Mahmoud Kosi

Growth hormone reverses impaired wound healing in protein-malnourished rats treated with corticosteroids

Corticosteroid (CS) administration amplifies the inhibitory effect of protein malnutrition (PM) on wound healing. Abdominal surgery in protein malnourished patients receiving corticosteroids (eg, advanced malignancy, transplant recipients) may be complicated by wound dehiscence or anastomotic breakdown. Although preoperative parenteral nutrition can reduce the incidence of these complications, this is not possible in patients requiring urgent surgical intervention. In a previous report we demonstrated that postoperative growth hormone (GH) administration could restore normal wound healing in PM rats. This study evaluates the effect of GH on wound healing in PM rats treated with CS. Forty-eight female Sprague-Dawley rats weighing 180 to 210 g were divided into four groups: (1) normally nourished; (2) PM only; (3) PM + CS; and (4) PM + CS + GH. PM rats (groups 2 to 4) received 5.5% protein chow every other day for 8 weeks. Control rats (group 1) received 23.4% protein chow for the same duration. Group 3 and 4 rats received prednisolone (2 mg/kg, intramuscularly) during the last 3 weeks of PM. All animals underwent precise 5-cm midline celiotomies. Postoperatively, rats in all groups were given 23.4% protein chow. Group 3 and 4 rats continued to receive CS postoperatively. Group 4 rats were given GH (0.5 mg/d, intraperitoneally) postoperatively for 5 days. Wound testing was performed on the 6th postoperative day after removal of the sutures. A balloon inserted into the peritoneal cavity through the vagina was gradually inflated. The pressure at which the wound disrupted was recorded as the wound bursting strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained pulmonary vasodilation after inhaled nitric oxide for hypoxic pulmonary hypertension in swine

It has been shown that pulmonary vasodilation is sustained after discontinuation of inhaled nitric oxide (INO) during moderate hypoxic pulmonary hypertension (HPH) in swine. The present investigations demonstrated how INO dose, hypoxia duration, and endogenous NO production influence this important phenomenon. Fifteen adolescent Yorkshire swine were randomly assigned to three groups (n = 5 each) and underwent the following phasic experimental protocol: (I) Baseline ventilation (FIO2 = .3); (II) Initiating HPH (FIO2 = .16 to .18, PaO2 = 45 to 55 mm Hg); (III) INO at 10 ppm; (IV) Posttreatment observation; (V) INO of 80 ppm; and (VI) Posttreatment observation. Phase II (pretreatment hypoxia) lasted 30 minutes in group A (short hypoxia) and 120 minutes in group B (long hypoxia). N-nitro-L-arginine methyl ester (NAME) was used to inhibit nitric oxide synthase (NOS) throughout the experiment in group C (short hypoxia + NAME). Hemodynamics and blood gases were monitored by systemic and pulmonary artery catheters placed by femoral cutdown. Analysis of variance with post-hoc adjustment was used to compare groups at each phase, and the paired t test was used for comparisons within a group. With respect to baseline mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance (PVR), there were no significant differences among the three groups. MPAP and PVR were significantly higher in group C than in group A during phase II, (MPAP, 76% +/- 8% v 33% +/- 2%; PVR, 197% +/- 19% v 78% +/- 10%; P < .05). There were no significant differences in MPAP or PVR during phases III through VI. When MPAP was expressed as percent dilation, 80 ppm caused significantly more dilation than did 10 ppm in all three groups. Groups A and C had significantly higher sustained pulmonary artery dilation after 80 ppm than after 10 ppm (A, 82% +/- 31% v 17% +/- 11%; C, 68% +/- 10% v 42% +/- 12%; both P < .05), but group B did not (43% +/- 15% v 30% +/- 9%; P = .25). High dose results in stronger vasodilation than low dose during and after INO for moderate HPH of short duration. Long hypoxia blunts this high-dose advantage. Endogenous NO inhibition augments HPH but does not decrease pulmonary vasodilation during or after INO.

Severity of Hypoxia Predicts Response to Nitric Oxide in a Porcine Pulmonary Hypertension Model

Although inhaled nitric oxide (NO) has been variably successful in resolving pulmonary hypertension in neonates, children, and adults, no parameters predictive of response to this therapy have been elucidated. We conducted an animal study to determine if severity of hypoxia can predict magnitude and sustenance of response to inhaled NO therapy. Seven Yorkshire swine weighing 11 to 20 kg underwent 16 experiments, each consisting of four phases: Phase 1: Control period of ventilation on FIO2 .3; phase 2: Hypoxic period on FIO2 .10 to .15, establishing pulmonary hypertension; phase 3: Treatment period with NO starting at five parts per million (ppm), doubling dose every 10 min to 80 ppm; phase 4: Posttreatment observation period after discontinuation of NO while maintaining hypoxia for 1 hour or until circulatory failure or pulmonary hypertension of pre-NO magnitude developed. Each animal underwent a maximum of three experiments in random order of hypoxia severity before sacrifice with pentobarbital overdose. Continuous hemodynamic parameters, intermittent cardiac output and pulmonary capillary wedge pressure, and intermittent arterial blood gas analyses were obtained through pulmonary and systemic artery catheters placed by femoral cutdown. Pulmonary and systemic vascular resistances (PVR and SVR) were calculated by standard formulas. Experiments were divided into two groups (n = 8 in each): group 1 with severe hypoxia (PaO2, 25 to 35) and group 2 with moderate hypoxia (PaO2, 36 to 65). Data for all hemodynamic parameters were expressed as mean percentage change from baseline (phase 1) +/- SEM under each set of conditions, and the two groups were compared by two-way analysis of variance and covariance adjusted for order of experimentation.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal Membrane Oxygenation in Lambs through Umbilical Vessel Perfusion: Cardiac and Hepatic Complications

Twin lambs were delivered by ceasarean section near term, aralyzed, sedated and randomly assigned to either mechanical ventilation or umbilical arteriovenous ECMO for 48 hours. Umbilical arteriovenous ECMO provided adequate gas exchange with minimal or no ventilation of the native lungs. However, at autopsy, animals treated with umbilical ECMO showed right heart dilation and liver necrosis or hemorrhage compared to their twins treated with mechanical ventilation.

Length of transplanted small bowel required for adequate weight gain in rats

Progress has been made toward developing a clinically successful small-bowel transplant procedure, but there has been little research concerning the functional aspects of the transplanted small bowel. Using a rat model, our study examined the length of transplanted small bowel required to provide adequate weight gain. The rats were divided into six groups; groups I and 2 were considered controls. Group 1 (n = 6) underwent a gastrostomy. Group 2 (n = 3) underwent a jejunoileectomy followed by re-establishment of intestinal continuity and anastomosis of the native proximal small bowel to an abdominal stoma and the distal portion to the ascending colon. Groups 3 (n = 5), 4 (n = 4), 5 (n = 5), and 6 (n = 4) underwent small-bowel transplantation, receiving 100%, 50%, 25%, and 15% transplants, respectively. The donor small-bowel anastomoses were the same as the native small-bowel anastomoses in group 2. All of the rats began to produce stool within 4 days of becoming dependent upon the transplanted small bowel. By the end of postoperative week 4, there was no significant difference between the percentages of preoperative body weight in groups 1–4 (range 125.7%–130.0%). Although the weight gain in group 5 was significantly less than that in groups 1–4 (P < 0.05), it was adequate (111.8%); group 6 animals lost weight (94.7%). It is concluded that a 50% or more small-bowel transplant with or without an ileocecal valve provides ample weight gain; minimally adequate weight gain is achieved by a 25% transplant without an ileocecal valve; and the graft begins to function soon after transplantation.