Pulmonary intravascular macrophages appear in rats after long-term administration of lipid emulsion and amino acid solution. An ultrastructural morphometric study.

Intravascular macrophages have rarely been seen in normal lungs of humans and rats, but in rats endotoxaemia has induced their presence. To study whether substrates used for parenteral nutrition could have a similar stimulatory effect on mononuclear phagocytes, rats were given lipid emulsion (n=5), amino acid solution (n=5), or isotonic saline (n=5) through central venous catheters for 3 weeks. Structural changes in the lung microvessels were evaluated using electron microscopy. The areal fraction of pulmonary intravascular mononuclear phagocytes was 19.6% (SD=8.2) in rats given lipid emulsion (p<0.05) and 8.2% (SD=8.2) in rats given amino acid solution n.s. compared to 2.4% (SD= 4.0) in rats given saline. The increase in areal fraction was mainly due to an increase in cell numbers. In rats given lipid emulsion the intravascular phagocytes were only slightly larger than in rats given saline, but had the morphological features of mature macrophages. The study demonstrates that lipid emulsion recruits pulmonary intravascular macrophages in rats, indicating a stimulatory effect on the mononuclear phagocyte system. The effect was less pronounced with amino acid solution.

[Surgical treatment of infective endocarditis]. / Operativ behandling av infeksiøs endokarditt.

Patients operated on for infective endocarditis (n = 69) at two regional hospitals between 1988 and 1994 are reviewed. 70% had a known valvular heart disease and 16% had prosthetic valve endocarditis. In 28% the offending microorganism was Staphylococcus aureus; in 26% Streptococcus viridans. Therapy was intended to be a six-week antibiotic course before operating, but 55% of the patients had to be operated on earlier. The postoperative course was uncomplicated in 59%, mortality was 16% and one-year survival 81%. Increased risk of death was associated with operating before the six-week course of antibiotics was completed (p = 0.005), with preoperative renal failure (p = 0.006) or lung failure (p = 0.008), with the growth of microorganisms from tissue samples extirpated during the operation (p = 0.01), with additional surgical procedures concomitant to valvular replacement (p = 0.02), S. aureus endocarditis (p = 0.03), and with the presence of paravalvular abscesses or intracardial fistulas (p = 0.03). The study shows that infective endocarditis is a serious disease. Wherever clinically feasible, all patients should be given antibiotics for six weeks before evaluating surgery. However, close surveillance of infection and haemodynamics is necessary to allow for the possibility of acute surgery before the development of organ failure. Special attention must be paid to cases of S. aureus endocarditis.

Modification of mononuclear cell function after incubation with albumin-bound unsaturated fatty acids or soybean oil emulsion.

Administration of total parenteral nutrition (TPN) with soybean oil emulsion leads to a linoleic acid enrichment of the plasma membrane that may explain an in vivo activation of mononuclear cells (MNC) seen in our previous studies. Fatty acids from the lipid emulsion may have been accessible to MNC after endocytosis of lipid particles, or by direct uptake of fatty acids after lipoprotein lipase hydrolyzation of the emulsion triglycerides. To resemble the incorporation of fatty acids in vivo, we have modified MNC membrane lipid composition by incubation with different albumin-bound unsaturated fatty acids (UFA) or soybean oil emulsion. After incubation with albumin-bound linoleic and oleic acid, the unstimulated release of superoxide anion was unchanged, while zymosan-stimulated release was 140% (n.s) and 112% (p < 0.05) and phorbol-myristate-acetate (PMA)-stimulated release 148% (p < 0.05) and 124% (p < 0.05) of controls, respectively. Incubation with other UFAs or emulsion did not change superoxide anion release. Unstimulated lymphocyte proliferation increased 3 to 13-fold (p < 0.05) after incubation with all UFAs compared to controls, while UFA incubation did not change phytohemagglutinin (PHA) or PMA-stimulated proliferation. Unstimulated lymphocyte proliferation was decreased after incubation with emulsion, while PHA/PMA-stimulated proliferation was unchanged. Increase in membrane fluidity was detectable only after incubation with emulsion. The increased reactivity may have been caused by changes in the lipid environment surrounding membrane-bound enzymes important for signal transduction through the plasma membrane.

Surgical elimination of an atrial septal aneurysm causing cerebral embolism.

Atrial septal aneurysms have been recognized as sources of arterial embolism. An intraatrial aneurysm was demonstrated in the fossa ovalis of a 45-year-old woman who suffered an episode of cerebral embolism. The disorder is rarely treated surgically. Most patients with this condition are given life-long anticoagulation, a treatment that may have serious complications. As an alternative treatment with possible lower risk, we removed the aneurysm surgically.

Long term lipid-based parenteral nutrition causes pulmonary hypertension in pigs.

OBJECTIVE: To study pulmonary perfusion after long term intravenous lipid-based total parenteral nutrition (TPN). DESIGN: Open experimental study. SETTING: Teaching hospital, Norway. MATERIAL: 31 pigs. INTERVENTIONS: Infusion of TPN alone, TPN + pellets, or Ringer's solution alone through central venous catheters for 7 weeks. OUTCOME MEASURES: Haemodynamic variables during a standardised volume load, and measurement of plasma N-terminal pro-atrial natriuretic factor (ANF). RESULTS: Mean pulmonary artery pressure (PAP) was 12.9 (6.1) to 20.1 (3.0) mmHg in response to the volume load in control animals compared with 15.8 (8.5) to 25.4 (5.8) (p < 0.05) mmHg in those given TPN alone and 22.8 (10.3) (p < 0.05) to 28.0 (6.4) (p < 0.05) mmHg in those given TPN and pellets. Pulmonary vascular resistance index was also increased after TPN, but the plasma N-terminal pro-ANF concentration did not increase during infusion of TPN. CONCLUSION: Long term TPN caused moderate pulmonary hypertension, but not longstanding right-sided congestion.

Lipid entrapment and cellular changes in the rat myocard, lung and liver after long-term parenteral nutrition with lipid emulsion. A light microscopic and ultrastructural study.

We have demonstrated organ damage after long-term administration of lipid-based parenteral nutrition, possibly initiated by intravascular pooling of lipid and phagocytes, in both rats and pigs. To evaluate whether accumulation of lipid could simply be caused by mechanical filtration, a comparative study of three separate capillary beds was performed. Rats were given lipid emulsion (n = 5) or isotonic saline (n = 4) through central venous catheters for 3 weeks. Using both light and electron microscopy, lipid accumulation and structural changes in the rat myocard were compared to those in the lung and liver. The study provides evidence that within myocardial capillaries both peripheral blood monocytes and endothelial cells performed phagocytosis of lipid droplets following administration of lipid emulsion, but no large-scale intravascular pooling of lipid resulted. Morphometry of the myocard detected no lipid increase in the myocytes from the rats given lipid emulsion compared with controls and in neither were there any stigmata of vasculitis or myocardial damage, in contrast to the lung and liver, where intravascular pooling of lipid and phagocytes was seen. This indicates that phagocytosis was an important mechanism involved in entrapment and elimination of lipid.

Intravascular lung macrophages play an essential role in lipid entrapment and the inflammatory tissue reaction seen after long-term lipid-based parenteral nutrition in pigs. An ultrastructural study.

To detect possible interactions between lipid-based total parenteral nutrition (TPN) substrates and mononuclear phagocytes, ultrastructural in vitro and in vivo studies were carried out on material from pigs. Mononuclear phagocytes isolated from peripheral blood, phagocytosed lipid after incubation with 1 mg/ml Intralipid for 24 h. Similarly, lipid was taken up by intravascular macrophages in the lungs and liver after central venous administration of TPN containing 2.3 g/kg body weight/day of Intralipid for 5-7 weeks. Lipid accumulation was almost exclusively found intravascularly in the lungs and liver, and not in macrophages obtained from bronchoalveolar lavage fluid. A morphometric study of the lung capillaries showed that the macrophages in TPN animals had increased in size and number, and occupied a larger portion of the capillary lumina. The macrophages appeared to be activated, but the endothelial lining was well preserved. Free intravascular lipid droplets had a diameter both in vitro and in vivo of about 0.5 micron, indicating good stability of the emulsion. We suggest that the lipid uptake stimulates the macrophages and thereby plays a role in the lung tissue inflammation seen in response to long-term lipid-based TPN in pigs.

Mortality in patients supported by intra-aortic balloon pump in the course of cardiac surgery was related to perioperative myocardial infarction.

OBJECTIVE: To search for predictors of mortality for patients in need of intra-aortic balloon pump (IABP) support in the course of cardiac surgery. METHODS: A retrospective study of possible pre- and perioperative risk factors in 110 patients with mean age of 62 years (38-79). The IABP was inserted preoperatively in 19 (17%) and perioperatively in 91 (83%). RESULTS: Well known risk factors as advanced age (63.2/61.0; P = 0.25), NYHA functional class (OR = 1.59; 95% CI 0.23 to 13.31), female sex (OR = 2.40; 95% CI 0.81 to 6.73), emergency surgery (OR = 0.63; 95% CI 0.21 to 1.80), low left ventricular ejection fraction (62.9/60.7; P = 0.53), or elevated end diastolic pressure (19.4/21.0; P = 0.48), were not prognostic of death. Perioperative insertion of the balloon pump (OR = 3.83; 95% CI 1.07 to 14.95), perioperative myocardial infarction (OR = 23.3; 95% CI 7.62 to 81.8), low cardiac output (OR = 7.53; 95% CI 2.43 to 24.11), and renal failure (OR = 20.00; 95% CI 3.63 to 145), were strong predictors of death. CONCLUSIONS: Outcome seemed to be determined by perioperative events rather than preoperative risk factors. This could possibly explain the favourable mortality rates seen in patients on IABP support prior to surgery compared to patients who had IABP installed perioperatively.

Long-term lipid-based total parenteral nutrition activates mononuclear cells and modulates membrane lipid composition in pigs.

In previous studies we have found lung granulomas in pigs on long-term soybean-based total parenteral nutrition (TPN). In the present study we have investigated activities and membrane lipids of cells known to participate in a granulomatous process. Pigs were given TPN with soybean emulsion for 7 weeks, controls were given saline intravenously and consumed a similar caloric load in a standard oral diet. Spontaneous nitroblue tetrazolium (NBT) reduction increased 204% in peripheral blood mononuclear cells (MNC) from TPN animals compared to controls (p < 0.05), and 161% (p = 0.05) in alveolar macrophages. The spontaneous lymphocyte mitogen response (LMR) rate in MNC increased 299% (p < 0.05). Endotoxin-stimulated procoagulant activity in MNC tended to increase in TPN animals. Acid phosphatase and lysozyme production in alveolar macrophages were not significantly changed. The serum neopterin level at the end of the observation was 7.0 nmol l-1 in TPN animals compared to 3.9 nmol l-1 in controls (p < 0.01), while interleukin-1 and tumour necrosis factor were not detectable. These findings indicated in vivo activation of peripheral blood monocytes, lymphocytes and alveolar macrophages in pigs on TPN. The membrane lipid contents of linoleic acid (18:2, n-6) increased, while arachidonic acid (20:4, n-6) tended to decrease both in MNC and lung tissue. Thus, linoleic acid conversion did not lead to accumulation of arachidonate in the cell membranes. Direct effects on monocytes, lymphocytes and alveolar macrophages of TPN particles, and altered cell membrane function, due to linoleic acid enrichment, are tentative explanations for the raised cell responses. Such cell activation may have contributed to the formation of granulomas.

Risk factors associated with mortality and morbidity after elective splenectomy.

OBJECTIVE: To assess the effect of certain risk factors on the outcome of elective splenectomy. DESIGN: Retrospective cohort study. SETTING: University hospital, Norway. SUBJECTS: 135 patients who underwent elective splenectomy from 1978 to 1992 for autoimmune diseases (n = 58), myeloproliferative disorders (n = 58), and other diagnoses (n = 19). MAIN OUTCOME MEASURES: Morbidity and mortality, and the effect on outcome of age, malignancy, platelet count, treatment with steroids, and blood transfusion during the operative period. RESULTS: Three patients died, one from each diagnostic group; all had been treated with steroids. The overall complication rate was 31% (42/135). Most of the complications (31, 74%) were infective (pneumonia n = 23, abscess or sepsis n = 8). Nine patients required reoperation (haemorrhage, n = 6, and wound dehiscence, n = 2, and bowel obstruction, n = 1). Neither treatment with steroids nor severe thrombocytopaenia were risk factors for any complication, but age (p = 0.05) and a diagnosis of myeloproliferative disease (p = 0.08) had an important though not significant role. Blood transfusion during the operative period was the only independent risk factor (p = 0.001), and further analysis showed that transfusion of blood had a dose dependent effect on the incidence of infective complications (chi-square for linear trend 14.21 p < 0.001). CONCLUSION: To reduce the complication rate of elective splenectomy blood transfusion during the operative period should be avoided.

[Endarterectomy of left coronary arteries. An angiographic follow-up study]. / Endarterektomi av venstre koronararteries grener. En etterundersøkelse med angiografi.

From January 1989 to December 1993, 25 patients underwent endarterectomy on the left coronary artery system. Eight of the patients had concurrent endarterectomy of the right coronary artery. The operative mortality consisted of one high-risk patient who died from an intraoperative myocardial infarction. Two patients developed non-fatal perioperative infarction. The follow-up period averaged 27 months (range 4-58 months). At follow-up one patient was lost for evaluation owing to unexpected sudden death, no patients had experienced myocardial infarction, 17 patients (74%) were free of angina, two patients were in NYHA class I and four in NYHA class II. All patients showed an improvement in relation to their preoperative condition. Two asymptomatic patients refused recatheterization, while 21 patients had a control angiographic study. 25 of 34 grafts to endarterectomized vessels were open (patency 74%) compared with 41 of 45 grafts to non-endarterectomized arteries (patency 91%). We find the angiographic and functional results acceptable and they should be acknowledged with reference to patients with diffuse distal coronary artery disease, many of whom would otherwise be considered inoperable.

Development of granulomas and vascular fibrocellular proliferation in the lungs of pigs receiving long-term lipid-based parenteral nutrition.

The lungs of pigs receiving long-term total parenteral nutrition (TPN) have been studied. A total of 20 pigs were tentatively infused with TPN through central venous catheters for 7 weeks. To secure adequate nutrition and gastrointestinal absorbance of nutrients, an additional full oral diet was given to eight of these animals. Fifteen control animals received Ringer solution through central venous catheters in addition to the oral diet. All animals infused with TPN for 7 weeks developed lung granulomas, a finding not observed in control animals. No lung granulomas were seen in three TPN animals sacrificed after 3 to 5 weeks owing to illness. All TPN animals also developed tissue reactions suggesting long-standing lung vascular inflammation. Similar vascular changes were seen in seven control animals that had bacterial infection or endotoxemia. The total amount of neutral fat in lung homogenate tended to increase in animals given TPN, and the linoleic acid content was significantly increased. In conclusion, long-term TPN caused lung granulomas in pigs. Vascular damage seemed to be accelerated by bacterial infection as well as by the TPN. The tissue reactions presumably involved long-term activation of monocytes/macrophages.

Injuries to the heart.

During a 12-year period, 36 patients with cardiac injuries were recorded. Nine suffered penetrating injuries, nine blunt ruptures and 18 contusions. Only two patients with blunt rupture survived, in contrast to six out of seven patients with stab wounds to the heart. This reflects that heart stabs are easier to diagnose than blunt ruptures, and that the associated injuries are the most important factor for survival in patients with blunt injuries. All clinical manifestations of the heart injuries were present within the first 12 h. Cardiac monitoring of haemodynamically stable patients beyond this period may not be necessary.

Risk factors of septicemia and perioperative myocardial infarction in a cohort of patients supported with intra-aortic balloon pump (IABP) in the course of open heart surgery.

In 1325 open heart operated (OHO) patients with a perioperative mortality of 5.8% the incidence of septicemia and perioperative myocardial infarction (PMI) were much higher in a cohort of 110 patients given intra-aortic balloon pump (IABP) support during the operative course. Analysis of this cohort showed that peri/postoperative insertion of the pump, the presence of disease in the descending branch of left coronary artery (LAD) and the need of more than one saphenous vein graft were risk factors for PMI. The presence of LAD disease was the only independent risk factor for PMI with an odds ratio (OR) of 4.62. Well known risk factors such as NYHA functional class, emergency, low left ventricular ejection fraction (EF) or elevated end diastolic pressure (EDP) were not prognostic of PMI. Thus, the intraoperative seemed to be more important than the preoperative risk profile for the development of PMI. Independent risk factors for the development of septicemia were the duration of IABP with an OR of 1.5 for each pump day and implantation of a valve prosthesis with an OR of 6.3. To avoid septic complications, this study suggests pump removal as soon as possible.

Patency of the internal mammary artery used as sequential graft.

In 28 patients with the left internal mammary artery (IMA) used as a sequential coronary artery graft, clinical and angiographic evaluation was made 19-47 months postoperatively. Patency was 96% in the proximal anastomoses and 93% in all the anastomoses. Angiography, however, showed optimal function in only 75% of the distal graft ends. These observations indicate that routine use of left IMA as a sequential graft should be restricted to experienced surgeons. Clinical and angiographic findings did not always correlate, emphasizing that evaluation of IMA-graft patency should include angiography.

Effect of phlorizin on hepatic bile production before and during glucose infusion.

During intravenous infusion of glucose, bile secretion is reduced (cholestasis), indicating that hepatocellular metabolism of glucose could have harmful effects on the liver. Phlorizin has been identified as a compound capable of impeding glucose uptake of liver cells. To examine whether phlorizin had any effect on glucose-associated cholestasis, three groups of experiments were performed on anaesthetized pigs. In group I phlorizin (100 mg/kg body wt) during normoglycaemia stimulated bicarbonate-dependent bile secretion by 56 +/- 4%. After phlorizin, hyperglycaemia decreased both bile acid- and bicarbonate-dependent bile secretion by 37 +/- 4%. But after the glucose load normalization of plasma glucose concentration increased the bicarbonate-dependent fraction by 38 +/- 4%. In group II phlorizin (100 mg/kg body wt, infused intravenously) during hyperglycaemia stimulated bicarbonate-dependent bile secretion by 35 +/- 5%. In group III bile secretion was continuously stimulated by infusion of Na-taurocholate. Hyperglycaemia reduced bicarbonate-dependent bile secretion by 33 +/- 4%, but after phlorizin both bile acid- and bicarbonate-dependent bile secretion increased on average by 121 +/- 8%. The osmotic effect of hyperglycaemia cannot be blocked by phlorizin, but judged by the effect on bile secretion, phlorizin may decrease the cholestatic effect induced by metabolism of glucose. Phlorizin could be an interesting compound for use in solutions for organ preservation.