Journal of Cardiothoracic-Renal Research最新文献

This communication provides an insight that there is a differential response to stress by blood, which may directly reflect upon the induction of a proinflammatory state, with the goal of defining the sequence of oxido-inflammatory events that occur during extracorporeal circulation (ECC). In particular, we discussed if oxidative stress per se is one of the earliest pathophysiological events that occurs in ECC even before the inflammatory process sets in. The mechanism might involve the early activation of neutrophils, the most likely source of free radicals during the initial stages of ECC. However, the early increase in the oxidative stress (formation of 3-nitrotyrosine and lipid peroxidation) even before the initiation of ECC at a time when neutrophils are not yet to be activated, may suggest the existence of other factors responsible for the early oxidative stress.

Encouraged by the initial in vivo and clinical data on cardiac stem cell transplantation, the number of conducted clinical studies has increased exponentially. Pre-transplantation differentiation may provide, beyond proof of principal, more efficient cellular repopulation. This review concerns parameters implicated in transdifferentiation in vitro, besides cell medium composition and cytokines/growth factors. These include various chemicals, extracellular matrix cues, coculture assays and physical stimuli. Identification of all determinants in this process and possible interactions will augment in developing efficient protocols for targeted stem cell differentiation towards the cardiomyocyte lineage prior to transplantation.

Background

This study determined if patients with acutely decompensated heart failure (HF) have abnormal regional tissue oxygenation when compared with stable outpatients and if values change with treatment.

Methods

We prospectively used differential absorption spectroscopy to measure the subcutaneous tissue hemoglobin oxygen saturation (S_tO₂), both at presentation and discharge in patients admitted with acutely decompensated systolic HF. These values were compared with a convenience sample of stable HF patients to determine if admitted patients have different S_tO₂ values that, after undergoing inpatient treatment, approach those of the stable HF population.

Results

Stable outpatients (n = 45) had significantly higher S_tO₂ values than inpatients (n = 20), both at admission (p < 0.006) and discharge (p < 0.0002). There were no significant differences in the discharge and admission S_tO₂ values. Four inpatients died of HF related causes and 6 were readmitted with HF within 6 months.

Conclusions

Patients with acutely decompensated HF have significantly decreased tissue oxygenation that is lower than those found in the stable outpatient population and does not respond to inpatient treatment. Measurement of subcutaneous tissue hemoglobin oxygen saturation may enable clinicians to diagnose and treat HF more effectively.

Background

Oxidative damage induced by reperfusion is responsible for increased morbidity and mortality following lung transplantation. A stable and deleterious DNA adduct, 8-oxogaunine (8-oxoG) results due to oxidative DNA damage. Mut-Y homologue (MYH) is a DNA repair enzyme promoting DNA reconstruction through the mismatch repair pathway to repair 8-oxoG lesion. We investigated the role of DNA mismatch repair pathway mediated by MYH in the setting of lung ischemia and reperfusion.

Methods

Left lungs of the adult Sprague Dawley rats were subjected to 1 h ischemia and 2 and 4 h reperfusion. Un-operated animals served as controls. Quantification of 8-oxoG was performed using immunohistochemistry (IHC) and MYH was analyzed by Western blot. Apoptosis was assessed by caspase-3 levels.

Results

Indices of inflammation and permeability were raised in both reperfusion groups. There was significant increase in DNA damage as reflected by positive 8-oxoG staining in 2 h (22% increase) and 4 h reperfusion (31% increase) compared to control (p < 0.01). MYH staining by IHC was significantly reduced in 2 and 4 h reperfusion compared to controls (p < 0.05). Down regulation of DNA repair enzyme (MYH) was mirrored functionally by decreased protein levels in lung tissues subjected to reperfusion compared to controls. Increasing apoptosis was detected in the reperfusion groups as reflected by caspase-3 IHC and protein estimation by Western blot.

Conclusion

Reperfusion leads to increased DNA damage and down regulation of DNA mismatch repair pathway in a model of ischemia and reperfusion in lungs. Gene therapy targeted at this pathway may prove an attractive therapeutic intervention to reduce reperfusion injury in lung transplantation.

Recent developments in the field of regenerative stem cell therapy for ischaemic heart disease have lead to an explosion in the clinical trial realm. At present no consensus exists regarding, amongst others, the optimal cell type as well as the underlying mechanism of action for any clinical improvement observed. As de novo reconstitution of myocardial tissue from multipotent stem cells is one of the working theories, the transdifferentiation potential of cellular populations under investigation into cardiomyocyte lineage phenotypes must ideally be assessed in preclinical bench work. Culture medium composition and a variety of growth factors are crucial determinants in this process. We discuss all relevant data acquired from in vitro work.

Spinal cord ischemia leading to paraplegia is a rare, sporadic, but devastating complication of surgery on the thoracoabdominal aorta. Our patient, a 69-year-old man, succumbed from a stroke on the third hospital day following surgical repair. He also had bilateral leg paralysis. At autopsy done 4 h after death there were remarkable differences between the thoracic or normally perfused spinal cord and the lumbar potentially ischemia or reperfused spinal cord. The measurements of injury were small in the thoracic spinal cord and extensive in the lumbar spinal cord DNA D/R. Apoptotic cell numbers and apoptosis-related enzymes such as caspase-3 were increased in the lumbar spinal cord. These findings duplicated those we reported in the rabbit subjected to 30 min of aortic occlusion and reperfusion injury. This is the first report in humans documenting DNA oxidative injury and apoptosis in ischemia–reperfusion injury of the spinal cord.

While previous studies demonstrated that angiotensin II is a potent vasoconstrictor and mitogenic factor, the effect of angiotensin II on apoptosis in vascular smooth muscle cells remain controversial. Therefore, the current study was designed to investigate the action of angiotensin II on apoptosis in human vascular smooth muscle cells. Human saphenous vein was obtained from coronary artery bypass surgery (n = 6) and was minced and incubated in the special tissue culture system in the absence or presence of angiotensin II (10⁻⁷ M) for 24 h. These studies were repeated with co-incubation of losartan (AT-1 receptor antagonist, 10⁻⁶ M) or PD-123319 (AT-2 receptor antagonist, 10⁻⁶ M). To detect the in situ DNA fragmentation, TUNEL staining was performed. TUNEL staining demonstrated that angiotensin II increased apoptosis in human vascular smooth muscle cells. This action of angiotensin II was enhanced by losartan and attenuated by PD-123319. Furthermore, co-incubation with both losartan and PD-123319 significantly reduced apoptosis levels. In conclusion, these data demonstrated that angiotensin II has potent apoptotic effect in human vascular smooth muscle cells through both AT-1 and AT-2 receptors. Furthermore, angiotensin II through AT-2 receptor has more potent apoptotic action in human vascular smooth muscle cells. This study indicated that angiotensin II plays an important role in the processes of apoptosis via angiotensin II receptors in human vascular smooth muscle cells.