PURPOSE: Based on our preclinic studies with autologous unfractionated bone marrow (AUBM) via coronary sinus with transitory occlusion, a clinic study in patients with chronic stable angina was designed. The objectives were to evaluate safety, tolerance and feasibility. METHODS AND MATERIALS: A multicenter prospective study with inclusion and exclusion criteria defined by an Independent Clinical Committee was carried out. Fourteen patients underwent transcoronary sinus administration of freshly aspirated and filtered AUBM (60-120 ml). Safety and tolerance were evaluated. Feasibility was evaluated with Seattle Angina Questionnaire (SAQ), Canadian Cardiovascular Society (CCS) angina classification (baseline-Day 180), myocardial perfusion (baseline-Day 90) with independent core laboratory and coronary angiography (baseline and Day 30). RESULTS: There were no changes in the safety and tolerance parameters. Preliminary clinical efficacy at Day 180 disclosed a significant improvement of 38%, evaluated by the SAQ. The CCS angina classification shows that the mean angina class was 3.0+/-0.55 at baseline and improved to 2.0+/-0.00 at Day 180 (P <.001). Semiquantitative radionuclide perfusion imaging (core lab) showed a significant improvement at Day 90 in 13/14 patients, with a mean improvement of 24% at rest (P <.01) and 33% at stress (P <.05). Coronary angiography showed more collateral vessels in 9/14 patients. CONCLUSIONS: We can conclude that AUBM via coronary sinus with transitory occlusion is tolerable and safe. Significant improvement in the myocardial perfusion at Day 90 and in the quality of life at Day 180 was observed.

Angina Pectoris↗

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Transcoronary sinus delivery of autologous bone marrow and angiogenesis in pig models with myocardial injury.

PURPOSE: The aim of the investigation is to study myocardial injury on pig model with two objectives: (1) feasibility of stimulating angiogenesis with fresh autologous bone marrow; (2) administration of the same fresh autologous bone marrow via coronary sinus with transitory occlusion. METHODS: A controlled study was done in animal model with three phases, in a study group of 12 pigs (bone marrow administration) as well as in control group of 4 pigs (saline administration). Phase 1-production of coronary stenosis and myocardial injury; Phase 2-two weeks later, administration of bone marrow through coronary sinus with 10 min occlusion in the study group and saline solution in the control group. Phase 3-two weeks later, histological staining with hematoxylin-eosin and inmunohistochemical staining with monoclonal antibody for smooth muscle alpha-actin were conducted on both study and control groups. RESULTS: The percentage of angionenesis observed in the study group was 91% and 0% in control group. Counting of positive actin in affected and control areas showed statistically significant differences in relation to both groups: study group (1.37 vs. 0.79) and control group (0.47 vs. 0.51). The percentage of mononuclear immature cells observed in the myocardium in the study group was 25% and in the control group was 0%. There was no increment in the coronary collateral circulation when comparing coronary angiography. CONCLUSIONS: Autologous bone marrow in animal model with experimental myocardial injury enhances angiogenesis, as well as vessels with smooth muscles. The transitory occlusion of the coronary sinus might be an effective way to administer cells as those from the bone marrow.

Animals↗

PubMedDate not supplied

New Media. Pharmacology of nonionic dimers.

Nonionic dimers enable us for the first time to produce highly concentrated, blood isotonic contrast media. If the toxicity of contrast media is dependent on molar quantity, molar concentration, or the motility of small molecules, nonionic dimers could have advantages over the monomeric contrast media. Their higher viscosity is a basic disadvantage. Solutions of the nonionic dimers with an iodine concentration of up to 400 mg/ml often have an osmotic pressure that is lower than that of blood. THe new contrast media are extremely hydrophilic, show no binding to protein, and lead to complement activation only in extremely high concentrations. They do not cause the deformation of the erythrocytes that is known to occur with other contrast media. The LD50 after fast intravenous injection in the rat is higher that with all other known contrast media. In peripheral arteriography, the nonionic dimers are tolerated painlessly by rats, and in carotid angiography they cause as few side effects as metrizamide. The neural tolerance is better than that of metrizamide. In circulatory investigations no drop in blood pressure was found after intravenous injection. Elimination is almost exclusively renal. As with other nonionic contrast media, properties of the dimers that appear to be problematic are formation of supersaturated solutions and nephrotoxicity after extremely high doses.

Angiography↗

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