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Biomedical subjects

G W Machiedo

Publications and source records attributed to G W Machiedo.

At least 37 records · Page 2Linked to original sources

A "treated" model for severe hemorrhagic shock: a comparison of conventional and germ-free animals.

In an unanesthetized "treated" model of severe hemorrhagic shock, a bacteremia originating from the animal's enteric flora was demonstrated by finding radiolabeled Escherichia coli in the blood as early as 2 hr after the onset of shock. In 50 patients admitted to our trauma unit, the observation was similar, with 56% positive blood cultures, when their mean arterial blood pressure was 80 mmHg or less. The relationship of bacterial translocation and the high post-shock mortality in our conventional (CV) animal model is being evaluated in germfree (GF) Sprague-Dawley rats. Preliminary observations in 15 GF animals showed 80% survival at 24 hr post-shock, 54% at 48 hr, and 42% at 72 hr compared with those of CV animals in previous experiments with survival at similar times of 73%, 20% and 7%, respectively.

Animals↗

A comparison of intravenous access sites for bolus injections during shock and resuscitation after emergency room thoracotomy with and without aortic crossclamping.

Thoracotomy with aortic crossclamping is used to resuscitate trauma victims. Pharmacologic boluses are often given via intravenous lines of central, brachial, or femoral origin. This study was undertaken to determine the efficacy of intravenous access site on delivery of a bolus injection to the heart with thoracotomy and aortic crossclamping during shock and resuscitation. Six dogs were anesthetized, intubated, and underwent brachial and femoral venotomy and Swan-Ganz insertion (central). Baseline measurements of central, brachial, and femoral transit times for 10 cc cold saline were obtained via Swan-Ganz thermistor. Each animal then underwent thoracotomy, aortic crossclamping alone, hemorrhage to blood pressure (BP) 50 mm Hg for 30 minutes with aorta unclamped and then aorta crossclamped and resuscitation with lactated Ringer's Solution with aorta unclamped and then crossclamped. Femoral-Brachial Index (FBI) was determined by dividing femoral transit time by brachial transit time at each observation. The data suggest that femoral access significantly prolongs bolus transit time when compared with central or brachial access during aortic crossclamping in the euvolemic, shock, or aggressively resuscitated model. Brachial access is therefore the preferred route for bolus injection delivery in the emergency room thoracotomy with or without aortic crossclamping because it provides expedient bolus delivery equal to central access and superior to femoral access.

Analysis of Variance↗

The incidence of decreased red blood cell deformability in sepsis and the association with oxygen free radical damage and multiple-system organ failure.

We studied the incidence of decreased red blood cell deformability (RBCD) in sepsis and the association between decreased RBCD and oxygen free radical generation (as measured by malonyldialdehyde) and the occurrence of multiple-system organ failure (MSOF). Patients were divided into three groups: septic (n = 28), nonseptic (n = 15), and control (n = 5). Serial measurements of deformability index, malonyldialdehyde, and MSOF were made. The deformability index for the septic group (0.23 +/- 0.17) was significantly less than that for the nonseptic (1.12 +/- 0.48) and control (1.11 +/- 0.25) groups. The malonyldialdehyde levels for the septic group (4.5 +/- 1.0 nmol/mL) were significantly greater than those for the nonseptic (2.7 +/- 0.9 nmol/mL) and control (2.6 +/- 0.8 nmol/mL) groups. The MSOF index for the septic group (10.1 +/- 2.5) was significantly greater than that for the nonseptic (7.6 +/- 1.7) and control (6.0 +/- 0.0) groups. An inverse correlation existed between malonyldialdehyde and deformability index ( = .501, less than .001, n = 40) and between deformability index and MSOF index (= .350, less than .05, n = 61). We conclude that RBCD is decreased during human sepsis; free radicals generated during sepsis may play a role in the decrease in RBCD. Decreased RBCD may contribute to the MSOF that occurs during sepsis.

Adult↗

Does the bacteremia observed in hemorrhagic shock have clinical significance? A study in germ-free animals.

We have recently reported the rapid appearance of bacteria and endotoxin in the blood of rats and of trauma patients in the course of 30 minutes to 2 hours of hemorrhagic shock. The current study was designed to determine the effect of this bacteremia and endotoxemia on survival. Thirty-three conventional (C:group 1) and 36 germ-free (GF:group 2) Sprague Dawley rats were subjected to our previously described model of treated hemorrhagic shock. Survival in the GF group was significantly better than the C group at 24, 48, and 72 hours after shock. Endotoxin levels were elevated in 88% of C group during shock and in 28% of GF group. The gut of the GF animal contains endotoxin (26 ng/gm of stool) as does the sterile food supply (393 ng/gm of rat chow).

Animals↗

Red blood cell deformability in human and experimental sepsis.

Red blood cell (RBC) "deformability" is necessary for maintenance of normal microcirculation. To determine whether RBC deformability was affected in human or murine sepsis, a deformability index was determined in a human study and a murine model. Deformability was decreased postoperatively in patients with sepsis (0.49 +/- 0.12) compared with patients without sepsis (1.62 +/- 0.13) and normal control volunteers (1.51 +/- 0.17). Deformability was decreased in rats that had undergone cecal ligation and puncture (0.37 +/- 0.06) compared with that of sham-operated rats (0.76 +/- 0.12), as well as in endotoxemic rats (0.38 +/- 0.4) compared with control rats (0.82 +/- 0.11). These data suggest that RBC deformability decreases in both human and murine sepsis. This effect could be an important factor in the disordered oxygen utilization noted in human sepsis, and its correction could lead to better tissue oxygenation and preserved organ function.

Animals↗

Temporal relationship of hepatocellular dysfunction and ischemia in sepsis.

To determine whether hepatic dysfunction in sepsis results from hypoperfusion or direct cellular injury, Sprague-Dawley rats underwent either cecal ligation and puncture or sham operation. After either two or six hours, effective hepatic blood flow was measured using the galactose clearance method. Hepatocytes were isolated and intracellular sodium and potassium and glucose production were measured. Hepatic blood flow in septic rats decreased as early as two hours after sepsis when compared with sham-operated rats (3.8 +/- 1.4 vs 8.7 +/- 3.1 mL/min/100 g body weight). Intracellular sodium and potassium levels and glucose production in septic rats were not significantly different when compared with controls at two hours. After six hours, hepatic blood flow remained depressed and intracellular sodium level was increased compared with sham-operated rats (41.7 +/- 10.4 vs 31.4 +/- 5.9 mmol/L [41.7 +/- 10.4 vs 31.4 +/- 5.9 mEq/L]) and potassium decreased compared with controls (90.7 +/- 7.9 vs 111.5 +/- 6.7 mmol/L [90.7 +/- 7.9 vs 111.5 +/- 6.7 mEq/L]). Glucose production was decreased in septic rats after six hours when compared with controls (4.7 +/- 1.5 vs 15.4 +/- 6.4 mumol/g hepatocytes). These data suggest that hepatic blood flow is decreased before alterations in intracellular sodium and potassium as well as glucose production.

Animals↗

The gut as source of sepsis after hemorrhagic shock.

In a model of severe hemorrhagic shock in rats, blood culture findings became positive within 2 to 4 hours of shock. The organisms cultured were primarily gram-negative. To test the hypothesis that the gut was the source of the bacteria, E. coli labeled with carbon-14 oleic acid were fed to rats undergoing hemorrhagic shock. Their plasma was then assayed for carbon-14 activity. Seven of the 14 shocked animals demonstrated increased plasma carbon-14 activity during or after shock. The mortality rate was 100 percent 80 hours postshock, and all animals had E. coli on subsequent blood culture. The seven rats without increased plasma carbon-14 activity had a survival rate of 83 percent postshock. Sham-shocked animals did not exhibit plasma carbon-14 levels greater than the background levels. These data suggest that bacterial translocation occurs during hemorrhagic shock and that the gut is the source of the bacteremia seen during hemorrhagic shock.

Animals↗

Detection of sepsis in the postoperative patient.

It becomes evident, therefore, that there is no one indicator, either clinical or laboratory, sufficient to diagnose infection in the postoperative patient. Only a skillful clinician using the multiple modalities available and combining them with a careful history and physical examination and a high index of suspicion will be able to diagnose and treat infection in a timely manner and so avoid the physical, emotional, and fiscal costs of a late or missed diagnosis.

Abdomen↗

Endotoxemia and bacteremia during hemorrhagic shock. The link between trauma and sepsis?

Previous investigations of a treated model of hemorrhagic shock in the rat indicated the frequent occurrence of bacteremia that appeared to derive from the gut. This paper determines the incidence of bacteremia and endotoxemia during the acute shock period and compares this with similar observations in humans in varying degrees of shock. Studies in 26 rats indicated that bacteremia and endotoxemia was present in 50% and 87%, respectively, by the end of 2 hours at a mean arterial pressure of 30 mmHg. Observations in 50 patients admitted to the trauma unit showed that positive bacterial blood cultures were present in 56% when the admission systolic blood pressure was 80 mmHg or less (p less than 0.01 compared with either of the other groups). Endotoxemia was noticed in two such patients. Direct access of bacteria and endotoxin to the blood stream may occur during hemorrhagic or traumatic shock and is the probable cause of subsequent sepsis in traumatized patients when no other source is apparent.

Acute Disease↗

Occurrence of bacteremia during and after hemorrhagic shock.

In recent research, hemorrhagic shock and septic shock have been studied as two separate entities. We have developed a treated model of hemorrhagic shock in which unrestrained and unanesthetized rats are bled to a mean arterial pressure of 30 torr until 80% of the maximum shed volume must be returned. Rats are maintained preshock and treated post shock with a 20% glucose-electrolyte solution. Survival of these animals is 62% at 24 hours post shock and all animals are dead at 72 hours post shock. Blood cultures obtained during shock become positive at 2 hours into the shock period and are significant compared to controls at 3 to 5 hours of shock (p less than 0.0001). Blood cultures obtained after the period of shock are significantly positive at 24 and 48 hours post shock (p less than 0.05) compared to controls. Intrashock cultures are monomicrobial; the majority of post-shock cultures are polymicrobial. All cultured organisms are normal rat enteric flora. Histologic changes of renal failure are also demonstrated post shock. We suggest that bacterial invasion, possibly from the gut, plays a role in the sepsis seen in patients following severe hemorrhagic shock. Sepsis may precede rather than follow the immune incompetence which accompanies shock.

Animals↗

Unsuspected perforation in bleeding duodenal ulcers.

A combination of bleeding and perforation rarely occurs simultaneously in peptic ulcer disease. The charts of 127 patients undergoing surgery for either complication were reviewed (bleeding, 91; perforation, 36). Nine of 91 (9.9%) patients in the bleeding group were found at operation to have a unsuspected perforated duodenal ulcer. The operative mortality in the patients with the combined complications (44%, 4/9) was significantly higher than that in patients with bleeding alone (8/82, 9.8, P less than 0.001) or those with perforation alone (4/36, 11.00, P less than 0.025). The mean age of nonsurvivors was significantly higher than that of the survivors (74 +/- 8.01 vs 50.4 +/- 5.65 years, P less than 0.005). The duration of symptoms until operation was longer in patients who died (63 +/- 12.7 hours) than in survivors (40.2 +/- 6.02 hours, P = NS). All patients who died, and three of five survivors, had preoperative fever (greater than 99.0 F), leukocytosis (greater than 12,000/mm3), and persistent tachycardia despite adequate hydration and blood replacement. Perforation in bleeding peptic ulcers is not an uncommon finding, and was present in 9.9 per cent of patients. The presenting symptom of bleeding may obscure signs of perforation, delay surgery, and contribute to the higher mortality rate. The presence of fever, leukocytosis, and tachycardia despite adequate fluid and blood replacement warrants a suspicion of perforation in patients with bleeding peptic ulcer.

Adult↗

Intra-abdominal infection following combined spleen-colon trauma.

The reality of late overwhelming post-splenectomy sepsis in adults as well as children has led to more frequent attempts at splenic salvage following splenic trauma. Less attention has been paid to early septic postoperative complications in the splenectomized patient. Associated colon injury has been believed to be a relative contraindication to splenic conservation. If splenectomy enhances the chance of early postoperative infection, then associated colon injury should be an indication for splenic salvage One hundred sixty one patients who had either splenic trauma (58), colon trauma (90), or combined spleen-colon trauma (13) were studied. All patients with splenic trauma had a splenectomy. There was a significantly higher incidence of intra-abdominal sepsis requiring reoperation in the spleen-colon patients (46.7%) than in either of the other groups (spleen = 5.7%, colon = 8.9%, P less than .002 for both comparisons). It is concluded that splenectomy enhances infection in the early postoperative period. When possible, combined spleen-colon trauma should be an indication rather than a contraindication for splenic salvage.

Abdomen↗

Biochemical and morphologic changes in hepatocytes from the shock injured liver.

It has been proposed that the isolated hepatocyte is an excellent model for the study of cellular changes during and after hemorrhagic shock. To investigate this proposition the biochemical and morphologic changes in the isolated hepatocyte of shock injured rats were documented. Use of the isolated hepatocyte allows direct measurement of intracellular biochemical changes which we find corroborates the results of basic shock studies done on rats using liver slices, perfused liver or specimens taken at biopsy. Morphologic changes in the shocked liver of the rat are noted using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The results are correlated with the biochemical changes. SEM of the isolated hepatocyte reveals marked swelling immediately after shock with some scattered blebs. The cells show some recovery at two hours with near complete normality restored at 24 hours. TEM of tissue and isolated cells reveal vacuolization and mitochondrial changes in the early post shock period with return to normality at 24 hours after shock. The shock injured hepatocyte is a reasonably faithful representative of the events which have taken place in the liver from which it is isolated. It can be used as a model for treatment in vivo or as a device for comparison of the effects of different environments in vivo or in vitro.

Adenine Nucleotides↗

Reoperation for sepsis.

A retrospective study of 50 patients undergoing reoperation for sepsis was performed to evaluate the ability of commonly available clinical and laboratory tests to predict the findings at reoperation and the outcome after operation. The influence of multiple organ failure on these parameters was also studied. No laboratory finding helped to predict operative findings. Computed tomographic scanning (80% accurate) was the most helpful radiographic procedure. A low total lymphocyte count and a high serum creatinine level both predicted a fatal outcome. No single organ failure or combination predicted a positive reexploration. Infection was found in 75 per cent of patients with multiple organ failure and 79 per cent of patients who did not have this syndrome. Patients having three-organ failure did have a significantly higher mortality. The mortality of a negative reexploration was 18.2 per cent, slightly lower than the 28.2 per cent mortality of patients with a positive exploration. No patient without organ failure died. The authors conclude that laboratory tests are not helpful in predicting the presence of infection on reexploration, that the decision to reoperate is one based primarily on clinical judgment, and that if reoperation is performed before the development of organ failure, the risk associated with a negative exploration is worth taking.

Adult↗

A simplified technique for gastric and duodenal decompression for duodenal injuries.

A simplified effective method of the decompression for use after repair of duodenal injuries is described. A Moss esophagogastric decompression tube is inserted as a gastrostomy to provide decompression of stomach and duodenum through a single tube. In addition, the complications associated with long-term nasogastric tube drainage are avoided.

Drainage↗

Traumatic aorto-caval fistula.

Trauma is an unusual cause of fistula formation between the aorta and the inferior vena cava. Two cases of traumatic aorto-caval fistula treated at the New Jersey Medical School affiliated hospitals are presented and the literature on traumatic aorto-caval fistula reviewed. We found 14 previously reported cases. Delayed repair was performed in 12 (86%). Delays ranged from 5 days to 12 years postinjury. Cardiac decompensation, judged either clinically or by cardiomegaly evident on chest X-ray, was present in 75% of the patients undergoing delayed repair. The techniques available for repair and the criteria for utilizing delayed repair are discussed. In young, previously healthy patients, usually with smaller fistulae, we conclude that delayed repair can be used.

Adult↗

Effect of age and splenectomy in murine endotoxemia.

The protective role of the spleen in gram-positive infections, particularly in infancy and childhood, is well established. Since it is not known whether the spleen is protective in gram-negative sepsis, particularly in elderly individuals as compared to young subjects, the following study was undertaken. Splenectomized and nonsplenectomized Swiss Webster mice, 3 months old (young), or 12 months old (elderly) were utilized. Splenectomy was performed 4 weeks prior to administration of E coli endotoxin. Mortality in elderly nonsplenectomized mice was significantly greater than that of young nonsplenectomized mice. Prior splenectomy significantly increased the mortality in young mice at 48 h, whereas the mortality of E coli endotoxemia (ECE) in elderly mice was not altered by prior splenectomy. The spleen, therefore, appears to have a protective role for young mice but does not protect elderly mice with ECE. It is postulated that this loss of splenic protection reflects deteriorating splenic function with age.

Aging↗

The hemodynamic effect of profound hypercapnia on acute hypoxic respiratory failure.

The effect of profound hypercapnia on acute hypoxic respiratory failure is evaluated. Eight dogs were subjected to oleic acid-induced acute respiratory failure. Four dogs were ventilated normally, and four dogs were made hypercapneic by rebreathing exhaled CO2. In the hypercapneic animals, heart rate and alveolar-arterial oxygen difference were significantly lower than in normocapneic animals, while mixed venous O2 cardiac index, oxygen delivery index, stroke volume index, and left ventricular stroke work were significantly higher. Mean arterial pressure was maintained at preinjury levels. Pulmonary and systemic vascular resistance increased in both experimental groups. There was no significant difference between groups for gravimetric determination of lung water. Cardiopulmonary performance in acute respiratory failure is improved with hypercapnia. This may be related to CO2-induced catecholamine release.

Acute Disease↗