Biomedical subjects

R N Garrison

Publications and source records attributed to R N Garrison.

At least 37 records · Page 2Linked to original sources

PubMed1998

Microvascular changes explain the "two-hit" theory of multiple organ failure.

OBJECTIVE: The objective was to determine intestinal microvascular endothelial cell control after sequential hemorrhage and bacteremia. SUMMARY BACKGROUND DATA: Sepsis that follows severe hemorrhagic shock often results in multiple system organ failure (MSOF) and death. The sequential nature of this clinical scenario has led to the idea of a "two-hit" theory for the development of MSOF, the hallmark of which is peripheral vasodilation and acidosis. Acute bacteremia alone results in persistent intestinal vasoconstriction and mucosal hypoperfusion. Little experimental data exist to support the pathogenesis of vascular dysregulation during sequential physiologic insults. We postulate that hemorrhagic shock followed by bacteremia results in altered microvascular endothelial cell control of dilation and blood flow. METHODS: Rats underwent volume hemorrhage and resuscitation. A sham group underwent the vascular cannulation without hemorrhage and resuscitation, and controls had no surgical manipulation. After 24 and 72 hours, the small intestine microcirculation was visualized by in vivo videomicroscopy. Mean arterial pressure, heart rate, arteriolar diameters, and A1 flow by Doppler velocimetry were measured. Endothelial-dependent dilator function was determined by the topical application of acetylcholine (ACh). After 1 hour of Escherichia coil bacteremia, ACh dose responses were again measured. Topical nitroprusside was then applied to assess direct smooth muscle dilation (endothelial-independent dilator function) in all groups. Vascular reactivity to ACh was compared among the groups. RESULTS: Acute bacteremia, with or without prior hemorrhage, caused significant large-caliber A1 arteriolar constriction with a concomitant decrease in blood flow. This constriction was blunted at 24 hours after hemorrhage but was restored to control values by 72 hours. There was a reversal of the response to bacteremia in the premucosal A3 vessels, with a marked dilation both at 24 and 72 hours. The sequence of hemorrhage and E. coli resulted in a progressive enhanced reactivity to the endothelial-dependent stimulus of ACh in the A3 vessels at 24 and 72 hours. Reactivity to endothelial-independent smooth muscle relaxation and subsequent vessel dilation was similar for all groups. CONCLUSIONS: These data indicate that there is altered endothelial control of the intestinal microvasculature after hemorrhage in favor of enhanced dilator mechanisms in premucosal vessels with enhanced constrictor forces in inflow vessels. This enhanced dilator sensitivity is most evident in small premucosal vessels. This experimental finding supports the premise that an initial pathophysiologic stress alters the subsequent microvascular blood flow responses to systemic inflammation. These changes in the intestinal microcirculation are in concert with the "two-hit" theory for MSOF.

Acute Disease↗

PubMed1998

Selective microvascular endothelial cell dysfunction in the small intestine following resuscitated hemorrhagic shock.

Following resuscitation (RES) from hemorrhagic shock (HEM), intestinal microvessels develop progressive vasoconstriction that impairs mucosal blood flow, despite central hemodynamic RES. These events might have clinical consequences secondary to occult intestinal ischemia. We hypothesized that the microvascular impairments were due to progressive endothelial cell dysfunction and an associated reduction in the dilator, nitric oxide (NO), following HEM/RES. Male Sprague-Dawley rats, were monitored for central hemodynamics and the terminal ileum was studied with in vivo videomicroscopy. HEM was 50% of baseline mean arterial pressure (MAP) for 60 min, and RES was with shed blood + 1 volume of normal saline (NS). Following HEM/RES, acetylcholine (10)(-7), 10(-5) M) was topically applied and ileal inflow (A1) and premucosal arteriolar diameters were measured to assess endothelial-cell function at 60 and 120 min post-RES. Normalization of MAP, cardiac output, and heart rate demonstrated adequate systemic resuscitation. Post-RES vasoconstriction developed in A1 (-25%) and premucosal (-28%) arterioles with an associated reduction in A1 flow (-47%). However, there was a selective impairment of endothelial-dependent dilation that was manifested only in the smaller premucosal arterioles and not in the inflow, A1 arterioles. This suggests that multiple mechanisms are involved in the development of the post-RES vasoconstriction. The premucosal response was likely mediated by endothelial cell dysfunction, while the A1 response was probably the result of enhanced vasoconstrictor forces. This early microvascular dysfunction might contribute to the late sequelae of intestinal ischemia and might alter microvascular responses to subsequent systemic insults.

Acetylcholine↗

PubMed1998

E. Coli bacteremia-induced changes in the skeletal muscle microcirculation vary with anesthetics.

AIM: To test if anesthetic procedures change the hemodynamic pattern in animals with experimental septic shock. METHODS: The effect of two anesthetics on systemic hemodynamic and skeletal muscle microcirculatory responses in high cardiac output live E. coli bacteremia was studied in rats and compared to the effect of two other anesthetic procedures in previously published studies. RESULTS: Baseline blood pressures and cardiac outputs were similar in rats with decerebrate, ketamine/xylazine, pentobarbital or urethane/chloralose anesthesia. There was a relative baseline tachycardia in decerebrate rats. Ketamine/xylazine anesthetized rats had reduced blood pressure, cardiac output, and heart rate. In decerebrate, pentobarbital, and urethane/chloralose anesthesia, cardiac output increased initially during bacteremia but did not remain elevated in pentobarbital anesthesia. Blood pressure and heart rate remained constant in pentobarbital, decerebrate, and urethane/chloralose anesth esia. During bacteremia, cardiac output, blood pressure, and vascular resistance did not change with ketamine/xylazine, but the heart rate increased. Baseline diameters of cremaster muscle large (A1) arterioles were higher in decerebrate anesthesia. A1 arterioles constricted during high cardiac output bacteremia in decerebrate rats, and pentobarbital or urethane/chloralose-anesthetized rats. A4 arterioles in bacteremia dilated in decerebrate and pentobarbital anesthesia, but did not change under urethane/chloralose and ketamine/xylazine anesthesia. CONCLUSION: Anesthetics influence baseline systemic variables and the response of systemic hemodynamics of rats to E. coli bacteremia. During bacteremia, anesthetics primarily affect the reactivity of skeletal muscle small arterioles. Ketamine/xylazine anesthesia has the most pronounced effect on systemic and microcirculatory variables and seems to be an inappropriate choice in sepsis experiments in rats.

Anesthetics↗

PubMed1997

Heme oxygenase-dependent carbon monoxide production is a hepatic adaptive response to sepsis.

The hemodynamic effects of sepsis have been attributed in part to increased nitric oxide (NO) production and activation of guanylate cyclase, resulting in increased cGMP and relaxation of vascular smooth muscle. Heme oxygenase-1 (HO-1), a heat shock protein, has been shown to increase intracellular cGMP levels by formation of carbon monoxide (CO). We hypothesized that HO may be an important mediator of the hepatic response to infection. Male Swiss Webster mice underwent standard cecal ligation and puncture (CLP, 18 gauge 2X) or sham operation, and received either normal saline (NS) or Zn protoporphyrin IX (ZN PP IX), a competitive HO inhibitor (n = 6-8/group). Hepatic tissue samples were collected at 3, 6, 12, and 24 hr from separate mice. Serum was collected at 3 and 24 hr. A semiquantitative reverse transcriptase polymerase chain reaction method was used to measure HO-1 mRNA levels. Hepatic cGMP levels were measured by ELISA. Groups were repeated (n = 10/group) to assess mortality. Serum was collected at 3 and 24 hr to measure serum aspartate aminotransferase (AST) levels. HO-1 mRNA expression increased significantly by 3 hr after CLP and with HO inhibition alone (P < 0.05 vs sham + NS). HO-1 mRNA remained elevated through 24 hr. CLP animals with HO inhibition showed a significant reduction of hepatic cGMP following CLP compared with CLP + saline at 24 hr (P < 0.05). Mortality was significantly increased in the CLP + ZN PP group at 24 hr (P < 0.05 CLP NS vs CLP ZN PP). CLP caused a marked increase in AST activity, which was increased further with HO inhibition. HO-1 mRNA expression was induced by CLP. AST levels following CLP were markedly increased with HO inhibition. HO-1 function appeared to contribute to elevation of hepatic cGMP during peritonitis and may be an important hepatic adaptive response to infection.

Animals↗

PubMed1997

Lazaroids prevent acute cyclosporine-induced renal vasoconstriction.

BACKGROUND: Cyclosporine (CsA)-induced nephrotoxicity may be due to intrarenal vasoconstriction and glomerular hypoperfusion. Several factors, including endothelin and prostanoids, are suggested mediators of this response. Recent evidence suggests that CsA leads to increased oxygen-derived free radical (ODFR) production and lipid peroxidation in renal tissue. Whether this leads to alterations in renal vessel reactivity is unclear. Lazaroids, such as U74389G, are radical-quenching antioxidants that inhibit ODFR-induced lipid peroxidation and may improve renal function after ischemia and reperfusion. We hypothesized that ODFRs contribute to CsA-induced alterations of the renal microcirculation. METHODS: Rat hydronephrotic kidneys were studied by video microscopy. Interlobular arteriolar diameter and flow, afferent and efferent arteriolar diameters, and cardiac output were measured at 15-min intervals for 120 min. U74389G or its vehicle was infused 15 min before topical application of CsA to the kidney. The results were compared with U74389G alone and normal saline. RESULTS: CsA administration caused renal microvascular vasoconstriction (10-25% below baseline) and hypoperfusion (35% below baseline). Both vasoconstriction and hypoperfusion were significantly attenuated by U74389G (5-8% and 20% below baseline, respectively). CONCLUSIONS: Inhibition of lipid peroxidation by U74389G maintained renal blood flow during acute CsA administration. These data suggest that ODFRs are involved in the renal microvascular response to CsA. Inhibition of ODFR-induced lipid peroxidation may help prevent CsA-induced glomerular hypoperfusion. Lazaroids may prove an effective adjunct in reducing CsA-induced nephrotoxicity.

Animals↗

PubMed1997

Oral presentations for surgical meetings.

Each year the Association for Academic Surgery sponsors the "Fundamentals of Surgical Research" course which is established for residents who are beginning research training. A lecture outlining various aspects of effective scientific presentations, such as that delivered at a national or regional surgical meeting, is part of the course. Faculty from our institution have organized this lecture for several years. The lecture content has been revised each year to reflect the recommendations of the participating residents and faculty. Herein, we summarize the requirements for composing and delivering a scientific surgical presentation that is noted for its clarity, easily understood methods, interpretable data, and scientific and/or clinical implications.

Communication↗

PubMed1997

Differential intestinal microvascular dysfunction occurs during bacteremia.

Altered vascular responsiveness is the hallmark of septic shock. Recently, these changes have frequently been attributed to increased production of nitric oxide (NO). Continued exposure to high levels of NO may alter both endothelial and vascular smooth muscle cell function. Although ex vivo studies demonstrate hyporeactivity of large conduit arteries during established sepsis, it is unclear if the same phenomena exist during early sepsis. This is especially true in the small resistance arterioles of the viscera. We used in vivo microscopy of the rat small intestine to assess (1) endothelial-dependent relaxation and vasomotion (periodic contraction and relaxation of blood vessels) in response to acetylcholine (ACH; 10(-8) to 10(-5) M), (2) endothelial-independent relaxation to nitroprusside (NTP; 10(-5) M), and (3) vascular smooth muscle response to norepinephrine (NE; 10(-10) to 10(-7) M) in normal and bacteremic rats (Escherichia coli). There were no alterations in endothelial-dependent or -independent relaxation during bacteremia as measured by mean diameters. However, acute E. coli bacteremia severely impaired vasomotion in A1 (inflow) and A3 (premucosal) arterioles. Vasomotion was returned to baseline levels in A1 with low-dose ACH (10(-8) M) but only partially improved in A3 arterioles (P < 0.05). A1 response to NE was impaired, while A3 were minimally altered despite being more sensitive to E. coli-induced vasoconstriction. These data suggest that bacteremia causes a rapid, differential impairment of both endothelial-dependent (A3 vasomotion) and vascular smooth muscle cell (A1 constriction) functions. These microvascular impairments occur much earlier than previously described and may contribute to sepsis-induced mucosal ischemia of the intestines.

Acetylcholine↗

PubMed1997

Glucose-induced intestinal hyperemia is mediated by nitric oxide.

UNLABELLED: Glucose-induced absorptive hyperemia of the intestine has been well demonstrated through microsphere blood flow experiments. We have previously demonstrated that glucose, when applied topically to rat ileal epithelium, restores microvascular vessel diameters and blood flow following Escherichia coli bacteremia or hemorrhage/resuscitation. However, the mechanisms of this hyperemia are not completely understood. We hypothesize that nitric oxide is a mediator of the microvascular response to glucose exposure on the rat intestinal epithelium. METHODS: Male Sprague-Dawley rats, 200-225 g, were monitored for hemodynamic stability with mean arterial blood pressure and heart rate. A 2-cm segment of the terminal ileum with intact neurovascular supply was exposed for intravital videomicroscopy. Intestinal arteriolar diameters (A1D, inflow; and A3D, premucosal arterioles) and microvascular blood flow (A1Q) were measured following topical application of isoosmotic glucose or saline, with or without l-NAME (LN, 100 mM), a competitive inhibitor of nitric oxide synthase. Statistical analysis was performed by ANOVA followed by Tukey-Kramer honestly significant difference test. RESULTS: All data are expressed as mean percentage changes from baseline +/- standard error of the mean. Hemodynamic variables did not change during the experimental procedure and there were no significant differences among group baselines. Addition of isotonic glucose to the bath solution caused a significant increase in A3D that persisted throughout the experiment (at 30 min, 19.2 +/- 4.2 vs -3.9 +/- 4.5, P < 0.05). This vasodilation was blocked by topical administration of LN (3.1 +/- 2.9, P < 0.05). A1D remained at baseline levels (saline and glucose) or constricted (LN) in all groups. Topical LN also attenuated A1Q in both the saline and glucose groups. CONCLUSIONS: These data demonstrate that glucose-induced intestinal hyperemia is primarily characterized by premucosal A3 arteriole dilation in this model and that nitric oxide is a mediator of glucose-induced intestinal hyperemia. These findings suggest that either (1) glucose directly causes endothelial nitric oxide production or (2) epithelial cells transduce a vasodilatory signal through vascular endothelial-derived nitric oxide during postprandial intestinal hyperemia.

Analysis of Variance↗

PubMed1997

Poor outcome from peritonitis is caused by disease acuity and organ failure, not recurrent peritoneal infection.

OBJECTIVE: The purpose of the study is to determine whether organ failure develops in patients despite control of peritoneal infection and whether the process is, in part, neutrophil (polymorphonuclear leukocyte [PMN]) mediated. SUMMARY BACKGROUND DATA: Peritonitis generally responds to prompt surgical intervention and systemic antibiotics; however, some patients continue a septic course and progress to organ failure and death. METHODS: One hundred five consecutive patients with peritonitis between 1988 and 1996 who required operation and a postoperative hospital stay greater than 10 days were studied. Mice were injected with a monoclonal anti-PMN antibody 24 hours before cecal ligation and puncture (CLP) to deplete PMNs. RESULTS: Thirty-eight patients died, and all but 1 had identified organ failure. Seventy-seven patients had either pulmonary failure alone (25 patients) or as a component of multisystem organ failure (52 patients). All but one of these patients showed resolution of their intraperitoneal infection as evident by clinical course, abdominal computed tomographic scan, second-look laparotomy, or autopsy. Recurrent intra-abdominal infection developed in 15 patients, but only 1 had organ failure, and 2 died. At 18 hours after CLP, lung injury, PMN content, interleukin-1 mRNA expression, and liver injury were significantly reduced by anti-PMN treatment, whereas serum endotoxin levels actually increased. CONCLUSIONS: Disease acuity and organ failure, and not recurrent peritoneal infection, are the major causes of adverse outcome in patients with peritonitis. The authors' experimental data indicate that such organ injury is, in part, PMN mediated but not endotoxin mediated. Attraction of PMNs toward the site of primary infection, and thereby away from remote organs, is a logical future therapeutic approach in such patients who are critically ill with peritonitis.

APACHE↗

PubMed1997

Intraoperative duplex scanning reduces both residual stenosis and postoperative morbidity of carotid endarterectomy.

To evaluate the effect of intraoperative duplex scanning (IDS) on the incidence of perioperative and postoperative strokes as well as residual and recurrent stenosis, we reviewed 141 patients who underwent 152 consecutive carotid endarterectomies (CEAs) between July, 1990 and June, 1995. Follow-up of 129 cases, with a mean follow-up of two years, revealed no perioperative deaths and three strokes for a combined perioperative stroke-death rate of 2.3 per cent. In 50% (64 of 129) of the CEAs, intraoperative duplex scans were obtained based on the attending surgeon's preference. We noted that the incidence of residual stenosis (>50% stenosis on the first duplex after CEA) was significantly lower in those undergoing IDS (3/64) versus those without IDS (13/65) (P < 0.05; risk ratio 0.31; 95% confidence interval 0.11, 0.91). IDS resulted in a modification of the internal carotid reconstruction in 9 per cent (6 of 64) of the cases with no resulting postoperative strokes or residual/recurrent stenosis. There was no significant difference in the frequency of recurrent stenosis (>50% stenosis after a normal duplex) in the two groups (3 of 64 with vs 2 of 65 without). Of patients not undergoing intraoperative scanning, four underwent redo CEA for symptomatic residual stenosis due to a retained intimal flap in the internal carotid artery. There were three strokes observed within 30 days of the initial CEA, all of which occurred in patients who did not undergo IDS at their initial operation. We conclude that IDS can identify technical defects following internal carotid reconstruction, thereby reducing the incidence of both residual stenosis and postoperative morbidity in patients undergoing CEA.

Carotid Stenosis↗

PubMed1997

A new standard of care: administration of preoperative antibiotics in the operating room.

Surgical site infections increase total hospital expenses and extend the length of hospital stay. Properly administered antibiotics are successful in minimizing postoperative subcutaneous wound infection secondary to perioperative bacterial contamination at the surgical site and are effective in most clean-contaminated surgical procedures. It is imperative that therapeutic levels of antibiotics be present during the time when the wound is open to maximize their effect to prevent the development of surgical wound infections. Only 32 per cent of 97 patients sampled from 1992 to 1994 at the Louisville Veterans Affairs Medical Center were administered preoperative antibiotics within 1 hour prior to surgical incision. Changing the responsibility for preoperative antibiotic administration from ward or holding room nurses to the anesthesiologist in the operating room rendered such antibiotics delivered closer to the induction of anesthesia and subsequent incision. Eighty-eight per cent of 220 patients sampled in 1995 had antibiotics administered within 1 hour of incision. This change in institutional policy of antibiotic administration maximizes the likelihood of appropriate antibiotic tissue levels and thereby their potential efficacy. Routine prophylaxis should be administered as close to the time of induction of anesthesia as possible to provide the best chance for appropriate tissue levels above the minimum inhibitory concentration for potential bacterial contamination.

Antibiotic Prophylaxis↗

PubMed1997

Lazaroid improves intestinal blood flow in the rat during hyperdynamic bacteraemia.

BACKGROUND: Intestinal mucosal hypoperfusion and loss of barrier function during sepsis may contribute to maintaining the septic state. Free radicals are produced during sepsis and antioxidants improve survival from experimental sepsis. It is unclear whether endothelial cell injury from free radicals results in altered microvascular reactivity. Lazaroids are antioxidants which scavenge radicals and block lipid radical chain reactions. The authors sought to determine whether lazaroids altered the intestinal microvascular responses to sepsis. METHODS: In vivo video microscopy was used to study the ileal microcirculation of the rat. A1 (inflow) arteriolar diameter and flow, A3 (premucosal) arteriolar diameters, and cardiac output were measured. Lazaroid or vehicle was infused before a bolus injection of live Escherichia coli or saline. RESULTS: Lazaroid alone had no effect on the intestinal vessels or haemodynamics. E. coli caused vasoconstriction (A1, -21 per cent, A3, -19 per cent of baseline) and hypoperfusion (-36 per cent) despite increased cardiac output (+31 per cent). Lazaroid significantly attenuated both constriction (A1, -11 per cent; A3, 10 to -1 per cent) and hypoperfusion (-15 per cent), but did not increase cardiac output (30 per cent). CONCLUSION: E. coli bacteraemia led to intestinal vasoconstriction and hypoperfusion. Lazaroid reduced this effect without altering central haemodynamic responses, suggesting that free radicals have a deleterious effect on the intestinal microcirculation during bacteraemia.

Animals↗

PubMed1996

Intraoperative duplex scanning reduces the incidence of residual stenosis after carotid endarterectomy.

We studied the effect of intraoperative duplex scanning on the incidence of residual and recurrent stenosis and stroke after carotid endarterectomy (CEA). We retrospectively analyzed 98 veteran patients undergoing 106 consecutive CEAs between July 1990 and June 1994. Follow-up duplex scans were available for 86 cases (81%, mean follow-up 20 months). There were no perioperative deaths. Intraoperative duplex scans were obtained in 39 (45%) of 86 CEAs. The incidence of residual stenosis was lower in the patients scanned at the time of surgery (O of 39) than in those who underwent CEA without intraoperative scan (7 of 47, P < 0.04). One patient who did not receive intraoperative duplex scanning underwent redo CEA for symptomatic residual stenosis due to an intimal flap of the carotid artery. Operative management was changed in 9 of 39 cases because of abnormal intraoperative duplex scans, with no postoperative strokes or residual/recurrent stenosis. The incidence of recurrent stenosis was not different in the two groups (2 of 39 vs 2 of 47, ns). There was no difference in stroke rate. There were three strokes, one perioperative and two postoperative (mean 3.5 months, range 0.5 to 9). Two of the three patients did not undergo an intraoperative duplex scan, but none had developed restenosis >50% over a mean of 21 months of follow-up. Intraoperative duplex scanning significantly reduced the incidence of residual stenosis, but did not affect the incidence of recurrent stenosis or stroke following CEA.

Aged↗

PubMed1996

Platelet-activating factor mediates pulmonary macromolecular leak following intestinal ischemia-reperfusion.

Platelet-activating factor (PAF) causes hypotension, cardiac dysfunction, increased vascular permeability, intestinal necrosis, and pulmonary microvascular injury when administered experimentally. Receptor antagonism attenuates or abolishes many of these effects in animal models of bacteremia, endotoxemia, and intestinal ischemia/reperfusion (I/R). The purpose of this study was to further examine the role of PAF in intestinal I/R-induced pulmonary injury using the PAF receptor antagonist WEB 2086. Sprague-Dawley rats were anesthetized and cannulated for measurement of mean arterial pressure, heart rate, and cardiac output. Laparotomy and thoracotomy were performed and the superior mesenteric artery was occluded for 45 min and reperfused for 120 min. Sham animals were treated similarly but without I/R. In the treatment groups, iv WEB 2086 (20 mg/kg/l cc NS) was administered as a bolus 15 min prior to reperfusion. Hemodynamic and videomicroscopic data were obtained before and during ischemia, and after reperfusion at 30-min intervals. Alveolar leak index was calculated offline via computer analysis of videomicroscopic images. Intestinal I/R caused pulmonary macromolecular leakage and hemodynamic instability. Treatment with WEB 2086 attenuated the pulmonary leak during the entire reperfusion period but improved cardiac output only during the first 30 min of reperfusion and had no effect on other hemodynamic variables. These data suggest that PAF is an important, but not the exclusive, mediator of pulmonary injury after intestinal I/R. PAF appears to play a minor role in the hemodynamic derangements observed after rat intestinal I/R.

Animals↗

PubMed1996

Vasomotor response to pentoxifylline mediates improved renal blood flow to bacteremia.

Bacteremia leads to rapid intrarenal vasoconstriction, mediated by endogenous vasoconstrictors such as TXA2 and endothelin. These changes occur before the onset of neutrophil adherence, platelet aggregation, or increases in proinflammatory cytokines. Pentoxifylline (PTX) increases red cell deformability, reduces neutrophil adhesion, abrogates rises in TNFalpha, and lessens the deleterious effects of other cytokines during prolonged sepsis. PTX also improves renal function in models of established sepsis, but the specific mechanisms of this effect are unclear. Because PTX is a relatively selective visceral vasodilator we sought to determine whether PTX improves renal microvascular hypoperfusion during bacteremia and whether the mechanism involves altered vascular reactivity. Rat hydronephrotic kidneys were studied by videomicroscopy. Interlobular (ILA) arteriolar diameter and flow, afferent (AFF) and efferent (EFF) arteriolar diameters, and cardiac output (CO) were measured at 15-min intervals for 120 min. PTX was infused alone or prior to a bolus injection of live Escherichia coli. The responses were compared to controls infused with equivalent volumes of normal saline alone. PTX led to improved renal blood flow and to pre- and postglomerular vasodilatation. This improvement remained significant compared to bacteremic animals throughout the period of observation. We conclude that PTX improves renal blood flow during bacteremia due to pre- and postglomerular vasodilation. These responses may be a consequence of increased intracellular cAMP and release of vasodilator prostanoids.

Animals↗

PubMed1996

Heparan preserves intestinal perfusion after hemorrhage and resuscitation.

BACKGROUND: Multiple system organ failure (MOF) remains a major source of morbidity and mortality in trauma patients. Despite restoration of central hemodynamics, intestinal hypoperfusion can persist. Mucosal ischemia and barrier breakdown are factors in the genesis of MOF. Heparan sulfate is a gycosaminoglycan similar to heparin, but with minimal anticoagulant properties. As an adjunct to resuscitation, it improves immunologic function and restores mucosal oxygenation and function. We hypothesized that resuscitation with heparan following hemorrhage wound prevents intestinal hypoperfusion. MATERIALS AND METHODS: In vivo videomicroscopy was used to study small intestine microcirculation in rats. Animals were hemorrhaged to 50% of baseline mean arterial pressure (MAP) and maintained there. Resuscitation was initiated when the return of 10% shed blood was required to keep MAP at 50%. Animals received either heparan (7 mg/kg/1 ml saline) or saline (1 ml) followed by the remaining shed blood and an equal volume of saline. MAP, cardiac output (CO), A1 arteriole diameters, and flow were determined. RESULTS: Resuscitation of the saline control group resulted in normal MAP with elevation of CO to 25-40% above baseline. The heparan group had return of MAP but only a moderate increase in CO (7-15%). Saline resuscitation led to progressive deterioration in A1 diameters and flow. The addition of heparan prevented delayed A1 constriction and significantly improved perfusion. CONCLUSIONS: Heparan prior to resuscitation improved intestinal perfusion, despite a relative reduction in CO. Improvement in nutrient blood flow may protect the mucosal barrier, reducing the incidence of MOF, and suggests that heparan may be useful in resuscitation of trauma patients.

Animals↗

PubMed1996

Free radical scavenging by lazaroids improves renal blood flow during sepsis.

BACKGROUND: Acute kidney failure in surgical patients is often related to severe infection. Renal vasoconstriction is a major factor in the genesis of kidney failure. Reactive oxygen species (ROS) are known to mediate kidney injury after ischemia-reperfusion and are increased during sepsis. The role of ROS as mediators of intrarenal vasoconstriction and renal dysfunction during sepsis is unclear. Lazaroids such as U74389G are radical quenching antioxidants that inhibit ROS-induced lipid peroxidation. We sought to determine whether radical scavenging affected the renal microvascular response to a septic challenge. METHODS: In vivo videomicroscopy was used to study the rat hydronephrotic kidney. Interlobular artery (ILA) diameter and flow, afferent and efferent arteriolar diameters, and cardiac output were measured. U74389G or vehicle was infused before a bolus injection of live Escherichia coli or normal saline solution. RESULTS: U74389G alone had no effect on the renal vessels or hemodynamics. E. coli caused preglomerular vasoconstriction (ILA, -32%; afferent, -30% of baseline) and hypoperfusion (-66%) despite increased cardiac output (+54%). U74389G significantly attenuated both the constriction (ILA, -16%; afferent, -9%) and hypoperfusion (-38%) but not increased cardiac output (+41%). CONCLUSIONS: E. coli bacteremia led to preglomerular vasoconstriction and hypoperfusion. Inhibition of lipid peroxidation with the radical scavenger U74389G reduced this effect without altering central hemodynamic responses. Free radicals have a deleterious effect on the renal microcirculation during bacteremia, and these data suggest that antioxidants may be of value in preventing sepsis-associated kidney failure.

Animals↗

PubMed1996

Operative strategies for management of abdominal aortic gunshot wounds.

BACKGROUND: Although management of penetrating abdominal trauma has greatly improved, abdominal aortic gunshot wounds (AAGSWs) remain a highly lethal injury. Our experience with AAGSWs was reviewed to define operative strategies that may improve survival. METHODS: Forty-one patients with AAGSWs were treated between 1976 and 1996. Preliminary thoractomy was performed in seven patients. Thirty-nine patients had at least one major associated injury (average, 3.2). RESULTS: Twenty-one patients died. Six of seven patients who underwent preliminary thoracotomy died; all developed coagulopathy, which appeared to contribute to death. Four patients had missed vascular lesions, two of which contributed to their death. Associated injuries are currently managed by "damage control" strategy, in which some injuries are left untreated to focus on hemorrhage control. CONCLUSIONS: We have identified seven operative principles and procedures that we believe may improve survival: (1) thorough knowledge of supraceliac exposure; (2) rapid aortic control at the hiatus rather than by a preliminary thoracotomy; (3) use damage control or abbreviated laparotomy; (4) use packing and mesh closure when coagulopathy and hypothermia are present; (5) primary concern should be cessation of hemorrhage rather than the maintenance of flow; (6) delayed reconstruction using extraanatomic bypass can restore flow; and (7) use angiography to detect missed vascular lesions or problems with vascular repair.

Adult↗