Biomedical subjects

R N Garrison

Publications and source records attributed to R N Garrison.

At least 55 records · Page 3Linked to original sources

PubMed1996

Organ donor potential and performance: size and nature of the organ donor shortfall.

OBJECTIVES: To estimate the potential for solid organ donation; to identify modifiable reasons for nondonation. DESIGN: Retrospective medical records review. SETTING: Sixty-nine acute care hospitals in four geographic areas of the United States in 1990, and a stratified random sample of 89 hospitals in three of the same areas and 33 of the same hospitals in 1993. PATIENTS: PATIENTS < or = 70 yrs of age who were brain dead and medically suitable for donation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Standard forms were used to record patient demographic and hospital information. Reasons for nondonation were coded as "not identified," "family not asked," "consent denied," or "other." The main outcome measures were rate of donation and rates of nonidentification, not asking, and nonconsent. Organ donation occurred among 33% (299/916) of medically suitable cases identified in 1990 (95% confidence interval 30% to 36%). Ninety-four potential donors were not identified, 156 were not asked, 326 families denied consent, and 41 potential donors were categorized as "other," including patients who had suffered a cardiac arrest, and medical examiner prohibition of donation. In the 1993 study, organ donation occurred in an estimated 33% of suitable cases. In 1990, rates of donation were highest among patients <50 yrs of age, patients who died of traumatic causes, and non-Hispanic white patients. Logistic regression showed lower odds of donation for African American patients (odds ratio 0.38, 95% confidence interval 0.23 to 0.63) independent of potentially confounding hospital and patient variables (p=.0001). Donation rates did not vary by hospital size or type. CONCLUSIONS: Despite legal and policy initiatives, only one third of potential donors became donors in 1990, with similar results in 1993. Extrapolating the 1990 findings to the United States suggests a pool of 13,700 medically suitable donors per year. Prospective identification and requesting donation in all suitable potential donor cases could lead to 1,800 additional donors per year.

Adolescent↗

PubMed1996

Fluid resuscitation attenuates early cytokine mRNA expression after peritonitis.

OBJECTIVE: To study the hypothesis that fluid resuscitation alters cytokine gene expression after experimental murine peritonitis. MATERIALS AND METHODS: Mice underwent cecal ligation and puncture (CLP) to induce peritonitis and were randomized to receive variable amounts of normal saline (0, 0.25, 1.0 ml. subcutaneously) and serum (0 or 0.1 mL) after operation. Hepatic and small intestinal (ileal) tissue were harvested at 3 or 6 hours after CLP, and total tissue RNA was extracted. Reverse transcriptase polymerase chain reaction was used to provide relative quantitation of tumor necrosis factor-alpha and interleukin (IL)-1 beta messenger RNA (mRNA) compared with beta-actin. RESULTS: CLP without resuscitation resulted in significant increases in hepatic tumor necrosis factor-alpha mRNA (1190% at 6 hours compared with normal animals), and IL-1 beta mRNA (1475%), and intestinal IL-1 beta mRNA (1243%). Volume administration attenuated cytokine expression at both 3 and 6 hours, and saline seemed to have more potent effects than serum. The volume of resuscitation correlated with survival at 18 hours. Survival in the saline (1 mL) + serum group was 90% at 18 hours compared with 20 to 40% in the groups with little or no resuscitation. Overall, there were no survivors at 30 hours. CONCLUSIONS: Fluid resuscitation (amount, composition, timing) should be an important consideration in the utilization of experimental infection models. Furthermore, optimization of the patient's intravascular volume status during sepsis may have important effects on immune responses, in addition to improving hemodynamic variables.

Animals↗

PubMed1996

Age-related differences in intestinal arteriolar responses to venous pressure elevation in the rat.

OBJECTIVE: We previously reported differences in intestinal arteriolar responses of adult and suckling rats to three stressors (hemorrhage, hypoxia, and hypothermia) that decreased intestinal blood flow. The small, premucosal arterioles of adult rats dilated in response to all three stressors, whereas the premucosal arterioles of suckling rats constricted or remained unchanged. One explanation for this difference might be absence of myogenic responsiveness in the premucosal arterioles of the immature rat. METHODS: We used in vitro videomicroscopy to observe the intestinal arteriolar responses to venous pressure elevation (a myogenic stimulus) in adult (8- to 12-week-old) and suckling (8- to 12-day-old) Sprague-Dawley rats. We increased portal venous pressure by 25 and 50% above the baseline pressure. RESULTS: Arterioles in the rats displayed the expected "myogenic" response to venous pressure elevation (diameters decreased 12-29% when venous pressure was increased by 50%). In contrast to adult rats, arterioles in the suckling rats failed to constrict in response to increases in venous pressure (diameters increased 14-21% in response to a 50% increase in venous pressure). CONCLUSIONS: These results suggest that the myogenic constrictor mechanisms for control of the microcirculation appear to be either nonfunctional or suppressed in the intestinal microcirculation of suckling rats.

Aging↗

PubMed1996

Preoperative saline loading improves outcome after elective, noncardiac surgical procedures.

Patients with multiple system disease undergoing elective noncardiac surgical procedures are at variable risk for developing postoperative complications and death. To determine whether preoperative expansion of plasma volume would improve outcome, 306 patients were admitted to the Surgical Intensive Care Unit of the Veterans Administration Center for Swan-Ganz catheter placement and measurement of hemodynamic responses to a 2 L infusion of normal saline over 2 hours. Intraoperative stability and postoperative outcome were assessed by chart review and compared with similar operative groups of patients who did not receive saline infusion. Eighty-eight per cent of the patients had a positive expansion of blood volume with saline infusion. In patients undergoing aortic reconstructive procedures, there was a reduction in the incidence of postoperative complications (52% to 28%) primarily attributed to a reduction in pulmonary complications. In all patients there was an improvement in intraoperative cardiovascular stability (57% saline vs 38% control), a reduction in the need for pharmacologic support of blood pressure (19% saline vs 30% control), and reduction in the amount of intraoperative fluid administration (hydration index: 5.12 saline vs 8.61 control). We therefore conclude that preoperative saline loading is associated with improved outcome in high risk elderly patients undergoing elective, noncardiac surgical procedures.

Adult↗

PubMed1995

Haemophilus pneumonia is a common cause of early pulmonary dysfunction following trauma.

BACKGROUND: Haemophilus species are a common cause of community-acquired pneumonia; however, their significance in posttraumatic pneumonia is unclear. DESIGN: Case series. SETTING: University hospital, level I trauma center. PATIENTS: Two hundred fifty-seven consecutive patients with blunt and penetrating trauma treated for pneumonia. MAIN OUTCOME MEASURES: Length of stay in the intensive care unit, duration of ventilatory support, rate of recurrent or persistent pneumonia, and mortality. RESULTS: Ninety-six (37%) of 257 patients treated for pneumonia had a Haemophilus species isolated on sputum culture. Of these 96 patients, 49 (51%) had only Haemophilus species, while 33 (34%) had associated gram-positive organisms and 14 (15%) had gram-negative organisms. Seventeen pure cultures (29%) and seven mixed cultures (15%) (P < .05) were beta-lactamase-positive trains. Compared with patients who had pneumonia caused by other bacteria, patients with Haemophilus species were younger (mean +/- SE, 35 +/- 1.7 vs 42 +/- 1.6 years; P < .05) and more severely injured (Injury Severity Score, 20.7 +/- 1.1 vs 17.5 +/- 0.9; P < .05). There were no differences in any outcome variables between the two groups. Only one (1%) of 96 patients had persistent Haemophilus species on sputum cultures after 7 days of treatment. CONCLUSIONS: Haemophilus species are a frequent cause of pneumonia following traumatic injury. This occurs primarily in the early postinjury phase and therefore should be included in the differential diagnosis of early posttraumatic pulmonary insufficiency.

Adult↗

PubMed1995

Pentoxifylline attenuates pulmonary macromolecular leakage after intestinal ischemia-reperfusion.

OBJECTIVE: To assess the effects of pentoxifylline posttreatment on hemodynamic variables and acute pulmonary injury in the rat intestinal ischemia-reperfusion (I-R) model, using a recently developed method of fluorescent intravital pulmonary videomicroscopy. DESIGN: Anesthetized male Sprague-Dawley rats were cannulated for measurement of mean arterial pressure, heart rate, cardiac output, arterial blood gas values, and hematocrit. Rats underwent isolation of the superior mesenteric artery for intestinal I-R (45 minutes of ischemia, 120 minutes of reperfusion) and right lateral thoracotomy for pulmonary videomicroscopy. Epi-illumination fluorescent videomicroscopy was used to quantitate leakage of intravascular fluorescently labeled albumin into alveoli, while hemodynamic variables were simultaneously recorded. In the treatment groups, pentoxifylline was administered after 30 minutes of intestinal ischemia. Data (mean +/- SEM) were recorded before and during intestinal ischemia and after reperfusion at 30-minute intervals. MAIN OUTCOME MEASURE: The appearance of fluorescently labeled albumin into alveolar airspaces was quantitated off-line by computer and reported as the alveolar leak index. RESULTS: Intestinal I-R caused alveolar macromolecular leakage, marked by a 300% +/- 48% increase from baseline (P < .05) in the alveolar leak index. Intestinal I-R also produced systemic hemodynamic instability demonstrated by a decrease in the mean arterial blood pressure (-36% +/- 5% vs baseline, P < .05) and cardiac output (-42% +/- 6% vs baseline, P < .05), metabolic acidosis (final arterial pH of 7.17, P < .05 vs initial pH), and a 2.3-fold increase in the intravenous fluid requirement when compared with that in sham animals (P < .05). Treatment with pentoxifylline 30 minutes after intestinal ischemia attenuated pulmonary macromolecular leakage (P < .05 vs nontreated I-R) and reduced the decrease in cardiac output (-15% +/- 7% vs baseline, not statistically significant). Pentoxifylline treatment had no effect on the mean arterial blood pressure, heart rate, metabolic acidosis, or intravenous fluid requirement. CONCLUSIONS: Pentoxifylline reduces alveolar capillary membrane injury and subsequent protein leakage and improves cardiac output when administered after 30 minutes of intestinal ischemia. These data suggest that pentoxifylline may be a possible candidate as a future therapy for acute pulmonary dysfunction. Further studies in human patients are necessary.

Animals↗

PubMed1995

An experimental study of altered nitric oxide metabolism as a mechanism of cyclosporin-induced renal vasoconstriction.

Nephrotoxicity caused by cyclosporin A (CSA) is the result of vasoconstriction of the renal microcirculation. The endothelium-derived relaxing factor nitric oxide (NO) regulates microvascular blood flow in various tissues, and mediates the microcirculatory response during hypertension and sepsis. This study investigated the role of NO in CSA-induced renal vasoconstriction. Hydronephrotic kidneys in rats were suspended in an environmentally controlled tissue bath, and interlobular, afferent and efferent arteriolar diameters and blood flow were measured by in vivo videomicroscopy. CSA was administered alone, with the nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) or with exogenous NOS substrate L-arginine. CSA significantly constricted the whole of the renal microvasculature whereas L-NAME alone preferentially constricted the preglomerular vessels. L-Arginine reversed the vasoconstriction induced by CSA whereas L-NAME had no further effect. Preglomerular basal vascular tone is dependent on continuous production of NO and alterations in the L-arginine-NO pathway contribute to CSA-induced renal vasoconstriction.

Animals↗

PubMed1995

Platelet-activating factor and sepsis-induced small intestinal microvascular hypoperfusion.

Platelet-activating factor (PAF) and bacteremia both cause small intestinal (SI) hypoperfusion which may contribute to mucosal injury, and PAF has been postulated to mediate impaired SI microvascular blood flow during sepsis. Our previous studies demonstrate that sepsis-induced SI hypoperfusion is associated with both arteriolar and venular constriction, but the microvascular mechanisms by which PAF impairs SI blood flow are not well defined. Microcirculation studies in other tissues indicate that PAF is an arteriolar dilator, but this effect in the SI would not explain PAF-mediated hypoperfusion. We studied the effects of PAF on SI microvessels to characterize the microvascular mechanisms which mediate PAF-induced hypoperfusion. We also determined the role of PAF as a mediator of microvascular effects in the intestine during bacteremia by PAF receptor antagonism. Animals received either 10(9) live Escherichia coli IV or PAF applied topically to the SI (30, 80, and 300 nM). Arteriolar and venular diameters and red blood cell velocity (A1, V1) were measured with intravital microscopy and velocimetry. Both PAF and sepsis resulted in impaired SI blood flow (maximum decrease in blood flow -37 and 65%, respectively), but sepsis was associated with both arteriolar and venular constriction (20 and 30% diameter reduction each), whereas PAF produced only venular constriction (50% diameter reduction). Inhibition of PAF action prevented the microvascular alterations of bacteremia (blood flow unchanged, P < 0.05; venular diameter unchanged, P < 0.05), suggesting that PAF is an important mediator of these responses.

Animals↗

PubMed1995

The effect of soluble tumor necrosis factor receptor-II on endotoxin-mediated hemodynamic instability.

Tumor necrosis factor-alpha (TNF-alpha), a central mediator in the hemodynamic response to injury and infection, is a primary mediator of endotoxin-induced hemodynamic instability. Two types of naturally occurring soluble TNF receptors circulate in human experimental endotoxemia and the recombinant proteins of both have been hypothesized as potential therapeutic agents antagonizing TNF-mediated effects of endotoxemia. The administration of recombinant sTNFr-I has been previously shown to attenuate the hemodynamic collapse of lethal bacteremia. In the current study, we investigated the role of recombinant sTNFR-II at low (0.5 mg/kg) and high (2.5 mg/kg) doses as a potential therapeutic agent for the inhibition of endotoxin lipopolysaccharide (LPS)-mediated hemodynamic instability. Eighteen male Sprague-Dawley rats were anesthetized and cannulated for continuous blood pressure monitoring and cardiac output measurement by thermodilution. Groups of animals received saline, LPS (1 mg/kg), or sTNFr-II (at 0.5 or 2.5 mg/kg) 15 min prior to LPS (1 mg/kg). Hemodynamic variables (blood pressure, cardiac output, heart rate) were monitored every 15 min for 2 hr. LPS caused a 30% decrease in mean arterial pressure by 60 min, which began to recover by 120 min. sTNFr-II was unable to prevent LPS-induced hypotension at low or high dose. Serum levels of immunoreactive TNF-alpha, undetectable in control animals, were significantly increased by sTNFr-II compared to LPS alone. Serum from animals treated with high-dose sTNFr-II showed significantly less TNF cytotoxicity than those treated with low-dose sTNFr-II, indicating that high doses of sTNFr-II are required for the inhibition of the bioactivity of TNF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Pulmonary subpleural arteriolar diameters during intestinal ischemia/reperfusion.

Adult respiratory distress syndrome (ARDS) often occurs in response to sepsis, shock, or ischemia/reperfusion (I/R) of a remote organ and is a frequent cause of mortality in the ICU patient. Pulmonary vascular resistance (PVR) increases during ARDS, yet direct observations of the pulmonary microcirculation are needed to characterize the vascular response. The purpose of this study was to quantitate the changes in hemodynamic variables, subpleural arteriolar diameters (AD), and alveolar cross-sectional areas (ACSA) during intestinal I/R-induced lung injury in rats, using a new method of in vivo videomicroscopy. Sprague-Dawley rats were anesthetized and cannulated, and superior mesenteric arteries were looped. A thoracotomy was performed with animals ventilated with air with 1 cm PEEP. Hemodynamic and videomicroscopic data were obtained before and during 45 min of SMA occlusion and after reperfusion, up to 120 min. Maximal vessel dilation was measured using topical 10(-5) M nitroprusside. The ability of vessels to constrict was confirmed by applying topical 10(-6) M endothelin-1. Intestinal I/R produced decreases in arterial pH, mean arterial pressure, and cardiac output. Despite these alterations, subpleural AD remained maximally dilated. Arterioles maintained the ability to constrict as demonstrated by the response to topical endothelin-1. ACSA did not change, indicating a uniform inflation of the lung. Using a unique method of in vivo pulmonary videomicroscopy, we have shown that AD do not change following 120 min of intestinal I/R, despite systemic hemodynamic instability. It appears that pulmonary arteriolar vasoconstriction does not contribute to increased PVR during the early phase of lung injury.

Animals↗

PubMed1995

Alpha-adrenergic receptor antagonism prevents intestinal vasoconstriction but not hypoperfusion following resuscitated hemorrhage.

Resuscitation (RES) after hemorrhage (HEM) results in persistent arteriolar constriction and hypoperfusion of the small intestine (SI) despite restoration of mean arterial pressure (MAP) and cardiac output (CO) to normal values. We postulated that increased adrenergic activity contributes to this vasoconstriction and impairment of flow. A loop of SI from decerebrate rats was exteriorized and suffused with Krebs' solution (37 degrees C, pH 7.4). In initial experiments, the effectiveness of alpha-adrenergic receptor antagonism by phentolamine (PHEN) was assessed. Subsequent groups received either topical PHEN (10(-6) M, n = 6) or saline (n = 6) in the suffusion and were then bled to 50% baseline (BL) MAP for 60 min and resuscitated to BL with shed blood/lactated Ringer's. Intravital microscopy and optical Doppler velocimetry were used to measure large (A1) and small, premucosal (A3) arteriolar diameters and RBC velocity; microvascular blood flow was calculated. MAP and transpulmonary CO were measured. During HEM, control animals developed A1 constriction and hypoperfusion with A3 arteriolar dilation. PHEN treatment prevented A1 constriction and enhanced A3 dilation but did not improve flow. Immediately after RES in controls, microvascular diameters and A1 flow returned to BL; however, over the 2-hr post-RES period there was progressive A1 and A3 vasoconstriction and hypoperfusion despite maintenance of BL MAP and CO. After RES in PHEN-treated animals, A1 flow returned to BL, but progressive hypoperfusion was only partially prevented. alpha-Adrenergic-mediated vasoconstriction contributes to intestinal hypoperfusion after HEM, but other mechanisms are also involved in microvascular responses during RES.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1995

Intensive surveillance of femoropopliteal-tibial autogenous vein bypasses improves long-term graft patency and limb salvage.

OBJECTIVE: The authors determined the impact of an intensive surveillance program of autogenous vein bypasses on patency and limb salvage. SUMMARY BACKGROUND DATA: Surveillance protocols of vein bypasses can identify graft-threatening lesions to permit elective revisions before thrombosis. The authors compared follow-up based on clinically indicated procedures with intensive surveillance. METHODS: From 1985 to 1994, 615 autogenous vein bypasses (454 in situ, 161 reversed/composite) to popliteal (n = 169) and tibial (n = 446) arteries were performed for critical limb ischemia (n = 507), claudication (n = 88), and popliteal aneurysm (n = 20). Intensive surveillance of autogenous vein bypasses consisted of ankle brachial index and duplex scan with graft velocities measured at 1 month, 3 months, 6 months, and every 6 months subsequently. After surgery 317 bypasses had intensive surveillance, 222 bypasses were clinically indicated for follow-up, and 76 bypasses were excluded because follow-up or patency was less than 31 days. RESULTS: Primary patency at 5 years was similar for bypasses treated by intensive surveillance (56%) and those treated with clinically indicated procedures (67%). Secondary patency and limb salvage at 5 years was significantly improved (p < 0.02) for bypasses followed by intensive surveillance (80% and 94%) compared with clinically indicated procedures (67% and 73%). Revision of patent bypasses was higher (p < 0.000001) for bypasses treated by intensive surveillance (61 of 70, 87%) compared with those treated with clinically indicated procedures (9 of 34, 26%). Secondary patency at 2 years was significantly higher (p < 0.02) for revision of patent bypasses (79%) compared with thrombosed bypasses (55%). CONCLUSIONS: Long-term autogenous vein bypass patency and limb salvage is significantly improved by intensive surveillance, permitting identification and correction of graft threatening lesions before thrombosis.

Aged↗

PubMed1995

Nitric oxide mediates redistribution of intrarenal blood flow during bacteremia.

The normal or hyperdynamic circulatory response during the early phases of the systemic septic response is associated with renal microvascular constriction and can result in renal dysfunction. Intrarenal redistribution of blood flow from the outer cortex to the medulla appears to account for decreased glomerular filtration in spite of normal or elevated renal blood flow, but the mechanisms of this response are not well described. Nitric oxide is recognized as an important regulator of regional blood flow during both normal and pathologic conditions including sepsis, and we hypothesized that alterations in nitric oxide contribute to redistribution of renal blood flow during sepsis. The current study used laser Doppler fluximetry and clearance of p-aminohippuric acid (effective renal plasma flow, ERPF) to study intrarenal distribution of blood flow during basal conditions and during normodynamic Escherichia coli bacteremia, with and without inhibition of nitric oxide. Inhibition of nitric oxide in normal animals resulted in a decrease in ERPF (-19%) with a decrease in cortical flux (-39%) without alteration of medullary flux. Bacteremia resulted in a decrease in cortical flow (-17%), an increase in medullary flow (36%), and a modest reduction (-9%) in ERPF. Inhibition of nitric oxide synthase during bacteremia worsened cortical flow (-43%), reversed the increase in medullary flux (-42%), and further impaired ERPF (-28%). These data suggest that nitric oxide regulates renovascular tone during normal conditions and bacteremia, and indicate that it is a prime mediator of intrarenal redistribution of blood flow during sepsis.

Animals↗

PubMed1995

Endothelin-1 expression in the small intestine during chronic peritonitis.

Endothelins (ET) have been demonstrated to mediate intestinal microvascular constriction during acute Escherichia coli bacteremia, however, their role during chronic infection is unknown. The purpose of this study was to determine whether ET-1 is synthesized in the small intestine in a more chronic peritonitis model. ET-1 mRNA levels of the terminal ileum in mice following cecal ligation and puncture (CLP) were compared to sham-operated animals and normal unoperated animals. ET gene expression was analyzed using differential reverse transcriptase chain reaction (RT-PCR) with co-amplification of beta-actin as an internal standard. To assess ET peptide expression, serum and intestinal tissue levels were measured using a specific enzyme immunoassay (ELISA). The pattern of ET-1 gene expression post-CLP with a single puncture of the cecum with a 23 ga. needle demonstrated a 3.6-fold increase at 8 h, and a return to sham levels by 24 h (374 +/- 64% at 8 h, p < .05, 128 +/- 13%). An increase of mRNA levels at 24 h post-CLP was observed with a double puncture with an 18 ga. needle (230 +/- 36%, p < .05) accompanied by an increase in serum ET levels (270 +/- 31%, p < .05) and higher tissue ET levels. These data indicate a time-dependent response of ET-1 gene expression in the terminal ileum post-CLP which is related to severity of infection.

Animals↗

PubMed1994

Interleukin-2-induced lymphocyte infiltration of multiple organs is differentially suppressed by soluble tumor necrosis factor receptor.

Interleukin-2 (IL-2) mediates the regression of metastatic cancer, but clinical application is restricted by associated toxicities. Previous studies implicate tumor necrosis factor (TNF) as an important mediator of certain IL-2-induced toxicities. We hypothesized that soluble TNF receptor (sTNFr), a TNF antagonist, would alter lymphocyte trafficking into normal tissues and ameliorate IL-2-induced toxicity. Four groups of C57BL/6 mice were treated for 4 days with intraperitoneal injections of 100,000 IU IL-2 alone, 100,000 IU IL-2 and 30 micrograms sTNFr combined, 30 micrograms sTNFr alone, or equal volumes of saline. Animal activity was graded and blood obtained for SGPT and SGOT. At necropsy, organs were harvested for wet:dry ratios as a measurement of organ edema. The lung, liver, and thymus were examined histologically for lymphocytic infiltration and graded on a scale of 1 to 5. IL-2-treated groups had a statistically significant increase in organ edema, lymphocytic infiltration into the lung and liver, liver enzyme elevation, and pancytopenia when compared with controls. Soluble TNFr significantly suppressed IL-2-induced pulmonary lymphocytic infiltration and associated serum lymphopenia without significant alteration of other IL-2-induced effects. These data implicate TNF as a mediator of the pulmonary lymphocytic infiltration and of lymphopenia that accompanies IL-2 therapy and further suggest that alternative mechanisms are involved in other IL-2-induced deleterious effects.

Animals↗

PubMed1994

Renal microvascular responses to sepsis are dependent on nitric oxide.

Nitric oxide (NO) is an important mediator of the hemodynamic response to sepsis; however, its visceral microcirculatory effects are largely unknown. To determine the role of NO in renal microvascular responses to bacteremia, rat hydronephrotic kidneys with intact neurovascular supplies were exteriorized into a tissue bath. Videomicroscopy was used to measure vessel diameters (interlobular artery, ILA; afferent arteriole, AFF; efferent arteriole, EFF) and optical Doppler velocimetry was used to quantitate ILA flow. In controls, topical L-arginine (L-Arg; 10(-4) M), the NO synthase (NO-S) substrate, resulted in mild pre- and postglomerular dilation and increased flow. Inhibition of NO-S by N omega-nitro-L-arginine methyl ester (L-NAME: 10(-4) M) caused preglomerular constriction (ILA = -22%; AFF = -20% from baseline) and reduced ILA flow by 39%, while postglomerular diameters (EFF) were unchanged. Bacteremic rats had similar alterations (ILA = -22%; AFF = -20%; flow = -56%). Topical L-NAME in bacteremic rats resulted in further constriction (ILA = -38%; AFF = -37%), decreased ILA flow (-75%) and constricted EFF (-30%). L-Arg ameliorated constriction (ILA = -11%; AFF = -7%) and flow (-34%) during bacteremia. We conclude that: (1) NO is important in basal preglomerular tone; (2) Escherichia coli causes selective preglomerular constriction and hypoperfusion; (3) maintenance of EFF tone during bacteremia is NO dependent; and (4) different pre- and postglomerular NO mechanisms exist during basal and bacteremic states. These data indicate that NO is an important mediator of renal microvascular responses to sepsis.

Animals↗

PubMed1994

Endothelium-dependent microvascular responses to activated complement.

Infusion of Escherichia coli bacteria to cause high cardiac output bacteremia produces a differential microvascular response with constriction of large arterioles and dilation of small arterioles in skeletal muscle of rats. An important component to host-defense mechanisms during bacteremia is activation of the complement system. One part of this study explored the possibility that microvascular responses to bacteremia could be mediated by activation of the alternative complement cascade to alter skeletal muscle blood flow during sepsis. Complement activation by iv zymosan into unanesthetized (decerebrate) Sprague-Dawley rats caused constriction of large arterioles and dilation of small arterioles in cremaster muscle, while cardiac output stayed normal or was elevated. These microvascular responses mimic those during bacteremia, suggesting that components of the complement system mediate skeletal muscle microcirculatory responses to live E. coli sepsis. The vasodilation response of small arterioles in skeletal muscle during bacteremia is endothelium-dependent and is mediated at least partially by endothelial-derived relaxing factor (EDRF). Complement activation gives products which interact with endothelial cells. Thus, a second part of this study explored the role of EDRF in the vasodilation of skeletal muscle small arterioles during activation of the alternate complement pathway. Blockade of EDRF action by hydroquinone totally abolished small arteriole dilation and large arteriole constriction responses to complement activation by zymosan infusion.

Animals↗

PubMed1994

Pedal or peroneal bypass: which is better when both are patent?

PURPOSE: We compared autogenous vein pedal and peroneal bypasses, focusing on extremities that could have a bypass to either artery. METHODS: From 1985 to 1993 we performed a total of 175 pedal and 77 peroneal autogenous vein bypasses for rest pain (n = 75, 30%) and tissue loss (n = 177, 70%). One hundred ninety-six (78%) in situ saphenous vein and 56 (22%) reversed or composite vein bypasses were performed. One hundred fifty-two of these 252 bypasses were performed in extremities with both the pedal and peroneal arteries patent by arteriography. The vascular surgeon chose to perform 99 pedal and 53 peroneal vein bypasses in these 152 extremities. RESULTS: The angiogram score of the outflow arteries were similar for pedal and peroneal bypasses with the Society for Vascular Surgery and the International Society for Cardiovascular Surgery and modified scoring systems. At 2 years the primary and secondary patency rates for pedal bypasses (70% and 77%) were not significantly different compared with those for peroneal bypasses (60% and 72%). Limb salvage rates at 2 years were similar for pedal and peroneal bypasses for all patients (74% and 73%), patients with both pedal and peroneal arteries patent (83% and 72%), diabetics (76% and 66%), and patients with tissue necrosis (77% and 71%). CONCLUSIONS: Pedal and peroneal artery bypasses with equivalent angiogram scores have similar long-term graft patency and limb salvage. The choice between pedal or peroneal artery bypass should be based on the quality of vein and the surgeon's preference.

Aged↗