A Ivarsen

Publications (3)14.95 Total impact

• Article: Characterisation of corneal fibrotic wound repair at the LASIK flap margin.

  A Ivarsen, T Laurberg, T Møller-Pedersen
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  ABSTRACT: To characterise temporal changes in corneal wound repair at the LASIK flap margin. 18 rabbits received monocular LASIK and were evaluated during 6 months using slit lamp and in vivo confocal microscopy. In three corneas, the exposed stroma was stained with DTAF. At various time points, corneas were processed for histology and stained for nuclei, f-actin, ED-A fibronectin, alpha-smooth muscle actin, TGF-beta1, TGF-beta2, TGF-beta receptor II, and CTGF. At day 1, leucocytes migrated from the conjunctival vessels into the cornea. Near the limbus, the leucocytes were organised in long chains stretching towards the flap edge. From day 4, elongated fibroblasts migrated from the periphery to align in a circumferential band (approximately 250 microm wide) next to the flap edge. The lateral extension of this stromal band was delimited by the incisional gap in the epithelial basement membrane. TGF-beta1, TGF-beta2, TGF-beta receptor II, and CTGF were expressed in the band from day 2. Myofibroblasts were identified at week 3 and over time a 50 microm thick layer of fibrotic matrix was deposited. Concurrently, the peripheral circumferential band became narrower (width decreasing to 33% (SD 7%) at 4 months; n = 5) and showed an increased organisation with a gradual decline in reflectivity. At all time points, keratocytes within and below the flap remained quiescent and only minimal fibrosis developed at the interface. Fibrotic wound repair following LASIK is restricted to a narrow band peripheral to the corneal flap edge. The lateral extension of the fibrosis is sharply delimited by the incisional gap in the epithelial basement membrane. The fibrotic wound healing at the LASIK flap margin is associated with myofibroblast transformation and wound contraction and involves a TGF-beta signalling pathway.
  British Journal of Ophthalmology 11/2003; 87(10):1272-8. · 2.90 Impact Factor
• Article: Hypothesis for the initiation of vasomotion.

  H Peng, V Matchkov, A Ivarsen, C Aalkjaer, H Nilsson
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  ABSTRACT: Vasomotion is the regular variation in tone of arteries. In our study, we suggest a model for the initiation of vasomotion. We suggest that intermittent release of Ca(2+) from the sarcoplasmic reticulum (SR, cytosolic oscillator), which is initially unsynchronized between the vascular smooth muscle cells, becomes synchronized to initiate vasomotion. The synchronization is achieved by an ion current over the cell membrane, which is activated by the oscillating Ca(2+) release. This current results in an oscillating membrane potential, which synchronizes the SR in the vessel wall and starts vasomotion. Therefore, the pacemaker of the vascular wall can be envisaged as a diffuse array of individual cytosolic oscillators that become entrained by a reciprocal interaction with the cell membrane. The model is supported by experimental data. Confocal [Ca(2+)](i) imaging and isometric force development in isolated rat resistance arteries showed that low norepinephrine concentrations induced SR-dependent unsynchronized waves of Ca(2+) in the vascular smooth muscle. In the presence of the endothelium, the waves converted to global synchronized oscillations of [Ca(2+)](i) after some time, and vasomotion appeared. Synchronization was also seen in the absence of endothelium if 8-bromo-cGMP was added to the bath. Using the patch-clamp technique and microelectrodes, we showed that Ca(2+) release can activate an inward current in isolated smooth muscle cells from the arteries and cause depolarization. These electrophysiological effects of Ca(2+) release were cGMP dependent, which is consistent with the possibility that they are important for the cGMP-dependent synchronization. Further support for the model is the observation that a short-lasting current pulse can initiate vasomotion in an unsynchronized artery as expected from the model.
  Circulation Research 05/2001; 88(8):810-5. · 9.49 Impact Factor
• Article: On the cellular mechanism for the effect of acidosis on vascular tone.

  H L Peng, A Ivarsen, H Nilsson, C Aalkjaer
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  ABSTRACT: The role of smooth muscle [Ca2+]i and membrane potential for the relaxation to hypercapnic (increased CO2) and normocapnic (unchanged CO2) acidosis is not complete understood. It is often stated that membrane hyperpolarization plays an important role but this has not been vigorously tested. In this study we investigated isolated rat cerebral small arteries under isobaric conditions. Lumen diameter was measured simultaneously with either [Ca2+]i or membrane potential, and acidosis was induced by increasing PCO2 or reducing HCO3- of the bathing solution or by adding HCI to a nominally bicarbonate-free solution. Confocal microscopy verified loading of smooth muscle cells with fluorescent dyes. Acidosis always reduced myogenic tone at transmural pressures between 20 and 120 mmHg. Acidification at a transmural pressure of 40 mmHg caused an increase in diameter and a decrease in [Ca2+]i. This was also seen in the presence of L-NNA and after depolarization with 50 mM K+. The response to hypercapnic and normocapnic acidosis was similar. However, while hypercapnic acidosis caused hyperpolarization, normocapnic acidosis caused depolarization. Dilatation, decrease of [Ca2+]i and depolarization, was also seen with reduction of pH in bicarbonate-free solution. We conclude that the isobaric relaxation to both hypercapnic and normocapnic acidosis is most likely mediated by a reduction of [Ca2+]i. Membrane potential may on the other hand not play a major role for this reduction of [Ca2+]i and it is possible that molecular CO2 has an effect on the membrane potential.
  Acta Physiologica Scandinavica 01/1999; 164(4):517-25. · 2.55 Impact Factor