Chronic portal hypertension: effects on gastrointestinal blood flow distribution

Benoit, Joseph N.; Womack, W. A.; Korthuis, Ronald J.; Wilborn, Walter H.; Granger, D. Neil

doi:10.1152/ajpgi.1986.250.4.g535

Cited by 23 publications

(15 citation statements)

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“…Because of the fact that very little DNA appears to be transferred into the vessels during electroporation, it is unlikely that significant amounts of the DNA are reaching the bloodstream which could lead to gene transfer in distal sections of the vascular tree. Moreover, since the flow rate through the rat mesenteric arteries is on the order of 130 ml/min/100 g small intestine [19], any plasmid reaching the lumen would be quickly diluted in the blood supply and degraded over time, thereby minimizing any safety concerns.…”

Section: Discussionmentioning

confidence: 99%

Gene Transfer to Intact Mesenteric Arteries by Electroporation

Martin

Young²,

Benoit³

et al. 2000

J Vasc Res

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The purpose of the present study was to develop a rapid, reproducible method of non-viral gene transfer to the intact vasculature. Male Sprague-Dawley rats were anesthetized, a midline abdominal incision was made and segmental branches of the superior mesenteric artery were dissected free of surrounding mesentery. A specially designed electroporation probe was placed around the neurovascular bundle and the electroporation chamber filled with a solution containing the firefly luciferase expressing plasmid (pCMV-luxDTS) or the green fluorescent protein expressing plasmid (pEGFP-N1). Vessels were electroporated with eight 10 msec pulses of 200V/cm. Sixty seconds after electroporation, the DNA solution was removed, the intestine returned to the abdomen and the abdominal wall closed with suture and metal wound clips. Six hours to 5 days later, rats were sacrificed and electroporated vessels were recovered. Luciferase activity of the blood vessels was monitored. Gene expression was detected as early as 6 h postelectroporation, peaked at 1-3 days with levels up to 1 ng of reporter gene per vessel segment and returned towards baseline by day 5. Histological analysis of blood vessel segments revealed GFP positive cells throughout the thickness of the vessel wall (endothelial cells to adventitia). Responses of electroporated vessels to vasoconstricting stimuli were indistinguishable from those of control vessels at either 2 or 40 days post-treatment. The results of this study provide evidence that electroporation is an effective means for introducing naked DNA into the blood vessel wall and form the basis for future studies on targeted gene therapy to the intact vasculature.

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Section: Discussionmentioning

confidence: 99%

Gene Transfer to Intact Mesenteric Arteries by Electroporation

Martin

Young²,

Benoit³

et al. 2000

J Vasc Res

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“…Blow flow distribution within the bowel wall is not altered despite the intense hyperemia (35). The hyperemic response is not limited to the splanchnic circulation; blood flow is also increased in skeletal muscle and kidneys.…”

Section: Chronic Portal Hypertensionmentioning

confidence: 91%

The Gastrointestinal Circulation: Physiology and Pathophysiology

Granger

Holm

Kvietys

2015

Comprehensive Physiology

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The gastrointestinal (GI) circulation receives a large fraction of cardiac output and this increases following ingestion of a meal. While blood flow regulation is not the intense phenomenon noted in other vascular beds, the combined responses of blood flow, and capillary oxygen exchange help ensure a level of tissue oxygenation that is commensurate with organ metabolism and function. This is evidenced in the vascular responses of the stomach to increased acid production and in intestine during periods of enhanced nutrient absorption. Complimenting the metabolic vasoregulation is a strong myogenic response that contributes to basal vascular tone and to the responses elicited by changes in intravascular pressure. The GI circulation also contributes to a mucosal defense mechanism that protects against excessive damage to the epithelial lining following ingestion of toxins and/or noxious agents. Profound reductions in GI blood flow are evidenced in certain physiological (strenuous exercise) and pathological (hemorrhage) conditions, while some disease states (e.g., chronic portal hypertension) are associated with a hyperdynamic circulation. The sacrificial nature of GI blood flow is essential for ensuring adequate perfusion of vital organs during periods of whole body stress. The restoration of blood flow (reperfusion) to GI organs following ischemia elicits an exaggerated tissue injury response that reflects the potential of this organ system to generate reactive oxygen species and to mount an inflammatory response. Human and animal studies of inflammatory bowel disease have also revealed a contribution of the vasculature to the initiation and perpetuation of the tissue inflammation and associated injury response.

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“…37 Our findings were confirmed by others in different models of portal hypertension. 19,36,38 Regarding gastric mucosal blood flow in humans with cirrhosis, findings in patients with portal hypertensive gastropathy are few and contradictory. Some investigators have found increased gastric mucosal blood flow, 39 while others have reported decreased perfusion.…”

Section: Gastric Mucosal Blood Flowmentioning

confidence: 99%

Does portal hypertension contribute to the pathogenesis of gastric ulcer associated with liver cirrhosis?

Kitano

Baatar

2000

Journal of Gastroenterology

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The prevalence of gastric ulcers in patients with liver cirrhosis is increased compared with that in the general population, and portal hypertension may contribute to the increased risk of gastric ulcer in cirrhosis patients. Aggressive factors involved in the pathogenesis of gastric ulcer are diminished in association with portal hypertension. In contrast, most of the important gastric mucosal defense mechanisms are shown to be impaired in portal hypertension; many of these mechanisms are also found to be altered in patients with liver cirrhosis. Portal hypotensive treatment with propranolol reduces ethanol-induced gastric mucosal damage in portal hypertensive rats and improves endoscopic signs of portal hypertensive gastropathy in cirrhosis patients. Together, these findings suggest portal hypertension-induced impairment of the gastric mucosal defenses to be an important factor in the pathogenesis of gastric ulcer in patients with liver cirrhosis. Prospective studies of portal pressure-reducing procedures, such as pharmacotherapy with propranolol, and their effect on the incidence of gastric ulcer in cirrhosis patients are needed to confirm this suggestion.

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Chronic portal hypertension: effects on gastrointestinal blood flow distribution

Cited by 23 publications

References 0 publications

Gene Transfer to Intact Mesenteric Arteries by Electroporation

Gene Transfer to Intact Mesenteric Arteries by Electroporation

The Gastrointestinal Circulation: Physiology and Pathophysiology

Does portal hypertension contribute to the pathogenesis of gastric ulcer associated with liver cirrhosis?

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