Extracellular matrix remodeling in canine and mouse myocardial infarcts.

Extracellular matrix proteins not only provide structural support, but also modulate cellular behavior by activating signaling pathways. Healing of myocardial infarcts is associated with dynamic changes in the composition of the extracellular matrix; these changes may play an important role in regulating cellular phenotype and gene expression. We examined the time course of extracellular matrix deposition in a canine and mouse model of reperfused infarction. In both models, myocardial infarction resulted in fragmentation and destruction of the cardiac extracellular matrix, extravasation of plasma proteins, such as fibrinogen and fibronectin, and formation of a fibrin-based provisional matrix providing the scaffold for the infiltration of granulation tissue cells. Lysis of the plasma-derived provisional matrix was followed by the formation of a cell-derived network of provisional matrix composed of cellular fibronectin, laminin, and hyaluronic acid and containing matricellular proteins, such as osteopontin and osteonectin/SPARC. Finally, collagen was deposited in the infarct, and the wound matured into a collagen-based scar with low cellular content. Although the canine and mouse infarcts exhibited a similar pattern of extracellular matrix deposition, deposition of the provisional matrix was more transient in the mouse infarct and was followed by earlier formation of a mature collagen-based scar after 7-14 days of reperfusion; at the same timepoint, the canine infarct was highly cellular and evolving. In addition, mature mouse infarcts showed limited collagen deposition and significant tissue loss leading to the formation of a thin scar. In contrast, dogs exhibited extensive collagen accumulation in the infarcted area. These species-specific differences in infarct wound healing should be taken into account when interpreting experimental infarction studies and when attempting to extrapolate the findings to the human pathological process.

Prevention of restenosis with intravascular beta-radiotherapy.

Beta radiation has been clearly shown, in a specific dose range, to be highly effective in the inhibition of the restenotic process after balloon or stent injury in animal experiments, as well as in randomized, placebo-controlled human trials. The major advantage of beta radiation, in comparison with gamma radiation, is a significantly lower radiation exposure to the personnel and patient, and easier adaptability to existing cardiac catheterization laboratories. Rapidly accumulating evidence indicates that the two major problems, late thrombosis and edge stenosis, may be minimized with prolonged antiplatelet therapy (6 months or more) and broader radiation coverage of the intervention site. Although there may be better, safer, and easier options to reduce restenosis in the years to come, intravascular radiotherapy is the first breakthrough modality that has been shown to significantly reduce restenosis after percutaneous vascular interventions.

Dose-response study of intracoronary beta-radiation with 32P in balloon- and stent-injured coronary arteries in swine.

PURPOSE: A dose-response study was performed in swine to investigate the vascular effects of 32P over a broad range of doses in order to define the therapeutic window of intracoronary radiotherapy (ICR) with 32P. METHODS AND MATERIALS: A total of 131 porcine arteries were subjected to balloon injury or stenting followed by 0-36 Gy of ICR from a centered 32P source wire to 1 mm beyond lumen surface or a sham ICR procedure. Animals were euthanized at 4 weeks, and vessels were harvested for histomorphometry. RESULTS: In the balloon-injured arteries, doses of 7 and 9 Gy did not impact restenosis. At doses of 14-36 Gy, neointima was markedly reduced, with mild dilatation at the highest dose, 36 Gy. In the stent-injured arteries, the lowest dose of 9 Gy failed to reduce neointimal growth, while 14-26 Gy showed the most favorable response. CONCLUSIONS: ICR with 32P features a broad therapeutic window. Doses of 14-26 Gy to 1 mm beyond lumen surface provided an optimal combination of efficacy and safety. Doses of 7 and 9 Gy were generally ineffective, suggesting a minimum threshold for ICR with 32P to effectively inhibit restenosis.

[The assessment of safety of enoxaparin administration during percutaneous transluminal coronary angioplasty after ticlopidine pretreatment. Application of low molecular weigh heparins in prevention of coronary micro-embolization]. / Ocena bezpieczenstwa stosowania enoxaparyny podczas zabiegów przezskórnej rewaskularyzacji serca u pacjentów uprzednio otrzymujacych tiklopidyne Zastosowanie heparyn drobnoczasteczkowych w zapobieganiu zatorowosci mikrokrazenia wiencowego.

BACKGROUND: Administration of enoxaparin to patients with acute coronary syndromes can result in better outcomes in comparison to patients treated with unfractionated heparin. Use of enoxaparin during percutaneous coronary interventions (PCI) can also improve the outcome. Administration of ticlopidine and aspirin for a few days before PCI decreases frequency of ischaemic complications. There is lack of data about safety and efficacy of combined administration of enoxaparin, ticlo-pidine and aspirin during PCI. METHODS: 61 patients with coronary artery disease were involved in the study. All patients were pretreated with aspirin (75-325 mg/d) and ticlopidine (2 x 250 mg) for at least 3 days before PCI. PCI procedures were conducted after i.v. administration of 1 mg/kg of enoxaparin. After PCI bleeding and ischaemic complications were monitored. RESULTS: In the treated group, no major bleeding occurred, while minor bleeding was noted in 6.5% of patients. No periprocedural major adverse cardiac events (death, Q wave infarction, urgent revascularisation) were observed. Microembolisation was present in 4.9% patients (expressed as CK-MB > 3 times the reference level). CONCLUSIONS: Intravenous administration of enoxaparin 1 mg/kg during PCI in patients pretreated with aspirin and ticlopidine for at least 3 days before intervention appears to be safe. Safety and high efficacy of enoxapirine in this pilot trial justify initiating the randomized, multicenter trial comparing use of low molecular weight heparin to unfractionated heparin during PCI.

[Depressive disturbance and quality of life in patients with coronary artery disease]. / Zaburzenia depresyjne a jakosc zycia u pacjentów z choroba niedokrwienna serca.

The aim the study was to evaluate the impact of mood disturbances on the subjective quality of life in patients with coronary artery disease after an effective angioplasty. The study covered 100 patients with the optimum result of PTCA. Their condition was evaluated one day before and four weeks after angioplasty. Significant differences in the subjective quality of life assessment were detected depending on the occurrence and dynamics of depressive symptoms. The authors postulate evaluation of psychological state and introduction of anti-depressive therapy in patients with coronary artery disease subjected to revascularisation.