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Biomedical subjects

J Brunkwall

Publications and source records attributed to J Brunkwall.

At least 73 records · Page 4Linked to original sources

Endovascular stent-anchored aortic grafts: a comparison between self-expanding and balloon-expandable stents in minipigs.

PURPOSE: To study endovascular graft attachment with self-expanding Gianturco Z-stents and balloon-expanded Palmaz stents and the effect of these devices on the renal ostia. METHODS: Ten stent-grafts were constructed, 5 with Gianturco Z-stents and 5 with Palmaz stents. The endografts were implanted under fluoroscopic guidance into the abdominal aorta of 10 pigs so that the uncovered portion of the proximal stent extended over the renal artery orifices. Distal aortic blood pressure and flow were measured before and after graft placement and 1 hour postprocedure. The aorta was then exposed surgically, and the central portion of the stent-graft was inspected through an aortotomy to assess perigraft leakage. RESULTS: Stent-graft implantation was accurate and hemostatic in all cases, despite longitudinal folding of the graft due to oversizing. However, transverse folds produced pressure gradients (> 15 mmHg) between the ends of the graft in two cases. In another case, a pressure gradient resulted from partial thrombosis of the graft. In two cases, renal artery occlusion and thrombosis occurred due to coverage by the graft material. In two other animals, one of the renal arteries was entirely uncovered by a stent. The remaining 16 renal arteries were covered by the proximal stent but not the graft, as intended. One (6.25%) of these arteries thrombosed, but the remainder were grossly patent when the animals were sacrificed at 1 hour. CONCLUSIONS: Both Palmaz and Gianturco Z-stents produced hemostatic endovascular graft attachment, even in the presence of moderate graft oversizing. The risk of acute renal artery occlusion from juxtarenal stenting does not appear to be prohibitive, but longer term observations are needed.

Animals↗

Selective attenuation of neuropeptide-Y-mediated contractile responses in blood vessels from patients with diabetes mellitus.

Vascular smooth muscle contractile responses to neuropeptide Y, alpha,beta-methyleneATP and noradrenaline were studied in circular segments of isolated vessels with intact endothelium in vitro from 12 patients with diabetes mellitus type 2 (NIDDM) and 12 control subjects. The dilatory effect of acetylcholine was used to test the function of the endothelium. Subcutaneous arteries and veins (diameter 0.1-1.1 mm) were obtained during surgery. There was no difference in contractile responses to noradrenaline or alpha,beta-methyleneATP between diabetic and control vessels. The contractile response to neuropeptide Y, however, was markedly reduced in the diabetic group. The maximal contractile effect (46.0 +/- 14.0%, p < 0.05) but not the sensitivity to neuropeptide Y was significantly less in diabetic veins compared to control (107.5 +/- 19.6%). Thus, the attenuation of neuropeptide Y responses was present in humans as previously observed in alloxan-induced diabetes mellitus in rabbits. There was no difference in the dilator effect of acetylcholine between the diabetic and the control group in any of the vessel types, indicating that the difference in vascular reactivity to neuropeptide Y was not endothelium-dependent. In conclusion, the present study has shown that the postjunctional effects of neuropeptide Y, a co-transmitter of the peripheral sympathetic nervous system, is selectively attenuated in diabetes mellitus.

Acetylcholine↗

Hydrotherapy of patients with intermittent claudication: a novel approach to improve systolic ankle pressure and reduce symptoms.

OBJECTIVE: To study the effects of alternating cold and hot water therapy on walking ability and systolic blood pressure in claudicants. EXPERIMENTAL DESIGN: A prospective case study with repeated measurements before and 1, 4 and 12 months after treatment. The systolic blood pressure levels were measured with an occlusion cuff for brachial and ankle and with a strain gauge for the first toe. STUDY POPULATION: Twenty consecutively included patients, 11 women and 9 men; mean age 73.9 yrs, with intermittent claudication according to clinical examination and ankle-arm systolic blood pressure (AAI) below 0.90. INTERVENTION: Alternate hot and cold hydrotherapy of the legs were given at ten 25-minute treatments during a three-week period. The outcome measures were maximal walking ability (MW), walking ability before pain (PW) and systolic blood pressures of toe, ankle, arm and AAI. RESULTS: Fourteen patients (70%) reported reduced pain after treatment and their PW increased from 134 +/- 29 m to 415 +/- 119 m 12 months later (p < 0.05) and the MW in the total group increased form 348 +/- 75 m to 523 +/- 103 m. Systolic blood pressure increased in right ankle and toe one month after treatment in the total group. Among those who reported improved walking ability one year after treatment, systolic blood pressure in both right and left ankles and toes increased; e.g. right toe increasing from 72 +/- 7 to 86 +/- 2 (p < 0.001). Improvements of systolic blood pressure in left and right leg and changes of walking ability were correlated, in the order of 0.60 to 0.81, p < 0.05. CONCLUSIONS: Showering the legs of claudicants improved walking ability and blood pressures which sustained up to 1-year later. This therapy might be an additional alternative to conservative treatment of intermittent claudication.

Aged↗

Neuropeptide Y stimulates proliferation of human vascular smooth muscle cells: cooperation with noradrenaline and ATP.

Since the sympathetic nervous system has been shown to exert a trophic influence on vascular smooth muscle cells (SMC), we studied the growth regulating effects of neuropeptide Y (NPY) in cooperation with the sympathetic co-transmitters noradrenaline and adenosine triphosphate (ATP) in human vascular SMC. NPY stimulated DNA synthesis in human SMC grown from subcutaneous arteries and veins (diameter: 0.4 mm) measured by [3H]thymidine incorporation. Also cell number and protein synthesis were stimulated. The effect was mediated through the Y1-receptor and not Y2 or Y3 since the Y1-selective NPY analogue Pro34-NPY and peptide YY stimulated mitogenesis in the same magnitude as NPY while the NPY-fragment NPY13-36 only had minor effects. The effect was blocked by pretreating the cells with pertussis toxin indicating a Gi/o-coupled effect. The other sympathetic co-transmitters, noradrenaline and ATP, also stimulated mitogenesis in the human SMC in a similar magnitude as NPY. When added together NPY and noradrenaline potentiated each other in the mitogenic response. ATP had mainly additive effects. This is the first demonstration that NPY, noradrenaline and ATP stimulates growth in human vascular SMC. This suggests a role of the sympathetic cotransmitters in modulating vascular tone, but also by inducing hypertrophy/hyperplasia with possible clinical consequences.

Adenosine Triphosphate↗

Long-term results of arterial reconstruction of the upper extremity.

Arterial reconstructive surgery for upper limb ischaemia of non-traumatic non-embolic origin is uncommon in comparison to that of the lower extremities and long-term follow-ups are rare. Forty-eight patients (27 females, 21 males) with a median age of 58 years (range 22-88) were retrospectively analysed for risk factors, survival and patency rates. Seventy-three per cent were smokers, 42% had hypertension and 33% had had previous vascular interventions. Diabetes was only seen in 4% of the cases. Effort fatigue was the dominant cause for surgery followed by micro-embolism and rest pain or gangrene. The left side was more frequently affected with 30 procedures compared to 18 on the right. Bypass with either Dacron, ePTFE or autologous vein was the most frequent procedure in 56% of the cases followed by thrombendarterectomy (23%) and subclavio-carotid transposition (11%). Arm-arm index rose from 0.63 (SD 0.28) preoperatively to 1.02 (SD 0.12) after 1 month and at the end of follow-up (median 75 months) it was 0.96 (SD 0.15). Cumulative survival rates were at 1 month 98%, 1 year 91%, 5 years 81% and at 10 years 73%. Cumulative primary patency rates at the same intervals were 96, 96, 88 and 80%, respectively. Thus the survival rate and patency rate are favourable in comparison with arterial surgical procedures of the lower extremity.

Adult↗

Human neuropeptide Y Y1 receptor antisense oligodeoxynucleotide specifically inhibits neuropeptide Y-evoked vasoconstriction.

This paper describes a new approach for the development of an inhibitor of the contractile responses of neuropeptide Y in human blood vessels by the use of an antisense oligodeoxynucleotide complementary to human neuropeptide Y Y1 receptor mRNA. One micromolar of an antisense 18-base oligodeoxynucleotide (hY1-AS), corresponding to the human Y1 receptor NH2-terminus, was incubated with segments of human subcutaneous arteries and veins for 48 h at 37 degrees C. Control vessels were incubated with the corresponding sense oligodeoxynucleotide (hY1-S) or a 3-base mismatched antisense oligodeoxynucleotide (hY1-MM) or no oligodeoxynucleotide. The contractile response to neuropeptide Y was markedly attenuated in both arteries and veins after treatment with hY1-AS, but was unaffected by hY1-S or hY1-MM. The pD2 values, i.e. the potency of neuropeptide Y, did not differ in hY1-AS treated vessels, suggesting a non-competitive receptor interaction as a result of down-regulation of Y1 receptors. Responses to noradrenaline or high K+ were unaffected by hY1-AS. This study may represent a new and highly specific approach to vascular pharmacology.

Base Sequence↗

The effect of cyclosporine A dissolved in chremofore or in ethanol and of cortisone on the arterial release of prostacyclin.

Cyclosporine A has been suggested to increase thromboembolic complications after renal transplantation. Therefore, the effect of cyclosporine A (at the clinically used dose of 10 mg/kg) dissolved in either chremofore or ethanol on rabbit vascular prostacyclin release was investigated in an ex vivo perfusion system. The animals received the drugs intravenously either as a single injection the day before operation or daily for 1 month prior to operation. Rabbits given cyclosporine A dissolved in chremofore released less prostacyclin than controls, both after a single injection and after 1 month of daily injections. The vehicle chremofore also gave a significantly lower release of prostacyclin than the control. The response to arachidonic acid with increased release was equal in all groups. Cyclosporine A dissolved in ethanol did not alter the initial release, and ethanol alone did not influence the prostacyclin release. Cortisone depressed the vascular prostacyclin release after daily injections for 1 month, but did not after only one injection. Cyclosporine A dissolved in chremofore and cortisone given in combination did not result in an additive reduction. These findings indicate that the intravenous administration of cyclosporine A dissolved in chremofore, but not that dissolved in ethanol, as well as cortisone, might decrease the vascular defense against thrombus formation. The action of these substances is higher up in the arachidonic acid cascade than the cyclooxygenase level.

6-Ketoprostaglandin F1 alpha↗

Prostanoid release immediately after balloon angioplasty in three models of atherosclerosis in rabbits.

OBJECTIVE: To evaluate the effect of angioplasty on the production of prostanoids in atherosclerotic vessels in rabbits. DESIGN: Open study. MATERIAL: 38 Rabbits. INTERVENTIONS: Rabbits in group A (n = 12) were given a cholesterol rich diet (2%) for 10 weeks, and then treated with angioplasty. Rabbits in group B (n = 11) were given a cholesterol rich diet for 10 weeks, and then returned to a normal diet until the serum cholesterol concentration returned to the reference range (a further 12 weeks). Rabbits in group C (n = 15) were anaesthetised, and a 3 mm balloon was introduced into the right femoral artery, fed 20 cm proximally, inflated, and pulled twice along the aorta; the animals were then given a cholesterol rich diet (2%) for eight weeks, and treated with angioplasty. MAIN OUTCOME MEASURES: Serum cholesterol concentrations were measured once a week. Prostacyclin and thromboxane were measured as 6-keto prostaglandin F1 alpha and thromboxane B2 in both treated and control segments of aorta. RESULTS: 15 Rabbits died while atherosclerosis was being induced, leaving 23 for analysis. Angioplasty reduced the amounts of prostanoids released in animals in which the atherosclerosis had been induced by diet alone. When endothelial injury and diet were used together, there was no difference between the treated and control segments in the amounts of prostanoids released. CONCLUSION: These findings could be of use in the comparison of methods used to induce atherosclerosis, and in the study of the mechanisms of thrombosis after transluminal angioplasty.

6-Ketoprostaglandin F1 alpha↗

Diminished contractile responses to neuropeptide Y of arteries from diabetic rabbits.

The vascular smooth muscle contractile response to neuropeptide Y (NPY), potassium, noradrenaline, histamine and serotonin was studied in circular segments of isolated vessels in vitro from rabbits with alloxan-induced diabetes mellitus. The injection of alloxan resulted in a marked and maintained increase in serum glucose as early as 1 week after treatment. Four vessel types were examined: abdominal aorta, and renal, left anterior descending coronary and middle cerebral arteries. There was no difference in the contractile response to histamine or serotonin between control and diabetic vessels. However, in the cerebral artery the contractile response to noradrenaline was reduced in the diabetic group, while in the aorta and the renal artery no significant differences were seen. Noradrenaline failed to evoke any contractile response in the coronary arteries in either group. NPY induced strong, concentration-dependent contractions of coronary and cerebral arteries, but did not have any contractile effect per se in aorta or renal arteries, either in control or in alloxan-treated rabbits. The maximal contractile effect and the sensitivity to NPY was significantly less in diabetic coronary and cerebral vessels as compared to control. There was no difference in dilator effect of acetylcholine and substance P between the diabetic animals and the control group in any of the vessel types, indicating that the changed vascular responses to NPY and noradrenaline were not endothelium-dependent. In conclusion, the present study has shown that the postjunctional effects of NPY and noradrenaline in the peripheral sympathetic nervous system are selectively attenuated in this model of chronic diabetes.

Animals↗

Storage in sodium chloride does not impair arterial prostacyclin release.

Heparinised sodium chloride solution is often used for the storage of veins and to prevent clotting in the arterial tree during vascular surgery. Sodium chloride deranges the morphology of endothelial cells and has therefore been interpreted as "toxic" to the endothelial cell. Perfused human saphenous veins and rabbit aortas show the same pattern of prostanoid release even though veins have a lower release than arteries. Excised rabbit aortas were stored in either (a) 0.9% sodium chloride or (b) 0.9% sodium chloride with heparin 5 I.U. ml-1 prior to being mounted in a perfusion model. The vessels were perfused ex vivo for 5 x 15 min with either Hanks' balanced salt solution (HBSS), calcium- and magnesium-free HBSS or 0.9% sodium chloride. For the last period, arachidonic acid (AA) 4 micrograms ml-1 was added. The release of prostacyclin, measured as the stable degradation product 6-keto-PGF1 alpha by radioimmunoassay, was not altered by storage in sodium chloride, or 0.9% sodium chloride plus heparin when compared with control segments. Perfusion with 0.9% sodium chloride did, however, significantly (p greater than 0.05) decrease the prostacyclin production when AA was added. This is most likely to be due to the low pH of the sodium chloride solution. It is concluded that short-term storage of rabbit aorta in sodium chloride plus heparin or 0.9% sodium chloride does not impair the prostacyclin cascade from the vessel wall, which might be of importance when choosing storage medium for reversed veins and veins used for coronary bypass surgery.

6-Ketoprostaglandin F1 alpha↗

Prostacyclin is produced from endothelial cell-seeded grafts: an experimental study in sheep.

Endothelial cell seeding might be of value in reducing the thrombogenicity of small-diameter vascular grafts. We investigated the capacity of endothelial cell-seeded grafts to produce prostacyclin and compared this with that of the unseeded graft as well as the native artery. Twelve sheep were operated on with carotid interposition of externally supported knitted dacron grafts. On one side of the neck the graft was seeded with endothelial cells, enzymatically harvested from the left jugular vein. After 3 weeks, three out of 12 seeded grafts, and one out of 12 unseeded grafts were occluded (N.S.). After excision, the grafts were mounted and perfused ex vivo for five 15-min periods. During the last period, arachidonic acid (4 micrograms/ml) was added to the perfusate. The resected carotid artery was used as a control. Prostacyclin was determined as the stable degradation product 6-keto-PGF1 alpha using radio-immunoassay, and expressed as pg mm-2 luminal surface. The native artery had a significantly higher release of prostacyclin than the seeded graft, which in turn had a significantly higher release than the unseeded graft. Histological examination showed weakly positive staining for factor VIII-related antigen on the luminal surface of seeded grafts. Scanning electron microscopy showed endothelial cells with typical endothelial tufts and was evaluated blindly from 10 areas of each graft. The extent of endothelial cell coverage was evaluated and scored from 0 to 2.5. The median score for the unseeded grafts was 0.3 and for the seeded grafts 1.5 (p = 0.008). Prostacyclin production was higher in seeded than unseeded grafts, but did not influence patency in this model.

Animals↗

Vessel repair after balloon angioplasty: morphological appearance and prostacyclin synthesising capacity.

Immediately after balloon dilatation of the rabbit aorta the release of prostacyclin is diminished. In this study the morphological appearance and time course for recovery of prostacyclin production after balloon dilatation have been investigated. Healthy rabbit aortas were analysed 1 h (n = 12), 1 week (n = 13) and 1 month (n = 13) after angioplasty. The production of prostacyclin, from dilated and non-dilated aortic segments, was recorded in a perfusion system. Prostacyclin was measured as its stable degradation product 6-keto-PGF1 alpha. Scanning electron microscopy and light microscopy were used to analyse the type of cells present at the luminal surfaces of the segments. When endothelial cells were found their degree of coverage was also estimated. One hour after balloon dilatation there was a lower production of prostacyclin from the angioplasty segments than from controls. Also, the response to added arachidonic acid (AA) was lower in the angioplasty segments. No endothelial cells were present in the angioplasty segments. After 1 week there was no difference in the basic production of prostacyclin but there was still a lower response from angioplasty segments to the addition of AA. The inner surfaces of the angioplasty segments were covered by three to five layers of smooth muscle cells (SMC). After 1 month, there was no difference in either the basic production or after the addition of AA between control and angioplasty segments. The angioplasty segments were covered with a multilayer of SMC. The control segments had an almost complete cover of endothelial cells at every time interval after angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

Diet-induced atherosclerosis in rabbits alters vascular prostacyclin release.

Atherosclerosis is complicated by thrombosis and it has been suggested that a decreased prostacyclin and/or an increased thromboxane release from the vascular wall could play a part in this process. There are few reports dealing with determinations of prostanoid release from physiologically perfused normal and atherosclerotic vessel walls or from perfused atherosclerotic hearts. Therefore, fourteen rabbits were given 2% cholesterol added to the diet for 26 weeks, which led to atherosclerosis, verified by scanning electron microscopy. Five animals died, and in the surviving nine, as well as from ten healthy rabbits, the aorta was excised. The vessels were perfused with pulsatile flow at physiologic pressure five times for fifteen minutes with the addition of arachidonic acid to the last perfusate. Prostacyclin and thromboxane were determined as their stable degradation products 6-keto-PGF1 alpha and TxB2 by radio-immuno assay. Atherosclerotic and normal animals had the same initial release of prostacyclin but in the atherosclerotic animals the release did not decline with time as it did in the normal animals. The response to arachidonic acid was also higher in the atherosclerotic group. The release of thromboxane was not altered in the atherosclerotic group compared to the control group. It is concluded that prostacyclin release from aortas is altered in rabbits with diet-induced atherosclerosis compared to normal rabbit aortas, but that vascular thromboxane production is not.

Animals↗

Chyluria treated with renal autotransplantation: a case report.

We report a rare case of chyluria in a patient from an area not endemic to filariasis. Initial surgical treatment consisted of stripping of the renal pedicle, following which the patient was free of symptoms for 3 months. Recurrence was noted and renal autotransplantation was performed. Chyluria has not recurred 12 months after the second operation. The etiology and various treatments of chyluria are discussed.

Adult↗

Influence of transluminal angioplasty on the prostanoid release from the arterial wall.

Vasospasm and thrombosis complicate percutaneous transluminal angioplasty (PTA). To study if the release of the prostanoids PGI2 and TxA2 are affected by PTA, the following experiment was undertaken: In ten rabbits, the upper or lower half of the aorta was randomised either to transluminal angioplasty or control segment. After excision the segments were simultaneously but separately perfused ex vivo with Hank's balanced salt solution for five consecutive 15 min periods. Arachidonic acid was added to the perfusate for the last 15 min period. PGI2 and TxA2 were measured by radioimmunoassay in the perfusate as the stable degradation products 6-keto-PGF1 alpha and TxB2. After perfusion, the two aortic segments were prepared for scanning electron microscopy (SEM). Angioplasty decreased the basic release of PGI2 as well as the response to arachidonic acid. This is likely to be due to endothelial denudation as seen by SEM. The release of TxA2 from the vessel wall was very low and was not increased by dilatation. The influence of angioplasty on the prostanoid system may be of importance in the complications of vasospasm and thrombosis.

Angioplasty, Balloon↗

Treatment of superficial thrombophlebitis. A comparative trial between placebo, Hirudoid cream and piroxicam gel.

A prospective randomized trial on the treatment of superficial thrombophlebitis has been performed in 68 patients randomized to either Hirudoid cream, piroxicam gel or placebo. Both spontaneous and infusion thrombophlebitis were included. Treatment effect was evaluated using the status of thrombophlebitis, the thrombophlebitic area, pain intensity with a visual analogue scale, and side effects were registered. Both in the treatment groups and the placebo group there was a significant decrease of signs and symptoms during the treatment period. There was no statistical difference between the treatment groups and no difference between spontaneous and infusion thrombophlebitis.

Administration, Topical↗