ascorbic-acid and Intestinal-Perforation

Compromised microvascular responsiveness is one of the key factors associated with mortality of septic patients. The present study addresses the mechanism of protection by ascorbate against impaired vasoconstriction in septic mice. Sepsis (i.e., cecal ligation and puncture (CLP) model) elevated both plasma protein carbonyl (i.e., an index of oxidative stress) and plasma nitrite/nitrate (NOx) levels, reduced baseline mean arterial blood pressure (MABP), and inhibited the MABP pressor response to angiotensin II (Ang II) at 6 h post-CLP. At the microvascular level, sepsis increased the inducible nitric oxide synthase (iNOS) mRNA level in cremaster muscle arterioles (18-25 microm diameter) at 3 h post-CLP, and impaired vasoconstriction to Ang II in these arterioles at 6 h post-CLP. At 24 h post-CLP, sepsis resulted in 9% survival. An intravenous bolus of ascorbate (200 mg/kg body wt) given 30 min prior to CLP prevented the protein carbonyl and NOx increases, partially restored the baseline arterial pressure, and completely protected against all arteriolar iNOS mRNA increases, arteriolar constriction hyporesponsiveness, and pressor response impairment. Survival increased to 65%. In septic mice, iNOS gene knockout resulted in protection of arteriolar constriction and pressor responses identical to that provided by ascorbate. Ascorbate bolus given 3 h post-CLP protected against the increase in plasma NOx concentration and against the pressor response impairment. We conclude that ascorbate may protect arteriolar vasoconstrictor responsiveness in sepsis by inhibiting excessive NO production.

Topics: Angiotensin II; Animals; Arterioles; Ascorbic Acid; Blood Pressure; Cecum; Drug Administration Schedule; Enzyme Induction; Intestinal Perforation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitrites; Oxidative Stress; RNA, Messenger; Sepsis; Vasoconstriction

This series presents further evidence for an association between reticulosis of the intestine and steatorrhoea. Although some patients have a definite past history of gluten enteropathy, it seems likely that in certain patients the reticulosis itself is the primary cause of the steatorrhoea.

Topics: Ascorbic Acid; Blood Transfusion; Body Weight; Bone Marrow Examination; Celiac Disease; Diet; Diet Therapy; Fats; Feces; Folic Acid; Humans; Intestinal Neoplasms; Intestinal Perforation; Intestine, Small; Iron; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Nandrolone; Neomycin; Neoplasms; Pathology; Prednisone; Sarcoma; Steatorrhea; Surgical Procedures, Operative; Vitamin A; Vitamin B 12; Vitamin B Complex; Vitamins; Water-Electrolyte Balance