Attenuation of ischemic liver injury by augmentation of endogenous adenosine

Hepatic grafts from non-heartbeating donors may alleviate the organ shortage, but they inherently suffer from warm ischemia. In the present study, we tested our hypothesis that augmentation of endogenous adenosine by inhibition of nucleoside transport with R75231 attenuates ischemic liver injury. Adult female beagle dogs underwent 2-hr hepatic vascular exclusion with venovenous bypass. R75231 was given to the animals by continuous intravenous infusion for 30 min before ischemia at a dose of 0.1 mg/kg (Group 2, n=6), 0.05 mg/kg (Group 3, n=6), or 0.025 mg/kg (Group 4, n=6). Nontreated animals were used as the control (Group 1, n= 10). Animal survival, hepatic tissue blood flow, liver function, and histopathology were analyzed. Two- week animal survival was 30% in Group 1, 83% in Group 2, 100% in Group 3, and 100% in Group 4. Postreperfusion hepatic tissue blood flow was markedly improved by the treatment. Treatment significantly attenuated liver enzyme release, lipid peroxidation, and changes in adenine nucleotides and purine catabolites. Structural abnormality of the liver after reperfusion was markedly improved by R75231 treatment, showing better architecture and less neutrophil infiltration. Preischemic administration of a nucleoside transport inhibitor ameliorated ischemic liver injury due to the positive effects of augmented endogenous adenosine, and is applicable clinically when the liver is procured from a controlled non-heartbeating donor

Influence of mild heat and restrictive external support on functional changes in vein grafts implanted into arterial circulation. Experimental study

Introduction. Vein grafts placed in the arterial circulation undergo a set of morphological and functional changes. The aim was to investigate the effects of external mild heat combined with internal cooling and external restrictive support on vascular reactivity of the venous grafts implanted into arterial system. Material and methods. Reversed external jugular vein interposition grafting of the carotid artery on the mongrel dogs (n = 18) was performed. The experimental animals were split into three groups: H (n = 6) - grafts were exposed to mild heat and an external sleeve was placed around, S (n = 6) - grafts only with the sleeve and C (n = 6) - control group. The grafts were explanted after 3 months. The rings from all the explanted grafts as well as from jugular veins before implantation were taken and tension study was performed. Contractions to norepinephrine (NE), phenylephrine (Phe), 5-hydroxytryptamine (5-HT) and relaxation to acetylcholine (Ach), calcium ionophore A23187 (A23187) and sodium nitroprusside (SN) were assessed. Results. After pre-treatment with mild heat reaction to the maximal concentrations of NE (37.8 &plusmn; 1.9 g/mm2 before vs. l2.0 &plusmn; 1.6 g/mm2 after), Phe (20.2 &plusmn; 1.6 g/mm2 vs. 2.0 &plusmn; 0.4 g/mm2) were markedly (p < 0.001) diminished. Vein grafts before implantation were insensitive to 5-HT. Only endothelium-independent relaxation to SN was preserved in the grafts after mild heat employment, whereas Ach, A23187 did not produce any endothelium-mediated reaction. Three months after implantation markedly lower contractile responses to maximal doses of NE (1.4 &plusmn; 0.2 g/mm2, 2.1 &plusmn; 0.3 g/mm2 and 15.4 &plusmn; 1.6 g/mm2 for H, S and C respectively), and Phe (0.4 &plusmn; 0.2 g/mm2, 1.3 &plusmn; 0.2 g/mm2 and 12.3 &plusmn; 1.2 g/mm2 for H, S and C respectively) were noted. The maximal examined dose of 5-HT provoked 66.2% of the maximal reaction to NE in group H, 66.5% in group S and 53.2% in group C. The grafts in group H and S were insensitive to endothelium-dependent relaxants, but in C the maximal responses to A23187 were significantly weaker (p < 0.05) than before implantation (40.7 &plusmn; 3.8% vs. 67.4 &plusmn; 2.3%). SN-induced endothelium-independent relaxation was observed in all groups. Conclusion. Mild heat of the venous grafts functionally destroys endothelium and significantly impairs smooth muscle cells' function. Employment of mild heat combined with external support may produce venous conduits less sensitive to vasoactive chemicals including also mitogens involved in neointima formation.Introduction. Vein grafts placed in the arterial circulation undergo a set of morphological and functional changes. The aim was to investigate the effects of external mild heat combined with internal cooling and external restrictive support on vascular reactivity of the venous grafts implanted into arterial system. Material and methods. Reversed external jugular vein interposition grafting of the carotid artery on the mongrel dogs (n = 18) was performed. The experimental animals were split into three groups: H (n = 6) - grafts were exposed to mild heat and an external sleeve was placed around, S (n = 6) - grafts only with the sleeve and C (n = 6) - control group. The grafts were explanted after 3 months. The rings from all the explanted grafts as well as from jugular veins before implantation were taken and tension study was performed. Contractions to norepinephrine (NE), phenylephrine (Phe), 5-hydroxytryptamine (5-HT) and relaxation to acetylcholine (Ach), calcium ionophore A23187 (A23187) and sodium nitroprusside (SN) were assessed. Results. After pre-treatment with mild heat reaction to the maximal concentrations of NE (37.8 &plusmn; 1.9 g/mm2 before vs. l2.0 &plusmn; 1.6 g/mm2 after), Phe (20.2 &plusmn; 1.6 g/mm2 vs. 2.0 &plusmn; 0.4 g/mm2) were markedly (p < 0.001) diminished. Vein grafts before implantation were insensitive to 5-HT. Only endothelium-independent relaxation to SN was preserved in the grafts after mild heat employment, whereas Ach, A23187 did not produce any endothelium-mediated reaction. Three months after implantation markedly lower contractile responses to maximal doses of NE (1.4 &plusmn; 0.2 g/mm2, 2.1 &plusmn; 0.3 g/mm2 and 15.4 &plusmn; 1.6 g/mm2 for H, S and C respectively), and Phe (0.4 &plusmn; 0.2 g/mm2, 1.3 &plusmn; 0.2 g/mm2 and 12.3 &plusmn; 1.2 g/mm2 for H, S and C respectively) were noted. The maximal examined dose of 5-HT provoked 66.2% of the maximal reaction to NE in group H, 66.5% in group S and 53.2% in group C. The grafts in group H and S were insensitive to endothelium-dependent relaxants, but in C the maximal responses to A23187 were significantly weaker (p < 0.05) than before implantation (40.7 &plusmn; 3.8% vs. 67.4 &plusmn; 2.3%). SN-induced endothelium-independent relaxation was observed in all groups. Conclusion. Mild heat of the venous grafts functionally destroys endothelium and significantly impairs smooth muscle cells' function. Employment of mild heat combined with external support may produce venous conduits less sensitive to vasoactive chemicals including also mitogens involved in neointima formation

Mitral Valve Prolapse

Mitral valve prolapse (MVP) is the most common valvular abnormality, affecting 2.4% of the population. Usually MVP is a benign disease and remains asymptomatic. The diagnosis of MVP is based on clinical presentation, physical examination and echocardiography. Some atypical symptoms that are not correlated with mitral valve function, are described as the MVP syndrome. Potential complications such as infective endocarditis, thromboembolic events, atrial and ventricular arrhythmias, and progressive mitral valve regurgitation may occur. Management should concentrate on adequate guidance of the patients, relief of symptoms and avoidance of complications

Does mild heat combined with external stenting prevent from intimal hyperplasia and medial thickening in the venous grafts? Experimental study

Introduction. Intimal hyperplasia and medial thickening of the venous grafts used in coronary artery bypass grafting (CABG) often leads to wall thickening and ultimately to conduit occlusion. The purpose was to investigate the effects of mild heat (85°C) followed by utilization of restrictive sleeve on histological changes of the venous grafts implanted into an arterial system. Material and methods. Reversed external jugular vein interposition grafting of the carotid artery on the mongrel dogs (n = 18) was performed. The experimental animals were split into three groups: H (n = 6) - grafts were exposed to mild heat and an external sleeve was placed around, S (n = 6) - grafts only with the sleeve and C (n = 6) - control group. The grafts were explanted after 3 months. Prior to explantation the grafts&#8217; patency was checked using flowmeter. Afterwards harvested veins were examined in light (LM), scanning (SEM) and transmission electron microscope (TEM). Cross-sectional intima (IA), media (MA) and relative intima area (RIA) for all grafts were calculated. Tissue samples from all grafts before implantation (harvested veins and veins after exposition to mild heat) were also examined. Results. Mild heat destroyed endothelial cells (ECs) and, to a lesser degree, basement membrane but did not influence IA, MA and RIA values. Medial smooth muscle cells (SMCs) located closer to the adventitia were affected by heat pretreatment. After 3 months all grafts were patent. Intimal hyperplasia was observed in group S and C, but not in H. Intimal area was markedly higher (p < 0.05) in group S (1.97 &plusmn; 0.57 mm2) and C (1.51 &plusmn; 0.77 mm2) than in H (0.38 &plusmn; 0.08 mm2). Scanning scans 3 months after implantation showed the luminal surface of all grafts was mostly covered by ECs. Smoth muscle cells were present in the intima of all grafts in group C and S, not in H. Some of them were active synthetic type SMCs with many mitochondria and well developed Golgi apparatus (TEM). The media was atrophic in group H and S, where collagen bundles were dissociated, the collagen fibers disrupted and in random orientation in the matrix. Media area was significantly higher (p < 0.05) in group C (2.64 &plusmn; 0.32 mm2) than in S (1.71 &plusmn; 0.45 mm2) and H (1.74 &plusmn; 0.48 mm2). Conclusion. Mild heat pre-treatment and external sleeving may mitigate the formation of intimal hyperplasia and reduce medial thickening after implantation in the arterial circulation.Introduction. Intimal hyperplasia and medial thickening of the venous grafts used in coronary artery bypass grafting (CABG) often leads to wall thickening and ultimately to conduit occlusion. The purpose was to investigate the effects of mild heat (85°C) followed by utilization of restrictive sleeve on histological changes of the venous grafts implanted into an arterial system. Material and methods. Reversed external jugular vein interposition grafting of the carotid artery on the mongrel dogs (n = 18) was performed. The experimental animals were split into three groups: H (n = 6) - grafts were exposed to mild heat and an external sleeve was placed around, S (n = 6) - grafts only with the sleeve and C (n = 6) - control group. The grafts were explanted after 3 months. Prior to explantation the grafts&#8217; patency was checked using flowmeter. Afterwards harvested veins were examined in light (LM), scanning (SEM) and transmission electron microscope (TEM). Cross-sectional intima (IA), media (MA) and relative intima area (RIA) for all grafts were calculated. Tissue samples from all grafts before implantation (harvested veins and veins after exposition to mild heat) were also examined. Results. Mild heat destroyed endothelial cells (ECs) and, to a lesser degree, basement membrane but did not influence IA, MA and RIA values. Medial smooth muscle cells (SMCs) located closer to the adventitia were affected by heat pretreatment. After 3 months all grafts were patent. Intimal hyperplasia was observed in group S and C, but not in H. Intimal area was markedly higher (p < 0.05) in group S (1.97 &plusmn; 0.57 mm2) and C (1.51 &plusmn; 0.77 mm2) than in H (0.38 &plusmn; 0.08 mm2). Scanning scans 3 months after implantation showed the luminal surface of all grafts was mostly covered by ECs. Smoth muscle cells were present in the intima of all grafts in group C and S, not in H. Some of them were active synthetic type SMCs with many mitochondria and well developed Golgi apparatus (TEM). The media was atrophic in group H and S, where collagen bundles were dissociated, the collagen fibers disrupted and in random orientation in the matrix. Media area was significantly higher (p < 0.05) in group C (2.64 &plusmn; 0.32 mm2) than in S (1.71 &plusmn; 0.45 mm2) and H (1.74 &plusmn; 0.48 mm2). Conclusion. Mild heat pre-treatment and external sleeving may mitigate the formation of intimal hyperplasia and reduce medial thickening after implantation in the arterial circulation

Glucose Tolerance and Left Ventricular Pressure-Volume Relationships in Frequently Used Mouse Strains

We investigated glucose tolerance and left ventricular contractile performance in 4 frequently used mouse strains (Swiss, C57BL/6J, DBA2, and BalbC) at 24 weeks. Glucose tolerance was tested by measuring blood glucose levels in time after intraperitoneal glucose injection (2 mg/g body weight). Left ventricular contractility was assessed by pressure-conductance analysis. Peak glucose levels and glucose area under the curve were higher (all P < .05) in C57BL/6J (418 ± 65 mg/dL and 813 ± 100 mg·h/dL) versus Swiss (237 ± 66 mg/dL and 470 ± 126 mg·h/dL), DBA2 (113 ± 20 mg/dL and 304 ± 49 mg·h/dL, P < .01), and BalbC mice (174 ± 55 mg/dL and 416 ± 70 mg·h/dL). Cardiac output was higher (all P < .05) in Swiss (14038 ± 4530 μL/min) versus C57BL/6J (10405 ± 2683 μL/min), DBA2 (10438 ± 3251 μL/min), and BalbC mice (8466 ± 3013 μL/min). Load-independent left ventricular contractility assessed as recruitable stroke work (PRSW) was comparable in all strains. In conclusion, glucose tolerance and load-dependent left ventricular performance parameters were different between 4 mice background strains, but PRSW was comparable

Gene Expression Study of Monocytes/Macrophages during Early Foreign Body Reaction and Identification of Potential Precursors of Myofibroblasts

Foreign body reaction (FBR), initiated by adherence of macrophages to biomaterials, is associated with several complications. Searching for mechanisms potentially useful to overcome these complications, we have established the signaling role of monocytes/macrophages in the development of FBR and the presence of CD34+ cells that potentially differentiate into myofibroblasts. Therefore, CD68+ cells were in vitro activated with fibrinogen and also purified from the FBR after 3 days of implantation in rats. Gene expression profiles showed a switch from monocytes and macrophages attracted by fibrinogen to activated macrophages and eventually wound-healing macrophages. The immature FBR also contained a subpopulation of CD34+ cells, which could be differentiated into myofibroblasts. This study showed that macrophages are the clear driving force of FBR, dependent on milieu, and myofibroblast deposition and differentiation