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Biomedical subjects

R Ekroth

Publications and source records attributed to R Ekroth.

At least 37 records · Page 2Linked to original sources

Cytokine production and hemofiltration in children undergoing cardiopulmonary bypass.

Multiorgan dysfunction still occurs after cardiopulmonary bypass and remains a major cause of morbidity and mortality, especially in the pediatric age group. This is consequent upon the so-called systemic inflammatory response to bypass with an increase in inflammatory mediators. Hemofiltration may be able to attenuate the effects of this response by elimination of some or all of these mediators. We undertook a prospective, randomized study to investigate the effect of hemofiltration on plasma levels of the cytokines tumor necrosis factor alpha, interleukin-8, and interleukin 6 in 18 infants and children undergoing deep hypothermic bypass. Serial plasma samples were taken before, during, and after bypass. Assay of the plasma samples revealed presence of the cytokines in a number of subjects in both groups, in some cases before operation. There were significant reductions in levels of tumor necrosis factor after hemofiltration, with no reduction noted in the group not undergoing hemofiltration. A similar difference (p < 0.05) was detected in the levels of interleukin-6 between the two groups after bypass, although this was largely due to changes in 2 subjects. Interleukin-8 was detected in a small number of subjects insufficient for statistical analysis, but with higher values in the group undergoing hemofiltration. We conclude that hemofiltration has the potential to remove cytokines from the circulation, with consequent beneficial effects.

Cardiopulmonary Bypass↗

Absent diastolic cerebral blood flow velocity after circulatory arrest but not after low flow in infants.

It is controversial whether profound hypothermia (15 degrees C) provides adequate cerebral protection during a limited period of total circulatory arrest during pediatric cardiac surgery. In the present study, transcranial Doppler echography was used to monitor the blood flow velocity (BFV) pattern in the middle cerebral artery (MCA). The purpose of the study was to investigate the influence of a period of circulatory arrest on MCA BFV, as judged from the reperfusion flow velocity pattern. The MCA BFV was studied in 22 small children undergoing profound hypothermic cardiac operations after induction of anesthesia. Twelve of the children had a period of profound hypothermic circulatory arrest (15 to 74 minutes; arrest group). Circulation was maintained in the remaining 10 children (nonarrest group). Time-averaged MCA BFV was decreased and diastolic BFV was absent immediately after cardiopulmonary bypass in 10 of 12 children in the arrest group. In contrast, only 1 of 10 patients in the nonarrest group (p < 0.05) showed this pattern. Diastolic BFV normalized 54 to 328 minutes after the arrest in the arrest group. Circulatory arrest during profound hypothermia is followed by a period of low cerebral perfusion, whereby time-averaged MCA BFV is decreased and MCA BFV is absent during diastole. We speculate that this can be explained by an increase in intracranial pressure after brain edema.

Blood Flow Velocity↗

Myocardial uptake and release of lactate after high dose neurolept endotracheal intubation in coronary surgery.

To evaluate the relationship between the hemodynamic and ECG variables used in routine surveillance of coronary surgery and myocardial lactate metabolism, 23 middle-aged, male, beta 1-blocked patients about to undergo coronary surgery were monitored before and after endotracheal intubation with high dose (30 micrograms/kg) fentanyl-midazolam anesthesia. The induction of anesthesia was followed by a mean arterial pressure decrease (from 98 +/- 4 to 76 +/- 3 mm Hg) and heart rate increase (from 53 +/- 3 to 66 +/- 2 beats/min). After intubation the hemodynamic variables were stable except for a further, transient increase in heart rate (to 69 +/- 2 beats/min). The myocardial uptake of lactate decreased after intubation, from 48 +/- 5 mumol/min to a lowest level of 24 +/- 3 mumol/min. A lactate release was exhibited in 7/23 patients (30%). No ST-segment changes were observed. The correlation between the myocardial lactate uptake/release and hemodynamic or ECG variables was unimpressive or non-existent (r < or = 0.20). Thus, a reduced uptake and even a release of lactate occurred irrespective of the ST-segment, heart rate, or systemic or pulmonary artery pressures. In conclusion, endotracheal intubation in patients with coronary disease was consistently (17/23 patients) followed by a reduced myocardial uptake of lactate, in spite of high dose neurolept anesthesia and beta 1-blockade. This metabolic event was not consistently related to hemodynamic changes.

Adrenergic beta-Antagonists↗

Acute renal failure after coronary surgery--a study of incidence and risk factors in 2009 consecutive patients.

To obtain a model for the prediction of acute renal failure (ARF) after coronary surgery, 2009 consecutive patients were investigated. ARF was defined as a peak postoperative serum creatinine value exceeding the preoperative value by 50% or more or a need for dialysis. A postoperative increase in serum creatinine of less than 50% was associated with an early mortality (< or = 30 days postop.) of 0.4%. Sixteen per cent of the patients increased their serum creatinine by more than 50% and in this group there was a mortality of 1.3%. Twenty-five patients (1.2%) required postoperative haemodialysis because of ARF and of these 11 (44%) died early, whereas another 7 patients with chronic renal failure, requiring both pre- and postoperative haemodialysis, all survived. Peak postoperative serum creatinine and changes from the preoperative value were analyzed and related to clinical variables. Multivariate analysis indicated that high preoperative serum creatinine, high age and postoperative haemodynamic instability were the most important risk factors for developing renal failure. A logistic model including these risk factors versus the probability of developing ARF is presented.

Acute Kidney Injury↗

Influence of beta 1-blockade on myocardial substrates early after a coronary operation.

A high adrenergic strain during reperfusion after ischemia impedes functional recovery. Conversely, adrenergic blockade may be beneficial during reperfusion. This study was undertaken to find out if early postoperative high-dose infusion of the selective beta 1-blocking agent metoprolol tartrate has additional effects on metabolic variables related to myocardial energy supply/demand balance compared with those obtained with a late preoperative oral dose. The study included 21 male patients undergoing coronary bypass grafting. All patients received an oral dose of metoprolol before the operation. After the operation, patients were randomized to a control group or a group receiving intravenous infusion of metoprolol. Myocardial uptake of oxygen and substrates was determined before and during atrial pacing. Metoprolol reduced arterial concentrations of free fatty acids, reduced myocardial uptake of free fatty acids, and enhanced myocardial uptake of lactate. During paced tachycardia, the metoprolol concentration correlated negatively with myocardial uptake of free fatty acids (r = -0.80; p < 0.001) and positively with myocardial uptake of lactate (r = 0.53; p < 0.05). It is concluded that postoperative infusion of metoprolol induces myocardial metabolic changes compatible with an improved energy supply/demand balance.

Administration, Oral↗

High-dose intravenous beta 1-blockade in patients early after cardiac operations. Negative inotropism versus myocardial oxygen economy.

A high adrenergic strain during reperfusion after ischemia impedes functional recovery. Conversely, adrenergic blockade may be beneficial during reperfusion. Negative inotropic effects may outweigh the expected benefit, however. Against this background hemodynamic and metabolic effects of early postoperative infusion with the beta 1-selective agent metoprolol were studied in 22 patients after coronary operations. During basal postoperative conditions, intravenous metoprolol reduced cardiac index and stroke volume index compared with control patients, while other variables were unaffected. During the higher adrenergic level of a dopamine infusion (7 micrograms/kg per minute), the heart rate, rate pressure product, and myocardial oxygen uptake were attenuated in proportion to the plasma level of metoprolol. Intravenous beta 1-blockade did not affect the cardiac output or stroke volume responses to dopamine (the cardiac output was still, however, 19% lower than in control patients). A release of myocardial creatinine kinase isoenzyme myocardial band was observed during dopamine infusion, suggesting that myocardial ischemia was induced. The release was not influenced by metoprolol, but it correlated with heart rate (r = 0.60; p < 0.01). It is concluded that infusion of metoprolol early after coronary operations depresses myocardial contractility with some 19%, which was without clinical significance in straightforward patients; the increased myocardial metabolic demand during a period of increased adrenergic stress was attenuated by metoprolol. This may be of importance for myocardial recovery.

Aged↗

Effects of insulin on myocardial uptake of branched chain amino acids soon after cardiac operations.

Infusion of insulin-glucose-potassium is used to support the failing heart after cardiac operations. Although the effects on myocardial uptake of carbohydrates and lipids have been described, the effects on myocardial extraction of amino acids are unknown. This study was undertaken to clarify the effect of insulin-glucose-potassium on the pattern of amino acid uptake/release in myocardial and skeletal muscle after coronary operations. The amino acid uptake/release of the heart and of the leg was studied in 18 patients 1 hour after coronary bypass operations. The patients were randomized to treatment with 25 U of fast-acting insulin as a bolus injection followed by a continuous infusion of 1 U/kg body weight for 1 hour, or to serve as control patients. The hyperinsulinemic "clamp" technique was used to keep blood glucose unchanged during the study. In the insulin-treated group, the arterial concentration of 17 of 22 individual amino acids, including the three branched chain amino acids, decreased, the remainder being unchanged. The amino acid uptake/release of the leg was unchanged. The net myocardial uptake of leucine and isoleucine shifted to a no-uptake/no-release in the insulin-treated group, whereas the no-uptake/no-release of tyrosine and phenylalanine turned into a significant release. A positive correlation was observed between arterial concentration and myocardial uptake/release of the three branched chain amino acids. It is suggested that insulin, by lowering the arterial concentration of leucine and isoleucine, inhibited the myocardial uptake of these amino acids. This may have a negative effect on postoperative myocardial protein balance suggested by the release of tyrosine and phenylalanine.

Amino Acids, Branched-Chain↗

Dopamine and high-dose insulin infusion (glucose-insulin-potassium) after a cardiac operation: effects on myocardial metabolism.

Myocardial insulin resistance, in association with surgical stress, restricts the availability of carbohydrates and increases the load of free fatty acids (FFAs) on the heart. On theoretical grounds adrenergic drugs may be expected to aggravate this situation, whereas the opposite is expected from insulin. The influence of dopamine and a combination of dopamine (7 micrograms/kg body weight/min) and high-dose insulin (7 IU/kg) on myocardial energy metabolism was studied in 19 patients 4 to 6 hours after a coronary operation. Infusion of dopamine (7 micrograms/kg body weight/min) induced metabolic changes that may be unfavorable to the strained myocardium. There was an increase of the myocardial FFA load and a rise in myocardial oxygen expenditure by 60% to 70%. There changes were, however, not matched by an increase in myocardial substrate uptake. "Oxygen wastage" of FFA metabolism at high circulating catecholamine levels is suggested. There were also signs suggesting an amplified systemic trauma response: systemic oxygen consumption increased by 15%, and an increase in the arterial levels of FFAs, glucose, and ketones was observed. Divergent metabolic effects of dopamine and insulin were demonstrated. The most prominent metabolic effects of adding high-dose insulin to dopamine were a marked reduction of arterial FFA levels and a shift toward myocardial carbohydrate utilization at the expense of FFAs. Myocardial uptake of FFAs ceased. Myocardial insulin resistance may thus to a significant extent be overcome by supraphysiological doses of insulin, even during infusion of adrenergic drugs.

Adult↗

Continuous vectorcardiography in cardiac surgery: natural course of vector changes and relationship to myocardial oxygen uptake.

Continuous vectorcardiography was registered before and during the first 18 hours after cardiac surgery in 53 patients. QRS vector changes (QRS-VD) occurred during the operation, but no further changes were observed postoperatively. The ST vector (ST-VM) increased during the operation, and a further slight increase occurred postoperatively. Perioperative myocardial infarction occurred in three patients. Their ST-VM was higher than the average in patients without myocardial infarction, while QRS-VD did not differ from the average pattern. Twelve other patients were studied in pacemaker-induced moderate tachycardia. QRS-VD increased in proportion to heart-rate changes (rs median = 0.93, p less than 0.01). QRS-VD also correlated with myocardial oxygen uptake (rs median = 0.62, p less than 0.05). The ST-VM responses were not uniform. The data suggest that vectorcardiogram variables can provide information related to myocardial energy metabolism.

Adult↗

High-dose insulin improves the efficacy of dopamine early after cardiac surgery. A study of myocardial performance and oxygen consumption.

The influence of dopamine (7 micrograms/kg b.w./min) and of combined high-dose insulin (7 IU/kg) and dopamine on the relationship between haemodynamic performance and myocardial oxygen consumption was studied 4-6 hours after aortocoronary bypass surgery. The ten patients in the 'dopamine' group and the nine in the 'insulin-dopamine' group responded equally to dopamine alone. In a second study period the cardiac output was increased 41.8 +/- 4.7% by insulin-dopamine and 25.9 +/- 6.7% by dopamine alone (p less than 0.05). As the heart-rate response was similar in both groups, the difference was mainly due to greater response of stroke volume in the insulin-dopamine group. Systemic vascular resistance decreased 27.4 +/- 5.1% in the insulin-dopamine group but was unchanged in the dopamine group (p less than 0.05). Myocardial oxygen consumption increased 70.7 +/- 15.6% in the dopamine group and 78.8 +/- 18.4% in the insulin-dopamine group (NS). The addition of high-dose insulin to dopamine thus improved the haemodynamic efficacy of dopamine without further increasing myocardial oxygen expenditure.

Adult↗

Transcranial Doppler-estimated versus thermodilution-estimated cerebral blood flow during cardiac operations. Influence of temperature and arterial carbon dioxide tension.

The ability of the noninvasive continuous transcranial Doppler technique to reflect changes in cerebral blood flow during cardiac operations was evaluated in seven adults. Middle cerebral artery blood flow velocity changes were compared with simultaneous thermodilution measurements of venous blood flow in the ipsilateral internal jugular vein during 11 preset stages of the procedure. Cerebral blood flow was varied by changes in arterial carbon dioxide tension and temperature. High-dose fentanyl-droperidol anesthesia and alpha-stat pH management were employed. To facilitate comparisons between the two methods, the individual awake values of middle cerebral artery flow velocity (45.1 +/- 3.3 cm/sec, mean +/- standard error of the mean) and jugular venous blood flow (382 +/- 37 ml/min) were normalized (100%). Cerebral metabolic rate for oxygen was calculated as the product of jugular arteriovenous oxygen content difference and middle cerebral artery flow velocity or jugular venous blood flow, respectively. The individual correlations between the two flow estimates varied between 0.76 and 0.87 (median 0.83), and the correlation of the combined data from all seven patients was 0.77 (p less than 0.0001). Variations in arterial carbon dioxide tension induced significant changes in the two flow estimates both during normothermia before cardiopulmonary bypass and at deep hypothermia (20 degrees C) during cardiopulmonary bypass. The significant arterial carbon dioxide tension changes had no significant effects either on Doppler- or thermodilution-estimated cerebral metabolic rate for oxygen. Deep hypothermia (20 degrees C) reduced Doppler- and thermodilution-estimated cerebral metabolic rate for oxygen to 22.0% +/- 3.9% and 20.6% +/- 6.9% of the awake levels, respectively. The study supports the validity of using middle cerebral arterial flow velocity changes as an estimate of changes in volume flow through the brain during cardiac operations.

Aged↗

Myocardial uptake of amino acids and other substrates in relation to myocardial oxygen consumption four hours after cardiac operations.

Myocardial metabolism seems to be markedly abnormal during the first hours of reperfusion after aortic crossclamping. Thus we previously demonstrated no uptake of carbohydrate or lipid substrates 1 hour after coronary operations. Amino acids were the only exogenous substrates taken up by the heart. The aim of the present study was to examine if this metabolic abnormality persisted a few hours later. This was done by measuring coronary sinus blood flow and arterial-coronary sinus differences of oxygen, glucose, free fatty acids, glycerol, lactate, beta-OH-butyrate, and amino acids in a similar group of 19 patients 4 to 5 hours after coronary operations. The results demonstrate a change toward normalization of myocardial free fatty acid use, although the threshold for free fatty acid uptake seemed elevated in comparison with that in the normal postabsorptive state. No correlation was found between free fatty acid uptake and myocardial oxygen consumption. Despite elevated arterial levels of glucose, lactate, pyruvate, and beta-OH-butyrate, no uptake was observed. Myocardial amino acid exchange demonstrated a pattern suggestive of postischemic metabolic adaptation. Several amino acids were extracted, glutamate and branched chain amino acids being the quantitatively most important. The uptake of glutamate and branched chain amino acids correlated with myocardial oxygen consumption, which suggests a direct link to myocardial energy metabolism. Myocardial glutamate uptake seemed to be limited by substrate availability.

3-Hydroxybutyric Acid↗

Cerebral perfusion and metabolism during profound hypothermia in children. A study of middle cerebral artery ultrasonic variables and cerebral extraction of oxygen.

Flow velocity of the right middle cerebral artery was studied in eight children during cardiac operations performed with profound hypothermia. Cerebral oxygen consumption was estimated by relating the difference in oxygen content between arterial and venous blood (jugular bulb) to flow velocity. In another six children, also during profound hypothermic procedures, the diameter of the middle cerebral artery was studied with an electronic echo-tracking instrument connected to a real-time ultrasound scanner. Flow velocity and estimated oxygen consumption decreased during cooling in proportion to the temperature decrease (r = 0.67, p less than 0.001, and r = 0.86, p less than 0.001, respectively), whereas the diameter was unaffected by temperature. At a nasopharyngeal temperature of 16.9 degrees +/- 1.9 degrees C flow velocity was reduced to 33.1% +/- 7.0% of the value obtained at 35 degrees C after induction of anesthesia. Correspondingly, the oxygen consumption decreased to 20.1% +/- 6.4%. The increase in oxygen consumption per 10 degrees C change in temperature was 3.6 (2.0 to 3.9) during surface cooling, 2.6 (1.9 to 2.7) during cardiopulmonary bypass cooling, and 2.7 (1.5 to 4.6) during rewarming. Flow velocity was not influenced by perfusion pressure during profound hypothermia within the range of 20 to 42 mm Hg (r = 0.14, p = 0.52) but was related to pump flow (r = 0.73, p less than 0.001). A pump flow down to 0.5 L/min/m2 was found to be adequate during stable profound hypothermia, as judged from the maintained high jugular bulb venous oxygen saturation (70% to 80%). It is concluded that flow velocity is reduced at hypothermia in proportion to the reduced metabolic rate, although modified by other factors that influence cerebral blood flow.

Blood Flow Velocity↗

Myocardial recovery after cardiac surgery: a study of hemodynamic performance and electrophysiology during the first 18 postoperative hours.

Hemodynamic and vectorcardiographic variables were monitored in 23 patients with acquired heart disease, before and during the first 18 postoperative hours of cardiac surgery. The hemodynamic pattern directly after surgery was characterized by left ventricular depression and increased heart rate. Thus, stroke volume index had decreased from the preoperative 29 +/- 1 to 24 +/- 1 mL/beat/m2, and heart rate had increased from 61 +/- 2 to 94 +/- 4 beats/min. During the following hours a gradual normalization of stroke volume occurred, leading to a cardiac index that was adequate after 8 to 10 hours, judging from the mixed venous oxygen saturation (68% +/- 1%). Fourteen patients had an uneventful postoperative course, with no signs of acute myocardial infarction, and did not require inotropic support. These patients had small but consistent vectorcardiographic changes; the QRS vector difference increased moderately, and the ST vector magnitude also increased. No correlation was found between hemodynamic and vectorcardiographic variables, nor between timing of hemodynamic recovery and vectorcardiographic changes. Patients with a perioperative myocardial infarction had a vectorcardiographic pattern that was compatible with acute myocardial infarction. These patients had markedly elevated ST vector magnitude and QRS vector difference values, which were discernible during the first postoperative hours. The present data suggest that the timing of metabolic and electrophysiological recovery of the heart differ, and a computerized vectorcardiographic system may be of value in the early detection of perioperative myocardial infarction.

Adult↗

Trauma metabolism and the heart: studies of heart and leg amino acid flux after cardiac surgery.

Flux of plasma amino acids was measured across the heart and the leg (reflecting mainly skeletal muscle) in 18 patients 1 hour after completion of aorto-coronary bypass surgery. There was a net loss of amino acids from the leg (-324.9 +/- 39 nmol/min/100 ml tissue) while amino acid flux across the heart was not statistically different from zero. There were however positive intertissue correlations between leg and myocardial flux of tyrosine and most other amino acids, suggesting that protein metabolism of both tissues were affected in the same catabolic direction by the trauma response. Alanine and glutamine accounted for 50% of the amino acid release from the leg, which is in accordance with observations in association with other types of trauma. Alanine and glutamine also dominated amino acid release from the heart. Glutamate and aspartate were taken up by both tissues. The principal difference between the tissues was a myocardial uptake of leucine and isoleucine, in contrast to a leg release.

Adult↗

Brain type creatine kinase in relation to oxygen desaturation in the blood of children with congenital heart disease.

The concentration of brain type creatine kinase (CK-BB) was measured in blood from the internal jugular vein in 32 children (less than 1 year old) with congenital heart disease. In transposition of the great arteries the CK-BB levels were significantly higher than in children without cyanosis (10.1 +/- 4.1 vs. 3.0 +/- 0.5 ng/ml). A negative correlation was found for CK-BB concentration and arterial oxygen saturation (r = -0.41, p less than 0.02 for all children and r = -0.62, p less than 0.05 for those with tetralogy of Fallot). It is suggested that the increased CK-BB levels in the blood of cyanotic children reflect chronic cerebral hypoxia, which may explain other reports of reduced psycho-intellectual function in patients with cyanotic heart disease.

Brain↗

Trauma metabolism and the heart. Uptake of substrates and effects of insulin early after cardiac operations.

In a controlled, randomized study the myocardial uptake/release of individual free fatty acids, glucose, lactate, pyruvate, alanine, and glycerol was studied 1 hour after completion of coronary operations. The effects of insulin were evaluated by means of a hyperinsulinemic "clamp" technique. No significant uptake of free fatty acids was found despite markedly elevated arterial concentrations (mean +/- standard error of the mean, 2.01 +/- 0.19 mmol.L-1), oleic acid, together with palmitic and linoleic acid, constituting 80% of the total plasma free fatty acid level. Insulin treatment (1 unit.kg bw-1.hr-1) prevented a further increase of the plasma free fatty acid level, observed concomitantly in the control group. Insulin affected all individual free fatty acids similarly. Changes in plasma free fatty acid levels occurring during the study and the corresponding myocardial uptake correlated (rS = 0.50 to 0.81). No significant uptake or release of glucose, lactate pyruvate, and glycerol occurred, whereas a myocardial release of alanine was seen. The heart and the concomitant leg uptake/release of glucose (rS = 0.40, p less than 0.05) and lactate (rS = 0.67, p less than 0.01) correlated. A substantial uptake of glucose was achieved and a more positive myocardial balance was obtained for alanine, lactate, and pyruvate with insulin. The changes in heart and the concomitant leg uptake/release correlated (glucose, rS = 0.62, p less than 0.01; lactate, rS = 0.64, p less than 0.01; pyruvate, rS = 0.71, p less than 0.01). It is concluded that the myocardial uptake of substrates during the first hours after coronary surgery is markedly abnormal with no uptake of free fatty acids or carbohydrates. These changes can be explained to some extent by the insulin resistance of trauma metabolism and can be modified by insulin treatment.

Adult↗