Changes in protein and gene expression of angiotensin II receptors (AT1 and AT2) in aorta of diabetic and hypertensive rats

Diabetes and hypertension have been associated with cardiovascular diseases and stroke. Some reports have related the coexistence of hypertension and diabetes with increase in the risk of developing vascular complications. Recently some studies have shown results suggesting that in the early stages of diabetes and hypertension exist a reduced functional response to vasopressor agents like angiotensin II (Ang II), which plays an important role in blood pressure regulation mechanism through the activation of its AT₁ and AT₂ receptors. For that reason, the aim of this work was to study the gene and protein expression of AT₁ and AT₂ receptors in aorta of diabetic SHR and WKY rats. Diabetes was induced by the administration of streptozotocin (60?mg/kg i.p.). After 4 weeks of the onset of diabetes, the protein expression was obtained by western blot and the mRNA expression by RT-PCR. Our results showed that the hypertensive rats have a higher mRNA and protein expression of AT₁ receptors than normotensive rats while the AT₂ expression remained unchanged. On the other hand, the combination of diabetes and hypertension increased the mRNA and protein expression of AT₁ and AT₂ receptors significantly. In conclusion, our results suggest that diabetes with hypertension modifies the mRNA and protein expression of AT₁ and AT₂ receptors. However, the overexpression of AT₂ could be associated with the reduction in the response to Ang II in the early stage of diabetes.     

Early thrombolysis in acute myocardial infarction: limitation of infarct size and improved survival

The effect of thrombolysis in acute myocardial infarction on infarct size, left ventricular function, clinical course and patient survival was studied in a randomized trial comparing thrombolysis (269 patients) with conventional treatment (264 control patients). All 533 patients were admitted to the coronary care unit within 4 hours after the onset of symptoms related to the infarction. Baseline characteristics were similar in both groups. Informed consent was requested only of patients allocated to thrombolysis; no angiography was performed in 35. The infarct-related artery was patent in 65 patients and occluded in 169. Recanalization was achieved in 133 patients. The median time to angiographic documentation of vessel patency was 200 minutes after the onset of symptoms. The clinical course in the coronary care unit was more favorable after thrombolysis. Infarct size, estimated from myocardial enzyme release, was 30% lower after thrombolysis. In patients admitted within 1 hour after the onset of symptoms the reduction of infarct size was 51%, in those admitted between 1 and 2 hours it was 31% and in those admitted later than 2 hours it was 13%. Left ventricular function measured by radionuclide angiography before hospital discharge was better after thrombolysis (ejection fraction 48 +/- 15%) than in control patients (44 +/- 15%). Similar improvement was observed in patients with a first infarct only (thrombolysis 50 +/- 14%, control subjects 46 +/- 15%), in patients with anterior infarction (thrombolysis 44 +/- 16%, control subjects 35 +/- 14%) and in those with inferior infarction (thrombolysis 52 +/- 12%, control subjects 49 +/- 12%). Similar results were obtained by contrast angiography. Mortality was lower after thrombolysis. After 28 days 16 patients allocated to thrombolysis and 31 control patients had died. One year survival rates were 91 and 84%, respectively. On the other hand, nonfatal reinfarction occurred more frequently after thrombolysis (36 patients) than in control subjects (16 patients). Early thrombolysis by intracoronary streptokinase leads to a smaller infarct size estimated by enzyme release, preserves left ventricular function at the second week and leads to improved 1 year survival.     

Neuroprotective effect of carnosine in the olfactory bulb after vanadium inhalation in a mouse model

Carnosine (β‐alanyl‐L‐histidine) is synthesized in the olfactory system, has antioxidant activity as a scavenger of free radicals and has been reported to have neuroprotective action in diseases which have been attributed to oxidative damage. In neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, impairment of olfactory function has been described. Vanadium derivatives are environmental pollutants, and its toxicity has been associated with oxidative stress. Vanadium toxicity on the olfactory bulb was reported previously. This study investigates the neuroprotective effect of carnosine on the olfactory bulb in a mice model of vanadium inhalation. Male mice were divided into four groups: vanadium pentoxide (V₂O₅) [0.02 mol/L] inhalation for one hour twice a week; V₂O₅ inhalation plus 1 mg/kg of carnosine administered daily; carnosine only, and the control group that inhaled saline. The olfactory function was evaluated using the odorant test. Animals were sacrificed four weeks after exposure. The olfactory bulbs were dissected and processed using the rapid Golgi method; cytological and ultrastructural analysis was performed and malondialdehyde (MDA) concentrations were measured. The results showed evidence of olfactory dysfunction caused by vanadium exposure and also an increase in MDA levels, loss of dendritic spines and necrotic neuronal death in the granule cells. But, in contrast, vanadium‐exposed mice treated with carnosine showed an increase in dendritic spines and a decrease in neuronal death and in MDA levels when compared with the group exposed to vanadium without carnosine. These results suggest that dendritic spine loss and ultrastructural alterations in the granule cells induced by vanadium are mediated by oxidative stress and that carnosine may modulate the neurotoxic vanadium action, improving the olfactory function.     

Characteristics of bifocal pacing: right ventricular apex versus outflow tract. An interim analysis

Bifocal RIGHT ventricular stimulation (BRIGHT) is an ongoing, randomized, single-blind, crossover study of atrial synchronized bi-right ventricular (RV) pacing in patients in New York Heart Association heart failure functional class III, a left ventricular ejection fraction <35%, left bundle branch block and QRS complexes >/=120 ms. This analysis compared the electrical and handling characteristics, and the complications of pacing at the RV apex (Ap) with passive, versus RV outflow tract (OT) with active fixation leads. A mean of 1.6 +/- 0.9 and 2.2 +/- 2.0 attempts were needed to position the Ap and OT leads, respectively (ns). R-wave amplitudes at Ap versus OT were 23 +/- 13 mV versus 14 +/- 8 mV (n = 36, P < 0.001). R-wave amplitudes at the Ap remained stable between implant and M7. R-wave amplitudes at the OT could not be measured after implantation. In two patients, atrioventricular block occurred during active fixation at the OT. Conduction recovered spontaneously within 4 months. Ventricular fibrillation was induced in one patient during manipulation of an Ap lead in the RV. Marked differences were found between leads positioned in the OT versus Ap, partly related to the difference in lead design. Mean R-wave amplitude was higher at the Ap that at the OT. Ease and success rate of lead implant was similar in both positions.     

Ice mapping during cryothermal ablation of accessory pathways in WPW: the role of the temperature time constant.

AIM: Cryothermal energy has the ability reversibly to demonstrate loss of function with cooling, ice mapping, at less deep temperatures. The purpose of this study was to investigate the time course of the temperature during ice mapping of accessory pathways. METHODS AND RESULTS: Thirteen patients with the Wolff-Parkinson-White (WPW) syndrome underwent cryoablation. After identification of a prospective ablation site, ice mapping was performed by cooling the tip to a minimum of -30 degrees C. Successful ice mapping was defined by loss of accessory pathway (AP) conduction. A total of 104 ice maps were analyzed. Successful ice mapping was demonstrated in 17 attempts. There was no significant difference in mapping temperature between successful and unsuccessful ice mapping (-29.4+/-3.2 degrees Celsius vs -30.4+/-1.7 degrees Celsius). The temperature time constant tau during successful ice mapping was significantly shorter compared with unsuccessful ice mapping (7.0+/-1.1 s vs 10.1+/-1.3 s; P<0.0001). The response time (RT) to mapping temperature of -30 degrees C was significantly prolonged in unsuccessful ice mapping attempts (35.8+/-4.5 s vs 53.5+/-11.0 s; P<0.0001). Significant correlations were found between successful ice mapping and the temperature time constant, and between RT and the temperature time constant (P<0.001). CONCLUSION: The ability to identify prospective ablation sites by ice mapping was demonstrated. Successful ice mapping attempts were characterized by a short temperature time constant and a short response time to mapping temperature with a sudden disappearance of pathway conduction.