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Biomedical subjects

M Farstad

Publications and source records attributed to M Farstad.

At least 19 recordsLinked to original sources
PubMed2006

Reduced fluid gain during cardiopulmonary bypass in piglets using a continuous infusion of a hyperosmolar/hyperoncotic solution.

BACKGROUND: The aim of this study was to evaluate how a continuous infusion of a hyperosmolar/hyperoncotic solution influences fluid shifts and intracranial pressure during cardiopulmonary bypass in piglets. METHODS: Fourteen animals, randomized to the control (CT) group or the hypertonic saline/hydroxyethyl starch (HyperHaes) (HSH) group, received acetated Ringer's solution as prime and supplemental fluid. The HSH group received, in addition, HyperHaes 1 ml/kg/h. After 1 h of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass (28 degrees C) was initiated and continued for 90 min. Fluid balance, plasma volume, tissue water content, acid-base parameters and intracranial pressure were recorded, and protein masses and fluid extravasation rates were calculated. RESULTS: At the start of normothermic cardiopulmonary bypass, the fluid extravasation rates (ml/kg/min) increased from 0.19 (0.06) to 1.57 (0.71) and 0.19 (0.09) to 0.82 (0.14) in the CT and HSH groups, respectively, with no between-group differences (P = 0.081) During hypothermic cardiopulmonary bypass, the fluid extravasation rates (ml/kg/min) increased from 0.19 (0.14) to 0.51 (0.10) (P < 0.01) and 0.15 (0.08) to 0.33 (0.08) (P < 0.05), respectively, with significantly lower extravasation rates in the HSH group (P < 0.01). In the HSH group, the total fluid gain during cardiopulmonary bypass decreased by about 50% (P < 0.05) and the tissue water content was significantly lower in the left and right heart as well as in the lungs. The intracranial pressure remained stable in the HSH group, but increased in the CT group. CONCLUSIONS: A continuous infusion of HSH (HyperHaes) during cardiopulmonary bypass reduced the fluid extravasation rate and the total fluid gain during bypass. No electrolyte or acid-base disturbances were present. The intracranial pressure remained stable in the HSH group.

Acid-Base Equilibrium↗
PubMed2005

Fluid shift is moderate and short-lived during acute crystalloid hemodilution and normothermic cardiopulmonary bypass in piglets.

BACKGROUND: Crystalloids are commonly used as priming solutions during cardiopulmonary bypass (CPB). Consequently, hemodilution is a regular occurrence at the start of a CPB. This study describes the time-course variations of hemodynamic parameters, plasma volume (PV) and fluid exchange following crystalloid hemodilution at start of normothermic CPB. METHODS: Forty-five anesthetized piglets were given 60-min normothermic CPB. Ringer's solution was used as priming solution and maintenance fluid. Fluid input/losses, PV, colloid osmotic pressures (plasma/interstitium), hematocrit, and s-proteins were measured, and fluid extravasation rates (FER) and intravascular protein-masses calculated. RESULTS: Start of CPB resulted in a 25-30% hemodilution. To keep the fluid level of the CPB-reservoir constant after start of bypass, fluid addition [2.08 +/- 0.36 (mean +/- SEM) ml kg(-1) min(-1)] was necessary during the first 5 min. Thereafter the fluid needs to be leveled off [0.17 +/- 0.03 ml kg(-1) min(-1) (10-60 min), P < 0.001]. Fluid extravasation rate increased immediately following hemodilution from a baseline value of 0.08 +/- 0.01 to 1.75 +/- 0.34 ml kg(-1) min(-1) with a delayed decrease compared to fluid additions, to reach a 'steady-state' level of 0.22 +/- 0.03 ml kg(-1) min(-1) after 30 min (P < 0.001). Differences in time-course variations between fluid added and fluid extravasated were accompanied by changes in PV and mean arterial pressure. The colloid osmotic gradient decreased about 50% throughout the study and could partly explain the increased FER. CONCLUSION: Acute crystalloid hemodilution contributes to fluid overload during normothermic CPB. The resulting increase in fluid extravasation is, however, moderate, short-lived and levels off to baseline values within 30 min.

Animals↗
PubMed2005

Low arterial pressure during cardiopulmonary bypass in piglets does not decrease fluid leakage.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with increased fluid filtration occasionally leading to post-operative organ dysfunction. One of the factors determining fluid filtration is the capillary hydrostatic pressure which depends on arterial pressure, venous pressure and pre- to post-capillary resistance ratio. The purpose of this study was to assess whether lowering of the mean arterial pressure and/or the central venous pressure could reduce fluid extravasation during normothermic and hypothermic CPB. METHODS: Seven piglets were given nitroprusside to a mean arterial pressure of 35-40 mmHg during 60 min of normothermic and 90 min of hypothermic CPB (LP group). They were compared with a control group (C group, n = 7) without blood pressure interventions. Blood chemistry, net fluid balance, plasma volume, colloid osmotic pressure in plasma and interstitial fluid, intravascular protein masses, fluid extravasation rate and total tissue water content were measured or calculated. RESULTS: Mean arterial pressure was significantly lower in the LP group than in the C group during CPB. Plasma volume tended to increase in the LP group (P > 0.05), but remained essentially unchanged in the C group. Net fluid balance in the LP group was more positive than in the C group 30 min after CPB start [1.02 (0.15) vs. 0.56 (0.13) ml/kg/min (Mean (SEM) P < 0.05)]. Fluid extravasation rate tended to be higher in the LP group and total tissue water content of the gastrointestinal tract, left myocardium and skin was significantly elevated compared with the C group. CONCLUSION: During CPB, lowering of the mean arterial pressure using nitroprusside did not reduce fluid extravasation. On the contrary, the data may implicate an increase in edema formation during low pressure CPB.

Albumins↗
PubMed2004

Can the use of methylprednisolone, vitamin C, or alpha-trinositol prevent cold-induced fluid extravasation during cardiopulmonary bypass in piglets?

OBJECTIVE: Hypothermic cardiopulmonary bypass is associated with capillary fluid leakage, resulting in edema and occasionally organ dysfunction. Systemic inflammatory activation is considered responsible. In some studies methylprednisolone has reduced the weight gain during cardiopulmonary bypass. Vitamin C and alpha-trinositol have been demonstrated to reduce the microvascular fluid and protein leakage in thermal injuries. We therefore tested these three agents for the reduction of cold-induced fluid extravasation during cardiopulmonary bypass. METHODS: A total of 28 piglets were randomly assigned to four groups of 7 each: control group, high-dose vitamin C group, methylprednisolone group, and alpha-trinositol-group. After 1 hour of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass was initiated in all animals and continued to 90 minutes. The fluid level in the extracorporeal circuit reservoir was kept constant at the 400-mL level and used as a fluid gauge. Fluid needs, plasma volume, changes in colloid osmotic pressure in plasma and interstitial fluid, hematocrit, and total water contents in different tissues were recorded, and the protein masses and the fluid extravasation rate were calculated. RESULTS: Hemodilution was about 25% after start of normothermic cardiopulmonary bypass. Cooling did not cause any further changes in hemodilution. During steady-state normothermic cardiopulmonary bypass, the fluid need in all groups was about 0.10 mL/(kg.min), with a 9-fold increase during the first 30 minutes of cooling (P <.001). This increased fluid need was due mainly to increased fluid extravasation from the intravascular to the interstitial space at a mean rate of 0.6 mL/(kg.min) (range 0.5-0.7 mL/[kg.min]; P <.01) and was reflected by increased total water content in most tissues in all groups. The albumin and protein masses remained constant in all groups throughout the study. CONCLUSION: Pretreatment with methylprednisolone, vitamin C, or alpha-trinositol was unable to prevent the increased fluid extravasation rate during hypothermic cardiopulmonary bypass. These findings, together with the stability of the protein masses throughout the study, support the presence of a noninflammatory mechanism behind the cold-induced fluid leakage seen during cardiopulmonary bypass.

Animals↗
PubMed2003

Fluid extravasation during cardiopulmonary bypass in piglets--effects of hypothermia and different cooling protocols.

BACKGROUND: Hypothermic cardiopulmonary bypass (CPB) is associated with capillary fluid leak and edema generation which may be secondary to hemodilution, inflammation and hypothermia. We evaluated how hypothermia and different cooling strategies influenced the fluid extravasation rate during CPB. METHODS: Fourteen piglets were given 60 min normothermic CPB, followed by randomization to two groups: 1: rapid cooling (RC-group) ( approximately 15 min to 28 degrees C); 2: slow cooling (SC-group) ( approximately 60 min to 28 degrees C). Ringer's solution was used as CPB prime and for fluid supplementation. Fluid input/losses, plasma volume, colloid osmotic pressures (plasma, interstitial fluid), hematocrit, serum-proteins and total tissue water (TTW) were measured and fluid extravasation rates calculated. RESULTS: Start of normothermic CPB resulted in a 25% hemodilution. During the first 5-10 min the fluid level of the reservoir fell markedly due to an intravascular volume loss necessitating fluid supplementation. Thereafter a steady state was reached with a constant fluid need of 0.14 +/- 0.04 ml kg-1 min-1. After start of cooling the fluid needs increased in the following 30 min to 0.91 +/- 0.11 ml kg-1 min-1 in the RC group (P < 0.001) and 0.63 +/- 0.10 ml kg-1 min-1 in the SC-group (P < 0.001) with no statistical between-group differences. Fluid extravasation rates after start of hypothermic CPB increased from 0.20 +/- 0.08 ml kg-1 min-1 to 0.71 +/- 0.13 (P < 0.01) and 0.62 +/- 0.13 ml kg-1 min-1 (P < 0.05) in the RC- and SC-groups, respectively, without any changes in degree of hemodilution. TTW increased in most tissues, whereas the intravascular albumin and protein masses remained constant with no between group differences. CONCLUSION: Hypothermia increased fluid extravasation during CPB independent of cooling strategy. Intravascular albumin and protein masses remained constant. Since inflammatory fluid leakage usually results in protein rich exudates, our data with no net protein leakage may indicate that mechanisms other than inflammation could contribute to fluid extravasation during hypothermic CPB.

Animals↗
PubMed2003

Immediate control of life-threatening digoxin intoxication in a child by use of digoxin-specific antibody fragments (Fab).

Digoxin-immune antibody fragments (Fab) for treatment of digitalis intoxication was introduced in 1976. Many reports have been published concerning this therapy for children, but few have focused on its immediate reversal of cardiac as well as extracardiac life-threatening manifestations of digoxin toxicity. We present a case of life-threatening digitalis intoxication in a child with postoperative renal insufficiency, after a Sennings procedure for transposition of the great arteries. Digoxin administration according to the nationally recommended dosage and intervals unexpectedly resulted in serum levels in the toxic range. Severe cardiac arrhythmias, haemodynamic instability and a rapid-increasing serum potassium level resulted. This report demonstrates how administration of Fab according to the manufacturer's dosage recommendation reversed the tachyarrhythmia immediately and re-established a normal level of serum potassium within minutes.

Antibodies, Blocking↗
PubMed2002

Temperature-related fluid extravasation during cardiopulmonary bypass: an analysis of filtration coefficients and transcapillary pressures.

BACKGROUND: Cardiopulmonary bypass (CPB) as used for cardiac surgery and for rewarming individuals suffering deep accidental hypothermia is held responsible for changes in microvascular fluid exchange often leading to edema and organ dysfunction. The purpose of this work is to improve our understanding of fluid pathophysiology and to explore the implications of the changes in determinants of transcapillary fluid exchange during CPB with and without hypothermia. This investigation might give indications on where to focus attention to reduce fluid extravasation during CPB. METHODS: Published data on "Starling variables" as well as reported changes in fluid extravasation, tissue fluid contents and lymph flow were analyzed together with assumed/estimated values for variables not measured. The analysis was based on the Starling hypothesis where the transcapillary fluid filtration rate is given by: JV=Kf [Pc-Pi-sigma(COPp-COPi)]. Here Kf is the capillary filtration coefficient, sigma the reflection coefficient, P and COP are hydrostatic and colloid osmotic pressures, and subscript 'c' refers to capillary, 'i' to the interstitium and 'p' to plasma. RESULTS AND CONCLUSION: The analysis indicates that attempts to limit fluid extravasation during normothermic CPB should address primarily changes in Kf, while changes in both Kf and Pc must be considered during hypothermic CPB.

Animals↗
PubMed2002

Determination of plasma volume in anaesthetized piglets using the carbon monoxide (CO) method.

Based on measurements of the circulating red blood cell volume (V(RBC)) in seven anaesthetized piglets using carbon monoxide (CO) as a label, plasma volume (PV) was calculated for each animal. The increase in carboxyhaemoglobin (COHb) concentration following administration of a known amount of CO into a closed circuit re-breathing system was determined by diode-array spectrophotometry. Simultaneously measured haematocrit (HCT) and haemoglobin (Hb) values were used for PV calculation. The PV values were compared with simultaneously measured PVs determined using the Evans blue technique. Mean values (SD) for PV were 1708.6 (287.3)ml and 1738.7 (412.4)ml with the CO method and the Evans blue technique, respectively. Comparison of PVs determined with the two techniques demonstrated good correlation (r = 0.995). The mean difference between PV measurements was -29.9 ml and the limits of agreement (mean difference +/-2SD) were -289.1 ml and 229.3 ml. In conclusion, the CO method can be applied easily under general anaesthesia and controlled ventilation with a simple administration system. The agreement between the compared methods was satisfactory. Plasma volume determined with the CO method is safe, accurate and has no signs of major side effects.

Administration, Inhalation↗
PubMed2001

Rewarming from accidental hypothermia by extracorporeal circulation. A retrospective study.

OBJECTIVE: Twenty-six patients with accidental hypothermia combined with circulatory arrest or severe circulatory failure were rewarmed to normothermia by use of extracorporeal circulation (ECC). The aim of the present study was to evaluate our results. PATIENTS AND METHODS: The treatment of six female and 20 male patients (median age: 26.7 years; range 1.9--76.3 years) rewarmed in the period 1987--2000 was evaluated retrospectively. Hypothermia was related to immersion/submersion in cold water (n=17), avalanche (n=1) or prolonged exposure to cold surroundings (n=8). Prior to admission, the trachea was intubated and cardiopulmonary resuscitation (CPR) initiated in all patients with cardiorespiratory arrest (n=22), whereas in those with respiration/circulation (n=4) only oxygen therapy via a face mask was given. RESULTS: Nineteen of the 26 patients were weaned off ECC whereas seven died because of refractory respiratory and/or cardiac failure. Eight of the 19 successfully weaned patients were discharged from hospital after a median of 10 days. One patient died 3 days after circulatory arrest (complete atrioventricular block) resulting in severe cerebral injury. The remaining ten patients died following 1--2 days due to severe hypoxic brain injury (n=5), cerebral bleeding (n=1) or irreversible cardiopulmonary insufficiency (n=4). Based on the reports from the site of accident, two groups of patients were identified: the asphyxia group (n=15) (submersions (n=14); avalanche accident (n=1)) and the non-asphyxia group (n=11) (patients immersed or exposed to cold environment). Seven intact survivors discharged from hospital belonged to the non-asphyxia group whereas one with a severe neurological deficit was identified within the asphyxia group. CONCLUSION: Patients with non-asphyxiated deep accidental hypothermia have a reasonable prognosis and should be rewarmed before further therapeutic decisions are made. In contrast, drowned patients with secondary hypothermia have a very poor prognosis. The treatment protocol under such conditions should be the subject for further discussion.

Adult↗
PubMed2001

Studies on fluid extravasation related to induced hypothermia during cardiopulmonary bypass in piglets.

BACKGROUND: Hypothermia, commonly used for organ protection during cardiopulmonary bypass (CPB), has been associated with changes in plasma volume, hemoconcentration and microvascular fluid shifts. Fluid pathophysiology secondary to hypothermia and the mechanisms behind these changes are still largely unknown. In a recent study we found increased fluid needs during hypothermic compared to normothermic CPB. The aim of the present study was to characterize the distribution of the fluid given to maintain normovolemia. In addition, we wanted to investigate the quantity and quality of the fluid extravasated during hypothermic compared to normothermic CPB. METHODS: Two groups of anesthetized piglets were studied during 2 h of hypothermic (28 degrees C) (n=7) or normothermic (38 degrees C) (n=7) CPB. Net fluid balance (input-output) was recorded. Changes in colloid osmotic pressures of plasma (COPp) and interstitial fluid (COPi), plasma volume (PV), hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), s-osmolality, s-albumin and s-total protein was followed throughout the experiments. Fluid extravasation rate was calculated. In addition, total tissue water content was measured and compared with a control group (n=6) (no CPB). RESULTS: During hypothermic compared with normothermic CPB, the average net positive fluid balance from 10-120 min of extracorporeal circulation was 1.35+/-0.06 ml x kg(-1) x min(-1) and 0.33+/-0.03 ml x kg(-1) x min(-1) respectively (P<0.0001). We found a marked increase in fluid extravasation during hypothermic CPB. The extravasation rate during hypothermia was 1.8+/-0.2 ml x kg(-1) x min(-1), (1st hour) and 1.1+/-0.2 ml x kg(-1) x min(-1) (2nd hour) compared with 0.8+/-0.2 ml x kg(-1) x min(-1), and 0.1+/-(0.1) ml x kg(-1) x min(-1) during normothermia, respectively (P<0.01). The total intravascular protein and albumin masses remained constant in both groups. Following hypothermic CPB, the water content increased significantly in all tissues and organs. CONCLUSION: During hypothermic CPB an increased extravasation of fluid from the intravascular to the interstitial space was found. As no leakage of proteins could be demonstrated, based on stable values for albumin and protein masses throughout the experiments, the extravasated fluid contained mainly water and small solutes.

Albumins↗
PubMed2001

Endogenous glutathione and platelet function in platelet concentrates stored in plasma or platelet additive solution.

Platelet function was studied in platelet concentrates by assay of the thrombin-induced release of endogenous serotonin and presence of the swirling phenomenon in relation to endogenous glutathione (GSH) and cysteine. In platelets stored in plasma, addition of cysteamine resulted in only a moderate fall in GSH after 5 days of storage, from an average of 14.91 to 11.46 nmol per 109 platelets. Exogenously added GSH had no effect, and addition of buthionine sulfoximine (BSO) resulted in almost complete depletion of GSH, to an average of 0.65 nmol per 109 platelets. Addition of cysteamine or GSH resulted in increased endogenous cysteine whereas BSO had no effect. In platelets stored in a platelet additive solution (T-sol), complete depletion of GSH was found in the presence of cysteamine, GSH and BSO. Endogenous serotonin was unchanged during storage both in plasma and in additive solution (2.8 nmol per 109 platelets). Despite almost total depletion of endogenous GSH, the thrombin-induced release of serotonin after 5 days' storage was significantly affected only in the presence of BSO in platelets stored in additive solution (mean values 72.3% vs. 63.3% of endogeneous serotonin, P < 0.05). Similarly, addition of cysteamine or GSH had no significant effect on swirling but BSO reduced the swirling score after 5 days' storage in platelet additive solution compared with plasma. After 10 days' storage, there was a significant reduction in swirling in the concentrates where BSO was added (P < 0.05).

Blood Platelets↗
PubMed2000

[Rewarming of patients with accidental hypothermia with the help of heart-lung machine].

BACKGROUND: Different techniques have been used for treatment of victims with accidental hypothermia. We have used cardiopulmonary bypass (CPB) for rewarming hypothermic patients with circulatory failure or cardiac arrest. This report summarises our experiences with this patient group. MATERIAL AND METHODS: 23 patients, submersions (n = 15), avalanche (n = 1) and primary hypothermia (immersion/air cooling) (n = 7), were rewarmed using extracorporeal circulation with standard equipment for open-heart surgery. RESULTS: On a clinical basis, two patient populations could be identified; one group for whom asphyxia was probably present prior to and during cooling, and another group for whom asphyxia was unlikely. In the first group, one of 13 patients survived compared to the latter group where six out of ten survived. A search for laboratory and other variables that with certainty could contribute to the prediction of prognosis was unsuccessful. INTERPRETATION: Due to lack of safe prognostic predictors, all accidental hypothermic victims with circulatory failure should be rewarmed by cardiopulmonary bypass before further therapeutic decisions are made.

Accidents↗
PubMed2000

Cardiac biochemical markers after cardioversion of atrial fibrillation or atrial flutter.

BACKGROUND: Cardioversion or defibrillation of cardiac arrhythmias is often necessary in acutely ill cardiac patients. The electrical current may cause elevation of biochemical markers used to diagnose acute myocardial infarction. Therefore it is important to find cardiac markers with high specificity for myocardial necrosis. The purpose of this study was to assess the effects of elective cardioversion of atrial fibrillation or flutter on troponin T and I among conventional markers in patients with no evidence of acute ischemia. METHODS AND RESULTS: Fifty-seven consecutive patients underwent 1 to 4 direct current shocks (mean cumulative energy 407 J, range 100 to 920 J) under general anesthesia. At baseline, all had normal troponin levels; 50 patients (mean age 68 years, range 33 to 84 years) had normal cardiac enzymes and were included in the final analysis. Blood samples were drawn at baseline, and 1 to 2, 6 to 8, and 20 to 24 hours after cardioversion. The troponin levels were unaffected by cardioversion in all patients, whereas creatine kinase and myoglobin increased more than 10-fold. Creatine kinase MB mass and aspartate aminotransferase were above reference limits in 18% and 24% of patients, respectively, 20 to 24 hours after cardioversion. There was a significant association between elevated creatine kinase, myoglobin, and creatine kinase MB levels with cumulated energy delivered as well as when possible confounders such as age and sex were adjusted for. High international normalized ratio with warfarin use was associated with increased levels of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, and myoglobin. CONCLUSIONS: The increase of conventional biochemical markers after direct current cardioversion is positively associated with cumulative energy delivered and international normalized ratio (INR) values; neither influences levels of the cardiac troponins.

Adult↗
PubMed1999

Serotonin is associated with coronary artery disease and cardiac events.

BACKGROUND: Blood platelets are related to coronary atherogenesis. Platelets secrete serotonin (5-hydroxytryptamine) which has several effects on the vascular wall and promotes thrombogenesis, mitogenesis, and proliferation of smooth muscle cells. Serotonin may therefore be one of the factors involved in the development of coronary artery disease (CAD). We have assessed serotonin among conventional predictors for CAD in patients undergoing coronary angiography for chest pain or clinically suspected angina pectoris. METHODS AND RESULTS: Of 121 consecutive male patients (mean age 65, range 41 to 90 years) undergoing angiography, 96 had coronary artery stenosis and 25 had normal angiograms. Serotonin, blood platelet count, and conventional biochemical risk factors for CAD were determined in the morning the day before the angiography. High serotonin (cut-point 1000 nmol/L) was significantly associated with CAD with an odds ratio (OR) of 3.4 (95% confidence interval 1.2 to 9. 8). The corresponding OR for smokers was 4.8 (1.9 to 12.2); hypercholesterolemia (>7 mmol/L), 2.9 (1.1 to 7.6); high platelet count (cut-point 325 10(9)/L), 3.0 (1.0 to 9.5); and family history of heart disease, 2.3 (1.0 to 5.2). After adjustment with conventional risk factors, the OR for CAD was 3.8 (1.1 to 13.1), comparing high and low values of serotonin. The relation between serotonin and CAD was strengthened only when patients <70 years (n=82) were included in the analysis. In this age group, the occurrence of cardiac events during a mean of 3.7 years of follow-up was significantly associated with high serotonin values. CONCLUSIONS: The study suggests that serotonin is associated with coronary artery disease and occurrence of cardiac events, particularly in younger age groups. This association seems to persist after adjustment for conventional risk factors.

Adult↗
PubMed1999

The swirling phenomenon in stored platelets is influenced by their endogenous serotonin.

The presence of the swirling phenomenon is useful to define platelet concentrates that are suitable for transfusion. If it is possible to identify donor-related factors which are related to persisting swirling during storage, it is possible to select platelet donors. Endogenous platelet serotonin content is stable and easily measured and related to agonist-induced serotonin secretion. During a 3-month period, the swirling in 825 single donor platelet concentrates was controlled before issue. Endogenous serotonin, % serotonin release and swirling were tested in 21 concentrates with poor or no swirling during storage. Sixty-three concentrates were randomly selected from the routinely prepared platelet concentrates and were routinely tested with the same analyses on days 1 and 7. To evaluate an obvious effect of endogenous serotonin on the swirling phenomenon, eight platelet concentrates prepared from buffy coat, each from four donors, were divided. One part was stored in the presence of 8.5 micromol serotonin L-1, and analysed as the control concentrates. The endogenous serotonin content in the 'low- swirling' concentrates was significantly lower than in the control group (P < 0.001). PCO2 and pH were significantly lower, and PO2 and MPV significantly higher than in the controls. In the control group, swirling after 7 days was significantly correlated with serotonin release. In the eight buffy-coat concentrates enriched in endogenous serotonin, both swirling and the percentage serotonin release were improved after storage for 10 days, compared with nonenriched concentrates. This study suggests that endogenous serotonin content and serotonin release are factors that may be of significance concerning preservation of the swirling phenomenon in platelet concentrates during storage.

Blood Donors↗
PubMed1999

Benzalkonium chloride interferes with energy production, secretion and morphology in human blood platelets.

Benzalkonium chloride (BC) is a bactericidal compound used as a topical antiseptic and as a preservative in various products for local treatment, e.g., eye and nose drops. BC is toxic to human cells, including those of the respiratory mucosa. Few studies have, however, focused on what cellular functions BC interferes with. The effects of BC were studied on washed human blood platelets in vitro . Cellular energy production as well as secretion were studied. Incubation of platelets with BC resulted in rapid swelling and toxic morphological changes. After incubation with BC oxidation of [1-14C] palmitate was inhibited, and both lactate dehydrogenase and endogenous serotonin were spontaneously released. Thrombin-induced secretion of serotonin was strongly reduced after BC exposure. Histological changes with increased size, spherical form, decreased numbers of pseudopodia, loss of an intact continuous tubulus system and reduced number of granules were found by scanning and transmission electron microscopy. It is concluded that the toxic effects of BC are because of interference with membrane function and energy production.

Journal Article↗
PubMed1997

Plasma homocysteine levels and mortality in patients with coronary artery disease.

BACKGROUND: Elevated plasma homocysteine levels are a risk factor for coronary heart disease, but the prognostic value of homocysteine levels in patients with established coronary artery disease has not been defined. METHODS: We prospectively investigated the relation between plasma total homocysteine levels and mortality among 587 patients with angiographically confirmed coronary artery disease. At the time of angiography in 1991 or 1992, risk factors for coronary disease, including homocysteine levels, were evaluated. The majority of the patients subsequently underwent coronary-artery bypass grafting (318 patients) or percutaneous transluminal coronary angioplasty (120 patients); the remaining 149 were treated medically. RESULTS: After a median follow-up of 4.6 years, 64 patients (10.9 percent) had died. We found a strong, graded relation between plasma homocysteine levels and overall mortality. After four years, 3.8 percent of patients with homocysteine levels below 9 micromol per liter had died, as compared with 24.7 percent of those with homocysteine levels of 15 micromol per liter or higher. Homocysteine levels were only weakly related to the extent of coronary artery disease but were strongly related to the history with respect to myocardial infarction, the left ventricular ejection fraction, and the serum creatinine level. The relation of homocysteine levels to mortality remained strong after adjustment for these and other potential confounders. In an analysis in which the patients with homocysteine levels below 9 micromol per liter were used as the reference group, the mortality ratios were 1.9 for patients with homocysteine levels of 9.0 to 14.9 micromol per liter, 2.8 for those with levels of 15.0 to 19.9 micromol per liter, and 4.5 for those with levels of 20.0 micromol per liter or higher (P for trend=0.02). When death due to cardiovascular disease (which occurred in 50 patients) was used as the end point in the analysis, the relation between homocysteine levels and mortality was slightly strengthened. CONCLUSIONS: Plasma total homocysteine levels are a strong predictor of mortality in patients with angiographically confirmed coronary artery disease.

Adult↗