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Heme compounds in the plasma in small bowel ischemia in the rat.

The early diagnosis of acute mesenteric occlusion presents a difficult problem in abdominal surgery. In a study on rats the relation between graded small bowel ischemia and the concentration of heme compounds in the plasma was investigated. The ischemia was produced by ligation of terminal vessels at the mesenteric margin of the intestine (mesenteric end arcades) or the superior mesenteric artery. Heme compounds were assayed by a benzidine method developed by Crossby et al. The concentration of heme compounds in the plasma was higher in animals with various grades of intestinal ischemia than in animals subjected to laparotomy alone. This increase was noted as early as 4 hours after induction of moderate and severe grade of ischemia. The results indicate that an increase in plasma concentration of heme compounds takes place at an early stage of moderate and severe small bowel ischemia following mesenteric vascular occlusion but not until after 48 hours in mild ischemia. The clinical value of this method has to be tested in a clinical study.

Animals↗

Effects of ergotamine on isolated human vessels.

In isolated human mesenteric and crural veins, ergotamine induced long-lasting contractions. These contractions were resistant to repeated wash-out and were not affected by alpha-adrenoceptor blockade, but could be abolished by removal of extracellular calcium or by the presence of the calcium-blocker nifedipine. In contrast to its effect on human mesenteric and crural veins, ergotamine had no contractile effect, but a marked relaxant effect on mesenteric arteries mediated via blockade of alpha-receptors. The ergotamine-induced contraction was not affected by indomethacin (0.28--2.8 microM) nor was it influenced by serotonin (5-HT). In both mesenteric and crural veins, the ergotamine-induced contraction was diminished by the 5-HT blocking agent, methysergide. In veins, development of tachyphylaxis to 5-HT was demonstrated. It is concluded that ergotamine has a direct contractile effect on isolated human mesenteric and crural veins. These effects are dependent on unhindered influx of extracellular calcium and are at least partly mediated via 5-HT receptors. In mesenteric arteries, ergotamine acted as an alpha-adrenoceptor blocker, and had no contractant effect.

Adult↗

Increases in vascular alpha 1-adrenoceptor affinity and PI turnover in DOCA-salt hypertensive rats.

The pD2 value for norepinephrine and the pA2 value for prazosin in mesenteric larger resistance vessels from deoxycorticosterone acetate (DOCA)-salt hypertensive rats were significantly higher than the values of normotensive rats, suggesting that alpha 1-adrenoceptors have a higher affinity in hypertensive rats. The accumulation of [3H]inositol monophosphate induced by norepinephrine was significantly greater in the mesenteric artery from hypertensive rats than in the mesenteric artery from normotensive rats. These results suggest that the enhanced phosphatidylinositol turnover seen in DOCA-salt hypertensive rats may contribute, at least partly, to the higher affinity of alpha 1-adrenoceptors.

Animals↗

Vitronectin stabilizes thrombi and vessel occlusion but plays a dual role in platelet aggregation.

The role of vitronectin (Vn) in thrombosis is currently controversial; both inhibitory and supportive roles have been reported. To monitor directly the function of Vn in thrombotic events at the site of vascular injury, we studied Vn-deficient (Vn-/-) and wild-type (WT) control mice with two real-time intravital microscopy thrombosis models. In the mesenteric arteriole model, vessel injury was induced by ferric chloride. We observed unstable thrombi and a significantly greater number of emboli in Vn-/- mice. Vessel occlusion was also delayed and frequent vessel re-opening occurred. In the cremaster muscle arteriole model, vessel injury was induced by a nitrogen dye laser. We observed significantly fewer platelets, lower fibrin content, and unstable fibrin within the thrombi of Vn-/- mice. To define further the role of Vn in thrombus growth, we studied platelet aggregation in vitro. Consistent with our in vivo data, the second wave of thrombin-induced aggregation of gel-filtered platelets was abolished at a low concentration of thrombin in Vn-/- platelets. Interestingly, adenosine diphosphate (ADP)-induced platelet aggregation was significantly increased in Vn-/- platelet-rich plasma (PRP) and this effect was attenuated by adding purified plasma Vn. We also observed increased platelet aggregation induced by shear stress in Vn-/- whole blood. These data demonstrate that Vn is a thrombus stabilizer. However, in contrast to released platelet granule Vn which enhances platelet aggregation, plasma Vn inhibits platelet aggregation.

Adenosine Diphosphate↗

Pharmacokinetics of an active cadralazine metabolite in plasma and blood vessels of spontaneously hypertensive rats.

The plasma and blood vessel (aorta and mesenteric artery) levels of (+/-)-6-[ethyl(2-hydroxypropyl)amino]-3-hydrazinopyridazine (ISF-2405), an active metabolite of cadralazine, were determined and compared with the changes in blood pressure in spontaneously hypertensive rats after single oral administration of cadralazine. The mean plasma level of ISF-2405 reached a maximum at 0.5 h after oral administration of 3 mg/kg of cadralazine, followed by a rapid elimination with a half-life of 1.0 h, whereas the mean aorta level of ISF-2405 reached a maximum at 4 h after dosing, followed by a slow elimination with a half-life of 6.5 h. The mean mesenteric artery levels of ISF-2405 were almost the same as the mean aorta levels over the time investigated. Both patterns of aorta and mesenteric artery levels of ISF-2405 were in good agreement with those of the hypotensive effects. These findings substantiate the assumption that the slow onset and long duration of the pharmacological effect of cadralazine is closely related to the distribution pattern of the active metabolite ISF-2405 in blood vessels, a target tissue of antihypertensive vasodilator drugs.

Animals↗

[Gastrointestinal surgery and gastroenterology. VIII. Gastroenterologic aspects of chronic gastrointestinal ischemia].

The main cause of chronic gastrointestinal ischaemia is atherosclerosis. Stenotic lesions of the mesenteric circulation are relatively common, but lead to chronic ischaemic complaints due to collateral circulation in probably only 2-3 per 100,000 inhabitants per year. The classical presentation (post-prandial abdominal pain, weight loss, upper abdominal souffle) is present in a minority of patients only. Symptoms also occur after exercise. Gastric ulcers and diarrhoea are less frequent. Although patients with 2 and 3 vessel involvement (coeliac artery, superior mesenteric artery and inferior mesenteric artery) usually experience the most severe ischemic complaints, patients with single vessel involvement can also develop symptoms. In the diagnosis of cases with abdominal complaints, factors that aggravate or reduce the complaints anamnestically are the guideline for supplementary diagnostics. The more frequent causes of the symptoms are to be excluded first. Doppler-ultrasonography of the mesenteric vessels can detect most stenotic lesions accurately. To establish the diagnosis visceral angiography is needed. A new method of examination is magnetic resonance angiography (MRA). Another new method is tonometry during exercise: a PCO2 value in the lumen that is higher than that in the blood indicates ischaemia. Non-invasive treatment of chronic gastrointestinal ischaemia is aimed at reduction of the gastrointestinal metabolic workload by smaller meals, at suppression of acid secretion, at inhibition of the secretion of gastric acid and on risk factors for atherosclerosis.

Abdominal Pain↗

Magnetic resonance imaging and magnetic resonance angiography before postchemotherapy retroperitoneal lymph node dissection.

OBJECTIVES: Retroperitoneal lymph node dissection (RPLND) after primary chemotherapy is an accepted therapeutic approach for metastatic nonseminomatous germ cell testicular cancer. Because of the intense desmoplastic reaction and adherence to venous and arterial walls, accurate imaging of the retroperitoneal vasculature and its relation to residual tumor is essential. We report our experience with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), including the recently developed technique of bolus-contrast MRA, in patients undergoing postchemotherapy RPLND. METHODS: Eighteen patients underwent MRI of the retroperitoneal region before RPLND. In addition to routine sequences, MRA was performed in 10 patients, including 8 with a three-dimensional technique using bolus intravenous MR contrast. Results were compared with intraoperative and pathologic findings. RESULTS: MRI and MRA provided detailed information on retroperitoneal vasculature and its relation to tumor, including multiple renal vessels (n = 5), duplex inferior vena cava (n = 1), left retroaortic renal vein (n = 2), and common iliac vein thrombus (n = 1). In all cases, bolus-contrast MRA provided unique information on the location and number of renal and lumbar arteries, in addition to information on the aorta and the mesenteric and iliac vessels. The origin and number of renal arteries were accurately identified in all patients by bolus-contrast MRA; 2 patients had supernumerary renal arteries discovered at RPLND that had not been identified on non-bolus-contrast MRI. CONCLUSIONS: Bolus-contrast three-dimensional MRA provides unique information on renal and lumbar vessels. The potential benefit of avoiding vascular injury during dissection should be prospectively evaluated.

Adult↗

Distribution of small intestinal lesions in anaphylaxis of rats.

Hemorrhage and congestion were not uniformly distributed along the small intestine during systemic anaphylaxis in rats. Duodenum had little hemorrhage and congestion and the terminal ileum had even less. Maximum involvement occurred in jejunum of 13% of rats, in ileum of 47%, and in both jejunum and ileum of 40%. Sequential scoring along the entire length of small intestine revealed different patterns of distribution with more than one peak of intensity in some of the rats. Within a lesioned area, banding was common except where hemorrhage and congestion were so severe as to obliterate all patterns. Banding represented a gradient of injury with respect to the vascular supply. The pale stripes (less severe hemorrhage) contained the penetrating vessels derived from the terminal mesenteric arcades. The dark stripes (more severe hemorrhage) did not contain such vessels. In addition, the mesenteric side of the intestine was less affected than the antimesenteric side. This constituted a second gradient that might also be related to the distance from the vascular supply. In both instances, proximity to larger blood vessels had a protective effect. These two gradients and the variable sites and patterns of distribution have not been described previously in intestinal anaphylaxis. Gradients and the variability of the distribution of lesions in intestinal anaphylaxis should be considered in experiments on pathogenesis and altered function.

Anaphylaxis↗

Vasodilation induced by acetylcholine and by glyceryl trinitrate in rat aortic and mesenteric vasculature.

In endothelium-containing rings of rat aorta which had been precontracted with phenylephrine, addition of acetylcholine (ACh) (0.010-10 microM) resulted in concentration-dependent, graded relaxation through the release of endothelium-derived relaxing factor (EDRF). Hemoglobin (3 and 10 microM) and methylene blue (10 microM) both produced marked inhibition of this EDRF-mediated relaxation. In the perfused mesenteric arterial vasculature of the rat, ACh-induced vasodilation was also inhibited by hemoglobin and by methylene blue, although to a lesser extent than was ACh-induced relaxation of aortic rings by these two agents. These findings indicate that EDRF mediates in large part ACh-induced relaxation of resistance vessels in the mesenteric vascular bed as well as large arteries. The nitrovasodilator glyceryl trinitrate (GTN) caused endothelium-independent relaxation of aortic rings as well as vasodilation of mesenteric arterial vasculature. GTN-induced relaxation of aortic rings was antagonized by hemoglobin as well as methylene blue, but to a lesser extent than was ACh-induced relaxation. However, hemoglobin did not inhibit and methylene blue actually potentiated GTN-induced vasodilation in the perfused mesenteric vasculature. Possible explanations of these paradoxical results are discussed.

Acetylcholine↗

Left retroperitoneal exposure for distal mesenteric artery repair.

Distal disease in the mesenteric arteries has usually been repaired transabdominally since it is believed that only the proximal centimeter of each vessel is accessible through the retroperitoneum. We treated five patients with chronic visceral ischemia and lesions extending beyond the orifice using a retroperitoneal approach. Exposure was obtained with a left flank incision through the tenth interspace. The left crus of the diaphragm was divided in order to control the supraceliac aorta. The mesenteric vessels were identified and dissected until their entrance into the peritoneum. There were no difficulties in exposing the superior mesenteric artery (SMA) as it coursed under the pancreas and over the duodenum for an approximate length of 5 to 10 cm. The uncinate process of the pancreas was not a limiting factor for exposure of the SMA in this region and further distal exposure could be obtained by incising the peritoneum. The trifurcation of the celiac artery and the splenic artery were accessible through this exposure; however, only the first centimeter of the hepatic and gastric branches could be reached. Revascularization was performed with endarterectomy (2 patients) and bypass (3 patients). Bowel viability was assessed at the conclusion of the procedure by incising the peritoneum. There were no complications from this exposure and no patient required reoperation for ischemic bowel. We conclude that the left retroperitoneal approach is not only acceptable for orifice lesions but is also applicable for distal disease.

Blood Vessel Prosthesis↗

Compared myocardial and vascular effects of captopril and dihydralazine during hypertension development in spontaneously hypertensive rats.

When administered to young spontaneously hypertensive rats (SHRs), dihydralazine (25 mg kg-1, daily) and captopril (100 mg kg-1, daily) prevent with the same efficacy genetic hypertension development (GHD). Dihydralazine treatment increased vascular mesenteric compliance, as shown by a significant decrease in the stiffness of the vessels (-27%), and induced slight reductions in contractility (-12%) and in wall to lumen (W/L) ratio (-15%). After treatment withdrawal, all these parameters returned to control values within 7 weeks, as did blood pressure. Captopril treatment also strongly increased the mesenteric vessels compliance, vessel stiffness being decreased by 16%, and reduced their contractility (-15%) and their W/L ratio (-30%). These effects as well as those exerted on blood pressure persisted up to 7 weeks after treatment ceased although there was a slight trend to a progressive reduction in the intensity of both phenomena. These experiments show that captopril but not dihydralazine has a long-lasting effect in opposing the functional and morphological vascular alterations occurring during GHD in SHRs and this phenomenon probably contributes to a large extent to the sustained preventive effects of the drug against GHD.

Animals↗

Functional effects of 4-aminopyridine (4-AP) on pulmonary and systemic vessels from normoxic control and hypoxic pulmonary hypertensive rats.

The effects of the outward rectifying potassium channel blocker, 4-aminopyridine, on contractile tone and on contractile responses to the spasmogens, 5-hydroxytryptamine and endothelin-1, were examined in pulmonary arteries (main and intralobar) and systemic vessels (aorta and mesenteric artery) from rats with and without hypoxic pulmonary hypertension. Hypoxic pulmonary hypertension was induced by exposure of rats to 10% oxygen for 1 week. The development of pulmonary hypertension was associated with (i) depolarization of the cell membrane in intralobar pulmonary artery, but not aorta, and (ii) an increase in sensitivity to 5-hydroxytryptamine in pulmonary, but not systemic, vessels; sensitivity to endothelin-1 was unchanged. 4-Aminopyridine contracted all of the vessels studied. In pulmonary hypertension the sensitivity to 4-aminopyridine was increased ten-fold in pulmonary vessels but was unchanged in systemic vessels. Threshold concentrations of 4-aminopyridine (< or =3x10(-3) M) augmented contractions to 5-hydroxytryptamine in main pulmonary artery and aorta from control rats but failed to augment contractions to 5-hydroxytryptamine in main pulmonary artery from pulmonary hypertensive rats. Responses to endothelin-1 were not augmented by 4-aminopyridine. The membrane depolarization and the increases in sensitivity to 4-aminopyridine and 5-hydroxytryptamine seen in pulmonary hypertension are compatible with the concept that potassium channel function is altered in pulmonary, but not systemic, vessels from pulmonary hypertensive rats. Our data suggest that in main pulmonary artery a common mechanism is responsible for (i) the augmentation of 5-hydroxytryptamine responses by 4-aminopyridine in control rats, and (ii) the sensitization to 5-hydroxytryptamine seen in pulmonary hypertensive, compared with control, rats in the absence of 4-aminopyridine. Hence, we conclude that the sensitization to 5-hydroxytryptamine may be due to downregulation of 4-aminopyridine-sensitive potassium channels.

4-Aminopyridine↗

Vascular mechanisms of cyclosporin-induced hypertension in the rat.

Numerous studies have explored the pathogenesis of cyclosporin A (CysA)-induced hypertension; however, none has assessed the impact of CysA treatment on resistance arteries in the setting of elevated blood pressure. Therefore, we studied the chronic effect of CysA on rat mesenteric artery resistance vessels (ex vivo). CysA (25 mg/kg per d for 7 d), but not vehicle, significantly raised systolic blood pressure (13.4 +/- 2.2 mmHg, P < 0.003, n = 9 per group). The resistance vessels from CysA-treated rats showed a small but significant decrease in norepinephrine sensitivity (P < 0.03) and a pronounced decrease in endothelium-dependent and -independent relaxation (P < 0.001) compared to controls. Endothelin-1 sensitivity tended to be diminished (P = 0.07). The direct (in vitro) effect of CysA was subsequently evaluated in resistance vessels from nontreated animals (n = 8) and exposed to CysA (2 micrograms/ml) for 24 h. As observed in vivo, CysA significantly decreased endothelium-dependent and -independent relaxations (P < 0.05) and attenuated norepinephrine sensitivity (P = 0.06). Methylene blue, a nitric oxide quencher, significantly inhibited the acetylcholine-induced relaxation in control, but not in CysA vessels, suggesting a selective action of CysA on the nitric oxide pathway. We conclude that CysA-induced hypertension is the consequence of a primary effect on resistance vessel relaxation, not increased vasoconstriction, as previously suggested.

Acetylcholine↗

The use of spiral computed tomography in the evaluation of vessel encasement for pancreatic cancer.

CONCLUSIONS: Spiral CT allows for a noninvasive evaluation of the mesenteric arterial and venous vessels. This test can be performed quicker, with less expense, and with a reduced radiation and contrast load than angiography. Comparison studies of angiography and spiral CT are needed in patients with pancreatic cancer to determine the best method of evaluating possible vessel involvement. BACKGROUND: Preoperative imaging of patients with pancreatic cancer is crucial in determining resectability and planning management. Computed tomography (CT) remains the diagnostic procedure of choice for the evaluation of the primary tumor and angiography is the gold standard to evaluate vessel encasement. This case evaluates the usefulness of spiral computed tomography in determining vessel encasement. METHODS: A 53-yr-old female presented with vague abdominal complaints and evaluation revealed a mass in the pancreas. CT suggested portal vein involvement and collateralization was noted in the upper abdomen. Spiral CT revealed normal arterial anatomy and near complete obstruction of the portal vein at the superior mesenteric vein (SMV) splenic vein (SV) confluence. RESULTS: Operative findings confirmed the involvement of the portal vein at the confluence of the SMV and SV. Pancreatico-duodenectomy with portal vein resection and primary anastomosis was performed. The patient's postoperative course was uneventful and she was discharged home on the 13th postoperative day.

Female↗

On the vascular reactivity to angiotensin and noradrenaline in normotensive and spontaneously hypertensive rats.

Vascular reactivity to noradrenaline after angiotensin II and saralasin administration has been studied in vitro on isolated arterial vessels (aorta and mesenteric artery strips) of two strains of normotensive rats and spontaneously hypertensive rats. The results showed: 1. There were no differences in the response to noradrenaline and angiotensin II when they were applied separately on isolated arterial strips of spontaneously hypertensive rats as compared to two strains of normotensive Wistar rats; 2. The potentiated effect of noradrenaline in the presence of angiotensin II is higher on isolated arterial vessels of spontaneously hypertensive rats than on isolated arterial vessels of normotensive rats; 3. The potentiated effect of noradrenaline in the presence of angiotensin II was depressed after administration of angiotensin II-blocker.

Angiotensins↗

[Two cases of small bowel ischemia due to unusual cause].

The authors report 2 cases of small bowel ischemia due to unusual cause. In both cases, vasculopathy was the cause of ischemia, but with a different etiology. In the first case, a mesenteric inflammatory veno-occlusive disease, with striking features of extensive phlebitis and venulitis affecting the veins of the small intestine and mesentery, without arterial involvement of this district was observed and histological examination showed inflammatory lymphocytic infiltrates and myointimal hyperplasia of the veins. The second case affected by intestinal ischemia from secondary and multiple cholesterol embolism, the histological examination showed inflammatory infiltrates with (lymphocytes and granulocytes) in the vessels of submucosal mesenteric area, by loose intimal fibrosis incorporating cholesterol clefts. Both patients required surgical exploration with resection of ischemic bowel. In the second case laparoscopy was the initial approach which allowed to identify the extension of ischemia with special regard to the perforation. The ultimate diagnosis is possible only with histological examination. Clinically, patients show the general signs of intestinal ischemia with pain, vomiting and bloody diarrhea. Prognosis depends on the extension of the lesions and the early surgical treatment.

Aged↗

Mesenteric shunting decreases visceral ischemia during thoracoabdominal aneurysm repair.

PURPOSE: A technique to decrease visceral ischemic time during thoracoabdominal aneurysm (TAA) repair is reported. METHODS: A 10 mm Dacron side-arm graft is attached to the aortic prosthesis and positioned immediately distal to the planned proximal thoracic aortic anastomosis. On completion of the anastomosis, a 16 to 22 Fr perfusion catheter is attached to the side-arm graft and inserted into the orifice of the celiac axis or superior mesenteric artery. The cross-clamp is then placed on the aortic graft distal to the mesenteric side-arm graft. Pulsatile arterial perfusion is thus established to the visceral circulation while intercostal anastomoses or reconstruction of celiac, superior mesenteric, and right renal arteries is performed. Visceral ischemic time and the rise in end-tidal Pco2 after reconstruction of the visceral vessels in patients with mesenteric shunting was compared with a control group matched for aneurysm extent and treated immediately before use of the mesenteric shunt technique. RESULTS: Between July and Oct, 1996, the technique was applied in 15 patients undergoing type I, II, or III TAA repair with a clamp and sew technique. The mean decrease in systolic arterial pressure was 12.5 +/- 8.5 mm Hg, with a concomitant rise in end-tidal Pco2 (mean, 6.9 +/- 5.8 mm Hg), after perfusion was established through the mesenteric shunt. Mean time to establishment of visceral perfusion through the shunt was 25.5 +/- 4.4 minutes; the resultant decrement in visceral ischemic time averaged 31.3 minutes (i.e., until celiac, superior mesenteric, and right renal arteries were reconstructed). Compared with controls, patients with shunts had a significantly decreased (6.9 +/- 5.8 versus 21.6 +/- 8.4 mm Hg; p = 0.0003) rise in end-tidal CO2 on completion of visceral vessel reconstruction. CONCLUSIONS: In-line mesenteric shunting is a simple method to decrease visceral ischemia during TAA repair, and it is adaptable to clamp and sew or partial bypass and distal perfusion operative techniques.

Anastomosis, Surgical↗