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Biomedical subjects

D A Spain

Publications and source records attributed to D A Spain.

At least 19 recordsLinked to original sources
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

Predicting the need to pack early for severe intra-abdominal hemorrhage.

OBJECTIVE: To determine if the decision to pack for hemorrhage could be refined. MATERIALS AND METHODS: Seventy consecutive trauma patients for whom packing was used to control hemorrhage were studied. The patients had liver injuries, abdominal vascular injuries, and bleeding retroperitoneal hematomas. Preoperative variables were analyzed and survivors compared with nonsurvivors. RESULTS: Packing controlled hemorrhage in 37 (53%) patients. Significant differences (p < 0.05) between survivors and nonsurvivors were Injury Severity Score (29 vs. 38), initial pH (7.3 vs. 7.1), platelet count (229,000 vs. 179,000/mm3), prothrombin time (14 vs. 22 seconds), partial thromboplastin time (42 vs. 69 seconds), and duration of hypotension (50 vs. 90 minutes). Nonsurvivors received 20 units of packed red blood cells before packing compared to 13 units for survivors. CONCLUSION: Patients who suffer severe injury, hypothermia, refractory hypotension, coagulopathy, and acidosis need early packing if they are to survive. Failure to control hemorrhage is related to severity of injury and delay in the use of pack tamponade. A specific protocol that mandates packing when parameters reach a critical limit should be considered.

Abdominal Injuries↗
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

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

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

Is the timing of fracture fixation important for the patient with multiple trauma?

OBJECTIVE: The effect of timing of femur fracture fixation for patients with multiple trauma was studied to determine the effect of operative timing on eventual outcome. METHODS: The relationship between timing of intramedullary rod (IMR) placement, degree of injury, and pulmonary complications was studied in 424 consecutive patients. The authors focused on 105 patients undergoing IMR placement with an Injury Severity score (ISS) of greater than or equal to 18. The effects of timing of IMR placement on various pulmonary complications, organ failure, intensive care unit (ICU) admission, and ventilatory assistance were studied for various time intervals. RESULTS: Of the 424 patients, pulmonary complications increased slightly in the more seriously injured group (ISS > 18) but were not influenced by the timing of IMR placement. Of the 105 patients undergoing IMR placement with an ISS > or = 18, only 2 patients died. Both patients had an IMR placed in less than 24 hours and died later of head injury and delayed hemorrhage. The incidence of organ failure, number of ventilator days, and length of ICU stay did not differ between the groups based on timing of fracture fixation. The incidence of severe head injuries was higher in the group undergoing delayed IMR placement (> 48 hours). CONCLUSIONS: Modest delays in IMR placement did not adversely affect patient outcome. Pulmonary complications were related to the severity of injury rather than to timing of fracture fixation. In a well-integrated trauma system, clinical judgment regarding the timing of IMR placement was the most important determinant of outcome. Delays that were made to stabilize the patient, treat associated injuries, and plan orthopedic reconstruction did not adversely affect patient outcome.

Adult↗
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

Transpyloric passage of feeding tubes in patients with head injuries does not decrease complications.

Early enteral nutrition is reported to improve outcome of patients with severe closed head injuries (CHI). The efficacy and safety of nasoenteric tube (NET) feeds, however, has been questioned; the risk of aspiration is the major concern. Our purpose was to determine the rate of transpyloric migration, the efficacy of adjunctive measures to promote passage, and the effect on pulmonary complications. Seventy-four consecutive patients with moderate to severe CHI received enteral nutrition. Glasgow Coma Scale (GSC) score was 5.2 on admission and 6.9 at 48 hours. NETs were placed an average of 5.6 days after admission; an average of three abdominal films per patient were used to assess tube position. No patients had endoscopic NET placement during this period. Ten patients required fluoroscopic placement after failure to pass spontaneously by 5 days. Overall, transpyloric passage was achieved in 32 patients (43%), whereas 42 (57%) remained intragastric. There were no differences between the postpyloric and intragastric groups in days to full feeding (5 vs. 7 days), ventilator days (11.9 vs. 12.5), intensive care unit length of stay (15.5 vs. 15.1), or incidence of pneumonia (81 vs. 69%) or aspiration (6 vs 7%). Sixty-two patients (83%) were transferred to extended care facilities and 50 (68%) were still receiving NET feedings. Spontaneous transpyloric passage of NET occurred in less than one-half of patients with severe CHI. The routine use of adjunctive measures to promote transpyloric passage was not particularly successful, had no obvious benefit, and therefore may not be necessary.

Adolescent↗
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

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

Antibiotic overkill of trauma victims?

Antibiotic usage was assessed in a prospective, randomized trial of recombinant interferon-gamma (rIFN-gamma) versus placebo for 212 severely injured trauma patients in four university hospitals. All patients were observed until death or discharge from the hospital. We found the number of antibiotics used and their associated costs staggering and difficult to justify, although serious antibiotic-related complications were infrequent. Regular antibiotic administration following severe trauma should be re-evaluated since clinical evidence supports the use of shorter courses for these patients, with presumed similar outcomes and much-reduced expenses.

Adolescent↗
PubMed1994

Nitric oxide synthase inhibition aggravates intestinal microvascular vasoconstriction and hypoperfusion of bacteremia.

Nitric oxide (NO) is an important hemodynamic mediator of sepsis; however, its visceral microcirculatory effects are largely unknown. To determine the role of systemic nitric oxide synthase (NO-S) inhibition on the microcirculation of the small intestine (SI), an intact loop of SI was exteriorized from decerebrate rats into a controlled tissue bath. Videomicroscopy was used to measure arteriolar diameters (A1, A3) and optical Doppler velocimetry was used to quantitate flow. In nonbacteremic controls inhibition of NO-S by N omega-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg IV) caused vasoconstriction (A1 = -7%; A3 = -24% baseline values) and reduced A1 flow by 26%. Bacteremic controls received 10(9) Escherichia coli IV, which resulted in arteriolar constriction and hypoperfusion (A1 = -16%; A3 = -21%; A1 flow = -44%), despite increased cardiac output (+33%). Treatment of bacteremic rats with L-NAME corrected the increased cardiac output (-3%), but exacerbated vasoconstriction (A1 = -24%; A3 = -27%) and did not improve A1 flow (-49%). These data indicate that (1) NO mediates basal microvascular tone of the SI; (2) hyperdynamic bacteremia causes arteriolar constriction and hypoperfusion of the SI; and (3) although systemic NO-S inhibition normalizes cardiac output and increases blood pressure, it aggravates vasoconstriction in the SI and does not improve hypoperfusion.

Amino Acid Oxidoreductases↗
PubMed1994

Role of nitric oxide in the small intestinal microcirculation during bacteremia.

Nitric oxide (NO) is an important mediator of the hemodynamic effects of sepsis; however, its microcirculatory effects are unknown. To determine the role of NO in the small intestinal (SI) microcirculation, an intact SI loop was exteriorized from decerebrate rats into a controlled Krebs' bath. Bacteremic rats received 10(9) Escherichia coli intravenously. Videomicroscopy was used to measure arteriolar diameters (A1, A3) and optical Doppler velocimetry to quantitate flow. In controls, topical NO synthase (NO-S) substrate L-arginine (L-ARG; 10(-4) M) did not affect diameters or flow. Inhibition of NO-S by N omega-nitro-L-arginine methyl ester (L-NAME; 10(-4) M) caused constriction (A1 = -18%; A3 = -24% from baseline diameter) and reduced A1 flow by 62%. These alterations were similar to bacteremic controls (A1 = -20%; A3 = -18%; A1 flow = -42%), despite the increased cardiac output (+21%). L-NAME treatment of bacteremic rats resulted in further constriction (A1 = -31%; A3 = -32%) and decreased A1 flow (-75%). Topical L-ARG (10(-4) M) ameliorated constriction (A1 = -6%; A3 = +7%) and improved blood flow (-5%) during bacteremia. We conclude that: 1) NO is important for basal SI microvascular tone; 2) bacteremia causes SI arteriolar constriction and hypoperfusion; 3) NO-S inhibition during sepsis may exacerbate SI vasoconstriction and hypoperfusion.

Amino Acid Oxidoreductases↗
PubMed1994

Differential microvascular response to cyclooxygenase blockade in the rat small intestine during acute bacteremia.

To determine whether arachidonic acid metabolites are mediators of regional blood flow changes during sepsis, we examined the effects of cyclooxygenase blockade on intestinal microvascular diameters and blood flow during acute bacteremia, induced in the rat by the intravenous injection of 10(9) live Escherichia coli. Mean arterial pressure, cardiac output, intestinal microvascular diameters, and blood flow were measured in the presence or absence of a topically applied selective cyclooxygenase inhibitor (mefenamate). Bacteremia caused a diffuse constriction of both arterioles and venules and a concomitant 50% decrease in blood flow. Treatment with mefenamate did not affect baseline intestinal microvascular tone or bacteremia-induced arteriolar constriction and hypoperfusion, but did reverse an intense venular constriction. Our results suggest that the small intestinal microcirculation has a differential response to cyclooxygenase products of arachidonic acid metabolism during acute bacteremia. They appear not to be mediators of the intestinal arteriolar constriction and hypoperfusion observed during acute E. coli bacteremia, but profoundly influence the mesenteric venular constriction. These observations support the concept that microvascular control mechanisms are different not only between but within organ specific vascular beds.

Animals↗
PubMed1994

Nitric oxide synthase inhibition exacerbates sepsis-induced renal hypoperfusion.

BACKGROUND: Hyperdynamic sepsis is often complicated by renal dysfunction, caused in part by renal vasoconstriction and impaired blood flow. Nitric oxide (NO) is an important mediator of hemodynamic responses to sepsis; however, its importance in the renal microcirculation during sepsis is unknown. Our purpose was to determine the role of NO in the renal microcirculation during bacteremia. METHODS: In vivo videomicroscopy was used to study the microcirculation in five groups of hydronephrotic rat kidneys. Cardiac output (CO), mean arterial pressure, interlobular artery (ILA) diameter and flow, and afferent (AFF) and efferent arteriole diameters were measured. RESULTS: NO synthase inhibition in normal rats resulted in hypertension, decreased CO, selective preglomerular constriction (ILA, -21%; AFF, -26% of baseline), and hypoperfusion (-56%). Escherichia coli resulted in a normotensive, high CO state (+23%) with ILA (-25%) and AFF (-20%) constriction and hypoperfusion (-60%). NO synthase inhibition during bacteremia normalized CO and increased mean arterial pressure (+34%) but exacerbated constriction (ILA, -45%; AFF, -33%) and further impaired flow (-90%). CONCLUSIONS: NO maintains preglomerular tone and flow during basal conditions and appears to counteract intrarenal vasoconstrictors during E. coli bacteremia.

Amino Acid Oxidoreductases↗