Direct comparison of endothelial cell and smooth muscle cell response to supercooling and rewarming

BACKGROUND: Cryoplasty combines mechanical dilatation with the delivery of hypothermia to atherosclerotic plaques. The response of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) to supercooling and subsequent rewarming is still not clear. This study investigated the differential effects of vascular cell survival and proliferation in an in vitro model simulating cryoplasty. METHODS: Bovine aortic ECs and SMCs were cultured separately with medium supplemented with 10% fetal bovine serum. The samples were supercooled to -10 degrees C for 0, 60, or 120 seconds on a cooling stage and then rewarmed in an incubator at 37 degrees C for 0, 6, 12, or 24 hours. Terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling (TUNEL) and 5'-bromo-2'-deoxyuridine incorporation were used to measure the degree of apoptosis and proliferation respectively. Activation of protein kinase B (AKT), P70 S6 kinase, and P44/42 mitogen-activated protein kinase (MAPK) were assessed by Western blot and quantified using densitometry. Results are given as mean +/- standard error of mean and analyzed by analysis of variance. RESULTS: SMC and EC apoptosis were significantly increased with increasing supercooling and rewarming time, with a higher rate in SMCs. SMC apoptosis was maximal at 60 seconds cooling, followed by 24 hours rewarming (17.05% +/- 0.44%), whereas maximal EC apoptosis was after 120 seconds cooling, followed by 24 hours rewarming (4.21% +/- 0.22%, P < .05). Higher AKT activation was observed in ECs, with a maximum obtained of 3.34-fold at 120 seconds cooling with 24 hours rewarming (P < .05); only modest activation was found in SMCs. ECs had a decreased proliferation with cooling and rewarming time, and although SMCs maintained their low proliferative rate, ECs still had a higher overall proliferation rate that was statistically significant at 60 and 120 seconds cooling without rewarming compared with noncooling and nonrewarming (P < .05). Both p70S6 kinase and p44/42 MAPK activities decreased in SMCs, with significant drop at 60 seconds cooling, followed by 12 hours rewarming (P < .05). However, ECs showed a significant rise of P70 S6 kinase activity at 60 seconds cooling with 12 hours rewarming by 1.62-fold and P44/42 MAPK at 120 seconds cooling with 24 hours rewarming by 1.74-fold (P < .05). CONCLUSION: The higher apoptosis and lower proliferation of SMCs compared with ECs demonstrate the different effects of supercooling and rewarming on different vascular cell types. This information may be important in helping to understand the mechanism by which cryoplasty of atherosclerotic lesions may result in less restenosis.     

Predictors for the healing of transmetatarsal amputations: retrospective study of 91 amputations

This retrospective study reviewed 80 consecutive patients (mean age 62 years; range 21-91 years) who underwent 91 transmetatarsal amputations (TMAs) between 1995 and 2003. The mean follow-up was 12 +/- 1.36 months. Sixty-two TMAs healed initially (group 1), whereas 29 TMAs did not heal by 3 months (group 2). At the final examination, in groups 1 and 2, 63 of 91 (69%) limbs were healed. Of the 28 limbs that did not heal, 25 of 28 (89%) required further proximal amputation. Initial healing correlated significantly with the ability to ambulate (p < .0001) and overall limb salvage (p < .0001). In group 1, 20 of 27 (74%) limbs that were revascularized healed (p = .0336). Nonhealing amputations were associated with end-stage renal disease (13 of 19; 68%) (p = .0209) and leukocytosis (13 of 19; 68%) (p = .0052).     

Optic nerve sheath fenestration for treating papilloedema in the era of cerebral venous sinus stenting

Background

Pseudotumour cerebri (PTC) is the syndrome of intracranial hypertension without intracranial mass or hydrocephalus and is the commonest cause of papilloedema seen in many eye clinics. In the last 10 years, we have increasingly used TSS in patients whose papilloedema was not well controlled with medical treatment and have done fewer ONSFs. Here, we review our experience at Royal Prince Alfred Hospital Sydney with ONSF in 35 patients over the period 2002–2021.

Methods

Retrospective case series of 35 patients, 30 of whom had primary PTC [i.e., idiopathic intracranial hypertension (IIH)] and 5 with secondary PTC.

Results

Eighteen patients had bilateral ONSF and 17 patients unilateral ONSF, in each case of the worse eye. Thirteen patients then underwent transverse sinus stenting (TSS), in each case following ONSF. The primary outcome measures were visual acuity (VA) and mean deviation (MD) on visual field (VF) testing. MD improved by 5 dB or more in 34 of 70 total eyes (48.6%); VA improved by 0.2 logMAR (two lines on Snellen chart) or more in 21 eyes (30%), and by both in 15 eyes (21.4%). Final MD was −10 dB or better in 38 eyes (54.3%); final VA was 0.3 (6/12) or better in 54 eyes (77.1%), and both in 39 eyes (55.7%).

Conclusions

The results confirm that ONSF can relieve papilloedoema in both eyes and improve both VF and VA, even in cases of fulminant PTC with severe acute visual impairment.