Prostacyclin increases gastric mucosa blood flow via cyclic AMP.
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Animals↗
Biomedical subjects
H V Gaskill
Publications and source records attributed to H V Gaskill.
Prostacyclin-mediated gastric cytoprotection is dependent on mucosal blood flow.
Although prostacyclin (PGI2) causes an increase in resting gastric mucosal blood flow, this effect is not thought to be correlated with its cytoprotective action. This study questions that hypothesis by assessing whether PGI2 cytoprotection occurs in the presence of decreased gastric mucosal blood flow. Twenty-four miniature swine were anesthetized with chloralose, ventilated, and catheterized to measure cardiac output and arterial pressure and to inject microspheres. An orogastric tube was placed for infusion of 2.5% autogenous bile in isotonic HCl (2 ml/kg/hr). Four experimental groups were used: I, control (no drugs); II, vasopressin (0.25 U/min intravenously); III, PGI2 (0.1 micrograms/kg/min intravenously); and IV, vasopressin and PGI2 combined. Gastric mucosal blood flow was documented at baseline and at 1, 2, and 3 hours of drug infusion by radiolabeled-microsphere technique. Stomachs were harvested and photographed, and lesions were scored (0 to 3) by blinded observers. Gastric mucosal blood flow was decreased (50%) in both groups that received vasopressin, increased (300%) in animals that received PGI2 alone, and unchanged in controls. All animals that received vasopressin, whether alone or with PGI2, developed mucosal injury (mean score 2.5 versus (2.2). Group I and group III animals did not develop lesions. The results of this study demonstrate that PGI2 failed to elevate gastric mucosal blood flow, which was already depressed to vasopressin, and that PGI2 failed to protect the gastric mucosa from injury in the presence of reduced blood flow. This suggests that PGI2 cytoprotection is linked to its effect on gastric mucosal blood flow.
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Reassessment of the role of routine operative exploration in vascular trauma.
During the 5-year period ending December 1978, 390 patients were explored for suspected vascular injury either in the neck or in one of the extremities with 13% morbidity and a 1% mortality rate. Positive exploration for vascular injury in 139 patients (36%) resulted in 28% morbidity and 2% mortality. Negative exploration in 251 patients (64%) was associated with a 5% morbidity and 0.4% mortality. Per cent positive exploration by type of injury was: iatrogenic injury (100%), foreign body laceration (100%), blunt trauma (79%), stab wound (32%), and gunshot wound (31%). Per cent positive exploration by area was: brachium (68%), popliteal area (63%), femoral area (28%), axilla (27%), and neck (25%). Routine exploration of patients at risk for vascular injury can be accomplished with minimal morbidity and mortality but is associated with a low (36%) diagnostic yield. 'Exclusion' arteriography in hemodynamically stable patients with equivocal signs of vascular injury appears to be indicated to increase diagnostic accuracy.
Adolescent↗
Operations for peptic ulcer disease: paradigm lost.
Over the past several decades, the pharmacologic and endoscopic treatment of peptic ulcer disease (PUD) has dramatically improved. To determine the effects of these and other changes on the operative management of PUD, we reviewed our surgical experience with gastroduodenal ulcers over the past 20 years. A computerized surgical database was used to analyze the frequencies of all operations for PUD performed in two training hospitals during four consecutive 5-year intervals beginning in 1980. Operative rates for both intractable and complicated PUD were compared with those for other general surgical procedures and operations for gastric malignancy. In the first 5-year period (1980 to 1984), a yearly average of 70 upper gastrointestinal operations were performed. This experience included 36 operations for intractability, 15 for hemorrhage, 12 for perforation, and seven for obstruction. During the same time span, 13 resections were performed annually for gastric malignancy. By the most recent 5-year interval (1994 to 1999), the total number of upper gastrointestinal operations had declined by 80% (14 cases), although the number of operations for gastric cancer had changed only slightly. Operations decreased most markedly for patients with intractability, but the prevalence of operations for bleeding, obstruction, and perforation was also decreased. We conclude that improved pharmacologic and endoscopic approaches have progressively curtailed the use of operative therapy for PUD. Elective surgery is now rarely indicated, and emergency operations are much less common. This changed paradigm poses new challenges for training and suggests different approaches for practice.
Databases, Factual↗
Enhanced drug retention in VX2 tumors by use of degradable starch microspheres.
Twenty-nine rabbits with 12- to 14-day-old VX2 tumors in the hind leg were injected intraarterially with technetium-99m (99mTc) DTPA and various combinations of biodegradable starch microspheres, Spherex (Pharmacia, Sweden), to evaluate the efficacy of the microspheres in enhancing tumor retention of 99mTc DTPA. A gamma camera and nuclear medicine computer were used to generate time activity curves of 99mTc DTPA concentration in the tumors. Blood flow to the tumor and various muscles was also measured at intervals by left ventricular injection of 15 micron radiolabeled plastic microspheres. Ninety minutes following the administration of 99mTc DTPA, specimens from the tumor, plasma and different muscles were counted in a NaI well counter connected to a multichannel analyzer. When biodegradable microspheres mixed with 99mTc DTPA were injected and followed by a slow infusion of plain starch microspheres, the 99mTc DTPA was retained in the tumor at concentrations up to 11 times that seen when 99mTc DTPA alone was injected; the corresponding biological half-time was 13 times longer than control values. Additionally, the degree of drug retention was inversely related to blood flow, with retention increasing as blood flow decreased. The results have possible applications to the use of biodegradable microspheres in the intraarterial delivery of chemotherapeutic agents to solid tumors.
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