardial performance and resulted in faster recovery after coronary artery bypass grafting.

Total complement inhibition: an effective strategy to limit ischemic injury during coronary revascularization on cardiopulmonary bypass.

BACKGROUND Activation of complement during revascularization of ischemic myocardium accentuates myocardial dysfunction. Soluble human complement receptor type 1 (sCR1) is a potent inhibitor of complement, as are heparin-bonded (HB) cardiopulmonary bypass (CPB) circuits. This study sought to determine whether total complement inhibition with the combination of sCR1 and HB-CPB limits damage during the revascularization of ischemic myocardium. METHODS AND RESULTS In 40 pigs, the second and third diagonal coronary arteries were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 pigs, sCR1 (10 mg/kg) was infused 5 minutes after the onset of coronary occlusion (sCR1), 10 received HB-CPB only (HB-CPB), 10 received sCR1 and HB-CPB (sCR1+HB), and 10 received neither sCR1 or HB-CPB (unmodified). Addition of sCR1 to the HB group resulted in less myocardial tissue acidosis (DeltapH = -0.72+/-0.03 for unmodified; -0.46+/-0.05 for HB; -0.18+/-0.04 for sCR1; -0.13+/-0.01 for sCR1+HB), better recovery of wall motion scores (4 = normal to -1 = dyskinesia; 1.67+/-0.17 for unmodified; 2.80+/-0.08 for HB; 3.35+/-0.10 for sCR1; 3.59+/-0.08 for sCR1+HB), less lung water accumulation (5.46+/-0.28% for unmodified; 2.39+/-0.34% for HB; 1.22+/-0.07% for sCR1; 1.24+/-0.13% for sCR1+HB), and smaller infarct size (area necrosis/area risk = 44.6+/-0.7% for unmodified; 33.2+/-1.9% for HB; 19.0+/-2.4% for sCR1; 20+/-1.0% for sCR1+HB) (P<0.05 versus unmodified; P<0.05 versus unmodified and HB groups). CONCLUSIONS Total complement inhibition with sCR1 and sCR1+HB circuits optimizes recovery during the revascularization of ischemic myocardium.

High tissue affinity angiotensin-converting enzyme inhibitors improve endothelial function and reduce infarct size.

BACKGROUND Angiotensin-converting enzyme (ACE) inhibitors differ in their ability to inhibit tissue ACE. This study was, therefore, undertaken to determine whether high tissue affinity ACE inhibitors would improve endothelial function and thereby decrease tissue necrosis during ischemia. METHODS In a porcine model, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. During the period of coronary occlusion, 10 pigs received enalaprilat (low affinity tissue ACE inhibitor), 0.05 mg/kg intravenously, 10 received quinaprilat (high affinity tissue ACE inhibitor), 10 mg intravenously, and 10 others received no ACE inhibitor. RESULTS Wall motion scores (4, normal, to -1, dyskinesia) were higher in animals treated with ACE inhibitors (3.20+/-0.15 SE enalaprilat versus 3.08+/-0.23 quinaprilat versus 1.52+/-0.07 no ACE; both p < 0.0001 from no ACE). Endothelial-dependent relaxation to bradykinin was best preserved in the quinaprilat-treated hearts (32.1%+/-7.6% enalaprilat versus 65.8%+/-12.6% quinaprilat versus 30.6%+/-10.7% no ACE; p < 0.0001 from no ACE; p < 0.005 from enalaprilat). This was associated with a greater reduction in infarct size: area necrosis/area risk 24.3%+/-0.8% enalaprilat (p < 0.0001 from no ACE) versus 14.3%+/-3.2% quinaprilat (p < 0.0001 from no ACE; p < 0.005 from enalaprilat) versus 40.0%+/-1.7% no ACE. CONCLUSIONS ACE inhibitors with higher affinity to tissue ACE result in better preservation of endothelial function and less tissue necrosis during coronary revascularization.

Coronary Artery Bypass Grafting in Patients with Severe Left Ventricular Dysfunction—Early and Mid-Term Outcomes

Abstract  Background: The prevalence of patients with severe left ventricular dysfunction (LVD) referred for coronary artery bypass grafting (CABG) is increasing. The aim of the present study was to assess the outcomes of patients with severe LVD undergoing CABG. Methods: Outcomes of 115 consecutive patients with severe LVD (left ventricular ejection fraction [LVEF]≤ 30%, mean 22 ± 6%) undergoing isolated CABG between 1995 and 2000 were compared to 2335 patients with LVEF >30% (HEF). To further evaluate the LVD patients, they were divided into three subgroups base on LVEF: 0% to 10%, 11% to 20%, and 21% to 30%. Data were collected prospectively and entered into the departmental database of the Society of Thoracic Surgeons. Results: Patients in the LVD group had increased incidence of diabetes, chronic obstructive pulmonary disease (COPD), peripheral vascular disease, prior myocardial infarction (MI), congestive heart failure, and less elective procedures compared to the HEF group. Despite this greater risk profile, operative mortality (LVD 2.6% vs. HEF 1.2%, p = 0.19), the incidence of stroke (2.6% vs. 1.0%, p = 0.13), and perioperative MI (0.9% vs. 0.7%) were not statistically different between the groups. The incidence of respiratory (14.8% vs. 1.9%, p < 0.001), renal (5.2% vs. 1.0%, p < 0.001), and vascular (5.2% vs. 0.5%, p < 0.001) complications was significantly higher in the LVD group, resulting in a longer hospital length of stay (8 ± 8 vs. 6 ± 4 days, p < 0.0001). In a multivariate analysis, advanced age was as an independent predictor of hospital mortality. Average follow‐up in 108 (94%) LVD patients was 36 ± 22 months (range 2 to 78 months). Twenty‐one patients expired during the follow‐up, for nine the causes were cardiac‐related. Three‐ and 5‐year survival rates were 91 ± 3% and 76 ± 6%, respectively. Independent predictors of mid‐term mortality in the LVD group by a multivariate analysis included female gender, renal failure, respiratory complications, and grade I/II mitral regurgitation (MR). At the time of follow‐up, 72% of LVD patients were in functional class I/II. There were no statistically significant differences in short‐ and mid‐term outcomes among the LVD subgroups. Conclusion: CABG in patients with severe LVD can be performed with a low mortality, albeit with higher morbidity and longer length of hospital stay, than patients with LVEF >30%. Low ejection fraction per se was not a predictor of hospital mortality. CABG should be considered a safe and effective therapy for low ejection fraction patients with ischemic heart disease. Mitral valve repair/replacement in the presence of moderate degree of MR should be considered at the time of the initial operation.

Soluble Complement Receptor Type I Limits Damage During Revascularization of Ischemic Myocardium

BACKGROUND This study was undertaken to determine whether suppression of complement activation with soluble human complement receptor type I reduces myocardial damage during the revascularization of ischemic myocardium. METHODS In 20 pigs, the second and third diagonal coronary arteries were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 pigs, soluble human complement receptor type I (10 mg/kg) was infused over 30 minutes before the period of coronary occlusion; 10 other pigs received no soluble human complement receptor type I. Complement activation was measured by total hemolytic complement activity (expressed as a percentage of preischemic values). Ischemic damage was assessed by changes in myocardial tissue pH, wall motion scores (range, 4=normal to -1=dyskinesia), and infarct size (area of necrosis versus area at risk). RESULTS After 180 minutes of reperfusion, hearts treated with soluble human complement receptor type I had significantly less complement activation than nontreated hearts (1.1%+/-0.09% versus 7.8%+/-0.04%, respectively; p < 0.002), less myocardial acidosis (-0.41+/-0.03 versus -0.72+/-0.03, respectively; p < 0.0001), higher wall motion scores (3.1+/-0.09 versus 1.67+/-0.16, respectively; p < 0.0001), and smaller infarct size (24.6%+/-2.0% versus 41%+/-1.3%, respectively; p < 0.0001). CONCLUSIONS Complement inhibition with soluble human complement receptor type I significantly limits ischemic damage during the revascularization of acutely ischemic myocardium.

Endoscopic versus conventional radial artery harvest--is smaller better?

Abstract  Background: We sought to assess our initial experience with the recently introduced technique of endoscopic radial artery harvest (ERH) for coronary artery bypass grafting (CABG). Methods: Data were prospectively collected on 108 consecutive patients undergoing isolated CABG with ERH, and compared to 120 patients having conventional harvest (CH). Follow‐up was achieved in 227 patients (99%). At the time of follow‐up the severity of motor and sensory symptoms, as well as cosmetic result in the harvest forearm, were subjectively graded using a 5‐point scale. Grade 1—high intensity deficits, poor cosmetic result. Grade 5—no deficits, excellent cosmetic result. Results: Hospital mortality, myocardial infarction, and stroke rates were similar between the groups. Follow‐up mortality, reintervention rate, and average angina class were also similar. Harvest time was longer in the ERH group (61 ± 24 min vs. 45 ± 11 min, p < 0.001). Three patients in the ERH group were converted to CH and one radial artery was discarded. There were no vascular complications of the hand in either group. Average score of motor (ERH 4.4 ± 0.9, CH 4.2 ± 1.0) or sensory symptoms (ERH 3.7 ± 1.1, CH 3.8 ± 1.2) were similar. In the CH group sensory deficits were observed in the distribution of both the lateral antebrachial cutaneous and the superficial radial nerves (SRN). In contrast, sensory deficits in the ERH group were limited to the distribution of the SRN. Cosmetic result score was higher in the ERH group (ERH 4.2 ± 1.0, CH 3.1 ± 1.4, p < 0.0001). Conclusions: ERH is safe. It is technically demanding with a significant learning curve. Motor and sensory symptoms are not completely eliminated by using a smaller incision, but cosmetic results are clearly superior.

Heparin‐bonded Circuits Improve Clinical Outcomes in Emergency Coronary Artery Bypass Grafting

Abstract Compared to patients undergoing elective or urgent coronary artery bypass grafting (CABG), those undergoing emergency CABG (EM‐CABG) have a higher morbidity and mortality. The use of heparin‐bonded circuits (HBC) has been shown to improve clinical outcomes in nonemergent CABG patients. It is not known, however, whether the improved hemostasis and attenuation of the inflammatory response to cardiopulmonary bypass, conferred by HBC, can overcome the high incidence of comorbid risk factors in (EM‐CABG) patients and improve their outcomes. A retrospective analysis of 206 consecutive patients undergoing EM‐CABG over 4 years (1993–1997) at one institution was performed. Eighty‐one patients were treated with conventional non‐heparin‐bonded circuits (NHBC) with full anticoagulation protocol (FAR, activated clotting time [ACT] > 480 sec); 125 patients were treated with HBC and a lower anticoagulation protocol (LAP, ACT > 280 seconds). Outcomes and results were collected prospectively and are presented as mean ± SD. Preoperative risk profiles were similar in both treatment groups. Postoperatively, compared with the NHBC group, patients treated with HBC/LAP required fewer homologous donor units (4.1 ± 10.7 vs 8.2 ± 13.6 units, p = 0.005), were less likely to require inotropic support (18.6% vs 38.3%, p = 0.005), and had a lower incidence of perioperative myocardial infarction (Ml, 3.2% vs 12.3%, p = 0.04) and pulmonary complications (4.0% vs 12.3%, p = 0.04). The use of HBC/LAP resulted in a decreased incidence of postoperative complications (12.8% vs 28.4%, p = 0.01, odds ratio 0.37 with 95% confidence interval [Cl] 0.18‐0.76). This resulted in a shorter duration of ventilatory support (30.5 ± 54.0 vs 72.8 ± 16.7 hours, p = 0.009), ICU stay (38.2 ± 36.5 vs 91.5 ± 68.7 hours, p = 0.009), hospital stay (8.0 ± 7.1 vs 11.0 ± 8.9 days, p = 0.008), and therefore cost. In conclusion, the use of HBC/LAP in EM‐CABG resulted in a reduction of homologous transfusion and postoperative complications associated with decreased hospital stays and cost.

Aprotinin Decreases Ischemic Damage During Coronary Revascularization

Abstract  Background and Aim: This study sought to determine whether the favorable anti‐inflammatory effects of aprotinin might limit ischemic damage during the revascularization of ischemic myocardium. Methods: Twenty pigs underwent 90 minutes of coronary occlusion followed by 45 minutes of blood cardioplegic arrest and 180 minutes of reperfusion. Ten animals received a loading dose of aprotinin (40,000 kallikrein inhibiting units/kg) during the start of coronary occlusion followed by an infusion of 20,000 kallikrein inhibiting units/kg/hour. Ten other animals received no aprotinin. Summary statistics are expressed as the mean ± standard error. Results: The aprotinin‐treated animals required less cardioversions for ventricular arrhythmias (1.0 ± 0.7 vs. 3.6 ± 0.6; p < 0.001), accumulated less lung water (1.0 ± 0.2% change vs. 6.2 ± 0.9% change; p = 0.038), had more complete coronary relaxation to bradykinin (34.1 ± 5.9% change vs. 9.2 ± 3.5% change; p = 0.01), and had reduced infarct size (area necrosis/area risk = 20 ± 1.1% vs. 39 ± 1.2%; p = 0.003). Conclusions: Aprotinin limits ischemic injury during acute coronary revascularization by decreasing ventricular arrhythmias and lung edema, preserving endothelial function, and minimizing myocardial necrosis.

Pretreatment with angiotensin-converting enzyme inhibitors attenuates ischemia-reperfusion injury

BACKGROUND The Heart Outcomes Prevention Evaluation (HOPE) trial demonstrated that ischemic events are decreased in patients receiving angiotensin-converting enzyme (ACE) inhibitors. This study sought to determine whether pretreatment with ACE inhibitors would attentuate ischemic injury during surgical revascularization of ischemic myocardium. METHODS In a porcine model, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest, and 180 minutes of reperfusion. Ten pigs received quinapril (20 mg p.o. q.d.) for 7 days prior to surgery; 10 others received no-ACE inhibitors. RESULTS Quinapril-treated animals required less cardioversions for ventricular arrhythmias (1.58 +/- 0.40 vs 2.77 +/- 0.22; p < 0.05), had higher wall motion scores assessed by two-dimensional echocardiography (4 = normal to -1 = dyskinesia; 2.11 +/- 0.10 vs 1.50 +/- 0.07; p < 0.05), more complete coronary artery endothelial relaxation to bradykinin (45% +/- 3% vs 7% +/- 4%; p < 0.005), and lower infarct size (24.0% +/- 3.0% vs 40.0% +/- 1.7%; p < 0.0001). CONCLUSIONS ACE inhibition prior to coronary revascularization enhances myocardial protection by decreasing ventricular irritability, improving regional wall motion, lowering infarct size, and preserving endothelial function.