p21 protects cardiomyocytes against ischemia-reperfusion injury by inhibiting oxidative stress.

Ischemic heart disease is a major health threat, resulting in a large number of mortalities annually worldwide. Oxidative stress is one of the main causes of cell death during ischemia­reperfusion (IR) injury. Cyclin dependent kinase inhibitor 1A (known as p21) is important in protecting tissues against IR injury, however the mechanism remains unknown. In the present study, oxygen­glucose deprivation and subsequent reoxygenation (OGD/R) in H9c2 heart­derived myocytes was used as a model to study myocardial IR injury in vitro. mRNA and protein expression levels were determined by reverse transcription­quantitative polymerase chain reaction and western blotting, respectively. The levels of reactive oxygen species were measured using the fluorescence dye 2',7'­dichlorodihydrofluorescein diacetate. The present data demonstrated that p21 expression was upregulated by tumor protein p53 (p53) in H9c2 cells exposed to OGD/R. p21 protected H9c2 cells against OGD/R­induced oxidative stress. In addition, p21 mediated upregulation of NF­E2­related factor­2 (Nrf2), a regulator of antioxidant responses, which in turn suppressed cell death in H9c2 cells subjected to OGD/R. Thus, activation of the p53/p21/Nrf2 signaling pathway may be an important adaptive response that limits oxidative injury during IR.

Cardiac resynchronization therapy (CRT) with right ventricular sense triggered left ventricular pacing benefits for the hemodynamics compared with standard CRT for chronic congestive heart failure: A cross-over study.

BACKGROUND: The aim of this study was to investigate the effect of cardiac resynchronization therapy (CRT) with right ventricular (RV) sense triggered left ventricular (LV) pacing for chronic heart failure (CHF). METHODS: Thirty patients who were eligible for the Class I indication of CRT were enrolled and the informed consents were signed. Left ventricular ejection fraction (LVEF), diastolic mitral flow velocity time integral (VTI), mitral regurgitation flow VTI, and aortic valve flow VTI were measured with GE Vivid 7 (GE Medical, Milwaukee, WI, USA) before and after CRT. The echocardiographic measurements and the average annual costs of the device use were compared. RESULTS: The duration of QRS complex, the length of time used for optimization, and the average annual cost of the device use under RV sense triggered LV pacing were significantly less than that under standard biventricular (BiV) pacing (p < 0.01), while the average battery lifetime was longer. Subgroup analysis showed that LVEF, diastolic mitral flow VTI, and aortic valve flow VTI under RV sense triggered LV pacing were greater than that under standard BiV pacing with right or LV pre-activation. The average battery lifetime was significantly longer and the average annual cost of the device use was less. The mitral regurgitation flow VTI under RV sense triggered LV pacing was less than that under standard BiV pacing with RV pre-activation. CONCLUSIONS: RV sense triggered LV provides benefits for CHF patients over standard CRT in terms of maintaining the physiological atrio-ventricular delay of atrio-ventricular node and improving the acute hemodynamic effects.

Randomized and double-blind controlled clinical trial of extracorporeal cardiac shock wave therapy for coronary heart disease.

Our aim was to evaluate the safety and effectiveness of extracorporeal cardiac shock wave therapy (CSWT) for the patients with coronary heart disease (CHD) using a randomized, double-blind, controlled clinical trial design. Twenty-five patients with CHD were enrolled in this study. Fourteen of the patients were randomized into the CSWT group and 11 into the control group. We applied the CSWT procedure to each patient by using nine shock treatments during 3 months, but the shock wave (SW) energy was only applied to the patients in the CSWT group and not to the patients in the control group. Technetium-99m sestamibi myocardial perfusion, fluorine-18 fluorodeoxyglucose myocardial metabolism single-photon emission computed tomography (SPECT), and two-dimensional echocardiography were performed to identify segments of myocardial ischemia, myocardial viability, and ejection fraction before and after CSWT. We also followed the patients to evaluate adverse effects. After CSWT, the New York Heart Association class, the Canadian Cardiovascular Society angina scale, nitroglycerin dosage, myocardial perfusion and myocardial metabolic imaging scores of dual-isotope SPECT in the CSWT group were reduced significantly (P = 0.019, 0.027, 0.039, 0.000, 0.001, respectively), and the Seattle Angina Questionnaire scale, 6-min walking test, and left ventricular ejection fraction were increased significantly (P = 0.021, 0.024, 0.016, respectively) compared with those before the SW treatment. All of the parameters in the control group did not change significantly after the treatment (all P > 0.05). No serious adverse effects of CSWT were observed. Cardiac shock wave therapy is a safe and effective treatment for CHD patients.

A modified regimen of extracorporeal cardiac shock wave therapy for treatment of coronary artery disease.

BACKGROUND: Cardiac shock wave therapy (CSWT) improves cardiac function in patients with severe coronary artery disease (CAD). We aimed to evaluate the clinical outcomes of a new CSWT treatment regimen. METHODS: The 55 patients with severe CAD were randomly divided into 3 treatment groups. The control group (n = 14) received only medical therapy. In group A ( n = 20), CSWT was performed 3 times within 3 months. In group B ( n = 21), patients underwent 3 CSWT sessions/week, and 9 treatment sessions were completed within 1 month. Primary outcome measurement was 6-minute walk test (6MWT). Other measurements were also evaluated. RESULTS: The 6MWT, CCS grading of angina, dosage of nitroglycerin, NYHA classification, and SAQ scores were improved in group A and B compared to control group. CONCLUSIONS: A CSWT protocol with 1 month treatment duration showed similar therapeutic efficacy compared to a protocol of 3 months duration. CLINICAL TRIAL REGISTRY: We have registered on ClinicalTrials.gov, the protocol ID is CSWT IN CHINA.

[Effects of extracorporeal cardiac shock wave therapy in patients with ischemic heart failure].

OBJECTIVE: To evaluate the feasibility, safety and efficiency of extracorporeal cardiac shock wave therapy (CSWT) in patients with ischemic heart failure. METHODS: Fifty patients with ischemic heart failure and left ventricular ejection fraction (LVEF) < 50% were randomized to CSWT (shots/spot at 0.09 mJ/mm(2) for 9 spots, 9 times within 3 month) or control group. Dual isotope simultaneous acquisition single-photon emission computed tomography with (99)Tc(m)-sestamibi/(18)F-fluorodeoxyglucose ((99)Tc(m)-MIBI/(18)F-FDG) was performed before randomization and at 1 month after CSWT/control to locate and evaluate viable myocardium region. Canadian cardiovascular society (CCS) class sores, NYHA, Seattle Angina Questionnaire (SAQ), 6-min walk test (6 MWT), left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD) and the dosage of nitroglycerin use were compared between two groups at each time point. RESULTS: All patients completed the study protocol without procedural complications. At 1 month, patients in CSWT group experienced improvement in NYHA (P < 0.01), CCS (P < 0.01), SAQ (P = 0.021), 6 MWT (P = 0.012) and dosage of nitroglycerin use (P < 0.01) compared to baseline. LVEF [45.0 (39.0, 48.0) vs. 47.0 (42.0, 50.0) P = 0.001], LVEDD [58.0 (56.0, 59.0) vs. 56.0 (55.0, 58.0) P = 0.002], summed perfused score [23.0 (20.5, 24.5) vs. 20.0 (18.0, 22.0) P < 0.01] and metabolic score [25.0 (23.0, 26.0) vs. 24.0 (21.5, 25.0) P = 0.028] were also improved in CSWT group. All these parameters remained unchanged in control group between baseline and at 1 month. CSWT was independent factor for improved cardiac function, quality of life and echocardiography parameters after adjusting for known factors which might affect outcome. CONCLUSION: CSWT could improve symptom, cardiac function, quality of life and exercise tolerance in patients with ischemic heart failure, CSWT might serve as a new, non-invasive, safe and efficient therapy for these patients.