Acceleration of ageing processes by ionizing radiation (author''s transl)]

The dynamics of arterial, venous, and lymphatic flow in the mesentery were studied in dogs, using an electromagnetic flowmeter for the blood and cannulation and gravimetric measurement for the lymph. Ligation of veins caused an increased venous outflow in adjacent veins and a marked increase in lymph flow. When marginal vessels were ligated, eliminating the major collateral flow, venous flow decreased, but elevated lymph flow persisted. Simultaneous ligation of arteries and veins resulted in increases of both arterial and venous flow in adjacent vessels. Lymph flow decreased unless excessive arterial collateral flow persisted. When collateral marginal vessel flow was occluded, adjacent venous and arterial blood flow decreased to control levels. With arterial ligation, collateral arterial blood flow increased slightly, but venous and lymph flow decreased sharply. When collateral marginal vessels were eliminated, adjacent arterial blood flow decreased to control levels and venous flow virtually stopped. As a result of these studies, the technic of early primary arterial ligation followed by marginal vessel ligation appears to be the most satisfactory procedure for decreasing venous and lymphatic outflow and hopefully avoiding dissemination of cancer cells during the operation. This technic is now being used as a modification of the "no touch" technic for cancer of the colon.     

Inhibition of feline collateral vessel development following experimental thrombolic occlusion

We compared development of feline hindlimb collateral circulation after acute occlusion of the terminal aorta by ligation, thrombus formation, and formation of a "closed" aortic loop containing thromboplastin. Collateral circulation development was assessed by aortograms, scintillation scans, neurological signs following occlusion, measurement of hindlimb muscle blood flow, and forelimb and hindlimb temperature. In cats in which aortic occlusion was the result of ligation or thromboplastin in the aortic loop, paralysis was not evident. Aortograms and scintillation scans indicated hindlimb blood flow. Both muscle temperature and blood flow data indicated that the return of blood flow was rapid. The 5th lumbar artery appears to be the origin of the collateral vessels. The mid-zone component is a dorsal and ventral vertebral route and an epaxial muscle route. The reentry components are the 6th or 7th lumbar arteries. The collateral vessels arise from preexisting collateral vessels. Of those cats in which aortic occlusion was the result of a thrombus, all exhibited paralysis. Aortograms, scintillation scans, muscle temperature, and hindlimb blood flow data indicated reduced hindlimb blood flow. The results suggest that the thrombus has an inhibitory effect on the development of collateral circulation.     

Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion

PURPOSE: Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, and transgene expression from adenovirus vectors can provide in vivo delivery of proteins. On the basis of this knowledge, we hypothesized that local administration of a replication-deficient adenovirus vector expressing complementary DNA for VEGF (AdVEGF) would induce collateral vessel formation in the setting of ischemia that could protect against subsequent acute vascular occlusion. METHODS: Hindlimb ischemia was induced in Sprague-Dawley rats by means of unilateral ligation of the common iliac artery immediately followed by administration of 4 x 10(9)-plaque-forming units VEGF, the control vector AdNull, or phosphate-buffered saline solution into the iliofemoral adipose tissue and thigh muscles. Untreated rats with common iliac ligation were used as an additional control group. RESULTS: Local VEGF expression was observed for 5 days in AdVEGF-treated rats but not in controls. Three weeks after ligation and vector administration, the ipsilateral femoral artery was ligated for a model of an acute vascular occlusion in the setting of preexisting ischemia. Blood flow to the ischemic hindlimb relative to the contralateral hindlimb evaluated with color microspheres demonstrated significantly increased blood flow in the AdVEGF-treated rats compared with each control group (p < 0.0001). Relative blood flow assessed by means of 99mTc-sestamibi radionuclide scans also demonstrated increased blood flow to the ligated hindlimb of AdVEGF-treated rats compared with each control group (p < 0.002). AdVEGF-treated rats also demonstrated increased vascularity in the ligated limb compared with each control group as assessed by means of angiography (p < 0.0001) and histologic quantification of blood vessels less than 80 microm diameter in local adipose tissue and capillaries per muscle fiber (p < 0.0002). AdVEGF treatment prevented a rise in femoral venous lactate femoral venous concentrations 1 hour after femoral artery ligation in control rats (p < 0.04). CONCLUSIONS: An adenovirus vector expressing VEGF complementary DNA is capable of stimulating an angiogenic response that protects against acute vascular occlusion in the setting of preexisting ischemia, suggesting that in vivo gene transfer of VEGF complementary DNA might be useful in prophylaxis of advancing arterial occlusive disease.     

Early adaptations in collateral and microvascular resistances after ligation of the rat femoral artery

Collateral and microvascular (including feed artery) resistances in the rat hindlimb were determined immediately or 1 wk after ligation of the femoral artery. Collateral-to-microvascular resistance ratios were determined from in vivo pressure measurements proximal and distal to the ligation. Microvascular resistance was 32 +/- 2.5 and 41 +/- 1.5% of the total collateral-dependent vasculature in acutely and chronically ligated limbs, respectively, and decreased 20% in both groups during reactive hyperemia. Minimum resistances of collateral vessels and the microcirculation arising from arterial branches proximal and distal to the ligation were determined by using a modification of the standard hindquarter perfusion technique for determining maximum vascular conductance. One week postligation, minimum total hindquarter resistance was decreased by a reduction in the resistance of the collaterals (approximately 50%) and microcirculation (approximately 33%) proximal to the ligation. The results suggest that the microvasculature distal to the occlusion is able to increase flow by dilation both initially and at 1 wk postligation but that collateral adaptations are primarily responsible for decreases in the minimum total resistance of the collateral-dependent region.     

Ischaemic colitis in the experimental animal. II. Role of hypovolaemia in the production of the disease

Hypovolaemia alone did not lead to ischaemic colitis but when venesection was induced immediately after the acute ligation of the common colic artery large bowel ischaemia ensued. Similarly, hypovolaemia induced one month after two major blood vessels had been occluded led to ischaemic colitis. These findings suggest that states of low blood flow in the presence of previous arterial constriction or blockage may lead to enough reduction in mesenteric perfusion for intestinal ischaemia to develop. Using an electromagnetic flowmeter placed in the cranial mesenteric artery of the dog, it was shown that hypovolaemia may lead to 50-75% reduction in mesenteric blood flow without producing any significant change in the systemic blood pressure.     

Acute coeliac artery occlusion: initial collateral blood flow from the superior mesenteric artery. An experimental study

The collateral blood flow from the superior mesenteric artery after acute occlusion of the coeliac truck was measured in experiments in dogs. Immediately after clamping of the coeliac axis the collateral flow was about 30 % of the original coeliac blood flow. During an observation time of three hours the collateral flow increased, the corresponding value at the end of experiment being about 50 %. At the same time the blood pressure in the coeliac artery rose from a mean value of 20 mmHg to 35 mmHg. The initial collateral blood flow was evidently not sufficient, since after this short occlusion period ischaemic changes, even necrosis, were observed in the liver and stomach in some of the test animals.     

Coordinated induction of plasminogen activator inhibitor-1 (PAI-1) and inhibition of plasminogen activator gene expression by hypoxia promotes pulmonary vascular fibrin deposition

PURPOSE: In a rabbit model, transposition of a muscle pedicle flap to an ischemic hind limb has been shown to result in the development of new blood vessels that connect the arterial circulation of the flap to the circulation of the limb. The hypothesis that exogenous recombinant basic fibroblast growth factor (bFGF) would enhance the development of this new blood supply was examined and the regulation of bFGF in this process was investigated. METHODS: The right common iliac artery was ligated in 12 male New Zealand white rabbits. An abdominal wall muscle flap based on the left inferior epigastric artery was transposed to the right thigh. bFGF in phosphate-buffered saline (PBS) at 3 ng/h (n = 6), or PBS alone (n = 6), was infused for 7 days via mini-osmotic pumps with an infusion catheter positioned at the flap-muscle interface. The flap-muscle interface was immunostained with anti-alpha-actin antibody to determine blood vessel density (number of vessels/mm) and with anti-bFGF antibody to evaluate bFGF distribution. RNA was isolated from these sections, and polymerase chain reaction (PCR) was used to examine endogenous bFGF messenger RNA (mRNA) expression. RESULTS: Blood vessel density was significantly increased in animals receiving exogenous bFGF (22. 0 +/- 10.6 vessels/mm vs. 10.7 +/- 8.8 vessels/mm, P =.009). In the controls, neovessels were arranged in clusters with endogenous bFGF concentrated around these clusters. In bFGF-treated animals, vessels were diffusely scattered throughout the flap-limb interface, corresponding to the distribution pattern of infused bFGF. There was no difference in bFGF mRNA expression between the control and the bFGF-treated groups. CONCLUSION: Exogenous bFGF infusion significantly augmented new blood vessel development at the flap-limb interface. Endogenous bFGF was up-regulated around the newly developed microvessels in control animals, and vessel growth correlated with the diffuse distribution of exogenous bFGF, implicating bFGF as an important factor in angiogenesis. Exogenous bFGF did not affect bFGF mRNA expression, suggesting that the regulation of bFGF is not under autocrine control.     

Cerebral revascularization by omental free flap using contralateral superficial temporal vessels as recipient vessels: case report

BACKGROUND: Although the most common technique of cerebral revascularization is superficial temporal artery to middle cerebral artery bypass, we occasionally encounter a situation in which the ipsilateral superficial temporal artery is not available. Treatment may require several techniques including long vein graft bypass. METHODS: A 54-year-old man experienced transient ischemic attacks, and cerebral angiography revealed occlusion of the right common carotid artery. Cerebral blood flow study revealed reduced perfusion reserve capacity of the right cerebral hemisphere. We applied an omental free flap to the brain surface using the contralateral superficial temporal vessels as recipient vessels. RESULTS: Cerebral blood flow study revealed improvement of perfusion reserve capacity. Cerebral angiography revealed good collateral circulation from the omentum to the brain. The patient has not experienced a transient ischemic attack, following additional ligation of the occipital artery 13 months after the first operation. CONCLUSIONS: Because an omental flap has a long pedicle and its circulation can be monitored easily, this method is safe and as effective as a long bypass graft in a patient such as ours in whom the ipsilateral superficial temporal artery is not available for anastomoses.     

A method for galactose-1-phosphate uridyltransferase assay and the separation of its isozymes by DEAE-cellulose column chromatography

The resistance to coronary blood flow in various parts of the myocardium was studied with the tracer microspheres technique before and immediately after an acute coronary occlusion and several weeks after a more slowly occurring coronary occlusion by Ameroid constrictor. All experiments were carried out in the isolated, metabolically supported, empty, beating dog heart at maximal coronary vasodilation induced with adenosine. Coronary resistance of the normal empty beating heart at maximal coronary vasodilation was 0.20 mm mm Hg/(ml/min) per 100 g of tissue (subepicardium) and 0.16 mm Hg/(ml/min) per 100 g of tissue (subendocardium). After acute coronary occlusion the perfusion of the subtended myocardium was maintained at a much lower level by way of collateral vessels, which showed a resistance to flow of 3.52 mm Hg/(ml/min) per 100 g. If coronary artery occlusion proceeded more slowly the collateral vessels became more functional and myocardial infarction was avoided. During collateral enlargement collateral resistance fell from 3.52 to 0.22 mm Hg/(ml/min) per 100 g within a period of 8 weeks after implantation of the constricting device. The degree of compensation by collaterals for the loss of the occluded native coronary artery was 33% of its former conductance.     

Redistribution of collateral blood flow from necrotic to surviving myocardium following coronary occlusion in the dog

Early changes in collateral blood flow after acute coronary occlusion may be critical for survival of ischemic myocardium. We used 15-mum radioactive microspheres to study myocardial blood flow in thoracotomized dogs 10 minutes and 24 hours after occlusion of the left anterior descending coronary artery (LAD). The ischemic area was delineated by dye injected into the distal artery, and indentification of potentially ischemic samples was confirmed by a newly developed technique in which microspheres were excluded from the normally perfused LAD. Layers were separated into necrotic or normal as defined by gross inspection and confirmed by histological examination and creatine phosphokinase assay. Infarction always involved endocardial layers and extended toward the epicardium. Average myocardial blood flow in 48 necrotic samples from 16 dogs either remained low (less than 0.05 ml/min g-1) or declined, falling from 0.11 +/-0.02(SE) at 10 minutes to 0.05 +/-0.01 ml/min g-1 at 24 hours (P less than 0.001). In contrast, in the 32 normal-appearing samples which were ischemic at 10 minutes, flow increased from 0.24 +/-0.03 to 0.39 +/-0.04 ml/min g-1 (P less than 0.001). Flow in control myocardium was 1.43 +/-0.12 and 1.04 +/-0.07 ml/min g-1, respectively. Peripheral mean coronary arterial pressure increased from 26 +/- 3 to 35 +/- 3 mm Hg, largely because of enlargement of collateral vessels; collateral conductance calculated from retrograde flow in 14 dogs increased from 0.023 +/- 0.005 after occlusion to 0.051 +/- 0.009 ml/min mm Hg-1 24 hours later (P less than 0.001). Thus, coronary collateral blood flow is redistributed from necrotic endocardial layers to surviving epicardial ones. In combination with a developing collateral supply this process may be essential for sparing myocardium after coronary occlusion.     

Characterization of a class Ib gene of the rat major histocompatibility complex

Moyamoya disease is characterized occlusion of Willis' artery ring and abnormal "moyamoya" vessels. By supplying sufficient blood flow to the distal area of the stenosis or occlusion, ischemic symptom could be improved and the risk of the hemorrhage are lessen. Encephalo-Myo-Synangiosis (EMS) can increase the blood supply from external carotid artery to the ischemic area just put the temporal muscle on the brain surface. A kind of growth factor are thought to be exist around the brain of the Moyamoya disease patient. Basic fibroblast growth factor (bFGF) contribute angiogenesis in vitro and in vivo. This effect is considered to grow tumors and many experiments are done to use it for therapy by blocking this effect. Few trials are done to utilize the angiogenetic effect for therapy. We studied the effect of the bFGF on angiogenesis after EMS by using rats. We operated EMS on 10 male SDrats. 0.1 microgram of the bFGF was poured on 5 rats between the brain and muscle. On the other 5 rats just saline was poured. One week after rats were sacrificed, new vessels were observed with light microscope and scanning electron microscope. Molding models were also observed. bFGF group grew larger new vessels between the brain and muscle than non bFGF group. On the surface of brain, bFGF had more larger vessels (diameter is over 6 um) and non bFGF group had more small vessels (less than 6 um). Total area of vessel of bFGF group was twice as large as that of non bFGF group. On molding models many closed end of vessels were seen and they were thought to be the growing vessels. In molding models, bFGF group also has larger vessels than non bFGF group. We could prove that bFGF promotes angiogenesis on EMS of the rats, and we also expect that bFGF help the supplying blood flow of the Moyamoya patient.     

Etest for routine clinical antimicrobial susceptibility testing of rapid-growing mycobacteria isolates

Tumors depend on their blood supply for growth. The blood supply to metastatic neoplasia of lung is usually from the pulmonary circulation or both the pulmonary and systemic circulation. The antineoplastic effect of pulmonary artery occlusion was investigated in a rat model of methylcholanthrene-induced metastatic pulmonary sarcoma. Left pulmonary artery ligation was performed on day 7 after tumor inoculation, and animals were sacrificed on day 14. The tumor burden of the left lung decreased 44% when compared with the control group. The survival of non-tumor-bearing rats undergoing left pulmonary artery ligation for 24 hours followed by right pneumonectomy after 2 weeks was also studied. No significant lung damage after a period of left pulmonary artery ligation was seen, as evidenced by both survival after contralateral right pneumonectomy and histology. Balloon occlusion of pulmonary artery, together with regional chemotherapy for patients with lung metastases, may warrant investigation.     

Surgical treatment of traumatic aneurysms of the peripheral vessels

The article analyzes the surgical treatment of 64 patients with traumatic aneurysms of the extremity vessels. In late terms (from 1 to 8 years) the main blood flow was found to recover in 46 to 53 patients. An analysis of near and late results showed an expediency of recovery of the main blood flow after ablation of arterial and arterio-venous aneurysms with the help of a circular suture or plasty with autovenous tubular grafts. In arterio-venous shunts the best method was found to be liquidation of the shunt by ligation or suturing it with an apparatus for suturing the vessels.     

Treatment of thromboangiitis obliterans (Buerger's disease) by intramuscular gene transfer of vascular endothelial growth factor: preliminary clinical results

PURPOSE: Thromboangiitis obliterans (TAO), or Buerger's disease, a distinct form of vascular occlusive disease that afflicts the peripheral arteries of young smokers, is often characterized by an inexorable downhill course even in patients who discontinue smoking once a stage of critical limb ischemia associated with ulceration or gangrene is reached. As part of a phase I clinical trial to document the safety and efficacy of intramuscular gene transfer of naked plasmid DNA-encoding vascular endothelial growth factor (phVEGF165) in the treatment of critical limb ischemia, we treated TAO in 6 patients. METHODS: Seven limbs in 6 patients (3 men, 3 women; mean age, 33 years; range, 33 to 51 years) who satisfied the criteria for TAO and had signs or symptoms of critical limb ischemia were treated twice, 4 weeks apart, with 2 or 4 mg of phVEGF165, which was administered by direct intramuscular injection at 4 arbitrarily selected sites in the ischemic limb. The gene expression was documented by enzyme-linked immunosorbent assay that was performed on peripheral blood samples. RESULTS: The ulcers that were nonhealing for more than 1 month healed completely in 3 of 5 limbs after the intramuscular phVEGF165 gene therapy. Nocturnal rest pain was relieved in the remaining 2 patients, although both continue to have claudication. The evidence of the improved perfusion to the distal ischemic limb included an increase of more than 0.1 in the ankle brachial index in 3 limbs, an improved flow shown with magnetic resonance imaging in 7 of the 7 limbs, and newly visible collateral vessels shown with serial contrast angiography in 7 of the 7 limbs. The adverse consequences of the phVEGF165 gene transfer were limited to transient ankle or calf edema in 3 of the 7 limbs. Two patients with advanced distal forefoot gangrene ultimately required below-knee amputation despite the evidence of improved perfusion. A histologic section disclosed the classic pathologic findings of TAO. CONCLUSION: Therapeutic angiogenesis with phVEGF165 gene transfer, if instituted before the development of forefoot gangrene, may provide a novel therapy for patients with advanced Buerger's disease that is unresponsive to standard medical or surgical treatment methods.     

Perfusion of ischemic myocardium during anesthesia with sevoflurane

BACKGROUND: Sevoflurane produces direct vasodilation of coronary arteries in vitro and decreases coronary vascular resistance in vivo, pharmacologic properties that may contribute to the development of "coronary steal." This investigation examined the effects of sevoflurane on the distribution of regional myocardial perfusion in chronically instrumented dogs with steal-prone coronary artery anatomy. METHODS: Dogs were chronically instrumented for measurement of aortic and left ventricular pressure, diastolic coronary blood flow velocity and subendocardial segment length. After recovery from surgery, dogs underwent repetitive, brief, left anterior descending coronary artery (LAD) occlusions via an implanted hydraulic vascular occluder to enhance collateral development. A progressive left circumflex coronary artery (LCCA) stenosis was also obtained using an ameroid constrictor. After development of LCCA stenosis, the LAD was totally occluded to produce a model of multivessel coronary artery disease. Systemic hemodynamics, regional contractile function and myocardial perfusion measured with radioactive microspheres were assessed in the conscious state and during sevoflurane anesthesia at 1.0 and 1.5 MAC with and without restoration of arterial blood pressure and heart rate to conscious levels. RESULTS: Total LAD occlusion with simultaneous LCCA stenosis increased heart rate, mean arterial pressure, left ventricular systolic and end-diastolic pressures, end-diastolic segment length, and rate-pressure product in conscious dogs. Subsequent administration of sevoflurane caused dose-related decreases in arterial pressure, left ventricular systolic pressure, double product, and peak rate of increase of left ventricular pressure at 50 mmHg. Perfusion of normal myocardium was unchanged during sevoflurane anesthesia. In contrast, sevoflurane caused dose-dependent decreases in blood flow to myocardium supplied by the stenotic LCCA, which returned to control levels after restoration of heart rate and arterial pressure. No reduction in collaterally derived blood flow to the occluded region was produced by 1.0 or 1.5 MAC sevoflurane. No redistribution of blood flow away from the occluded LAD region to normal or stenotic myocardium occurred during sevoflurane anesthesia. In fact, increases in the ratio of blood flow between occluded and normal zones or occluded and stenotic zones were observed in the subepicardium during 1.5 MAC sevoflurane with maintenance of the heart rate and arterial pressure at conscious levels. CONCLUSIONS: The results demonstrate that sevoflurane does not reduce or abnormally redistribute myocardial blood flow derived from coronary collateral vessels in a chronically instrumented canine model of multivessel coronary artery obstruction.     

Comparison of relative risks of urinary stone formation after surgery for ulcerative colitis: conventional ileostomy vs. J-pouch. A comparative study

The main techniques which have been used to study skin microcirculation in patients with peripheral arterial occlusive disease include intravital microscopy with and without the use of fluorescent dyes, laser Doppler fluxmetry and transcutaneous oximetry. In patients with severe ischaemia (rest pain or incipient gangrene) the number of perfused skin capillaries is reduced. Parallel to the decreased number of microvessels containing blood, transcutaneous oxygen tension is low or even approaches the zero level. The tendency to oedema formation is documented by increased leakage of intravenously injected sodium fluorescein at the capillary apex of foot skin ('candlelight phenomenon'). Laser Doppler flux at rest may still be within the normal range even in advanced disease, since the sample volume of these instruments also contains non-nutritive shunt vessels. However, reactive hyperaemia after arterial occlusion is decreased and delayed in peripheral ischaemia. Whereas rhythmic low-frequency vasomotion is significantly enhanced in patients with intermittent claudication, vasoparalysis with no flux fluctuations prevails in patients with critical ischaemia.     

Left colon gangrene after acute inferior mesenteric artery occlusion

We report here an experience with five patients, aged 58 to 70, suffering gangrene of the left colon after spontaneous inferior mesenteric artery occlusion. All cases were the result of arteriosclerosis; in two, small aortic aneurysms were present and might have been responsible for emboli to the inferior mesenteric artery. The dead bowel was resected in all patients; three patients survived. No primary anastomoses were done and they are not recommended. Because ligation of the patent inferior mesenteric artery has been done so often without ill effects during aortic surgery, the collateral circulation to the left colon can be considered excellent. Gangrene is therefore rare and requires major interference with collateral circulation by emboli or arteriosclerotic occlusion. The clinical symptoms and signs may be confusing.     

Aortic foreign body resulting in ischemic neuromyopathy and development of collateral circulation in a cat

A cat evaluated for paraplegia had firm pelvic limb musculature and did not have femoral pulses. External wounds were not evident, but abdominal radiography revealed a round metallic foreign body on the midline ventral to the sixth lumbar vertebra. Angiography indicated stenosis or thrombosis of the aorta in association with the foreign body; collateral circulation arose from the fifth lumbar artery. Arteriotomy was performed to extract the foreign body and associated thrombi. Six weeks after surgery, angiography revealed blood flow in the abdominal portion of the aorta, but no evidence of obstruction or additional collateral vessels. The cat regained function of the pelvic limbs within 1 year after surgery. Ischemic neuromyopathy and paraplegia in cats is commonly associated with aortic thromboembolism. A thrombus is necessary to cause typical clinical signs, and vasoactive substances released by platelets in the thrombus are believed to cause ischemic neuromyopathy. Progression of the collateral circulation may allow for clinical improvement without surgical intervention.     

Technetium-99m MIBI to assess coronary collateral flow during acute myocardial infarction in two closed-chest animal models

Collateral flow is an independent determinant of infarct size in both animal and clinical studies of myocardial infarction. The purpose of this study was to quantitatively evaluate, in a closed-chest animal model, a noninvasive method of measuring coronary collateral flow over a wide spectrum of collateral flow rates from a tracer that can be injected during occlusion but measured after reperfusion. METHODS: Fourteen animals underwent 40 min of coronary occlusion using a closed-chest technique. Two closed-chest models representing different rates of collateral flow were used: canine and porcine. Coronary blood flow was measured by radiolabeled microspheres. Collateral blood within the risk zone was estimated from the severity of 99mTc-sestamibi tomographic perfusion defect. RESULTS: Collateral blood flow was significantly higher in the canine model than it was in the porcine model. There was close agreement (r = 0.90) between absolute collateral flow by microspheres and the severity of the tomographic perfusion defect. CONCLUSION: These results suggest that an accurate noninvasive estimate of collateral blood flow can be provided by an intravenous injection of 99mTc-sestamibi.     

Physiological and mechanical adaptations of rabbit medial collateral ligament after anterior cruciate ligament transection

Progressive physiological and mechanical changes in the medial collateral ligament of the adult rabbit were investigated for as long as 48 weeks after disruption of the anterior cruciate ligament. Eighty-one New Zealand White rabbits were separated into experimental, sham-operated control, and normal control groups. The experimental group underwent unilateral transection of the right anterior cruciate ligament, sham-operated animals served as controls for comparison, and normal animals were evaluated as age-matched, undisturbed (no surgery) controls. Blood flow to the medial collateral ligament (as a physiological measure) and mechanical function (structural and material properties) were assessed at 6, 14, and 48 weeks. The results indicated that loss of the anterior cruciate ligament leads to early mechanical deterioration of the medial collateral ligament with a corresponding loss of physiological homeostasis. Six to 14 weeks after the transection, values for cross-sectional area of the medial collateral ligaments rapidly increased to 1.5 times control values. The ligament became twice as large as the control ligament by 48 weeks. Concomitantly, medial collateral ligament stress at failure of the medial collateral ligament complex decreased rapidly 6-14 weeks after the transection and eventually fell to one-half that of controls by 48 weeks. In terms of low-load behaviour, laxity and load relaxation were significantly greater than that of controls 6 weeks after transection and were further increased by 14 weeks. By 48 weeks, laxity values had recovered somewhat and load-relaxation measures had recovered to near control values. At both 6 and 14 weeks, a statistically significant elevation in blood flow was demonstrated compared with controls. By 48 weeks, however, blood flow was no different from that of the sham-operated control. Thus, early after transection of the anterior cruciate ligament, both low-load and high-load mechanical properties of the medial collateral ligament deteriorated and the rate of blood flow was temporarily elevated. By 48 weeks, blood flow declined to near control values, with a corresponding recovery in viscoelastic behaviour. These findings suggest that, after transection of the anterior cruciate ligament, viscoelastic behaviour of the medial collateral ligament may be related to changes in blood flow and that restoration of normal flow patterns and vascular responses may be linked to the recovery of some low-load mechanical properties in the anterior cruciate ligament-deficient medial collateral ligament.