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

Functional and biomechanical evaluation of a completely recellularized stentless pulmonary bioprosthesis in sheep

ObjectiveIn a previous study we showed that recellularization of a stentless bioprosthetic valve is stimulated 1 month after implantation in the pulmonary position, when its matrix (acellular photo-oxidized bovine pericardium) was preseeded by intraperitoneal implantation during a 3-day period.MethodsThe present study reports on the functional and biomechanical properties of such valves (n = 19) in sheep up to 5 months after implantation. Similar valves (n = 20) that were not intraperitoneally preseeded served as controls.ResultsRecellularization was partial in control valves and excessive in preseeded valves: 66% versus 223% of cellularity of native valves, respectively (P < .05). The valves were endothelialized and contained interstitial cells depositing new matrix (collagens and elastin). However, phenotyping revealed an increased proportion of cells with contractile properties (30%–40% alpha smooth muscle actin+) in both groups. Intraperitoneally seeded valves had thicker and shorter leaflets that were associated with mildly increased peak gradients and regurgitation. Characterization of the matrix properties revealed a gradually degrading matrix (±25% loss of collagen organization at 5 months) and a concomitant alteration of its biomechanical properties, that is, decreased strength, stiffness, and maximum force. However, overall valve function remained intact, and the biomechanical properties of the whole valves were superior to that of the native valves.ConclusionThe ectopic in vivo seeding paradigm provides full recellularization. However, the volume fraction of the cellular phenotypes is not optimal, resulting in inadequate remodeling of the valves

Validation of Prosthetic Mitral Regurgitation Quantification Using Novel Angiographic Platform by Mock Circulation.

This study aimed to validate a dedicated software for quantitative videodensitometric angiographic assessment of mitral regurgitation (QMR).Quantitative videodensitometric aortography of aortic regurgitation using the time-density principle is a well-documented technique, but the angiographic assessment of mitral regurgitation (MR) remains at best semi-quantitative and operator dependent.Fourteen sheep underwent surgical mitral valve replacement using 2 different prostheses. Pre-sacrifice left ventriculograms were used to assess MR fraction (MRF) using QMR and MR volume (MRV). In an independent core lab, the CAAS QMR 0.1 was used for QMR analysis. In vitro MRF and MRV were assessed in a mock circulation at a comparable cardiac output to the in vivo one by thermodilution. The correlations and agreements of in vitro and in vivo MRF, MRV, and interobserver reproducibility for QMR analysis were assessed using the averaged cardiac cycles (CCs).In vivo derived MRF by QMR strongly correlated with in vitro derived MRF, regardless of the number of the CCs analyzed (best correlation: 3 CCs y = 0.446 + 0.994x; R = 0.784; p =0.002). The mean absolute difference between in vitro derived MRF and in vivo derived MRF from 3 CCs was 0.01 ± 4.2% on Bland-Altman analysis. In vitro MRV and in vivo MRV from 3 CCs were very strongly correlated (y = 0.196 + 1.255x; R = 0.839; p 0.001). The mean absolute difference between in vitro MRV and in vivo MRV from 3 CCs was -1.4 ± 1.9 ml. There were very strong correlations of in vivo MRF between 2 independent analysts, regardless of the number of the CCs.In vivo MRF using the novel software is feasible, accurate, and highly reproducible. These promising results have led us to initiate the first human feasibility study comprising patients undergoing percutaneous mitral valve edge-to-edge repair