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Biomedical subjects

G B Bulkley

Publications and source records attributed to G B Bulkley.

At least 127 records · Page 7Linked to original sources

The use of intraperitoneal xenon for early diagnosis of acute mesenteric ischemia.

We evaluated the technique of intraperitoneal use of xenon Xe 133, previously described for the diagnosis of early intestinal strangulation obstruction in rats and dogs, for the recognition of acute mesenteric vascular occlusion in these animals. 133Xe was injected intraperitoneally into five groups of six rats: control, sham operation, superior mesenteric artery (SMA) ligation, superior mesenteric vein ligation, and portal vein ligation. Residual gamma-activity was monitored by external counting and camera imaging. At 30 minutes after injection, the activity was significantly higher in the rats from the three groups with vascular ligation than in the control and sham operation animals (P less than 0.001). gamma-Camera images reflected these findings, with positive images only in the rats that underwent vascular ligation. "Blinded" readings of the 30 sets of scans confirmed the diagnostic accuracy of the images. Results were essentially the same in a second series of experiments in eight control dogs and six dogs with balloon occlusion of the SMA. Concentrations of isotope in ischemic intestine ranged from 10(3) to 10(5) times the levels in adjacent normal bowel. These levels and the positive images appeared early, prior to the development of tissue necrosis. The intraperitoneal use of 133Xe therefore continues to show promise for the recognition of patients with early intestinal ischemia.

Animals↗

[Studies on the prediction of intestinal recovery from ischemic injury by fluorescein fluorescence patterns].

Methods for the prediction of intestinal recovery from ischemic injury were evaluated in highly reproducible model of segmental intestinal strangulation in the rat. Systemic variables were minimized and survival was maximized by parenteral administration of antibiotics and nutrient solution, so that necrosis or recovery of the segment itself, not the rat, could be used as an endpoint of experiments. Recovery of ischemic intestine was assessed by two methods: Standard clinical criteria (color, peristalsis, pulsation.) Fluorescence after intravenous fluorescein injection. Findings were compared with ultimate viability assayed by histologic examination of each segment removed 48 hours after release of strangulation. Five distinctive patterns of fluorescein fluorescence were identified, two of which (normal pattern and fine granular pattern) reliably predicted survival of the segment, and two of which (perivascular pattern and no fluorescence) predicted subsequent necrosis. A fifth, coarse granular pattern usually, but not always, predicted non-recovery. Standard clinical criteria were relatively insensitive and could not be relied upon to detect nonviable segments. The fluorescein fluorescence method correctly identified all nonviable segments at the expense of an acceptably low overall false positive rate. This study suggests that the fluorescein methods is the method of choice for the prediction of small intestinal recovery following ischemic injury.

Animals↗

Preoperative recognition of intestinal strangulation obstruction. Prospective evaluation of diagnostic capability.

Early recognition of intestinal strangulation in patients with small bowel obstruction is essential to allow safe nonoperative management of selected patients. We prospectively evaluated preoperative diagnostic parameters as well as the preoperative judgement of the senior attending surgeon for the determination of the presence or absence of intestinal strangulation in 51 consecutive patients who were about to undergo laparotomy for complete mechanical small bowel obstruction. Strangulation was present in 21 (42 percent) of the 51 patients. No preoperative clinical parameter, including the presence of continuous abdominal pain, fever, peritoneal signs, leukocytosis, or acidosis, or a combination thereof proved to be sensitive, specific, and predictive for strangulation. Moreover, the senior surgeon's experienced clinical judgement detected strangulation in only 10 of 21 patients with strangulation preoperatively (sensitivity, 48 percent). Indeed, only 1 of these 10 patients had an early, reversible lesion, whereas 9 had advanced, irreversible infarction. Only 25 of 36 preoperative assessments of simple obstruction proved correct (predictive value of an assessment of no strangulation, 69 percent). Overall, the preoperative assessment was correct in only 35 of the 51 patients (efficiency, 70 percent). These data show that in patients with complete mechanical small bowel obstruction, the preoperative diagnosis of strangulation cannot be made or excluded reliably by any known clinical parameter, combination of parameters, or by experienced clinical judgement. Nonoperative management of complete intestinal obstruction is therefore undertaken at a calculated risk (31 +/- 51 percent in the present series) of delaying definitive treatment of intestinal ischemia.

Adolescent↗

Intraperitoneal xenon for the detection of early intestinal ischemia: effect of ascites, adhesions, and misdirected injections.

Significant delay in the washout of intraperitoneal xenon (133Xe) in rats and dogs with decreased splanchnic blood flow (bowel strangulation, superior mesenteric artery and vein occlusion) has been previously demonstrated as the basis for radionuclide imaging to detect early (prenecrotic) intestinal ischemia. In this study, the effect of ascites, adhesions, and misdirected injections on the validity of this technique is evaluated. Xenon-133 (0.6 mCi) in 3 ml saline was injected into the peritoneal cavity of anesthetized rats and the washout of gamma activity monitored externally for 90 min. Gamma camera images were obtained at 30-min intervals. After 60 min, only 12 +/- 2% of injected activity remained in the controls. Sham operation (13 +/- 1%) and simple obstruction (12 +/- 2%) had been previously shown not to significantly slow washout, but segmental strangulation had done so dramatically (32 +/- 2%, P less than 0.0001). In these experiments, ascitic fluid (Ringer's lactate) in volumes of 10 ml (13 +/- 1%), 20 ml (13 +/- 1%), and 40 ml (13 +/- 1%), did not significantly slow washout in nonischemic rats. Sixty and eighty milliliters produced very tense ascites and slight but significant delay in washout (14 +/- 1%, 17 +/- 1%, respectively, P less than 0.05). Moderate (11 +/- 1%) and severe (11 +/- 1%) adhesions produced by serosal scarification did not delay washout nor affect imaging. Injections of isotope intentionally misdirected into the abdominal wall (32 +/- 2%), bowel wall (18 +/- 1%), and bowel lumen (19 +/- 2%), each significantly (P less than 0.001) slowed washout. However, such misdirected injections were easily recognizable as such on the 1-min gamma camera images and could thereby be excluded as artifactual. Therefore, no false positive readings were obtained. It is concluded that the intraperitoneal xenon technique is not invalidated by mild to moderate ascites nor by moderate to severe adhesions. Misdirected injections produce invalid studies that are recognizable as such and thus are not misinterpreted. This approach should therefore be applicable to most patients with suspected intestinal ischemia.

Abdominal Muscles↗

The role of oxygen-free radicals in ischemic tissue injury in island skin flaps.

The contribution of free radical-mediated reperfusion injury to the ischemic damage caused by total venous occlusion of island skin flaps was investigated in a standardized rat model. Control flaps subjected to 8 hours of total venous occlusion showed complete, full thickness necrosis when followed for 7 days following release of the vascular occlusion. Treatment with superoxide dismutase, a scavenger of superoxide radicals, prior to and immediately following the onset of reperfusion, significantly enhanced island flap survival from 0/11 (0%) to 8/15 (53%), p less than 0.005, and from 0/9 (0%) to 6/12 (50%), p less than 0.02, respectively. These findings are consistent with the hypothesis that oxygen free radicals generated at the time of reperfusion following a period of ischemia contribute significantly to the ultimate damage caused by ischemic injury. Such findings are consistent with similar reported observations on other tissues and suggest a means by which ischemic tissue injury might be therapeutically modified, even after the period of ischemia.

Animals↗

Effects of cardiac tamponade on colonic hemodynamics and oxygen uptake.

The local hemodynamic response of the innervated but vascularly isolated colon to decreased systemic perfusion induced by cardiac tamponade was studied in anesthesized dogs as a model of nonocclusive mesenteric ischemia. Increasing levels of pericardial pressure caused progressive decreases in colonic blood flow associated with substantial increases in colonic vascular resistance. These increases in local colonic resistance were proportionately larger than concurrent increases in systemic resistance. The disproportionate response of the colonic resistance vessels was not diminished by colonic (sympathetic) denervation. Reductions of blood flow to 30 ml . min-1 . 100 g-1 resulted in compensatory increases in colonic oxygen extraction such that colonic oxygen consumption remained constant (flow independent) at about 1.5 ml . min-1 . 100 g-1. At blood flows below 30 ml . min-1 . 100 g-1 colonic oxygen consumption was markedly dependent on blood flow. This fundamental relation of colonic oxygen consumption to blood flow was the same whether ischemia was induced by cardiac tamponade, partial mechanical arterial occlusion, or vasoconstrictor (norepinephrine or digoxin) infusion. Furthermore, this relationship was not altered by vasodilation with isoproterenol after the induction of ischemia by any of the above means.

Animals↗

Role of oxygen-derived free radicals in digestive tract diseases.

Evidence is presented that supports a role of oxygen free radicals in the pathogenesis of various disorders of the digestive system. In the intestine, there is evidence that oxygen radicals play an important role in the endothelial and epithelial damage associated with certain models of ischemia. The mechanism for superoxide production in this condition differs from that described for other pathologic states (i.e., oxygen toxicity and neutrophil-mediated inflammation). This mechanism involves the reaction of xanthine oxidase, hypoxanthine, and molecular oxygen to produce a burst of oxygen radicals with reperfusion of the ischemic bowel. Evidence implicating oxygen radicals in inflammatory disorders of the digestive tract (i.e., pancreatitis), radiation injury, and hepatic cirrhosis is also presented. The available data suggest that oxygen radicals appear to be a fundamental mechanism of tissue injury in the pathogenesis of various disorders of the digestive system.

Allopurinol↗

Role of oxygen free radicals in shock, ischemia, and organ preservation.

Oxygen radicals appear to be involved in the microvascular and parenchymal cell injury associated with various pathologic disorders. Studies indicate that oxygen radicals increase microvascular permeability by creating large leakage sites predominantly in the small venules. The highly reactive hydroxyl radical appears to be responsible for the microvascular alterations associated with oxygen radical production. There is considerable indirect evidence implicating oxygen radicals in the pathogenesis of circulatory shock. The oxygen radicals are probably formed by the enzyme xanthine oxidase when intravascular volume is restored. Similar biochemical processes appear to be involved in reperfusion injury to the kidney and skin. Evidence is also presented that implicates oxygen radicals in the reperfusion injury associated with organ preservation and transplantation.

Animals↗

Relationship between acid secretion and blood flow in the canine stomach: role of oxygen consumption.

The relationship of acid secretion to blood flow and oxygen consumption was investigated in the isolated canine stomach during intraarterial infusion of pentagastrin. Blood flows above and below control values were achieved by pump perfusion and partial arterial occlusion, respectively. When blood flow was increased from a control value of 38 ml X min-1 X 100 g-1 to 85 ml X min-1 X 100 g-1, both acid secretion and oxygen consumption remained constant at 0.08 mEq X min-1 X 100 g-1 and 2.1 ml X min-1 X 100 g-1, respectively. A reduction in blood flow to 9.0 ml X min-1 X 100 g-1 caused acid secretion and oxygen consumption to decrease to 26% and 44% of control values, respectively. The results indicate that acid secretion is independent of blood flow at flow rates above 38 ml X min-1 X 100 g-1. A model of the interrelationships between blood flow, oxygen consumption, and acid secretion is proposed that may explain much of the conflict in the literature concerning these three parameters.

Animals↗

Regulation of oxygen uptake in resting and pentagastrin-stimulated canine stomach.

The relation between oxygen uptake and blood flow in the isolated dog stomach was investigated under resting conditions and during intra-arterial infusion of isoproterenol or pentagastrin. Blood flows above and below control values were achieved by pump perfusion and partial arterial occlusion, respectively. In the resting stomach oxygen uptake increased from 0.4 to 1.5 ml.min-1.100 g-1 as blood flow increased from 4 to 40 ml.min-1.100 g-1 and then remained constant for blood flows up to 100 ml.min-1.100 g-1. Isoproterenol did not significantly alter the relation between oxygen uptake and blood flow. In pentagastrin-stimulated stomachs oxygen uptake was maintained at 2.5 ml.min-1.100 g-1 at blood flows between 40 and 100 ml.min-1.100 g-1 and decreased at blood flows below 40 ml.min-1.100 g-1. The results indicate that pentagastrin increases oxidative metabolism in the stomach. Despite this increase in oxygen consumption with pentagastrin, the general shape of the relation between blood flow and oxygen uptake remained the same and was simply displaced vertically above the control data.

Animals↗

Pancreatic circulation: intrinsic regulation.

The purpose of the present study was to characterize the intrinsic mechanisms involved in the regulation of blood flow and oxygenation in the totally isolated, perfused canine pancreas. Arterial pressure, venous outflow pressure, blood flow, arteriovenous oxygen difference, and capillary filtration coefficient were measured during graded arterial pressure reductions and venous pressure elevation. Reductions in arterial pressure caused pancreatic blood flow and vascular resistance to decrease, whereas venous pressure elevation resulted in a decreased blood flow and increased vascular resistance. The reductions in blood flow produced by arterial and venous pressure alterations were associated with increases in oxygen extraction and capillary filtration coefficient. During the same pressure perturbations, oxygen uptake remained constant between blood flows of 40-100 ml.min-1.100 g-1, yet decreased progressively as blood flow was reduced below 40 ml.min-1.100 g-1. Arterial occlusion resulted in a postocclusive reactive hyperemia, the magnitude of which was related to the duration of occlusion. The findings of this study suggest that intrinsic regulation of pancreatic blood flow can be attributed to both metabolic and myogenic mechanisms. Resistance and exchange vessels both appear to play a role in the regulation of oxygen delivery to the pancreatic parenchyma.

Animals↗

Ischemic injury in the cat small intestine: role of superoxide radicals.

Hemorrhagic lesions in the small intestinal mucosa have been demonstrated in humans and experimental animals following hemorrhagic shock and intestinal ischemia. In order to define the role of superoxide radicals and xanthine oxidase in the pathogenesis of the mucosal lesions, we compared the microscopic mucosal changes produced by 3 h of regional hypotension (intestinal arterial pressure = 30 mmHg) in untreated cats and cats pretreated with either superoxide dismutase or allopurinol. In the untreated animals the mucosa was characterized by massive epithelial lifting down the sides of the villi, completely denuded villi, and most frequently by disintegration of the lamina propria, hemorrhage, and ulceration. Pretreatment with either superoxide dismutase or allopurinol significantly attenuated the necrosis of villus and crypt epithelium produced by 3 h of ischemia. The results of this study suggest that superoxide radicals are involved in the pathogenesis of ischemic mucosal lesions and that the enzyme xanthine oxidase is the source of superoxide radicals in the ischemic small bowel.

Allopurinol↗

Use of intraperitoneal xenon- 133 for imaging of intestinal strangulation in small bowel obstruction.

Iintraperitoneal xenon- 133 dissolved in saline solution was evaluated for the detection of early strangulation in a reproducible model of segmental intestinal obstruction in rats and dogs. There was a highly significant delay in externally detected isotope washout from animals with strangulated loops compared with normal, sham operated and simple (nonstrangulated) obstruction control groups. Concentrations of isotope obtained n ischemic intestinal tissue exceeded those previously reported by an order of magnitude. Corresponding anterior abdominal gamma camera images showed marked retention of isotope at 1 hour in the strangulation obstruction groups and the sites of this activity corresponded to the location of the ischemic loops. Blinded readings of these images by nuclear radiologists showed this method to be highly accurate for the detection of strangulation in these animal models. This method should be directly applicable to patients with intestinal obstruction.

Animals↗

Intraoperative determination of small intestinal viability following ischemic injury: a prospective, controlled trial of two adjuvant methods (Doppler and fluorescein) compared with standard clinical judgment.

Two adjuvant techniques for the intraoperative assessment of small intestinal viability were compared with standard clinical judgment in a prospective, controlled study of 71 ischemic bowel segments in 28 consecutive patients operated on for acute intestinal ischemic disease. Each segment was independently assessed 15 minutes after surgical correction of the underlying lesion by: 1) standard clinical judgment; 2) Doppler-detected pulsatile mural blood flow; and 3) fluorescein ultraviolet fluorescence pattern. Viability endpoint for each segment was determined objectively by patient follow-up or "blinded" microscopic evaluation of histologically unequivocal resection specimens using criteria established by previous animal studies. Seventeen histologically equivocal specimens were excluded from the final results. Standard clinical judgment proved moderately accurate overall (89%) but would have led to a relatively high rate (46%) of unnecessary bowel resection. The Doppler technique did not increase accuracy in any category of evaluation. The fluorescein fluorescent pattern was correct in all 54 determinant bowel segments, and proved more sensitive specific, predictive, and significantly more accurate overall than either standard clinical judgment or the Doppler method. This controlled study suggests that the fluorescein technique is the method of choice for the prediction of small intestinal recovery following ischemic injury.

Adolescent↗

Iliac artery ligation: the relative paucity of ischemic sequelae in renal transplant patients.

In order to assess the effect of iliac artery ligation on the distal extremity, the ten year experience of the Johns Hopkins renal transplantation program was reviewed. Among 467 transplant procedures in 390 patients there were six cases in which the common and/or external iliac artery had been ligated for control of untoward hemorrhage from an infected arteriotomy site. These six cases were studied in detail with particular attention to ischemic sequelae in the involved leg. There were no immediate or causally-related deaths. No patient lost a leg or required an immediate reconstructive procedure for limb salvage. Four of the six recovered ambulatory status, and only two of these required a later, elective reconstruction for claudication. The combination of these six with eight other similar patients previously reported provides a total of 14 cases of iliac artery ligation in renal transplant patients. No patient suffered actual limb loss, and only three underwent subsequent elective reconstruction for claudication. It is concluded that common and/or external iliac artery ligation without immediate revascularization may be performed for control of hemorrhage with little danger of limb loss in renal transplant patients.

Adult↗