Control of catecholamine release and blood pressure with octreotide in a patient with pheochromocytoma: a case report with in vitro studies

A 65-year-old male patient with pheochromocytoma, whose hypertensive episodes were uncontrolled using conventional therapy, was successfully treated with octreotide (SMS 201-995). The serum catecholamine level and the urinary excretion of catecholamines decreased after 300 microgram/day of octreotide was administered. To clarify the mechanisms of octreotide that lower catecholamine released from a tumor, we studied the in vitro effects of octreotide on membrane potentials and voltage-dependent Ca(2+) channel (VDCC) current using the whole-cell patch-clamp technique in single pheochromocytoma cells dispersed after tumor resection. The action potentials were reversibly inhibited with 10 microM octreotide. In addition, the VDCC current evoked by depolarized pulses from the holding potential of -60 mV was inhibited with 10 microM octreotide. Octreotide is useful for controlling blood pressure before surgery in some patients with uncontrolled hypertension caused by a pheochromocytoma.     

Malignant Pheochromocytoma Secreting Vasoactive Intestinal Peptide and Response to Sunitinib: A Case Report and Literature Review

ObjectiveMalignant pheochromocytoma is rare and may be sporadic or have a genetic basis. Vasoactive intestinal peptide (VIP)-secreting pheochromocytoma has rarely been described in the literature, and treatment remains challenging in the absence of well-controlled randomized trials. The hypoxia-inducible factor – vascular endothelial growth factor axis has been implicated in pheochromocytoma when associated with germline Von-Hippel-Lindau (VHL) or succinate dehydrogenase (SDH) mutations, suggesting potential clinical activity of sunitinib in this setting.MethodsWe present a case report of a patient with a VIP-secreting malignant pheochromocytoma manifested as severe watery diarrhea, with an exquisite clinical response to sunitinib. We review this rare clinical entity and the potential role of sunitinib in this context.ResultsA 51-year-old male initially presented with a pheochromocytoma causing symptoms related to norepinephrine excess. He underwent adrenalectomy, which resulted in complete resolution of his symptoms. Three years later, he developed multifocal metastatic disease from his primary tumor, showing immunohistochemical evidence of VIP production accompanied by severe watery diarrhea and hypokalemia. The patient had a rapid, complete, and durable clinical response to sunitinib, but with only a minor radiological response and without significant toxicity. Genetic testing was negative for germline mutations in VHL, SDHB, SDHC, SDHD, transmembrane protein 127 (TMEM127) and for neurofibromatosis type 1 (NF-1).ConclusionTo the best of our knowledge, this is the first report of a case of malignant VIP-producing pheochromocytoma that was responsive to sunitinib.     

生长抑素类似物治疗肿瘤化疗相关性腹泻的临床观察

目的评价生长抑素类似物(奥曲肽,下同)对肿瘤化疗相关性腹泻的疗效。方法对58例出现化疗相关性腹泻(CID)的患者给予奥曲肽治疗。按照NCI CTC标准,全组患者出现Ⅱ级腹泻12例,Ⅲ级腹泻38例,Ⅳ级腹泻8例。Ⅱ级、Ⅲ级CID给予皮下注射奥曲肽100μg bid或静脉持续泵入奥曲肽25μg/h,每天8 h,Ⅳ级CID给予静脉持续泵入奥曲肽25μg/h,每天12 h。结果全组58例患者的总有效率为89.7%。Ⅱ级CID奥曲肽治疗平均有效时间为2.6 d;Ⅲ级CID皮下注射奥曲肽的治疗有效时间平均为4.7 d,而静脉持续泵入奥曲肽的治疗天数平均为3.9 d,二者差异有统计学意义(P<0.05);Ⅳ级CID静脉持续泵入奥曲肽治疗平均有效时间为7.5 d。不良反应表现为5例皮下注射的患者出现一过性面部潮红,恶心,未作处理自行缓解。结论奥曲肽能有效地控制肿瘤化疗相关性腹泻,Ⅱ级以上CID患者宜采用静脉持续滴注治疗为宜。     

Clostridium difficile infection in adult hamsters.

Diarrhea was encountered in a group of adult female golden Syrian hamsters (Mesocricetus auratus) used for titrating the scrapie agent. Ninety percent of the cases occurred in animals over 210 days old even though animals of all age groups lived in the colony concurrently. The cause of diarrhea was investigated in both uninoculated animals and those receiving greater than a limiting dilution of scrapie infectivity, i.e., animals that were not expected to contract the experimental scrapie disease. Three forms of diarrhea were observed. The most commonly encountered was profuse and watery. A chronic form presented with semiformed, thin fecal material smearing the retroperitoneal region. Hemorrhagic diarrhea was observed rarely. Mortality was high among animals with acute watery or hemorrhagic diarrhea. Animals with semiformed soft stools were dehydrated, had a roughened hair-coat, and hunched back. Cardinal lesions were necrosis, inflammation, and mucosal hyperplasia of the cecum and colon and cholangiohepatitis with amyloid deposition. Diffuse renal amyloidosis was present in chronic cases. Toxigenic, cytotoxin B-positive Clostridium difficile was isolated from a majority of affected animals. Cytotoxin B was also present in cecal homogenates of diarrheic animals with C. difficile. The pathological and microbiologic findings indicated a typhlitis and colitis in adult hamsters that was associated with C. difficile infection.     

Pheochromocytoma With Histologic Transformation to Composite Type,Complicated By Watery Diarrhea,Hypokalemia, and Achlorhydria Syndrome

ObjectiveTo describe the rare occurrence of histologic transformation of a pheochromocytoma to a composite type of tumor during a long-term follow-up, which was complicated by watery diarrhea, hypokalemia, and achlorhydria syndrome.MethodsWe report the case of a 12-year-old girl who presented with headache, hypertension, and elevated catecholamine levels in the blood and urine. A tumor was found in the right adrenal gland and resected. When she was 15 years of age, multiple metastatic nodules were found in the lung and liver. Intensive chemotherapy was ineffective, and she underwent follow-up with conservative therapy. At 25 years of age, she complained of diarrhea. Laboratory studies revealed hypokalemia and an increase in the level of serum vasoactive intestinal polypeptide (VIP). A year later, she died of extensive metastatic disease. The primary and recurrent tumors at autopsy were histologically examined.ResultsThe primary tumor was pure pheochromocytoma, and the tumors at autopsy were a composite type of pheochromocytoma and ganglioneuroma. Only a few VIP-positive cells were found in the primary tumor, whereas both pheochromocytoma and ganglioneuroma cells of composite tumors were frequently positive for VIP.ConclusionOur case showed histologic transformation from pheochromocytoma to a composite type of tumor during a 14-year clinical course, which was associated with additional hormone production and a change in symptoms. Careful attention should be paid to the alteration of endocrine symptoms and hormone levels during prolonged follow-up of pheochromocytoma in young patients. (Endocr Pract. 2012;18:e91-e96)     

Does Lower Limb Exercise Worsen Renal Artery Hemodynamics in Patients with Abdominal Aortic Aneurysm?

Renal artery stenosis (RAS) and renal complications emerge in some patients after endovascular aneurysm repair (EVAR) to treat abdominal aorta aneurysm (AAA). The mechanisms for the causes of these problems are not clear. We hypothesized that for EVAR patients, lower limb exercise could negatively influence the physiology of the renal artery and the renal function, by decreasing the blood flow velocity and changing the hemodynamics in the renal arteries. To evaluate this hypothesis, pre- and post-operative models of the abdominal aorta were reconstructed based on CT images. The hemodynamic environment was numerically simulated under rest and lower limb exercise conditions. The results revealed that in the renal arteries, lower limb exercise decreased the wall shear stress (WSS), increased the oscillatory shear index (OSI) and increased the relative residence time (RRT). EVAR further enhanced these effects. Because these parameters are related to artery stenosis and atherosclerosis, this preliminary study concluded that lower limb exercise may increase the potential risk of inducing renal artery stenosis and renal complications for AAA patients. This finding could help elucidate the mechanism of renal artery stenosis and renal complications after EVAR and warn us to reconsider the management and nursing care of AAA patients.     

Abdominal Bruit after Renal Transplantation

Forty-seven recipients of renal allografts have been studied at varying intervals of up to five years after transplantation. Renal artery bruit occurred in eight of 16 patients observed over the first two post-transplant months and disappeared spontaneously in four of these. The disappearance of the bruit was associated with poor renal function. Renal bruits were audible in 10 patients examined more than two months after transplantation; nine of these were hypertensive and of six in whom arteriography was performed five were shown to have stenosis of the allograft artery. By contrast only eight of 37 patients without abdominal bruit were hypertensive, and arteriography in 10 normotensive patients without bruit showed no stenosis. It is concluded that while a renal artery bruit during the first two months after transplantation may be a marker of good renal blood flow at the time, its presence suggests a poor long-term prognosis since persistence of the murmur indicates that significant stenosis of the allograft artery is likely, while its disappearance is associated with poor renal function.     

Lanreotide Therapy in Carcinoid Syndrome: Prospective Analysis of Patient-Reported Symptoms in Patients Responsive To Prior Octreotide Therapy And Patients Naïve To Somatostatin Analogue Therapy in The Elect Phase 3 Study

Objective: This ELECT prospective analysis examined lanreotide depot/autogel for carcinoid syndrome (CS) symptom control in patients with neuroendocrine tumors (NETs) who were responsive to prior octreotide (prior octreotide group) compared with patients who were naïve to prior somatostatin analogue treatment (de novo group).Methods: Adults with histopathologically confirmed NET and stable CS (diarrhea and/or flushing) were randomized to subcutaneous (SC) lanreotide 120 mg or placebo every 4 weeks for 16 weeks. Patients reported diarrhea and/or flushing symptom severity and frequency and short-acting SC octreotide rescue therapy daily using an Interactive Voice/Web Response System. To evaluate the efficacy of lanreotide compared with placebo, the novel primary endpoint of patient-determined use of SC octreotide rescue therapy for breakthrough symptoms was used as a surrogate for symptom control. Clinically meaningful patient-reported treatment benefit was examined using daily patient-reported symptoms of diarrhea and flushing.Results: Of the 115 randomized patients, 51 (n = 26 lanreotide, n = 25 placebo) were octreotide-naïve (de novo) and 64 (n = 33 lanreotide; n = 31 placebo) received prior octreotide. Lanreotide versus placebo patients had a lower mean percentage of days of SC octreotide rescue therapy in de novo and prior octreotide groups (least squares &lsqb;LS] mean difference -19.1, P = .0477 and -6.9, P = .4332, respectively). The mean percentage of days with moderate/severe diarrhea and/or flushing was lower in lanreotide versus placebo patients in de novo and prior octreotide groups (LS mean difference -14.6, P = .0140 and -10.9, P = .0746, respectively). The transition from octreotide to lanreotide was generally well-tolerated.Conclusion: Improvement in CS symptoms occurred with lanreotide treatment, regardless of prior octreotide use.Abbreviations:CI = confidence intervalCS = carcinoid syndromeDB = double blindELECT = Evaluation of Lanreotide depot/autogel Efficacy and safety as a Carcinoid-syndrome TreatmentIOL = initial open-labelIVRS/IWRS = interactive voice/web response systemLS = least squareNET = neuroendocrine tumorOR = odds ratioSC = subcutaneousSSA = somatostatin analogueSSTR = somatostatin receptorTEAE = treatment-emergent adverse event     

全脑血管造影术中顺路行腹主动脉造影81例临床分析

目的评估在全脑血管造影术中顺路行腹主动脉造影的可行性、安全性及其临床意义。方法总结81例在全脑血管造影术中顺路行腹主动脉造影患者的临床资料,分析其肾动脉及髂动脉狭窄检出率及其相关因素,并测定术前术后血清肌酐变化,以评估该检查的安全性。结果全脑血管造影术中顺路行腹主动脉造影简单易行、安全,造影前后血清肌酐无明显变化[术前(76±11)μmol/L,术后(79±9)μmol/L](P0.05);肾动脉狭窄检出率为26%,髂动脉狭窄检出率为20%,肾动脉及髂动脉狭窄总体检出率为33%;有3个及3个以上危险因素的患者其肾动脉及髂动脉狭窄总体检出率明显增高(56%)。结论在全脑血管造影中顺路行腹主动脉造影是安全、简单、可行的,对发现肾动脉、髂动脉狭窄有重要意义。     

Renal extraction of circulating adiponectin in patients with renovascular hypertension

BACKGROUND: Patients with chronic renal failure are characterized by an elevated plasma adiponectin concentration, which is significantly lowered after successful kidney transplantation. The direct renal clearance and extraction of adiponectin have not yet been documented in humans. Therefore the aim of the study was to estimate separate kidney extraction of adiponectin, by measuring its concentration in the aorta and both renal veins, in patients with renovascular hypertension caused by unilateral renal artery stenosis. METHODS: In 30 patients with significant (> 70%) unilateral renal artery stenosis, plasma adiponectin was measured in blood samples taken from the aorta, both renal veins and the vena cava inferior below the orifices of the renal veins. RESULTS: Renal venous plasma adiponectin concentrations (both from the kidney with renal artery stenosis and from the contralateral organ) were only numerically lower than the concentrations measured in the aorta (11.10 [8.65-13.56]; 11.12 [8.81-13.42]; 11.35 [8.90-13.80] microg/ml, respectively). Fractional extraction of adiponectin was 5.0 [-1.6-11.0]% in the kidney with renal artery stenosis and 3.0 [-2.4-9.01% in the contralateral "normal" kidney. Slightly higher concentrations of plasma adiponectin were observed in the vena cava inferior below the orifices of the renal veins (11.79 [9.14-14.44] microg/ml). In patients with unilateral renal artery stenosis significant negative correlations were found between plasma adiponectin concentration obtained from the vena cava inferior below the orifices of renal veins and eGFR (r = -0.38; p < 0.05), systolic (r = -0.71; p < 0.0001) and diastolic blood pressure (r = -0.40; p < 0.04), as well as serum triglyceride concentrations (r = -0.64; p < 0.001). CONCLUSION: The findings indicate that the fractional renal extraction of adiponectin is rather low.     

Sustained-Release Delivery of Octreotide from Biodegradable Polymeric Microspheres

The study reports on the drug release behavior of a potent synthetic somatostatin analogue, octreotide acetate, from biocompatible and biodegradable microspheres composed of poly-lactic-co-glycolic acid (PLGA) following a single intramuscular depot injection. The serum octreotide levels of three Oakwood Laboratories formulations and one Sandostatin LAR^® formulation were compared. Three formulations of octreotide acetate-loaded PLGA microspheres were prepared by a solvent extraction and evaporation procedure using PLGA polymers with different molecular weights. The in vivo drug release study was conducted in male Sprague–Dawley rats. Blood samples were taken at predetermined time points for up to 70 days. Drug serum concentrations were quantified using a radioimmunoassay procedure consisting of radiolabeled octreotide. The three octreotide PLGA microsphere formulations and Sandostatin LAR^® all showed a two-phase drug release profile (i.e., bimodal). The peak serum drug concentration of octreotide was reached in 30 min for all formulations followed by a decline after 6 h. Following this initial burst and decline, a second-release phase occurred after 3 days. This second-release phase exhibited sustained-release behavior, as the drug serum levels were discernible between days 7 and 42. Using pharmacokinetic computer simulations, it was estimated that the steady-state octreotide serum drug levels would be predicted to fall in the range of 40–130 pg/10 μL and 20–100 pg/10 μL following repeat dosing of the Oakwood formulations and Sandostatin LAR^® every 28 days and every 42 days at a dose of 3 mg/rat, respectively.     

Splint renal function after captopril in unilateral renal artery stenosis.

The renal extraction ratios of 131I-sodium iodohippurate (131I-Hippuran) and 125I-thalamate were greatly reduced on the affected side by 50 mg captopril in seven out of 14 patients with unilateral renal artery stenosis. With long term captopril 150 mg daily the uptake of 99mTc-diethylenetriaminepenta-acetic acid by the affected kidney, which was determined by scintillation camera renography, became almost zero in these seven patients, indicating severe reduction of the glomerular filtration rate. Function of the affected kidney returned on discontinuing treatment. The reduced extraction of sodium iodohippurate probably reflected a shortened plasma transit time through the kidney due to intrarenal vasodilatation. The reduced extraction of thalamate reflected a low filtration fraction, suggesting that the vasodilatation was, at least in part, at the level of the postglomerular arterioles. Captopril had little effect on the contralateral kidney and on the kidneys of 17 patients with essential hypertension, and serum creatinine concentrations showed minor changes. Radioisotope renography should be performed after beginning captopril treatment in patients with renal artery stenosis. This is also recommended for patients given captopril as a third line drug when renal artery stenosis has not been excluded. Hypertension is these patients is often severe and difficult to control. Renal artery disease is not rare in this difficult group and finding seriously impaired renal function on one side during captopril treatment may be diagnostic.     

In vivo evidence of regulation by pituitary-adrenal axis of urinary epinephrine excretion in men

The effect of the pituitary-adrenal axis on epinephrine synthesis in the human adrenal medulla was examined by the estimation of the 24-h urinary epinephrine level after treatment with glucocorticoids in four patients with systemic lupus erythematodes (SLE), one patient with rheumatoid arthritis (RA) and one patient with adrenal pheochromocytoma. 24-h urinary catecholamines (CAs) were measured by HPLC before and after glucocorticoid treatment, dexamethasone or prednisolone was orally given for more than seven days to patients with SLE, RA or isolated ACTH deficiency and five days to a patient with adrenal pheochromocytoma. In patients with isolated ACTH deficiency, the 24-h urinary epinephrine level was significantly lower than the normal range. In patients with SLE or RA, the 24-h urinary epinephrine level was normal and it was significantly suppressed by therapeutic doses of prednisolone 30-40 mg/day. In a patient with adrenal pheochromocytoma, 24-h urinary epinephrine was extremely high and it was significantly increased after dexamethasone 0.5 mg/day. These results suggest that epinephrine synthesis in the human adrenal medulla may be dependent on the pituitary-adrenal axis. But the increase in epinephrine synthesis due to dexamethasone in a patient with pheochromocytoma may reflect the direct effect via the feeding artery to the tumor, as previously shown in an in vitro culture system.     

Tying with thread of the rat coronary arteries, a method for the production of experimental coronary stenosis]

A method is described for producing a localized coronary artery stenosis by tieing two threads around the Ramus descendens of the left coronary artery, which produces progressive cell proliferation of the vascular wall. Studies on 102 male Wistar rats (70 experimental and 32 sham-operated control animals) have shown coronary artery stenosis narrowing the lumen by more than 50% (up to and exceeding 90%) to develop after 7 days in 30% of the animals, after 14 days in 75%, and after 21 days (postoperatively) in 100%. In about one-third of the cases subtotal infarction in the supply area of the left coronary artery occured as a result of post-operative damage to the coronary artery with obturating thrombosis. The induction of effective coronary stenosis limiting the coronary reserve offers possibilities for further experimental studies on the role of relative coronary insufficiency in the pathogenesis of myocardial infarction.     

Renal actions of angiotensin II in renovascular hypertension

In renal artery stenosis severe enough to cause hypertension, angiotensin II maintains glomerular filtration rate (GFR) both in the initial high renin phase of hypertension and later when plasma levels are normal. Angiotensin II also maintains GFR in less severe stenosis, which does not cause hypertension. This homeostatic action of angiotensin II to maintain GFr has minimal effects on blood flow. In renal-wrap hypertension, plasma renin levels are elevated for longer than after renal artery stenosis, but in other respects this initial phase of the hypertension is similar to that after renal artery stenosis. GFR is reduced, the rate of development of hypertension is accelerated by angiotensin II, and angiotensin II maintains the glomerular filtration fraction. Renal resistance is markedly increased owing to both compression of the kidney by the hypertrophying renal capsule and to angiotensin II. Thus angiotensin II apparently plays a primarily homeostatic role in renovascular hypertension to maintain glomerular ultrafiltration. It is suggested that the angiotensin II may be formed intrarenally and may act on sites other than resistance blood vessels.     

Renal artery stenosis: an example of how the periphery can modulate voluntary alcohol drinking

Voluntary alcohol drinking, using a free-access procedure, was studied in rats three weeks after unilateral renal artery stenosis was produced by applying a 0.20 mm solid silver clip to the left renal artery (Two-Kidney, One-Clip, Hypertension). The group of animals with the arterial clip drank significantly less alcohol and more water than a sham-operated group. The two groups, however, drank similar amounts of a palatable glucose solution, suggesting that they did not differ in taste sensitivity. Blood alcohol levels measured for six hours following a 2.5 g/kg intraperitoneal injection of alcohol indicated that the difference in alcohol consumption between the two groups could not be accounted for in terms of differences in drug disposition or metabolism. These findings provide an example of a previously unknown type of control which originates in the periphery and contributes to the regulation of voluntary alcohol drinking.     

Plasma active and acid-activatable renin during the development of one-kidney, one-clip and two-kidney, one-clip hypertension in the rabbit.

Systolic blood pressure in the central ear artery of eight rabbits increased by 21 mmHg (1 mmHg = 133.32 Pa) over 40 days following renal artery clipping and contralateral nephrectomy (one-kidney, one-clip). Plasma active and acid-activatable (pH 2.8) renin did not change significantly. Similar data were obtained from a group of 12 rabbits following renal artery clipping alone (two-kidney, one-clip) except that blood pressure in this group increased for 26 days but then declined until 40 days. Two animals with one-kidney, one-clip hypertension and three rabbits with two-kidney, one-clip hypertension had large increases in plasma active and inactive renin levels, which followed a more exaggerated rise in blood pressure than in the previous two groups. Forty days after unilateral renal artery clipping, the unclipped kidney was removed in 10 animals with two-kidney, one-clip hypertension. A further increase in blood pressure (+29%) occurred in seven of the animals but no change in plasma active or inactive renin. Results were compared with two groups of control animals, a unilateral nephrectomy group and a laparotomy group. None of the surgical procedures used produced a consistent pattern of change in the relative amounts of active and inactive renin in plasma. No marked changes in sodium, potassium, or water balance occurred in any group of animals.     

Plasma adenosine 3′,5′ -cyclic monophosphate in human hypertension

In a previous study we observed an increase in urinary cyclic AMP in labile hypertension in the upright position and during isoproterenol infusion, in contrast to a decrease in control subjects. In the present study we measured the plasma level of cyclic AMP in control subjects and patients with various types of hypertension. We obtained the following results: (1) plasma cyclic AMP increases in response to upright posture in control subjects and hypertensive patients; (2) values of cyclic AMP in the recumbent and upright positions are comparable in control subjects and patients with essential hypertension, but are significantly higher in those with true renovascular hypertension due to bilateral renal artery stenosis; (3) propranolol inhibits the increase of plasma cyclic AMP in response to posture in control subjects, but has an opposite effect in labile hypertension where there is a further increase; (4) the rise in blood pressure in pheochromocytoma is associated with a considerable increase in plasma cyclic AMP.Present and previous data suggest that kidney handling of cyclic AMP is abnormal in hypertension, and that the specific defect may be related to the type of hypertension.     

Pressor and vascular responsiveness in renal prehypertensive rabbits with a nonfiltering kidney

This study examined the possibility that the renal tubules are the site of the sensors that respond to renal artery stenosis (RAS) and which initiate the events leading to pressor hyperresponsiveness. A nonfiltering kidney (NFK) was produced in 32 rabbits by 2 hr of total renal ischemia plus permanent ligation of the ureter; the opposite kidney remained undisturbed. Sixteen of these rabbits also received RAS of the NFK. An additional 16 rabbits received RAS without production of a NFK, and 16 more rabbits were sham-operated controls. In acute experiments 3 days later in conscious rabbits, infusions of norepinephrine at several doses resulted in greater increases in mean arterial pressure in the RAS rabbits, with filtering kidneys (2-K, 1-clip) and with NFKs (2-K, 1-clip with NFK), than in the NFK rabbits without RAS (2-K control with NFK) or in the control rabbits (2-K control). Measurements of cardiac output revealed greater increases in total peripheral resistance as well as in mean arterial pressure in response to norepinephrine in the RAS rabbits both without and with a NFK. Because production of a NFK in rabbits did not prevent the development of pressor and vascular hyperresponsiveness 3 days after RAS, these studies indicated that the renal sensors that detect changes in the kidney following RAS and which initiate the series of events leading to pressor and vascular hyperresponsiveness, probably are not located in the renal tubules.     

The use of cryopreserved arteries as arterial vascular prostheses]

The aim of the study is investigation of possibility to bypass small and medium-size arteries with cryopreserved artery allografts, storing 7-10 days at -196 degrees C under the protection of 15% dimethylsulfoxide. In experiments on 40 rabbits were placed a region of the left renal artery by cryopreserved bioprosthesis. Graft patency was 80% after observation up to 6 months. By angiography it was 8 cases of graft thrombosis (all during the 1st week after implantation) and 5 cases of moderate graft dilation (in 4 of them it was accompanied with stenosis of distal anastomosis). In 20 dogs we replaced a region of the femoral artery by cryostoring bioprosthesis. It was only one case of graft thrombosis which occurred on month 2 after the implantation during 1-year follow-up. After 3 months in 3 cases there developed 3 cases of diffuse narrowing of graft lumen without decreasing of blood flow through the prosthesis. Later, the graft lumen did not change. Histological investigations have revealed a viability of cryopreserved vessels, its almost complete de-endothelialization at 3 days and total re-endothelialization 2 weeks after implantation. During the first 2 weeks there were morphological events of graft rejection, which disappeared after 3 months.