Acute cardiotoxicity induced by doxorubicin in right ventricle is associated with increase of oxidative stress and apoptosis in rats.

Doxorubicin (DOX) is one of the most effective chemotherapeutic agents, but its efficiency is seriously limited by the risk of developing cardiomyopathy. The most recognized cardiotoxic effect is left ventricular (LF) dysfunction, but MRI and echocardiography data demonstrated significant right ventricle (RV) function impairment. In order to clarify this aspect, the present study investigated the potential of DOX to induce acute RV cardiotoxicity at the same time as LV impairment. Rats were intraperitoneally (i.p.) injected with a single dose of 15 mg/kg DOX. DOX-treated rats were characterized by decreased body and heart weights, elevated levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) activities compared to controls. Biochemical analyses on RV tissue revealed that the level of malondialdehyde (MDA) was significant increased (p<0.05) and activities of catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPX) antioxidant enzymes were decreased by 13%, 27% and 18%, respectively, compared to control. Histopathogical and electron microscopic studies revealed DOX-induced damage in both ventricles and an increase of interstitial collagen fibers compared to controls (p<0.001), whereas immunohistochemical analysis showed weak and irregular desmin expression. Furthermore, mitochondrion-induced apoptotic pathways were also activated in both ventricles, as reflected by the up-regulation of Bax/Bcl-2 mRNA expression ratio (p<0.001) and increase of Bax and caspase-3 protein expression, as well as by the significant elevation of TUNEL positive nuclei, compared to controls (p<0.001). The results showed that DOX exerted RV toxic effects at the same time as those reported in the LV, which might be mediated through the mitochondrial-dependent apoptosis.

Chrysin attenuates cardiomyocyte apoptosis and loss of intermediate filaments in a mouse model of mitoxantrone cardiotoxicity.

Chrysin (CHR) is a natural flavonoid and is present in high concentration in honey, propolis and many plant extracts. The aim of the present study was to evaluate the effects of CHR to reduce cardiomyocyte apoptosis and loss of intermediate filaments in a mouse model of mitoxantrone cardiotoxicity. Morphology of the cardiomyocytes was determined by optic and transmission electron microscopy and biochemistry methods. The expression of Bcl-2, Bax and Caspase-3 were assessed by immunofluorecence. Tunel assay was used to assess apoptosis in cardiomyocytes. In addition, the distribution of desmin protein was evaluated using immunohistochemistry. Our results show that MTX treatment significantly increased serum levels of creatine kinase isoenzyme (CK-MB), indicator of cardiac injury and withdrawn under CHR protection. Expression levels of Bcl-2 decreased, while those of Bax and caspase-3 increased following MTX treatment. 50 mg/kg of daily CHR intake reduced Bax and caspase-3 immunopositivity and restored Bcl-2 levels to a value comparable to the control. TUNEL (+) cardiomyocyte nuclei of MTX group showed typical signs of apoptosis which almost completely disappeared in response to 50 mg/kg CHR treatment. In parallel, an irregular distribution and a weak expression of desmin is associated with MTX induced cardiotoxic effects which was also restored by CHR treatment. In conclusion chrysin inhibits MTX-triggered cardiomyocyte apoptosis via multiple pathways, including decrease of the Bax/Bcl-2 ratio and caspase-3 expression along with preservation of the desmin disarray.

[Lower limb revascularization--a continuous challenge]. / Revascularizarea membrului inferior--între deziderat si posibilitati.

Revascularization of the lower extremity in patients with diabetes or chronic obstructive arterial disease is a challenging, still unsolved problem. Modern day technique (stem cell therapy, hyperbaric therapy) has yet to deliver satisfactory results. Homogenous (safenous vein) or heterogeneous (terom, dacron, PTFE-teflon) by-pass surgery is limited because of technical difficulty and positive outcomes have a short duration. All these lead to, in most patients, to amputations as first line therapy or as an alternative to failed approaches. By-pass surgery is limited by graft obstruction. One of the current approaches is the use of omental flap autotransplantation.

Microcirculation of the fingers in Raynaud's syndrome: (99m)Tc-DTPA imaging.

AIM: We investigated the circulatory characteristics of patients suffering of primary and secondary Raynaud's syndrome. PATIENTS, METHODS: We examined 106 patients presenting with the classical symptoms of Raynaud's syndrom (47 primary, 59 secondary) by hand perfusion scintigraphy developed by our Department of Nuclear Medicine. After visual evaluation we analyzed the images semiquantitatively, using the finger to palm ratio. We statistically compared the patients with primary and those with secondary Raynaud's syndrome. RESULTS: By visual evaluation we constated regional perfusion disturbances in 42 from 59 patients with secondary Raynaud's syndrome. However, this was observed in only 3 from 47 patients with the primary form of this disease. This difference was statistically significant (p<0.001). Semiquantitative analysis showed that the finger/palm ratios (FPR) were significantly lower (p<0.05) for the patients with primary Raynaud's syndrome. No differences in the FPR values concerning sex or right and left side. CONCLUSION: The hand perfusion scintigraphy with (99m)Tc-DTPA is a noninvasive, cost effective diagnostic tool, which objectively reflects the global and regional microcirculatory abnormalities of the hands, and provides quantitative data for follow-up.

Radial artery grafts: surgical anatomy and harvesting techniques(1).

At present more and more surgeons are using the radial artery as a graft for coronary bypass. The statistics until now show that the patency of radial grafts exceeds that of the venous grafts used up to the present. In our department we used radial artery for coronary bypass in 515 patients between January 1990 and December 2000. The radial artery harvesting with minimally invasive technique developed by us was applied in 50 of these patients while the rest were performed with the traditional method. No ischemic complications occurred in forearm or hand following either of the methods. One year after the operation we carried out control examinations on 197 consecutive patients. Our surveys showed that following the traditional technique of radial artery harvesting neurological complications (temporary dysaesthesia) occurred in 16.5% of the patients. After the minimally invasive procedure, temporary dysaesthesia occurred in one case (2%). These complaints ceased within 1-12 months (an average of 3.8 months). Definitive neurological complications did not occur in any of the patients. In summation, we experienced that both operating techniques can be safely applied. The proportion of temporary neurological complications is higher following the traditional procedure, therefore, further development and application of the minimally invasive procedure should be considered.

Minimally invasive harvesting of the radial artery as a coronary artery bypass graft.

We harvested radial arteries for coronary artery bypass procedures with a minimally invasive technique for 40 patients through two transverse 2-cm incisions in the forearm. With the help of instruments developed by us, the operation can be performed either with the use of an endoscope or with the naked eye. There were no complications in the forearm or the hand. The condition of the intima of the arterial grafts was checked by transmission and scanning electron microscopic methods and was found to be intact.

[Endoscopic harvesting of the radial artery at coronary artery bypass graft: a new surgical technique]. / Az arteria radialis nyerése endoszkópos eszközzel: új mútéti eljárás a koszorúér-sebészetben.

The radial artery as arterial graft is applied ever increasingly in coronary artery bypass grafting. With the endoscopic technique described by the authors, the radial artery can be lifted out extremely quickly and gently through transverse 2 cm incisions, using a so-called "spiral instruments for radial artery harvesting" and a 30 degrees endoscope. The ultrasonic knife used for incision and hemostasis does not cause thermic and mechanical damage. The radial artery and accompanying veins remain protected inside the spiral interior. The authors present a case where this method was applied successfully.

Why the internal mammary artery is an ideal graft for myocardial revascularisation? (an experimental model with omentoplasty).

Ten dogs underwent coronary artery bypass grafting through a right thoracotomy. Free internal mammary artery grafts (IMA) was used for aortocoronary bypass to right coronary artery (RCA) without temporary cardiopulmonary bypass. In upper median laparotomy approach, mobilization and lengthening of the omentum was performed through the retrosternal part of the diaphragm. An epiploic muff was effectuated surrounding the IMA graft. After three months the animals were sacrificed and the grafts folded by omentum were used for microscopical study. The histological evaluation has shown that the omentum has formed a new adventitia around the graft. In the new-formed adventitia, newly formed vessels can be found and these are grouped around the adventitia-media border zone, very rarely penetrating into the external layer of the media. This graft-omentoplasty offer a good experimental model which facilitates to investigate in vivo the blood supply needed by free IMA grafts through the adventitia in experimental conditions. The biological mechanism of angiogenesis in graft wall can be investigate as well.