The effect of alpha-adrenergic stimulation and blockade on perfusion of myocutaneous flaps

A porcine myocutaneous flap model was utilized to assess the development of denervation adrenergic hypersensitivity and to determine the effects of the alpha-adrenergic blocking agent--phenoxybenzamine--on flap blood perfusion. During intravenous administration of norepinephrine, blood flow to the flaps and control skin was monitored simultaneously, using laser Doppler velocimetry and dermofluorometry. A relative decrease in myocutaneous flap blood flow, as compared to control skin in response to norepinephrine infusion, was observed at between 2 and 7 days following flap elevation. This is the same time period during which norepinephrine content of skin flaps is diminished, and suggests development of an increased sensitivity to adrenergic stimulation. Administration of phenoxybenzamine blunted norepinephrine-induced pressor responses and blocked development of adrenergic hypersensitivity in the porcine myocutaneous flap model. Phenoxybenzamine significantly increased flap blood perfusion (as measured by dermofluorometry).     

Chronic extrinsic denervation of the small bowel: effect on adrenergic and cholinergic contractile mechanisms in canine ileal circular muscle

BACKGROUND: Small bowel transplantation necessitates chronic extrinsic denervation and is often followed by enteric dysfunction. Our aim was to study canine ileal contractile activity after extrinsic denervation. METHODS: In vitro dose responses to cholinergic and adrenergic agonists were evaluated in canine ileal muscle strips in control subjects and after jejunoileal extrinsic denervation (EX DEN) at 0, 2, and 8 weeks after operative preparation. RESULTS: Spontaneous activity and the increased activity after tetrodotoxin (enteric nerve blockade) did not differ between groups. Response to acetylcholine and bethanechol did not differ at any time in the control or EX DEN group. In contrast, the EX DEN group demonstrated a procontractile hypersensitivity to norepinephrine at 2 and 8 weeks that was not seen in the control group. This adrenergic hypersensitivity in the EX DEN group was insensitive to intramural neural blockade with tetrodotoxin. CONCLUSIONS: Extrinsic denervation does not affect basal contractile activity, augmented contractile activity to intramural neural blockade, nor response to cholinergic agonists. However, it induces a procontractile adrenergic hypersensitivity in canine ileal circular muscle mediated at the level of the smooth muscle and not at the enteric nervous system.     

Effect of small bowel transplantation,denervation and ischaemia on rat intestinal microflora

The effects of denervation and warm ischaemia on quantitative and qualitative changes in small intestinal microflora following rat heterotopic small-bowel isotransplantation were assessed. Animals with Thiry-Vella fistula, but without transplants, acted as controls. Thirty and 40-fold increases in bacterial colony counts were seen in the isografts compared to controls at 2 and 7 days, respectively (P< 0.05). Aerobic faecal organisms predominated at 2 and 7 days, but an overgrowth of Flavobacterium meningosepticum occurred at 28 days in the transplanted and host bowels. The effect of warm ischaemia on intestinal microflora was assessed by the application of a microvascular clamp to the superior mesenteric artery for 90 min. The effect of denervation was assessed following microsurgical division of all nervous tissue around the superior mesenteric artery. After 7 days, lengths of jejunum and ileum were removed and intraluminal microflora assessed. The number of bacterial colonies isolated from the ileum in the warm ischaemia group was six times greater than the number in the control group, whereas no significant changes were seen in the upper bowel. In contrast, denervation led to a slight, but consistent, decrease in colony counts. These findings suggest that the increase in bacterial numbers in an isografted small bowel primarily results from warm ischaemia rather than from mesenteric denervation, and that physical aspects of the procedure may affect the development of sepsis following smallbowel transplantation.     

Effects of renal denervation on cyclosporin induced hypertension in the Wistar rat

Summary: The effects of renal denervation were examined in cyclosporin A (CyA) treated Wistar rats 14 days prior to 1 day prior to and 10 days after CyA was administered. the rise in blood pressure was attenuated when the renal denervation was performed 1 day prior to and 10 days after administration, but not 14 days prior to CyA, presumably reflecting re-innervation of the kidney. Plasma renin activity (PRA) was increased by CyA 10 mg/kg per day and 20 mg/kg per day, but decreased by renal denervation 1 day prior to CyA. Plasma creatinine was increased by CyA at 10 mg/kg per day and decreased by renal denervation 1 day prior to CyA. These data support the notion that renal sympathetics play a role in CyA induced hypertension.     

Effect of muscle flap denervation on flow hemodynamics: A new model for chronic in vivo studies

The purpose of this study was to evaluate microcirulatory dynamics following muscle flap denervation. A modification of standard cremaster muscle flap was used. Fifty male Sprague-Dawley rats were studied in two experimental groups of 25 rats each, as follows: Group I (control), after flap isolation, the nerovascular pedicle was left intact; group II (denervation), following muscle isolation a 1 cm segment of genitofemoral nerve was excised and denervated muscle was preserved in the medial border of rat hind limb. For chronic evaluation the cremaster was withdrawn from the leg and prepared for in vivo observations after days 1, 3, 7, and 14. The following measurements were taken: vessel diameters, red blood cell velocities, and number of perfused capillaries. In groupII a 15% iuncrease in artriolar diameter was observed. Throughout the entire 14 day period denervated flaps presented 27% more perfused capillaries. Flap denervation proved to increase capillary perfusion significantly (P < 0.05). The cremaster muscle tube-flap model introduced in this study allows for chronic observtion of the microcirculation. © 1994 Wiley-Liss, Inc.     

Muscle study in experimental scoliosis in rabbits with costotransversectomy: evidence of ischemic process

Scoliosis involves the central nervous system diseases, ligaments, articulations and skeletal muscles, but there is no consensus on its pathogeny and progression of muscle abnormalities. In this study, we investigate the morphologic changes in the muscle of rabbit submitted to experimental scoliosis, with special emphasis on abnormalities related to blood supply. We studied 26 rabbits subjected to costotransversectomy by pulling out six transverse processes at thoracic level and six rabbits were used as controls. All the animals operated upon developed scoliosis showing an average angle of 29.1° on the 60th day, with its apices located at T4 and T12 when they were subjected to paraspinal muscle biopsy on both sides. The muscle biopsies were subjected to histological stains and histochemical reactions, as well as to a morphometric study. On the concave side, the changes were not statistically significant regarding the control group. On the convex side conjunctive tissue proliferation, infiltration by adipose tissue, central nucleus excess, inflammatory reaction, segmental fibrosis, type 1 fiber hypertrophy, type 2 fiber hypertrophy and atrophic angular dark fibers in the unspecific esterase were statistically significant. The segmental fibrosis reached a circumscribed muscle segment, compatible with an ischemic phenomenon. The histological diagnoses on the concave side of the animals had unspecific alterations (atrophy and hypertrophy) in 13, myopathy in 3, denervation in 3 and normal in 7. The convex side diagnoses were myopathy in 14, denervation in 8, mixed in 3 and normal in 1. The procedure determined morphologic changes on the convex side indicating possible denervation or myopathy of ischemic origin.     

C-Fos in enteric nerves after extrinsic denervation of guinea pig ileum

BACKGROUND. Gastrointestinal function is controlled partly by an interaction between extrinsic (sympathetic, parasympathetic, sensory) and intrinsic (enteric) nerves. However, normal gut function occurs in the absence of extrinsic innervation as enteric nerves adapt to the loss of extrinsic nerves from the gut wall. Expression of the proto-oncogene product, c-Fos, is a signal for activity-dependent changes in gene expression and immunocytochemical detection of c-Fos is used as a marker for changes in neuronal activity. The purpose of this study was to determine if enteric neurons in guinea pig ileum respond to loss of extrinsic innervation by expressing c-Fos protein. MATERIALS AND METHODS. Fos protein was localized using immunohistochemical methods and an antiserum raised against synthetic Fos. Segments of ileum were extrinsically denervated by crushing the mesenteric nerves in anesthetized animals or by treating animals with 6-hydroxydopamine (6-OH-DA) or capsaicin to destroy sympathetic and extrinsic sensory nerves, respectively. RESULTS. One week after surgical extrinsic denervation of loops of ileum, 12 +/- 1 nuclei/submucosal ganglion and 114 +/- 6 nuclei/myenteric ganglion contained Fos immunoreactivity (ir). These values were greater (P < 0.05) than those from unoperated segments from the same animals (4 +/- 1 Fos-ir nuclei/submucosal ganglion and 13 +/- 4 Fos-ir nuclei/myenteric ganglion) or from sham-operated segments. Significantly more nuclei contained Fos-ir at 4, 7, 10, and 24 weeks after denervation. Finally, capsaicin or 6-OH-DA treatment increased the number of Fos-ir nuclei in enteric ganglia. CONCLUSIONS. These data suggest that Fos expression may be part of the adaptation of enteric nerves to extrinsic denervation.     

Disturbance of inhibitory capacity of endothelial cell for platelet adhesion or aggregation following experimental subarachnoid hemorrhage

Time sequential changes of the endothelial cells of feline basilar arteries after experimental subarachnoid hemorrhage (SAH) were studied morphologically and functionally under the scanning electron microscope (SEM). Experimental SAH was induced by the two-hemorrhage method, and the basilar artery was removed at 1 hour, or 2, 4, 7, or 14 days respectively after the 1st cisternal blood injection. At each stage, morphological changes of the luminal surface and endothelial cells of the basilar artery were observed by SEM. In another group, adenosin diphosphate (ADP) was infused through the right vertebral artery at the various stages mentioned above, for the purpose of activating platelets, and the basilar artery was then removed. The platelet adhesion or aggregation on the luminal surface was observed quantitatively also by SEM, for evaluating the inhibitory capacity of the endothelial cells upon platelet adhesion or aggregation after SAH. The fold formation of the arterial luminal surface and the ballooning of the endothelial cells were observed initially at 1 hour and 2 days respectively after the 1st cisternal blood injection. The latter findings became most remarkable during the 4 to 7 days after the said blood injection. They were accompanied by intercellular gap formation. None of these findings were seen, however, in the specimens taken 14 days after the said blood injection. In the group with pre-sacrificing ADP infusion, adhesion or aggregation of platelets on the arterial luminal surface was scarcely seen before the second day, but became remarkable 4 to 7 days after the 1st cisternal blood injection, and were reduced by the time 14 days had passed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-level laser therapy of dentin hypersensitivity: a short-term clinical trial

The aim of this study was to evaluate low-level laser therapy in cervical dentin hypersensitivity. A randomized controlled clinical trial was conducted with a total of 64 teeth. Dentin desensitizer and diode laser were applied on the cervical dentin surfaces. Distilled water and placebo laser was used as the placebo groups. The irradiance used was 4?J/cm² per treatment site. The baseline measurement of hypersensitivity was made by using visual analog scale (VAS). Twenty-four hours and 7?days after the application of desensitizer, diode laser and placebo groups, a new VAS analysis was conducted for the patients?? sensitivity level. The mean pain scores of placebo groups were significantly higher than the desensitizer??s and diode laser??s mean scores (ANOVA, p?<?0.05). The VAS analysis revealed a significant decrease in dentin hypersensitivity in 7?days with the use of the desensitizer and low-level laser therapy and no statistically significant difference was observed between these two treatments (p?>?0.05). Although low-level laser and glutaraldehyde containing desensitizer present distinct modes of action, experimental agents caused a significant reduction of dentin hypersensitivity without showing secondary effects, not irritating the pulp or causing pain, not discoloring or staining the teeth, and not irritating the soft tissues at least for a period of 1?week with no drawbacks regarding handling and/or ease of application. Low-level laser therapy and desensitizer application had displayed similar effectiveness in reducing moderate dentin hypersensitivity.     

Ureteral obstruction in the neonatal rat: Renal nerves modulate hemodynamic effects

In the neonate, chronic unilateral ureteral obstruction (UUO) reduces renal blood flow (RBF) of the ipsilateral kidney and increases RBF of the opposite kidney. To determine whether renal nerves mediate or modulate these responses complete left UUO in the neonatal rat was used as a model of severe obstructive uropathy, and was compared with sham-operated controls. At 24–28 days of age, animals underwent left or right mechanical renal denervation or left sham renal denervation. One week after denervation, animals were anesthetized and blood pressure and heart reate were measured. Cardiac output and RBF were determined by the radioactive microsphere technique. UUO increased blood pressure and heart rate, and decreased RBF in the obstructed kidney, regardless of denervation. While left UUO increased RBF to the intact opposite kidney in rats with left renal denervation, this was attenuated by right renal denervation. Thus, in the neonatal rat, UUO modulates systemic renal hemodynamics, possibly through activation of the renin-angiotensin system. While renal nerves do not mediate the vasoconstriction of the obstructed kidney, renal nerves modulate vascular tone of the kidney contralateral to UUO.     

Mechanical Pain Hypersensitivity after Incisional Surgery Is Enhanced in Rats Subjected to Neonatal Peripheral Inflammation: Effects of N-Methyl-d-aspartate Receptor Antagonists

Background: Neonatal pain and inflammation may lead to a long-term effect on nociceptive processing in adults. The current study examined the characteristics of postoperative incisional pain behaviors in adult rats that were subjected to neonatal peripheral inflammation.

Methods: Rat pups received a subcutaneous injection of saline or carrageenan into the plantar surface of the left hind paw at postnatal day 1. Naive pups were used as the control. Paw withdrawal thresholds to punctuate mechanical stimuli were examined at postnatal days 35, 42, and 49. After rats received a plantar incision on the left or right hind paw at postnatal day 50, paw withdrawal thresholds were measured at 4 h, 1 day, 2 days, 3 days, 5 days, and 7 days after incision. In addition, spinal cord Fos expression was detected at 2 h after incision. Finally, the effects of intrathecal N-methyl-d-aspartate receptor antagonists dl-2-amino-5-phosphonovaleric acid and dizocilpine and the nitric oxide synthase inhibitor l-NG-nitro-arginine methylester on incisional pain were examined at 4 h after incision.

Results: Although the rats subjected to neonatal peripheral carrageenan injection developed mechanical hypoalgesia in bilateral hind paws at baseline, they displayed increased spinal cord Fos expression at 2 h and exaggerated mechanical pain hypersensitivity at 4 h (but not at other time points) after plantar incision. Intrathecal dl-2-amino-5-phosphonovaleric acid, dizocilpine, and l-NG-nitro-arginine methylester significantly attenuated incision-induced mechanical pain hypersensitivity at 4 h after incision in the neonatally carrageenan-treated rats, but not in the naive or neonatally saline-treated rats.     

Correlation of viability and laser Doppler flowmetry in ischemic flaps

Microvascular blood flow was measured by a laser Doppler flowmeter in rabbit epigastric island flaps made ischemic at 37 degrees C for either 6.5 hr (Group 1; n = 13) or 17.5 hr (Group 2; n = 4). Contralateral flaps raised without ischemia were used as controls. The survival of ischemic flaps in these groups at 7 days was 69 and 0%, respectively. After 6.5 hr of ischemia, microvascular blood flow in the ischemic flap was approximately 20% below that in the control flap for the first 3-4 days postoperatively, presumably reflecting ischemic damage to parts of the cutaneous microcirculation; thereafter, flow was not significantly different from controls up to 7 days postoperatively. Failed 6.5-hr ischemic flaps had initial sluggish blood flow which slowed to zero usually within 4 days postoperatively. After 17.5 hr ischemia, negligible microvascular flow was detectable postoperatively. Failure in the microcirculation as detected by the flowmeter occurred well in advance of any noticeable physical changes in the flap. It is concluded that the percentage ischemic flap flow of control flap flow for each animal (at any selected time up to 24 hr after revascularization) reliably predicts the viability of the flap after 7 days.     

Monoclonal antibody against beta7 integrins,but not beta7 deficiency,attenuates intestinal allograft rejection in mice

BACKGROUND: beta7 integrins mediate homing and retention of lymphocytes to the normal and inflamed small bowel in a tissue-selective fashion. In the present study, we investigated the expression of beta7 integrins after small bowel transplantation (SBT) and tested the effects of blocking beta7-mediated pathways by using monoclonal antibody (mAb) or knockout mice. METHODS: Heterotopic SBT from BALB/c to C57BL/6 (B6) was used as a surgical model. Expression of beta7 integrins was measured on recipient lymphocytes (CD4 and CD8 ) in spleen, blood, and mesenteric lymph nodes (MLN) using flow cytometry. To analyze the effects of blocking beta7 integrins on graft survival, either beta7-deficient B6 or wild-type B6 mice that were treated with mAb against beta7 were studied. RESULTS: After allogeneic SBT, there were markedly increased levels of alpha4beta7 recipient CD8 lymphocytes in MLN, blood, and spleen as early as 3 days postoperatively. In contrast, alpha4beta7 integrin levels in isograft recipients were similar to those of normal mice. Mean survival time of intestinal allografts was not affected by beta7 deficiency (7.3+/-1 days) compared with wild-type mice (7.5+/-0.8 days). However, mAb against beta7 integrins significantly prolonged graft survival (12.8+/-1 days) compared with treatment with control mAb (7.3+/-1 days, <0.001). Histologic changes of SBT rejection were significantly attenuated when mice were given mAb against beta7. CONCLUSION: As indicated by the increased levels of alpha4beta7 CD8 lymphocytes, activation of this integrin contributes to the immune response in SBT rejection. Furthermore, blocking beta7 integrins with mAb provides a suitable target for immunosuppressive therapy. The discrepancy in survival data obtained by mAb and beta7 deficiency may be a result of the more rapid activation of compensatory mechanisms in the knockout mice.     

Mechanical pain hypersensitivity after incisional surgery is enhanced in rats subjected to neonatal peripheral inflammation: effects of N-methyl-D-aspartate receptor antagonists

BACKGROUND: Neonatal pain and inflammation may lead to a long-term effect on nociceptive processing in adults. The current study examined the characteristics of postoperative incisional pain behaviors in adult rats that were subjected to neonatal peripheral inflammation. METHODS: Rat pups received a subcutaneous injection of saline or carrageenan into the plantar surface of the left hind paw at postnatal day 1. Naive pups were used as the control. Paw withdrawal thresholds to punctuate mechanical stimuli were examined at postnatal days 35, 42, and 49. After rats received a plantar incision on the left or right hind paw at postnatal day 50, paw withdrawal thresholds were measured at 4 h, 1 day, 2 days, 3 days, 5 days, and 7 days after incision. In addition, spinal cord Fos expression was detected at 2 h after incision. Finally, the effects of intrathecal N-methyl-D-aspartate receptor antagonists DL-2-amino-5-phosphonovaleric acid and dizocilpine and the nitric oxide synthase inhibitor L-N-nitro-arginine methylester on incisional pain were examined at 4 h after incision. RESULTS: Although the rats subjected to neonatal peripheral carrageenan injection developed mechanical hypoalgesia in bilateral hind paws at baseline, they displayed increased spinal cord Fos expression at 2 h and exaggerated mechanical pain hypersensitivity at 4 h (but not at other time points) after plantar incision. Intrathecal DL-2-amino-5-phosphonovaleric acid, dizocilpine, and L-N-nitro-arginine methylester significantly attenuated incision-induced mechanical pain hypersensitivity at 4 h after incision in the neonatally carrageenan-treated rats, but not in the naive or neonatally saline-treated rats. CONCLUSIONS: The authors' results suggest that early inflammatory insults during the neonatal period could produce excessive incision-associated mechanical pain hypersensitivity in adult rats. Spinal cord N-methyl-D-aspartate receptors and downstream nitric oxide signaling might contribute to this abnormal pain hypersensitivity, although the mechanisms underlying the long-term effect of neonatal inflammation are still unclear.     

Ultrastructural changes induced by experimental subarachnoid haemorrhage and 6-hydroxydopamine in cat cerebral arteries

Summary Transmission electron microscopy of the middle cerebral artery from cats exposed to subarachnoid injection of blood 3 and 7 days before, showed several damage of the vascular ultrastructure. The intima was thickened with swelling and vacuolization of endothelial cells, with a plump appearance and disruption of tight junctions. The cellular surface was corrugated and the subendothelial space contained proliferating and vacuolated smooth muscle cells capped by elastin and collagen fibres. The internal elastic lamina was also corrugated and disrupted. The adventitial changes were axonic cytoplasmic and mitochondrial swelling, virtual absence of synaptic vesicles, and disruption of the outer axonal membrane, suggesting denervation of cerebral vessels. With administration of 6-hydroxydopamine (6-OHDA), similar ultrastructural changes were observed in the adventitia. These observations indicate that denervation induced by subarachnoid bleeding could be involved in the pathophysiology of cerebrovascular spasm. Subarachnoid haemorrhage, but not 6-OHDA, affects also intima and tunica media, suggesting other mechanisms, in addition to denervation, can participate in the vasospasm.     

持续炎症伤害性刺激对新生后发育期大鼠痛行为的影响

目的:研究持续炎症伤害性刺激对新生后发育期大鼠痛行为的影响.方法:不同龄新生大鼠(出生后1、4、7、14、21、28 d,即P1、P4、P7、P14、P21、P28)足底皮下注射生理盐水和一定浓度的蜜蜂毒,应用持续自发缩足反射、热刺激缩足反射潜伏期(PWTL)和机械刺激缩足反射阈值(PWMT)的痛反应定量检测方法,观察...     

Effect of dopamine infusion on hemodynamics after hepatic denervation

BACKGROUND:. The effects of dopamine (DA) on systemic hemodynamics are better understood than its effects on hepatic hemodynamics, especially after liver denervation occurring during liver transplantation. Therefore, a porcine model was used to study DA's effects on hemodynamics after hepatic denervation. MATERIALS AND METHODS: Fifteen pigs underwent laparotomy for catheter and flow probe placement. The experimental group (n = 7) also underwent hepatic denervation. After 1 week, all pigs underwent DA infusion at increasing doses (3-30 mcg/kg/min) while measuring hepatic parameters [portal vein flow (PVF), hepatic artery flow (HAF), total hepatic blood flow (THBF = HAF + PVF), portal and hepatic vein pressures] and systemic parameters [heart rate (HR), mean arterial pressure (MAP)]. RESULTS: There was a significant increase in HAF from baseline to the 30 mcg/kg/min DA infusion rate (within-subjects P < 0.01), but the differences between the two groups were not significant. PVF and THBF showed large effects (increases) with denervation, but the increase in flow with DA infusion was not present after denervation. Perihepatic pressures were unchanged by denervation or DA. Heart rate differed significantly between the control and denervated animals at baseline, 3, 6, 12 (all P < 0.05), and 30 mcg/kg/min DA (P = 0.10). Control vs denervation MAP at baseline was 100 +/- 4 vs 98 +/- 4 Torr and at 30 mcg/kg/min it was 110 +/- 3 vs 101 +/- 5 mm Hg. CONCLUSIONS: Hepatic flows tended to be higher after denervation. HAF showed similar increases with DA in both control and denervation groups. Increases in PVF and THBF with DA infusion were not present after denervation. HR was significantly decreased and MAP tended to be lower after denervation. The HR and MAP response to DA was similar in both groups. Therefore, both denervation and DA infusion have an effect on systemic and hepatic hemodynamics.     

Rabbit urinary bladder blood flow changes during the initial stage of partial outlet obstruction

PURPOSE: The rabbit urinary bladder's early response to partial outlet obstruction includes bladder wall remodeling with marked urothelial and fibroblast hyperplasia (1 day) and smooth muscle hypertrophy (3-5 days) resulting in a 4-5 fold increase in bladder mass within 7 days. In this study, we examined the effect of partial outlet obstruction on bladder blood flow during the initial period of rapid growth (1-7 days). MATERIALS AND METHODS: Each New Zealand White rabbit was partially obstructed by tying a 2-0 silk ligature loosely around the vesical outlet. After 0 (unoperated), 4 hours, 1, 3, or 7 days of obstruction, 5 rabbits per group were anesthetized and the carotid and femoral arteries cannulated with polyethylene tubing. Additional rabbits receiving sham surgeries were treated like obstructed animals at 4 hours and 1 day post-obstruction (5/group). Using standard methods, fluorescent microspheres were infused through the right carotid artery. Bladder and right kidney were rapidly removed upon completion of sphere infusion; bladder mucosa and muscle were separated. Sphere densities in detrusor, mucosa, and kidney were measured by Interactive Medical Technologies, Ltd. A section of each detrusor tissue was fixed in formalin and immunostained for smooth muscle alpha-actin. RESULTS: Mucosal blood flow (0.20 +/- 0.03 ml./min./gm.) was approximately 4-fold greater than that of detrusor (0.05 +/- 0.01 ml./min./gm.). Sham surgery caused a significant increase in bladder blood flow at 4 hours post-obstruction that returned to control levels by 1 day. Both mucosal and muscle blood flows were slightly higher in rabbit bladders obstructed for 4 hours than in sham-operated rabbits, and substantially greater in those obstructed for 1 day: 0.68 +/- 0.13 ml./min./gm. (mucosa) and 0.26 +/- 0.04 ml./min./gm. (muscle). Blood flows returned to control values by 3 days post-obstruction and remained constant through 7 days. Kidney blood flow was unchanged. Although bladder weight increased 4-fold after 7 days of obstruction, the volume fraction of smooth muscle (transverse section) remained constant at approximately 40%. CONCLUSIONS: Blood flow was approximately 4-fold greater in bladder mucosa than in muscle, which may relate to the significantly higher metabolic rate and lower high energy phosphate concentration of mucosa than muscle. Partial outlet obstruction resulted in a significant increase in blood flow at 1 day post-obstruction, which coincides temporally with the early cellular hyperplasia and hypertrophy of obstructed rabbit bladder. This increase in blood flow may be an essential factor for the initial increase in bladder mass. By three days, the blood flow per gram of tissue returned to control levels. The mechanisms relating to the changes in blood flow induced by partial outlet obstruction are currently under investigation.     

Blood flow rate and total blood flow related to length density and total length of blood vessels in mini-pig urinary bladder after chronic outflow obstruction and after recovery from obstruction

Chronic partial bladder outlet obstruction was created in mini-pigs by implanting a 6–7 mm ring around the proximal urethra. After a median obstruction period of 63 days the ring was removed, and after a median recovery period of 60 days the animals were sacrificed. At each study occasion the blood flow rate (ml per 100 g per min) was measured by washout of locally injected ¹³³Xe in the bladder wall and the washout curves analyzed by the corrected initial slope method. Stereological estimation of length density and total length of blood vessels in the bladder were performed. The results can be summarized as follows: (1) no differences in the blood flow rate at the time of ring implantation, obstruction, or recovery, (2) no decrease in the blood flow rate in normal bladders after bladder distension, (3) a significant decrease in blood flow rate in obstructed bladders after distension, (4) a 6-fold increase in total bladder blood flow after obstruction, (5) an unchanged blood flow per length of blood vessels per min during the study, (6) no changes in length densities of blood vessels during the study, and (7) a 7-fold increase in total length of blood vessels after obstruction and reversion to control level after recovery. The unchanged blood flow per length of vessels implies that capillary proliferation matched the increased bladder mass during the study. © 1995 Wiley-Liss, Inc.     

Ranitidine for improvement of delayed hypersensitivity response in patients with sepsis

Twenty-five patients admitted to intensive or high-dependency surgical care units were randomized to receive ranitidine intravenously 50 mg every 6 hours for 8 days or no ranitidine. All had septicemia or intra-abdominal sepsis, with body temperature greater than or equal to 38.5 degrees C for more than 48 hours despite comprehensive medical and/or surgical treatment. Cell-mediated immunity was assessed by skin testing with seven common delayed type hypersensitivity antigens applied on days 1, 4 and 7 and all tests were read at 48 hours, i.e. on days 3, 6 and 9. The ranitidine/non-ranitidine regimen was initiated on day 1 and continued until day 9. Severity of illness was evaluated before and 3, 6 and 8 days after initiating the study, using the APACHE II scoring system. The scores before and during the study were similar in the ranitidine and non-ranitidine groups. Delayed type hypersensitivity improved in patients treated with ranitidine (p less than 0.001), but was unchanged in the untreated group (p greater than 0.7). These observations may suggest potential beneficial effects of ranitidine therapy in patients with trauma-induced immunosuppression.