Zhong-Kai Wu

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.

Beneficial Effects of Ischemic Preconditioning on Right Ventricular Function After Coronary Artery Bypass Grafting

BACKGROUND Preservation of right ventricular myocardium is unsatisfactory in patients with critical stenosis or occlusion of the right coronary artery. The aim of this study was to investigate whether ischemic preconditioning (IP) improved the recovery of right ventricular function after coronary artery bypass grafting. METHODS Forty patients with three-vessel disease who had coronary artery bypass grafting were randomly assigned to the IP group (n = 20) or control group (n = 20). In the IP group, two cycles of two minutes of ischemia after three minutes of reperfusion were given before cross-clamping. Hemodynamic data were collected. Right ventricular ejection fraction was measured by thermodilution. RESULTS Right ventricular ejection fraction and right ventricular systolic volume index were decreased post-operatively (lowest value at 6 hours postoperatively). The changes in right ventricular ejection fraction were significantly milder in the IP group postoperatively (p = 0.012). The decrease in right ventricular systolic volume index postoperatively was also less in IP patients (p = 0.002). Fewer inotropic drugs were used in the IP group compared with controls. CONCLUSIONS Ischemic preconditioning had a myocardial protective effect on recovery of right ventricular contractility in patients who had coronary artery bypass grafting.

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.

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.

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.

Ischaemic preconditioning has a beneficial effect on left ventricular haemodynamic function after a coronary artery biopass grafting operation.

OBJECTIVE Ischaemic preconditioning (IP) is the most effective procedure for endogenous myocardial protection. However, studies on the effects of IP in cardiac surgery are rare and controversial. The present aim was to investigate whether IP improves the haemodynamic recovery of CABG patients. DESIGN The study included 40 stable CABG patients with 3-vessel disease, randomized into an IP group (n = 20) and a control group (n = 20). In the IP group two cycles of 2-min ischaemia following 3-min reperfusion before cross-clamping were induced. The haemodynamics of the patients were followed-up to the first postoperative morning. RESULTS The cardiac index decreased at 1 and 6 h after surgery in the control group but increased in the IP group (-0.33 vs 0.09 l/min/m2, p = 0.02 and -0.15 vs 0.57 l/min/m2, p = 0.001, respectively). Depressions in the left ventricular stroke work index and the right ventricular stroke work index at 6 h after surgery were more severe in controls and were statistically significant (p = 0.049 and 0.007, respectively). Less inotropic support was used in the IP group. There were no differences in serum CK-MB, cardiac troponin I, myoglobin or lactate values between the two groups. CONCLUSION IP has a beneficial effect on left ventricular haemodynamic recovery after a CABG operation.

Protective effect of unstable angina in coronary artery bypass surgery

OBJECTIVE To test the hypothesis that recent ischaemic episodes in unstable cases have a protective effect on coronary artery bypass graft (CABG) patients. MATERIALS AND METHODS Twenty unstable patients with ischaemic episodes within 3 days before operation were compared with 20 stable patients. Haemodynamic data were monitored up to the first postoperative day. Biochemical markers were measured up to the second postoperative day. RESULTS The cardiac index decreased at 1 and 6 h after declamping in the stable group (89% and 97% of baseline) but increased in unstable patients (104% and 122%, p =0.038 and 0.036, respectively). The depression in the right ventricular stroke work index was significantly attenuated in the unstable group (58%, 67% and 83% in stable and 90%, 97% and 117% in unstable patients, p = 0.027, 0.010 and 0.049 at 1 and 6 h after declamping and 1st POD). The release of cardiac troponin I (CTnI) and CK-MB was significantly lower in the unstable group at 6 h after declamping (5.6 +/- 2.9 and 19.0 +/- 6.3 microg/l in unstable vs 17.4 +/- 9.6 and 25.8 +/- 12.3 microg/l in stable patients, p = 0.000 and 0.039, respectively). CONCLUSION Recent unstable angina before CABG might act as an ischaemic preconditioning stimulus and could improve haemodynamic function and cellular viability. Delayed preconditioning most likely causes this protective effect.Objective—To test the hypothesis that recent ischaemic episodes in unstable cases have a protective effect on coronary artery bypass graft (CABG) patients. Materials and methods —Twenty unstable patients with ischaemic episodes within 3 days before operation were compared with 20 stable patients. Haemodynamic data were monitored up to the first postoperative day. Biochemical markers were measured up to the second postoperative day. Results—The cardiac index decreased at 1 and 6 h after declamping in the stable group (89% and 97% of baseline) but increased in unstable patients (104% and 122%, p = 0.038 and 0.036, respectively). The depression in the right ventricular stroke work index was significantly attenuated in the unstable group (58%, 67% and 83% in stable and 90%, 97% and 117% in unstable patients, p = 0.027, 0.010 and 0.049 at 1 and 6 h after declamping and 1st POD). The release of cardiac troponin I (CTnI) and CK-MB was significantly lower in the unstable group at 6 h after declamping (5.6 2.9 and 19.0 6.3mg/l in unstable vs 17.4 9.6 and 25.8 12.3mg/l in stable patients, p = 0.000 and 0.039, respectively). Conclusion—Recent unstable angina before CABG might act as an ischaemic preconditioning stimulus and could improve haemodynamic function and cellular viability. Delayed preconditioning most likely causes this protective effect.

Atrial fibrillation alters the microRNA expression profiles of the left atria of patients with mitral stenosis

BackgroundStructural changes of the left and right atria associated with atrial fibrillation (AF) in mitral stenosis (MS) patients are well known, and alterations in microRNA (miRNA) expression profiles of the right atria have also been investigated. However, miRNA changes in the left atria still require delineation. This study evaluated alterations in miRNA expression profiles of left atrial tissues from MS patients with AF relative to those with normal sinus rhythm (NSR).MethodsSample tissues from left atrial appendages were obtained from 12 MS patients (6 with AF) during mitral valve replacement surgery. From these tissues, miRNA expression profiles were created and analyzed using a human miRNA microarray. Results were validated via reverse-transcription and quantitative PCR for 5 selected miRNAs. Potential miRNA targets were predicted and their functions and potential pathways analyzed via the miRFocus database.ResultsThe expression levels of 22 miRNAs differed between the AF and NSR groups. Relative to NSR patients, in those with AF the expression levels of 45% (10/22) of these miRNAs were significantly higher, while those of the balance (55%, 12/22) were significantly lower. Potential miRNA targets and molecular pathways were identified.ConclusionsAF alters the miRNA expression profiles of the left atria of MS patients. These findings may be useful for the biological understanding of AF in MS patients.

Ellagic acid prevents monocrotaline-induced pulmonary artery hypertension via inhibiting NLRP3 inflammasome activation in rats.

BACKGROUND Pulmonary artery hypertension (PAH) is characterized by vascular remodeling, high pulmonary blood pressure, and right ventricular hypertrophy. Oxidative stress, inflammation and pulmonary artery remodeling are important components in PAH. Ellagic acid (EA) is a phenolic compound with anti-oxidative, anti-inflammatory, and anti-proliferative properties. This study aimed to investigate whether EA could prevent the development of monocrotaline (MCT)-induced PAH in rats. METHODS Male Sprague-Dawley rats received EA (30 and 50mg/kg/day) or vehicle one day after a single-dose of monocrotaline (MCT, 60mg/kg). Hemodynamic changes, right ventricular hypertrophy, and lung morphological features were assessed 4weeks later. Activation of the NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome pathway in the lungs was assessed using Western blot analysis. RESULTS MCT induced PAH, oxidative stress, and NLRP3 inflammasome activation in vehicle-treated rats. EA reduced the right ventricle systolic pressure, the right ventricular hypertrophy and the wall thickness/external diameter ratio of the pulmonary arteries compared with vehicle. EA also inhibited the MCT-induced elevation of oxidative stress, NLRP3, and caspase-1, IL-β in the lungs and the elevated levels of brain natriuretic peptide (BNP) and inflammatory cytokines in serum. CONCLUSIONS Ellagic acid ameliorates monocrotaline-induced pulmonary artery hypertension via exerting its anti-oxidative property inhibiting NLRP3 inflammasome signal pathway in rats.

Comparative expression profiles of microRNA in left and right atrial appendages from patients with rheumatic mitral valve disease exhibiting sinus rhythm or atrial fibrillation

BackgroundThe atrial fibrillation (AF) associated microRNAs (miRNAs) were found in the right atrium (RA) and left atrium (LA) from patients with rheumatic mitral valve disease (RMVD). However, most studies only focus on the RA; and the potential differences of AF-associated miRNAs between the RA and LA are still unknown. The aim of this study was to perform miRNA expression profiles analysis to compare the potential differences of AF-associated miRNAs in the right atrial appendages (RAA) and left atrial appendages (LAA) from RMVD patients.MethodsSamples tissues from the RAA and LAA were obtained from 18 RMVD patients (10 with AF) during mitral valve replacement surgery. From these tissues, miRNA expression profiles were created and analyzed using a human miRNA microarray. Then, the results were validated using qRT-PCR analysis for 12 selected miRNAs. Finally, potential targets of 10 validated miRNAs were predicted and their functions and potential pathways were analyzed using the miRFocus database.ResultsIn RAA, 65 AF-associated miRNAs were found and significantly dysregulated (i.e. 28 miRNAs were up-regulated and 37 were down-regulated). In LAA, 42 AF-associated miRNAs were found and significantly dysregulated (i.e. 22 miRNAs were up-regulated and 20 were down-regulated). Among these AF-associated miRNAs, 23 of them were found in both RAA and LAA, 45 of them were found only in RAA, and 19 of them were found only in LAA. Finally, 10 AF-associated miRNAs validated by qRT-PCR were similarly distributed in RAA and LAA; 3 were found in both RAA and LAA, 5 were found only in RAA, and 2 were found only in LAA. Potential miRNA targets and molecular pathways were identified.ConclusionsWe have found the different distributions of AF-associated miRNAs in the RAA and LAA from RMVD patients. This may reflect different miRNA mechanisms in AF between the RA and LA. These findings may provide new insights into the underlying mechanisms of AF in RMVD patients.