Differential regenerative capacity of neonatal mouse hearts after cryoinjury.

Neonatal mouse hearts fully regenerate after ventricular resection similar to adult zebrafish. We established cryoinjury models to determine if different types and varying degrees of severity in cardiac injuries trigger different responses in neonatal mouse hearts. In contrast to ventricular resection, neonatal mouse hearts fail to regenerate and show severe impairment of cardiac function post transmural cryoinjury. However, neonatal hearts fully recover after non-transmural cryoinjury. Interestingly, cardiomyocyte proliferation does not significantly increase in neonatal mouse hearts after cryoinjuries. Epicardial activation and new coronary vessel formation occur after cryoinjury. The profibrotic marker PAI-1 is highly expressed after transmural but not non-transmural cryoinjuries, which may contribute to the differential scarring. Our results suggest that regenerative medicine strategies for heart injuries should vary depending on the nature of the injury.

RNA steady-state defects in myotonic dystrophy are linked to nuclear exclusion of SHARP.

We describe a new mechanism by which CTG tract expansion affects myotonic dystrophy (DM1). Changes to the levels of a panel of RNAs involved in muscle development and function that are downregulated in DM1 are due to aberrant localization of the transcription factor SHARP (SMART/HDAC1-associated repressor protein). Mislocalization of SHARP in DM1 is consistent with increased CRM1-mediated export of SHARP to the cytoplasm. A direct link between CTG repeat expression and SHARP mislocalization is demonstrated as expression of expanded CTG repeats in normal cells recapitulates cytoplasmic SHARP localization. These results demonstrate a role for the inactivation of SHARP transcription in DM1 biology.

The association between Chlamydia pneumoniae DNA in arherosclerotic plaque and major risk factors in patients undergoing coronary artery bypass grafting.

BACKGROUND AND AIM: This study was conducted to investigate the prevalence of Chlamydia pneumoniae pathogen inside the atherosclerotic plaque of patients undergoing CABG by using PCR assay and to determine whether there is any association between the presence of bacteria in atherosclerotic lesions and classical coronary risk factors. METHODS: In a cross-sectional study, 102 patients (20 to 79 years old; 73.5% male) undergoing CABG were evaluated in terms of major coronary risk factors and the presence of Chlamydia pneumoniae. RESULTS: Chlamydia pneumoniae was found in 23.4% of coronary plaque specimens. Of these, two patients had no risk factor and the rest of the patients had 1 to 3 risk factors. Patients with positive PCR were more likely to have hypercholesterolaemia (p = 0.009) and low HDL levels (p = 0.000) in comparison with the PCR-negative group. There were no statistical differences for other risk factors. CONCLUSION: Our results imply the synergic contribution of Chlamydia pneumoniae DNA and known dyslipidaemia to the development of atherosclerotic lesions in patients undergoing CABG.

Evaluation of the effects of ischemic preconditioning with a short reperfusion phase on patients undergoing a coronary artery bypass graft.

PURPOSE: This study was conducted to evaluate the effects of ischemic preconditioning (IP) with a short period of reperfusion (2 min) during brief ischemic preconditioning (6 min) on patients undergoing coronary artery bypass grafting (CABG). METHODS: In a randomized controlled trial, 40 patients undergoing on-pump CABG with cold blood cardioplegia were allocated into two groups, one IP and one control. IP was induced by 2 cycles of ascending aorta clamping (2 min for each) followed by two reperfusion phases (1 min for each). Left ventricular ejection fraction (LVEF) was measured before and after surgery. Creatine phosphokinase (CK) and CK-MB were measured 12 hrs before surgery, immediately after aortic clamping, and 24 hrs after CABG. Postoperative myocardial infarction (MI), ventricular arrhythmia, duration of inotropic support, and hemodynamic parameters were also noted. RESULTS: More patients in the control group needed inotropic support (65% vs. 40%, P<0.05). Moreover, duration of inotropic support was longer in the control group (9 ± 1.2 vs. 3.8 ± 1.4 hrs, P<0.05). There were no significant differences between two groups regarding development of ventricular arrhythmia, MI, values of CK, CK-MB, and postoperative LVEF. No patient needed an intra-aortic balloon pump, and no deaths occurred. CONCLUSION: A short period of reperfusion phase declined post-CABG inotrope requirements; however, it did not reduce the cardiac enzymes. Our results suggested that reperfusion should be longer than 2 min to be capable of reducing cardiac enzymes.

Effect of milrinone on short-term outcome of patients with myocardial dysfunction undergoing coronary artery bypass graft: A randomized controlled trial.

BACKGROUND: Myocardial dysfunction needing inotropic support is a typical complication after on-pump cardiac surgery. In this study, we evaluate the effect of milrinone on patients with ventricular dysfunction undergoing coronary artery bypass graft (CABG). METHODS: Seventy patients with impaired left ventricular function [left ventricular ejection fraction (LVEF) < 35%] undergoing on-pump CABG were enrolled. Patients were randomized to receive either an intraoperative bolus of milrinone (50 microg/kg) or saline as placebo followed by a 24-hour infusion of each agent (0.5 microg/kg/min). Hemodynamic parameters and transthoracic echocardiographic measurement of systolic and diastolic functions were the variables evaluated. RESULTS: Serum levels of creatine phosphokinase (CPK), the MB isoenzyme of creatine kinase (CK-MB), occurrence of myocardial ischemia or infarction, and mean duration of using inotropic agents were significantly lower in the milrinone group (p < 0.05). There were no significant differences between the two groups regarding the development of ventricular arrhythmia, duration of cardiopulmonary bypass, intra-aortic balloon pump and inotropic support requirement, duration of mechanical ventilation, duration of intensive care unit stay and mortality rate. Although mean pre-operative LVEF was significantly lower in the milrinone group, there was no significant difference between post-operative LVEFs. CONCLUSIONS: We suggest that perioperative administration of milrinone in patients undergoing on-pump CABG, especially those with low LVEF, is beneficial.