Nonlinear heart rate variability in CABG patients and the preconditioning effect.

OBJECTIVE: Heart rate variability (HRV) is the most frequently used noninvasive diagnostic method in the assessment of cardiac autonomic control. The clinical relevance of HRV, especially nonlinear HRV in CPB patients has not been well studied. Short brief myocardial ischemia has been reported to influence HRV. We therefore hypothesis that the protective mechanism of ischemic preconditioning (IP) may involve in cardiac autonomic regulation. METHODS: Eighty-six CABG patients were randomized into a control and an IP group. The IP patients received two periods of 2-min ischemia followed by 3-min reperfusion by aortic cross-clamped. Holter data were collected in 86 CABG patients before and after surgery. Arrhythmias, linear and nonlinear HRV measures were analyzed. RESULTS: All time and frequency domain HRV variables as well as nonlinear indexes of HRV, the short-term (4-11 beats) scaling exponent alpha1, were suppressed significantly after surgery in both study groups. The lower pre- and postoperative exponent alpha1 predict the higher incidence of postoperative AF and worse postoperative outcome. The suppressed exponent alpha1 was attenuated in the IP group as compared to controls (P = 0.008). No other differences were observed in the changes in linear HRV measures between the groups. IP significantly reduced the incidence of postoperative arrhythmias and improved postoperative outcome. CONCLUSIONS: The present findings show that cardiac autonomic regulation is impaired after CABG. Nonlinear HRV exponent alpha1 is a more sensitive measure to predict the postoperative outcome in CABG patients. IP alleviates the extreme autonomic reactions after surgery, suggesting that cardiac autonomic regulation is involved in the IP protective mechanism.

Antiarrhythmic effect of ischemic preconditioning in recent unstable angina patients undergoing coronary artery bypass grafting.

Coronary artery bypass grafting (CABG) for unstable angina pectoris patients results in a higher incidence of arrhythmia and higher arrhythmic cardiac mortality. Ischemic preconditioning (IP) has proved effective in suppressing ischemia reperfusion arrhythmias in animals and in humans. The purpose of the present study was to investigate whether IP protects against postoperative arrhythmias in recent unstable angina patients undergoing urgent CABG. Forty-one patients with recent unstable angina and three-vessel coronary artery disease admitted for CABG were randomized into an IP group and a control group. The IP protocol involved twice occluding the ascending aorta with a cross-clamp for 2 minutes, followed by 3 minutes of reperfusion. Twenty-four-hour continuous electrocardiography (24-h ECG) was recorded from the preoperative day to the 2nd postoperative day. The incidences of supraventricular extrasystole (SVES), ventricular extrasystole (VES), supraventricular tachycardia (SVT), and ventricular tachycardia (VT) were 95.2%, 85.7%, 26.2%, and 26.2%, respectively, before surgery and 100.0%, 100.0%, 88.1%, and 76.2%, respectively, after surgery. IP significantly reduced the incidence of VT and the severity of SVES, VES, SVT, and VT after surgery. The period of mechanical ventilation and the length of stay in the intensive care unit were significantly shorter in the IP group. In summary, rhythm disturbances are common in CABG patients with recent unstable angina. IP significantly reduces rhythm disturbances, including SVES, VES, SVT, and VT after CABG. The findings indicate that IP could constitute an additional myocardial protective strategy in recently unstable angina patients undergoing CABG.

Fibrillation in patients subjected to coronary artery bypass grafting.

OBJECTIVE: Atrial fibrillation is the most frequently encountered postoperative arrhythmic complication after coronary artery bypass grafting. Ischemic preconditioning has proved a potent endogenous factor in suppressing ischemia-reperfusion-induced arrhythmias. The protective effect of ischemic preconditioning on atrial fibrillation after coronary artery bypass grafting has not been studied. The purpose of the present study was to investigate whether ischemic preconditioning had an effect on postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting. METHODS: Eighty-five patients undergoing coronary artery bypass grafting were randomized into ischemic preconditioning and control groups. Holter data from 24-hour electrocardiography were collected 1 day before the operation to the second postoperative day. Atrial fibrillation was registered as positive if any atrial fibrillation event occurred. RESULTS: The overall incidence of postoperative atrial fibrillation and sustained atrial fibrillation was 34.1% and 27.1%, respectively. The occurrence of atrial fibrillation was significantly lower in the ischemic preconditioning group (21.4% in patients undergoing ischemic preconditioning and 46.5% in control subjects, P =.015). Preoperative recent unstable angina did not influence the incidence of atrial fibrillation. Patients with atrial fibrillation had longer intensive care unit stays and compromised postoperative hemodynamic outcomes. Binary logistic regression analysis showed that ischemic preconditioning, preoperative mean heart rate, and postoperative pulmonary capillary wedge pressure were the independent predictors of atrial fibrillation. CONCLUSIONS: Postcoronary artery bypass grafting atrial fibrillation is associated with more complicated postoperative outcome. Higher preoperative heart rate and postoperative pulmonary capillary wedge pressure were the independent predictors of atrial fibrillation. Recent unstable angina is not related to the occurrence of postcoronary artery bypass grafting atrial fibrillation. Ischemic preconditioning significantly suppresses postcoronary artery bypass grafting atrial fibrillation, suggesting that ischemic preconditioning can be used as an effective prophylactic method for postoperative atrial fibrillation.

Recent unstable angina and off-pump coronary artery bypass grafting is not related to postoperative atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) is the most frequently encountered postoperative arrhythmic complication after coronary artery bypass grafting (CABG). The purpose of the present study was to investigate the incidence and predictors of postoperative AF in patients with stable and unstable angina pectoris undergoing on-pump and off-pump CABG procedures. DESIGN: One hundred and seventeen stable, unstable on-pump and off-pump CABG patients were included in the present study. Holter data were collected 1 day before the operation to the 2nd postoperative day. AF was registered as positive if any AF event occurred. RESULTS: The overall incidence of postoperative AF and sustained AF was 31.6 and 25.6%, respectively. Postoperative AF incidences in stable on-pump, unstable on-pump and stable off-pump patients were 29.5, 39.0 and 25%, respectively (p = 0.412). Patients with AF had compromised postoperative haemodynamic function, greater need of inotropic support and antiarrhythmic medication, and longer intensive care unit (ICU) stays. CONCLUSION: Post-CABG AF is associated with more complicated postoperative outcome. Recent unstable angina and off-pump procedure is not related to the occurrence of post-CABG AF.

Arrhythmias in off-pump coronary artery bypass grafting and the antiarrhythmic effect of regional ischemic preconditioning.

OBJECTIVE: The authors sought to establish whether regional ischemic preconditioning (IP) reduces ischemic reperfusion arrhythmias in patients who undergo off-pump coronary artery bypass grafting (OPCAB). DESIGN: A controlled, randomized, prospective study. SETTING: A university hospital. PARTICIPANTS: Thirty-two patients with left anterior descending coronary artery (LAD) or 2-vessel heart disease (including LAD) who were to undergo OPCAB were randomized into an IP and a control group. INTERVENTIONS: IP was induced by occluding the LAD twice for a 2-minute period followed by 3-minute LAD reperfusion before bypass grafting of the first coronary vessel. MEASUREMENTS AND MAIN RESULTS: Twenty-four-hour electrocardiography was recorded from the preoperative day to the second postoperative day. The heart rate (HR) was significantly elevated after surgery. Supraventricular extrasystole (SVES) events were similar before and after surgery. The incidence of patients with ventricular extrasystole (VES), supraventricular tachycardia (SVT), atrial fibrillation (AF), and ventricular tachycardia (VT) was significantly increased after the operation. Ventricular arrhythmias occurred mostly during anastomosis and the early reperfusion period and recovered 2 hours after reperfusion. Supraventricular tachyarrhythmias were mostly encountered 24 hours after reperfusion. IP significantly suppressed HR elevation, SVT, and VT after surgery. SVES, VES, and AF episodes were similar between the groups. CONCLUSIONS: Arrhythmia was a common phenomenon during and after an OPCAB procedure. The present IP protocol significantly suppressed HR elevation, the episodes of SVT, and the incidence of VT after surgery.

Soluble adhesion molecules in coronary artery bypass surgery.

Plasma levels of sE-selectin, sP-selectin, and sICAM-1 were measured before anesthesia and at 0.5, 4, and 20 hours after cardiopulmonary bypass in 37 men undergoing coronary artery bypass surgery. Plasma sE-selectin remained close to the preoperative levels. The levels of sP-selectin increased significantly from 46.5 +/- 15.3 ng x mL(-1) to 69.3 +/- 39.6 ng x mL(-1) at 0.5 hours, 84.1 +/- 45.5 ng x mL(-1) at 4 hours, and 79.6 +/- 35.5 ng x mL(-1) at 20 hours. Plasma sICAM-1 levels decreased 0.5 hours after cardiopulmonary bypass, recovered at 4 hours, and showed a significant increase at 20 hours. The changes in plasma levels of adhesion molecules did not correlate with the duration of bypass or aortic crossclamping, hemodynamics, or creatine kinase-MB levels. However, sE-selectin and sICAM-1 levels increased considerably more in patients who needed norepinephrine in the intensive care unit. These results indicate that the transient changes in plasma levels of soluble adhesion molecules are not associated with postoperative myocardial injury in low-risk coronary grafting, although they correlate with the need for a vasopressor.

Cardiomyocyte apoptosis and ischemic preconditioning in open heart operations.

BACKGROUND: The aim of the present study was to ascertain the percentage of left apical myocardial apoptosis in three-vessel coronary artery bypass grafting patients quantitatively and the impact of ischemic preconditioning. METHODS: Twenty-one patients with three-vessel disease who had elective coronary artery bypass grafting were randomized in a ratio of 2:1 to ischemic preconditioning (n = 14) or a control group (n = 7). The ischemic preconditioning protocol was established by two cycles of ascending aorta occlusion for 2 minutes followed by 3 minutes of reperfusion. Myocardial samples from the apex of the left ventricle were taken using a Tru-Cut needle before aortic cross-clamping and immediately after declamping. The percentage of apoptosis was analyzed by TUNEL methods. Data on hemodynamics and biochemical markers were collected. RESULTS: Low levels of myocardial apoptosis were found before the operation (0.01% +/- 0.00%). During the early reperfusion period, the percentage of myocardial apoptotic cells significantly increased (0.15% +/- 0.05%, p = 0.008). Ischemic preconditioning significantly improved cardiac index and right ventricular ejection fraction recovery after the operation (p = 0.036 and 0.001 respectively, repeated measure) but had no effect on myocardial apoptosis before and after the operation (0.01 +/- 0.00 versus 0.01 +/- 0.00, p = 0.658 and 0.12% +/- 0.04% versus 0.23% +/- 0.14%, p = 0.302). CONCLUSIONS: Cardioplegic myocardial ischemia during open heart operation was associated with induction of cardiomyocyte apoptosis in humans. Attenuation of postoperative cardiac dysfunction by ischemic preconditioning appeared to be independent of apoptosis.

Perioperative and postoperative arrhythmia in three-vessel coronary artery disease patients and antiarrhythmic effects of ischemic preconditioning.

OBJECTIVE: Sudden cardiac death caused by arrhythmia remains a major unsolved problem after coronary artery bypass grafting (CABG). Ischemic preconditioning (IP) has proved effective in suppressing ischemia reperfusion arrhythmias in animals and humans. The purpose of the present study was to establish whether IP reduces postoperative arrhythmias in three-vessel coronary artery disease patients undergoing CABG. METHODS: Forty-five patients with stable angina and three main coronary artery stenosis admitted for primary CABG surgery were randomized into an IP and a control group. The IP protocol entailed twice occluding the ascending aorta by cross-clamping for 2 min, followed by 3 min of reperfusion. Electrocardiography was continuously recorded from the day before surgery to the second postoperative day. RESULTS: During the recording, all patients developed SVES and VES after the operation. The incidences of SVT and ventricular tachycardia (VT) after surgery were 73.3 and 77.8%, respectively. IP significantly reduced VES events per hour during 2h after reperfusion. The SVT and VT incidence and events per hour were significantly lower in the IP group during 2h after reperfusion and 24h later. CONCLUSIONS: IP significantly reduced VES, SVT, and VT after surgery. The antiarrhythmic effect 24h after surgery indicates a delayed antiarrhythmic IP phenomenon in these patients. These findings would indicate that IP constitutes a potential additional myocardial protective strategy in multi-vessel diseased patients undergoing CABG.

Imbalance of pro- and anti-inflammatory cytokine responses in elderly patients after coronary artery bypass grafting.

BACKGROUND AND AIMS: Increased inflammatory activity has been observed in elderly people. The aim of this study was to determine whether cytokine responses after coronary artery bypass grafting (CABG) in elderly patients are different from those in younger patients. METHODS: Fifty-five male patients admitted for first-time elective coronary artery bypass surgery were divided into two age groups: group I, patients younger than 70 years (N=40); and group II, patients aged 70 years or older (N=15). Perioperative levels of cytokines and CK-MB were measured. Hemodynamic data were recorded. RESULTS: Marginally higher IL-6 (p=0.048) and IL-8 (p=0.041) levels were observed during the intensive care unit (ICU) stay in the elderly as compared with younger patients. Lower IL-10 levels were detected in the elderly 5 minutes after reperfusion to the myocardium (p<0.05). Although the postoperative hemodynamic change was similar in both groups, the elderly needed vasopressor treatment more often during the ICU stay. This was associated with lower IL-10 levels 5 minutes after reperfusion. CONCLUSIONS: The present results show the age-related imbalance of pro- and anti-inflammatory responses after CABG, associated with hemodynamic instability in the elderly.

Ischemic preconditioning suppresses ventricular tachyarrhythmias after myocardial revascularization.

BACKGROUND: Ventricular fibrillation (VF) and tachycardia (VT) are the common and potential life-threatening complications after CABG. Ischemic preconditioning (IP) has been proved effective in reducing ischemia reperfusion arrhythmia in animals and humans. Whether IP is effective in suppressing postoperative VF/VT in patients with CABG has not been studied. METHODS AND RESULTS: Eighty-six patients with CABG with stable and unstable 3-vessel disease were equally randomly assigned into an IP and a control group. The patients who received IP received 2 periods of 2-minute ischemia followed by 3-minute reperfusion. Twenty-four-hour electrocardiographic data were collected. IP resulted in fewer cases of VF after declamping (48.8% versus 79.1% in IP and control, P=0.004) and a shorter VF period (2.28+/-0.44 versus 4.41+/-0.51 minutes, P=0.002). The episodes of VT were significantly reduced in patients in the IP group during early reperfusion and 24 hours after reperfusion (0.65+/-0.16 versus 3.71+/-0.46, P=0.000 and 0.07+/-0.04 versus 2.12+/-1.41, P=0.002, respectively). De novo sustained VT occurred in 3 control patients as against none in the IP group after surgery. As a result, IP significantly curtailed the mechanical ventilation period and reduced the need for inotropes. CONCLUSIONS: IP significantly reduced postoperative VF/VT in patients with CABG with 3-vessel disease. Suppression of VT during early reperfusion and 24 hours after reperfusion suggests early and delayed IP phenomena in patients undergoing CABG surgery.

Cardioprotective effect of pump prime aprotinin in coronary artery bypass grafting.

BACKGROUND: Several studies have reported that high-dose aprotinin is cardioprotective in coronary surgery. The cardioprotective efficacy of low-dose aprotinin is less well defined. The present randomised study evaluated the cardioprotective and anti-inflammatory effects of pump prime aprotinin in patients undergoing coronary bypass surgery. METHODS: Sixty-four male patients admitted for first-time elective coronary artery bypass surgery were randomised into control or aprotinin groups. Patients in the aprotinin group received 280 mg of aprotinin in the pump prime. Postoperative CK-MB release, leukocyte counts and hemodynamics were recorded. Perioperative myeloperoxidase, IL-6, IL-8 and IL-10 levels were measured in a subgroup of patients (15 patients in each group). RESULTS: There were no significant differences between the groups in mechanical ventilation time and ICU and hospital stay. Postoperative bleeding was less serious in the aprotinin group than in the controls (742.0 +/- 361.1 versus 885.2 +/- 335.1 ml, p = 0.12) and CK-MB values were significantly lower (6 hrs, 35.5 +/- 11.8 versus 4.5 +/- 24.0 U/L; 24 hrs, 32.3 +/- 25.0 versus 40.2 +/- 26.8 U/L; 48 hrs, 15.9 +/- 7.0 versus 24.7 +/- 21.1 U/L; p=0.041). Perioperative hemodynamics was similar in both groups. There was a tendency towards less vasopressor and inotropes use in the pump prime aprotinin group. There was no significant difference between groups in terms of perioperative myeloperoxidase, IL-6, IL-8 and IL-10 levels. CONCLUSIONS: Pump prime aprotinin marginally limits myocardial enzyme release, but fails to limit inflammatory responses after elective coronary surgery.

Soluble adhesion molecules in coronary surgery and cardiopulmonary bypass with pump prime aprotinin.

OBJECTIVE: The purpose of the present study was to establish whether pump prime aprotinin could influence soluble adhesion molecules in patients undergoing elective coronary artery bypass surgery. DESIGN: Thirty patients admitted for first-time elective coronary artery bypass surgery were randomized into control or aprotinin groups. Patients in the aprotinin group received 280 mg of aprotinin in the pump prime. Plasma levels of soluble adhesion molecules were analyzed perioperatively. RESULTS: There were no significant changes in plasma sE-selectin after the operation in either group. Plasma sP-selectin increased significantly up to 20 h after reperfusion to the myocardium. Plasma sICAM-1 decreased in the early stage after cardiopulmonary bypass (CPB), then recovered at 4 h after reperfusion and a significant increase in sICAM-1 was observed 20 h later. There were no significant differences between the groups in postoperative changes in sP-selectin (p = 0.21) and sICAM-1 (p = 0.91). CONCLUSION: Pump prime aprotinin did not influence plasma levels of E-selectin, P-selectin and ICAM-1 in the present patients. The present results do not support the concept of an anti-inflammatory effect of pump prime aprotinin.

Cytokine Responses in Low-Risk Coronary Artery Bypass Surgery.

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