Michal Vlašín

Intracoronary Delivery of Bone Marrow Cells to the Acutely Infarcted Myocardium

Objectives: Intracoronary cell transplantation during catheter balloon inflations may be associated with adverse events. We studied the effectiveness of an alternative transplantation technique – intracoronary cell infusion. Methods: Fourteen pigs, which had survived acute myocardial infarction, were randomized into 2 treatment groups and 2 controls. Three days after infarction, 12 pigs underwent allogeneic intracoronary mononuclear bone marrow cell transplantation using either the standard technique (short-term cell injections during repeat balloon inflations, technique A, n = 6) or continuous intracoronary cell infusion without balloon inflations (technique B, n = 6). Implanted cells were stained with fluorescent dye. After transplantation, the pigs were euthanized and myocardial samples were analyzed by fluorescent microscopy. Results: The mean numbers of fluorescently labeled bone marrow cells in the infarction border zone, in the infarction mid-area and in the center of myocardial infarction were 84, 72 and 55 using technique A, and 29, 57 and 46 using technique B, respectively. The mean cell retention in the infarction border zone of 84 cells for technique A and 29 cells for technique B differed significantly (p = 0.034, two-tailed t test). Conclusion: The continuous intracoronary cell infusion technique is a less efficient cell delivery technique as compared with the standard technique using repeat intracoronary balloon inflations.

Experimental model of myocardial infarction: Histopathology and reperfusion damage revisited

The goal of this pilot study was to create an experimental model of myocardial infarction (for subsequent evaluation of the effectiveness of an alternative way of stem cell application - intracoronary cell infusion in the management of acute myocardial infarction). Four experimental animals, female pigs weighing between 30 and 40 kg, were used in the initial phase of this study to create an experimental model of acute myocardial infarction. An experimental myocardial infarction was performed via occlusion of the interventricular arm of the left coronary artery for 90 min. The hearts were examined 1 h, 3 days, 5 days, and 7 days after the procedure. Macroscopically, red infarction characteristic of reperfusion was found. Microscopically, the healing process with granulation tissue production/collagen deposition was remarkably accelerated compared to literature data. Repair processes in reperfused experimental myocardial infarction and/or reperfused autopsy specimens should not be evaluated on the basis of literature data only. Large collections of extracellular calcium were present. This phenomenon is not well described in the literature and probably has the potential for significantly interfering with the repair process. The histopathology of reperfused acute myoardial infarction deserves to be studied in further investigations.

Direct comparison of enoxaparin and nadroparin in a rabbit model of arterial thrombosis prevention

INTRODUCTION The aim of the study was to evaluate and compare the efficacy of standard unfractionated heparin (UFH) and low-molecular weight heparins (LMWHs). MATERIALS AND METHODS We modified a previously published rabbit model of arterial thrombosis prevention [1,2] to compare unfractionated heparin and two different doses of two low-molecular weight heparin fragments--nadroparin and enoxaparin. Thrombosis in the distal aorta was triggered by vessel wall injury and critical stenosis. Blood flow in the damaged arterial segment was monitored by a flow probe placed distal to the constrictor. The primary endpoints of the study were: (1) cumulative flow, (2) time to occlusion and (3) residual clot weight. Thirty six animals were split into 6 groups with six animals in each group. Control groups were given saline or heparin and four more groups were used to compare LMWHs at 2 different doses. RESULTS In our study, all treatments were superior to the saline control group (alpha<or=0,01). Standard heparin was inferior (alpha<or=0,05) to both low molecular weight heparins for all primary endpoints (cumulative flow, time to occlusion and residual clot weight). There were no differences between the LMWHs except for cumulative flow at high doses. CONCLUSIONS This study revealed no relevant differences between nadroparin and enoxaparin for the primary endpoints of our model. Clinical use of each drug remains a personal preference.

Evaluation of a novel vascular graft with a distal bifurcation designed to reduce the development of intimal hyperplasia. Experimental study in a porcine aorta model

OBJECTIVE Abnormal haemodynamics is commonly agreed to be a major contributor to the development of distal anastomotic intimal hyperplasia. A new vascular graft design proposed by computational studies was used to demonstrate its surgical feasibility and to compare it with the conventional graft in a porcine model. METHOD The device was used in 12 eight-month-old pigs, six received the new graft and six had a conventional graft. The proximal graft end was implanted into the aorta, the distal graft end was implanted into the iliac artery. The host artery was ligated in order to simulate occlusion. At 20 weeks after surgery the pigs were killed and the device was excised for histological and morphometric analysis. RESULTS In five experimental grafts the reconstruction was occluded due to thrombosis; only one prosthesis was patent showing a minimum of neointimal hyperplasia. In the control group too only three of the six grafts were patent. A histological analysis revealed, as the cause of occlusion, fibrous tissue overgrowth corresponding in structure to neointimal hyperplasia. Differences in the number of obliterations and in occlusion rates between the profiles of the two groups were evaluated using the median test (P<0.05). The results were not statistically significant. CONCLUSION Although mathematical modelling had shown significant haemodynamic benefits of a naturally bifurcated graft, our study did not confirm its superiority over conventionally used prostheses.