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Biomedical subjects

B M O'Brien

Publications and source records attributed to B M O'Brien.

At least 19 recordsLinked to original sources
PubMed1992

Wound healing in foetal sheep: a histological and electron microscope study.

A study was made of the healing of excised, unsutured and sutured skin wounds in foetal sheep of 75, 90 and 120 days gestation and of wounds in newborn lambs and adult ewes. Foetal and postnatal wounds were found to heal in a very similar way. At each stage of development studied, excised wounds contract rapidly and histological and electron microscope examination demonstrates formation of granulation tissue and its maturation to scar tissue in all types of wound. Examination of polyvinyl sponges 7 and 14 days after subcutaneous implantation confirms the ability of foetal sheep to form vascularised scar tissue. The cellular inflammatory response to wounding is much less prominent in foetal than in postnatal sheep, the number and type of extravascular cells reflecting the changes in blood leucocyte content during development. From a very early stage foetal sheep react to insoluble irritants by the formation of multinucleate giant cells.

Actins↗
PubMed1992

Biochemical analysis of the venous flap in the dog.

There has been great interest stimulated by reports on factors influencing the survival of skin flaps which possess only venous inflow and outflow, i.e., venous flaps. The present study serially (Days 1, 2, and 4 postoperatively) observed several biochemical factors which might affect flap survival. ATP levels were measured to assess endogenous energy stores, malonyldialdehyde (MDA) and xanthine oxidase (XO) to estimate free radical production, superoxide dismutase (SOD) to quantify antioxidant defenses, and edema to measure inflammatory changes. Eighteen thighs on nine dogs were assigned randomly to one of three groups: full-thickness skin grafts, flaps based solely on the saphenous artery and vein (AV flaps), or flaps based solely on the saphenous vein (venous flaps). These were regarded as being mostly ischemic, totally perfused, and partially ischemic, respectively. Control skin biopsies were obtained adjacent to surgical sites. AV flaps and control skin were similar in all respects. Venous flaps compared with skin grafts were significantly less edematous (P less than 0.01) had less MDA and XO (P less than 0.05), but no significant differences in SOD and ATP levels. However venous flaps had significantly less ATP than AV flaps (P less than 0.01). Thus venous flaps survive despite depletion of ATP levels. These results suggest that decreased free radical production and lessened edema may be important factors in promoting ultimate survival of venous flaps.

Adenosine Triphosphate↗
PubMed1992

The response of the rabbit rectus femoris muscle to ischemia and reperfusion.

The rectus femoris muscle of the rabbit is perfused by a single artery and vein and is a valuable new model for study of ischemia-reperfusion injury of skeletal muscle. The consequences of increasing duration of ischemia to the rectus femoris have been examined. Postischemic muscle survival (means +/- SEM), as measured by Nitro blue tetrazolium (NBT) staining 24 hr after ischemia, was 90.5 +/- 1.5% after 2 hr normothermic ischemia, 77.1 +/- 7.7% after 3 hr, 41.8 +/- 7.6% after 3 1/2 hr, and 10.7 +/- 8.7% after 4 hr. Histology confirmed the NBT findings at 24 hr and showed considerable regeneration of muscle fibers 1-2 weeks after injury. The injury caused by 3 1/2 hr normothermic ischemia is the most suitable baseline for study of the effects of pharmacological agents in ischemic muscle injury. Further study of the effects of 3 1/2 hr ischemia by a quantitative Evan's blue method revealed a rapid increase in vascular permeability commencing at the start of reperfusion and lasting for 5-6 hr. Vascular labeling with saccharated ferric oxide showed widespread labeling of venules within the injured muscle and electron microscopic examination showed severe injury to both leaking and nonleaking small blood vessels. However, increased vascular permeability accounted for only a small part of the increase in weight of ischemic muscle.

Animals↗
PubMed1992

The biochemical basis of secondary ischemia.

In this study rat epigastric island flaps were used as a model to investigate selected tissue biochemical changes occurring during secondary ischemia. It was hypothesized that free radical damage, depletion of free radical scavengers, depletion of ATP, and increased edema might explain differences in flap survival between partial (venous obstruction) and total (arteriovenous obstruction) ischemia and decreased flap survival with increasing ischemia time. Flaps were given 2 hr or primary ischemia, 8 hr of normal perfusion, then secondary ischemia of 0, 2, 4, 8, or 12 hr with either arteriovenous obstruction or venous obstruction. Biochemical analysis of the skin was performed after 0, 24, or 96 hr reperfusion. Only minor differences were found between arteriovenous and venous ischemia for any of five biochemical parameters, despite a previous finding that venous ischemic flaps are more susceptible to necrosis. Levels of xanthine oxidase and malonyldialdehyde (both indices of free radical generation) increased with ischemia time. Levels of superoxide dismutase (a free radical scavenger) correspondingly decreased. Tissue levels of ATP decreased after ischemia and recovered to normal for shorter but not for longer ischemia times after 96 hr of reperfusion in parallel with flap survival. Edema increased immediately after the ischemic insult but decreased once the tissue became necrotic. These results imply roles for free radicals, ATP, and edema in secondary ischemia, but do not distinguish between arteriovenous and venous secondary ischemia.

Adenosine Triphosphate↗
PubMed1992

Radical microarteriolysis in the treatment of vasospastic disorders of the hand, especially scleroderma.

Arterial spasm due to exaggerated sympathetic response is an important mechanism for Raynaud's phenomenon in scleroderma associated often with periadventitial scarring. The results of cervical sympathectomy have been unsatisfactory in the upper limb because of additional sympathetic pathways. Flatt therefore devised a distal sympathectomy by stripping the vessels of their adventitia over a short length of artery. The results of this operation were found by Wilgis in a large series to be poor in patients with scleroderma. A radical distal microarteriolysis including adventitia and surrounding scar is described and the results in 13 patients, 11 with scleroderma, are reported. Minimum follow-up is one year. All patients had relief from pain at rest and healing of painful ulceration. Mild recurrence of small ulcers was seen in only four patients.

Adult↗
PubMed1992

Hair removal by a depilatory does not affect survival in rodent experimental flaps.

The current study looked at the effect of topically applied hair depilatory agent Nair on flap survival. In a 10 x 3-cm dorsal rat flap model, there were no statistically significant differences in survival noted on postoperative day 7 between control skin and flaps receiving 6 to 24 minutes of Nair preoperatively. Therefore, hair depilation by Nair can be used safely in this model.

Administration, Cutaneous↗
PubMed1991

Experience with calcium antagonists nitrendipine, diltiazem, and verapamil and beta 2-agonist salbutamol in salvaging ischemic skin flaps in rabbits.

This study investigated the efficacy of selected agents in the salvage of experimental skin flaps in rabbits after 21 hours of 25 degrees C ischemia. Calcium channel antagonists nitrendipine, diltiazem, and verapamil increased ischemic skin flap survival in rabbits from 33.3% for buffered saline infused controls to 71.4% (P less than 0.05), 71.4% (P less than 0.05), and 50.0% (not significant) respectively. The beta 2-adrenoceptor agonist salbutamol produced an increase in survival to 64.3%, which narrowly missed statistical significance. All four test agents invoked a vasodilatory response (greatest for nitrendipine, diltiazem, and salbutamol), a slight fall in blood pressure, and a small increase in heart rate. It is concluded that the vasodilatory response in the microcirculation of the ischemic flap helped to minimize the risk of occlusion due to thrombosis or cell sludging during reperfusion, thus leading to improved flap survival.

Albuterol↗
PubMed1991

Long term results of submandibular gland transfer for the management of xerophthalmia.

Free submandibular gland transfer is potentially the best surgical solution to total xerophthalmia. Experimentally, gland function has only previously been followed for 2 months. This study was designed to investigate the long term effects of free transfer on gland function. Simultaneous creation of experimental xerophthalmia and free microvascular transfer of the submandibular gland to the orbit was completed in 10 rabbits. Two died before the end of the experimental period and the study was based on the remaining eight. Six months after transfer, five of the eight transferred glands were histologically normal and contained healthy neurones and nerve terminals. In these animals, tear secretion in the transfer eye was significantly greater than that of the control eye at 2 (p less than 0.05) and 6 months (p less than 0.02) after transfer. In the transfer eye, tear secretion was also found to have significantly increased from preoperative levels at 2 (p less than 0.05) and 6 months (p less than 0.01). The observed innervation of the transferred glands may play a role in maintaining secretion in the long term.

Animals↗
PubMed1991

Prostacyclin and prostanoid modifiers aid ischemic skin flap survival.

Prostacyclin, the stable prostacyclin analogue carbacyclin, the thromboxane synthetase inhibitor UK-38,485, and the phosphodiesterase inhibitor dipyridamole were tested on rabbit epigastric free flaps for their ability to improve flap survival after a period of ischemia. Control flaps infused with a balanced salt solution had a 39.9% survival, whereas prostacyclin, carbacyclin, and dipyridamole significantly increased flap survival to 68.4% (P less than 0.05), 66.4% (P less than 0.05), and 66.9% (P less than 0.05), respectively. UK-38,485 improved survival slightly to 47.6% although not significantly. The improved flap survival correlated with the vasodilatory properties of the three successful agents whereas the antithrombotic properties of UK-38,485 were not sufficient, on their own, to increase flap survival.

Animals↗
PubMed1991

Secondary ischaemia in rabbit skin flaps: the roles played by thromboxane and free radicals.

1. Biochemical mechanisms of ischaemia were investigated in rabbit skin flaps subjected to 2 h of primary ischaemia then, 24 h later, to 4 h of secondary ischaemia. During secondary ischaemia, flaps underwent either total ischaemia (arterial and venous blood supply occluded) or partial ischaemia (vein only occluded). Some of these flaps were treated at the time of reperfusion with the free-radical scavenger superoxide dismutase (EC 1.15.1.1) and/or the thromboxane synthetase inhibitor UK-38,485. 2. After 30 min of reperfusion, superoxide dismutase treatment significantly reduced blood thromboxane levels, elevated during ischaemia. Superoxide dismutase also reduced tissue levels of malonyldialdehyde and xanthine oxidase, indicators of free-radical damage, and restored the depleted tissue levels of superoxide dismutase. 3. UK-38,485 treatment failed to significantly alter any of these tissue free-radical parameters, although this agent significantly reduced blood thromboxane levels. 4. Combined superoxide dismutase plus UK-38,485 treatment was not significantly better than either treatment alone with respect to any parameter. 5. Partial ischaemia led to consistently higher levels of tissue free radicals and blood thromboxane than did total ischaemia. Thus partial ischaemia appears to result in greater free-radical damage than total ischaemia. 6. These results are consistent with the hypothesis that thromboxane acts as a mediator for free-radical damage in the ischaemic changes within the flap.

Animals↗
PubMed1991

Enhancement of ischaemic rabbit skin flap survival with the antioxidant and free-radical scavenger N-acetylcysteine.

1. The burst of damaging oxygen free-radicals at the time of reperfusion is one of the crucial factors affecting skin flap survival after an ischaemic interval. In these experiments the efficacy of the antioxidant and free-radical scavenger N-acetylcysteine in improving the survival of ischaemic rabbit epigastric skin flaps was tested. 2. At the time of reperfusion flaps were given: (1) balanced salt solution by intravenous whole-body administration, (2) N-acetylcysteine (200 mg/kg) by intravenous whole-body administration, (3) balanced salt solution by intra-arterial infusion into the flap, (4) N-acetylcysteine (20 mg/kg) by intra-arterial infusion into the flap, or (5) N-acetylcysteine (200 mg/kg) by intra-arterial infusion into the flap. Flap survival at 1 week, and tissue levels of parameters related to free-radical production, blood levels of thromboxane B2 and peripheral resistance during reperfusion were determined. 3. Compared with controls (groups 1 and 3) which had flap survival rates (expressed as percentage surface area surviving) of 27.1% and 31.6%, respectively. N-acetylcysteine treatment in group 2 (55.2%) and group 4 (51.9%) resulted in significant (P less than 0.05) improvements in flap survival. The survival rate in group 5 (37.7%) was not significantly better than that of the controls. 4. N-Acetylcysteine significantly reduced parameters related to free-radical production in the skin flap after 30 min of reperfusion, determined as tissue levels of malonyldialdehyde and protein oxidation products. There was also a significant decrease in peripheral resistance when low-dose N-acetylcysteine (group 4) was infused intra-arterially into the flap.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1991

A biochemical study of acute ischemia in rodent skin free flaps with and without prior elevation.

Elevation of a vascular island flap 24 hours before an ischemic insult (prior elevation) has been shown to significantly increase flap survival, and to decrease blood thromboxane levels, compared with acutely ischemic flaps. The current study considered whether prior elevation causes other biochemical alterations that could be beneficial for flap survival. Tissue levels of adenosine triphosphate (a major tissue energy store), superoxide dismutase (a major defense against free radicals), xanthine oxidase (an enzymatic source of free radicals), and edema were measured. Rat epigastric flaps, with or without prior elevation, had 10 or 12 hours of acute ischemia. Biopsies were taken at 0, 12, or 24 hours after reperfusion. Skin from flaps with no ischemia (control flaps) or control skin was harvested at the same times. Acutely ischemic flaps had significantly lower levels of adenosine triphosphate and less edema than those in prior elevated ischemic flaps after 12 hours of ischemia (both, p less than 0.05). Superoxide dismutase and xanthine oxidase did not vary significantly. It is not clear whether the increased adenosine triphosphate level in prior elevated flaps is the cause or the result of increased tissue viability. Prior elevation did not alter free radical mechanisms. Furthermore, prior elevation was beneficial for flap survival despite increased edema.

Adenosine Triphosphate↗
PubMed1991

Combined coumarin and omental transfer treatments for canine proximal obstructive lymphoedema.

In a canine model both coumarin treatment (believed to act by increased local proteolysis) and surgical transfer of a bridge of vascularized, lymphatic-rich omentum cause significant reduction of experimental lymphoedema. The present paper describes the effects of consecutive application of these two types of treatment. Ten dogs were divided into two equal groups: Group 1 Coumarin treatment, 6 months; no treatment, 6 months; omental transfer, 6 months; or Group 2 Omental transfer, 12 months (biopsied at 6 months); coumarin treatment, 6 months. Prior to treatment the excess limb circumferences were 2.66 and 3.01 cm in Groups 1 and 2 respectively. In Group 1, 6 months coumarin treatment alone reduced swelling by 0.78 cm and the final reduction in swelling at 18 months was 1.03 cm. In Group 2, reduction in swelling 6 months after omental transfer alone was 0.96 cm and the final reduction at 18 months was 2.05 cm. The findings indicate that in Group 1 there is an additive effect of the two types of treatment. However, in Group 2 it is not possible to be certain whether the improvement that occurred between 6 and 18 months also reflects an additive effect or a later consequence of the earlier omental transfer.

Animals↗
PubMed1990

Interaction between thromboxane and free radical mechanisms in experimental ischaemic rabbit skin flaps.

The possible relationship between increased blood levels of thromboxane (TXA2) and tissue levels of free radicals during ischaemia was investigated. Rabbit epigastric skin flaps were subjected to 4 h of body temperature ischaemia, then infused with either the TXA2 synthetase inhibitor UK-38,485, the free radical scavenger superoxide dismutase (SOD), or both immediately prior to reperfusion. After 30 min of reperfusion, increases in the tissue levels of xanthine oxidase (XO) and malonyldialdehyde (MDA), both of which are indices of free radical generation and decreases in the tissue levels of SOD were found. SOD treatment completely restored XO, MDA and SOD levels to normal, whereas UK-38,485 only partially improved all three parameters. None of these changes was statistically significant. Effluent blood thromboxane B2 (TXB2) levels from the flap increased significantly (P less than 0.01) after ischaemia and were reduced significantly by both UK-38,485 and SOD (P less than 0.05). Combined UK-38,485 and SOD treatment was no better than treatment with either agent alone. ATP levels and oedema, which decreased and increased respectively due to ischaemia, were not significantly altered by drug infusion. These results suggest that free radical damage may be related to TXA2-generated thrombosis in ischaemia/reperfusion injury.

Adenosine Triphosphate↗
PubMed1990

Microsurgical transfer of the greater omentum in the treatment of canine obstructive lymphoedema.

In 13 dogs, experimental obstructive lymphoedema of the lower limb was created by combined radiotherapy and radical groin dissection. Six months later, when the degree of lymphoedema was stable, the lymphatic obstruction was bridged by microvascular insertion of a free omental graft. Six months after grafting, circumferential measurements indicated a statistically significant 38% reduction in the magnitude of lymphoedema. Biopsies showed the omental grafts were alive but contained much fibrous tissue. Lymphatic vessels were identified in 10 of 11 biopsies but connections between these lymphatics and lymphatics proximal to the graft could not be demonstrated by either lymphangiography or dye-injection techniques. The findings indicate that experimental obstructive lymphoedema in the dog can be reduced significantly by insertion of a vascularised omental graft. However, it could not be established that improvement was due to union of graft lymphatics with those of the lymphoedematous limb, although this union may have consisted of lymphatics too small to be demonstrated.

Animals↗