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Biomedical subjects

J P Rasmussen

Publications and source records attributed to J P Rasmussen.

At least 19 recordsLinked to original sources

Thermodilution cardiac output. Cold vs room temperature injectate and the importance of measuring the injectate temperature in the right atrium.

BACKGROUND: The feasibility of thermodilution cardiac output measurements with the more convenient room temperature thermal indicator instead of cold injectates has been repeatedly investigated. However, the issue has not been addressed with the appropriate statistical approach advocated by Altman and Bland. Furthermore, we wished to determine if the incorporation of a second thermistor in the thermodilution catheter, to measure the temperature of the thermal indicator where it is delivered into the right atrium/superior caval vein, would result in more precise cardiac output measurements. METHODS: Fifty patients were randomized to receive a single or dual thermistor pulmonary artery thermodilution catheter. Cardiac output was calculated as the average of four injections of 10 ml of isotonic saline. Precision (2 x SD of differences in replicate measurements) for the two catheters and injectate temperatures, and bias and limits of agreement between measurements, with cold and room temperature injectates, were determined. RESULTS: Precision was (0 degrees C) 0.42 l/min and (20 degrees C) 0.90 l/min, and bias and limits of agreement -0.83 l/min and -1.93-0.27 l/min for the single thermistor catheter. For the dual thermistor system precision was (0 degrees C) 0.34 l/min and (20 degrees C) 0.58 l/min. Bias and limits of agreement were -0.03 l/min and -0.61-0.55 l/min. CONCLUSION: The second thermistor is redundant if cold injectates are used. If one wishes to use room temperature injectates the single thermistor system is inadequate. A dual thermistor catheter is, on the other hand, acceptable.

Adult↗

Recombination at his-3 in Neurospora declines exponentially with distance from the initiator, cog.

By deletion of 1.8 kb of sequence between cog(L) and his-3 and replacement with sequences of different lengths, we have generated a set of Neurospora strains in which the distance between cog(L) and the site at which recombination is selected varies from 1.7 to nearly 6 kb. Each of the manipulated strains includes cog(L), a highly active recombination hotspot, and rec-2, thus allowing high-frequency recombination. In addition, each is a his-3 mutant, either K26 or K480. The frequency of His(+) recombinants in progeny of these crosses is inversely proportional to the distance between his-3 and cog. Specifically, there is a linear relationship between log(10) (recombination frequency) and the distance in base pairs, indicating that as distance decreases, the rate of interallelic recombination increases exponentially. An exponential relationship between distance separating markers and the chance of co-conversion has been found in both Drosophila and fission yeast, indicating that the extension of recombination events may be a stochastic process in most organisms. On the basis of these and additional data presented in this article, we conclude that recombination is initiated at cog(L) in >17% of meioses, that most conversion tracts are very short, and that few extend >14 kb.

Hydro-Lyases↗

Recombination events in Neurospora crassa may cross a translocation breakpoint by a template-switching mechanism.

To assist investigation of the effect of sequence heterology on recombination in Neurospora crassa, we inserted the Herpes simplex thymidine kinase gene (TK) as an unselected marker on linkage group I, giving a gene order of Cen-his-3-TK-cog-lpl. We show here that in crosses heterozygous for TK, conversion of a his-3 allele on one homolog is accompanied by transfer of the heterologous sequence between cog and his-3 from the other homolog, indicating that recombination is initiated centromere-distal of TK. We have identified a 10-nucleotide motif in the cog region that, although unlikely to be sufficient for hotspot activity, is required for high-frequency recombination and, because conversion of silent sequence markers declines on either side, may be the recombination initiation site. Additionally, we have mapped conversion tracts in His(+) progeny of a translocation heterozygote, in which the translocation breakpoint separates cog from the 5' end of his-3. We present molecular evidence of recombination on both sides of the breakpoint. Because recombination is initiated close to cog and the event must therefore cross the translocation breakpoint, we suggest that template switching occurs in some recombination events, with repair synthesis alternating between use of the homolog and the initiating chromatid as template.

Base Sequence↗

Effects of glutamine on the immune system: influence of muscular exercise and HIV infection.

Glutamine increased the proliferative response and the lymphokine-activated killer cell activity of blood mononuclear cells isolated from normal healthy subjects (n = 6) in a dose-dependent manner, with optimum at 0.3-1.0 mM. The relative fraction of CD3+, CD4+, CD8+, CD14+, CD16+, and CD19+ cells was not changed by glutamine at a concentration of 0.6 mM, except in the phytohemagglutinin-stimulated proliferation experiment where the fraction of CD4+, and therefore CD3+ cells, increased. The natural killer cell activity was not influenced by glutamine. Human immunodeficiency virus (HIV)-seropositive subjects (n = 8) who performed concentric bicycle exercise for 1 h at 75% of maximal O2 consumption had an overall lower phytohemagglutinin-stimulated proliferative response, compared with the HIV-seronegative control group (n = 7). The proliferation during exercise was lower in both the HIV-seropositive and the HIV-seronegative group. Addition of glutamine in vitro did not normalize the lower proliferation in the HIV-seropositive group or the attenuated proliferation seen during exercise in both groups.

Adult↗

Ventilation in ARDS and asthma: the optimal blood gas values.

Artificial ventilation of patients with acute respiratory diseases, i.e. ARDS and severe asthma, may involve the risk of pulmonary oxygen toxicity as well as volutrauma. The relationship between ventilator treatment and volutrauma suggests that only in patients with normal lungs the aim of ventilator treatment should be an arterial carbon dioxide tension and pH within the normal ranges. In patients suffering from a lung disease the clinical target must be based not only upon the arterial blood gases but also upon airway pressure and respiratory tidal volume. Thus during artificial ventilation of a patient with an acute pulmonary disease the following arterial pH and pCO2 optima are proposed: pH 7.35, with a range from 7.1 to 7.4; pCO2 is related to pH but an acceptable range is 5-12 kPa. The lowest acceptable fraction of inspired oxygen and thereby the safe lower level of arterial pO2 for an individual patient depends on many factors. The lower limit may be about 3 kPa, but the arterial pO2 should not be evaluated as an isolated parameter. It is related to the general oxygen transport capability of arterial blood, extractable oxygen, cardiac output and the microcirculation.

Asthma↗

Effect of methylprednisolone on endotoxemia and complement activation during cardiac surgery.

The influence of high doses of methylprednisolone on complement activation and endotoxin concentration was investigated in two groups of eight patients undergoing coronary artery bypass grafting. Group 1 received methylprednisolone, 30 mg/kg, at the induction of anesthesia; group 2 served as the control group. The endotoxin concentrations increased significantly in both groups at the start of cardiopulmonary bypass. During cardiopulmonary bypass, the endotoxin concentrations were significantly higher in the steroid group compared with the control group (p less than 0.01). After completion of surgery, the endotoxin concentrations declined to almost zero within seven days in both groups. Complement activation was significantly reduced in the steroid-treated group during cardiopulmonary bypass compared with the control group (P less than 0.01). The clinical outcome after the first postoperative week was the same in the two groups. It appears that high-dose steroids can reduce complement activation during cardiopulmonary bypass, although the clearance of endotoxins may also be reduced.

Aged↗

Endotoxemia and enhanced generation of oxygen radicals by neutrophils from patients undergoing cardiopulmonary bypass.

Plasma endotoxin concentrations and oxidative burst response of peripheral blood polymorphonuclear leukocytes were examined in 12 patients undergoing coronary artery bypass. The measurements were made just before the operation, 5 minutes after removal of the aortic crossclamp, and 24 hours after the operation. Endotoxin was quantitated by a combination of a sensitive Limulus amebocyte lysate assay and rocket immunoelectrophoresis measuring picogram amounts of endotoxin. Peripheral blood neutrophils were purified by a two-step dextran sedimentation and metrizoate sodium Ficoll (Lymphoprep., Nyegaard, Oslo, Norway) centrifugation. The oxidative burst response of these cells was measured for their ability to generate superoxide anion and was determined by a cytochrome c reduction assay. Preoperatively, all the plasma samples except one were free of endotoxin. The endotoxin levels reached 100 pg/ml 5 minutes after removal of the aortic crossclamp, and except in one sample they had decreased 24 hours after the operation. Studies on the generation of superoxide by neutrophils showed a decline in the response 5 minutes after removal of the aortic crossclamp and an enhancement of the response to f-Met-Leu-Phe by cells obtained from 11 of 12 patients 24 hours postoperatively. In vitro addition of bacterial lipopolysaccharide to blood from healthy individuals also enhanced the superoxide response of the neutrophils. We conclude that during cardiopulmonary bypass the circulating blood is contaminated by endotoxin and the neutrophils are primed for enhanced generation of oxygen radicals. The released oxygen radicals may be involved in the tissue damage observed in these patients.

Aged↗

Presence of circulating endotoxins during cardiac operations.

Ten patients having coronary artery bypass grafting were intraoperatively and postoperatively analyzed for endotoxins with the Limulus amoebocyte lysate test. A new highly sensitive rocket immunoelectrophoretic assay for reading the reactions of endotoxins with Limulus amoebocyte lysate was used. Preoperatively, all blood samples from the patients had negative Limulus amoebocyte lysate tests, negative blood cultures, normal total white cell counts, and were clinically without signs of infection. Intraoperatively, a substantial amount of endotoxins were found in samples from the extracorporeal circuit, the pulmonary artery, and the cardiac suction lines, which persisted during the cardiopulmonary bypass. The endotoxin content decreased significantly (p less than 0.05) 6 hours after cardiopulmonary bypass and further decreased within the seventh postoperative day (p less than 0.01). A positive Limulus amoebocyte lysate test was also found in some of the fluids administered during the operation, that is, the cardioplegic fluids, the priming fluids for the extracorporeal circuit, the blood transfusions, and the ice for local cooling. Postoperatively, all patients had rectal temperatures below 38.5 degrees C, but no correlation was found between the magnitude of endotoxin content and the degree of fever. Only one of the patients had positive blood cultures. Despite the measured endotoxin content, no intraoperative or postoperative complications were found.

Aged↗

Fiber-optic chemical sensors (Gas-Stat) for blood gas monitoring during hypothermic extracorporeal circulation.

Measurements of pO2, pCO2 and pH by optical fluorescence microsensing technology has recently become available for monitoring blood gases during extracorporeal circulation ECC). We have compared simultaneous measurements with fiber-optic sensors (Gas-Stat, Bentley) and electrochemical sensors (ABL-4, Radiometer) on discrete samples. In 10 patients undergoing coronary artery bypass grafting during hypothermic (25 degrees C) ECC and hemodilution (hemoglobin concentration 4 mmol.l-1) arterial and venous pO2, pCO2 and pH were measured in-line in the extracorporeal circuit at the actual blood temperature. Simultaneous and anaerobically collected blood samples in glass syringes were analyzed within five minutes at 37 degrees C in the ABL-4. Linear regression analysis of the values at actual temperature shows the following equations: Gas-Stat = Y, ABL-4 = X: pO2 (kPa): Y = 1.04 X + 0.5 r = 0.95 n = 136; pCO2 (kPa): Y = 0.71 X + 1.5 r = 0.79 n = 136; pH: Y = 0.788 X + 1.590 r = 0.76 n = 136. The advantage of the Gas-Stat is continuous monitoring of blood gas parameters during ECC. The present study shows that measurements of pO2, pCO2 and pH with fiber-optic chemical sensors may be reliable. The differences between the two principles of measurement may be due to unknown factors interfering with the in-line measurements or to variations in sensitivity and stability of the individual sensor.

Blood Gas Analysis↗

PEEP reverses nitroglycerin-induced hypoxemia following coronary artery bypass surgery.

Intravenous nitroglycerin is increasingly used during and after cardiac surgery to control blood pressure and improve subendocardial and peripheral circulation. A dramatic decrease in arterial oxygenation has, however, been reported in a number of poorly controlled clinical trials. In the present investigation 16 patients were studied 2-4 h after coronary artery bypass procedures. All were treated with a continuous infusion of nitroglycerin (1 microgram X kg-1 X min-1). Utilizing an on-off-on drug design, it was clearly established that nitroglycerin depresses arterial oxygenation by increasing the pulmonary venous admixture. Three possible underlying mechanisms are discussed, but at the present time no firm conclusion can be drawn as to the nature of the changes. Eight patients were ventilated with 1 kPa (10 cmH2O) positive end-expiratory pressure (PEEP) during the nitroglycerin infusion. PEEP-ventilation reversed nitroglycerin-induced changes in arterial oxygenation and pulmonary shunting without adversely affecting hemodynamic stability.

Coronary Artery Bypass↗

Hemodynamic effects of alfentanil in verapamil-treated dogs.

The hemodynamic effects of alfentanil were investigated in six dogs receiving verapamil 0.5 mg X kg-1 and six dogs receiving saline in equal volume. Basic measurements were done after 30 min and the dogs were then given alfentanil 160 micrograms X kg-1 with measurements at 5, 15, and 30 min. Significant increases in central venous pressure (CVP), mean pulmonary arterial pressure and pulmonary wedge pressure (PWP) were found 30 min after verapamil. After verapamil-alfentanil, increases were seen in CVP and PWP at 5 and 15 min and in PWP at 30 min. Mean arterial pressure and cardiac index were unchanged, while a decrease in heart rate was fully compensated by an increase in stroke volume. Indices of contractility were unchanged. All values were within the limits of normal hemodynamic function. We conclude that high-dose alfentanil has no adverse effects on hemodynamic parameters during calcium blockade.

Alfentanil↗

Alfentanil and skeletal muscle circulation, oxygen consumption and P50.

The preservation of blood flow to skeletal muscles has low priority in the intact organism. If cardiovascular function is disturbed, for example by anesthetic drugs, skeletal muscle circulation diminishes or stops. Skeletal muscle surface pH (m-pH) is a sensitive indicator of muscle cell oxygenation and a fall in m-pH therefore provides an early warning of deterioration in overall cardiovascular performance. In the present study we investigated the peripheral effects of a new short-acting fentanyl derivative, alfentanil. Twelve dogs were anesthetized with a bolus injection of alfentanil 0.16 mg . kg-1 i.v. M-pH was recorded continuously, while total body oxygen consumption, oxygen transport and P50 were calculated. No changes were found. In the second part of the study, we pretreated six of the dogs with the "calcium antagonist" verapamil 0.5 mg X kg-1, while the other six dogs served as controls. After a rechallenge dose of alfentanil, we again found the peripheral perfusion sufficient to meet the oxygen demand of the muscles. Side-effects to alfentanil were a decrease in Pao2, due to an increase in pulmonary shunting of venous blood, and an increase in PaCO2. The changes in pulmonary ventilation-perfusion relationships were, however, not of a magnitude that should cause concern when alfentanil is used in normal subjects.

Adjuvants, Anesthesia↗

Nitroglycerin for ergotism. Experimental studies in vitro and in migraine patients and treatment of an overt case.

Ergotamine was used to induce arterial contraction in vitro (measurement of isometric tension in segments from 3 human temporal arteries) and in vivo (peripheral systolic blood pressure measured by strain gauge plethysmography in 5 migrainous patients). In both these models of ergotism, the directly acting vasodilator nitroglycerine (NTG) effectively relieved the ergotamine-induced arterial contractions. A case of ergotism treated successfully with NTG infusion is reported. The diagnosis was based on history and measurement of peripheral systolic blood pressure by strain gauge plethysmography. The latter technique was also used to monitor the response to treatment for 20 h. Blood levels of ergotamine during ergotism were in the therapeutic range. Possible explanations for this finding are discussed.

Adult↗

Skeletal muscle circulation during sufentanyl and morphine anesthesia in propranolol treated dogs.

Sufentanyl is a new, potent, short-acting, fentanyl-like morphinomimetic. In the present study we compared the effects of high doses of sufentanyl and morphine on the peripheral circulation in beta-blocked dogs. Skeletal muscle surface pH (m-pH) was recorded continuously as an index of the microcirculation. Sufentanyl (0.01 mg/kg) had no adverse effects on the peripheral perfusion. Morphine (4 mg/kg) caused a severe and rapid fall in m-pH from 7.34 to 7.14 during the 30-min experimental period. At the same time calculated blood volume decreased by 20%. This hypovolemic deterioration of the circulation was probably caused by a histamine-mediated increase in capillary pressure and filtration of plasma from the intravascular space to the interstitial space. As sufentanyl could be safely administered to beta-blocked dogs, we recommend human studies. On the other hand, we discourage the use of high-dose morphine anesthesia until human studies have proved that the collapse of the peripheral perfusion seen in this study is species specific.

Adrenergic beta-Antagonists↗

Early response in central hemodynamics to high doses of sufentanil or morphine in dogs.

The hemodynamic effects of high doses of sufentanil, a newly synthetized highly potent analgesic, were investigated in dogs. This study compared the early (30 min) cardiovascular effects of sufentanil 0.01 mg . kg-1 and morphine 4 mg . kg-1. Sufentanil caused a moderate and insignificant decrease in mean arterial pressure (MAP). A 30% decrease in cardiac index (CI) was almost outbalanced by an increased systemic vascular resistance (SVRI). The lowering of CI was due to a more than 50% decrease in heart rate (HR) which was partly compensated for by a greater stroke volume index (SVI). In the first 5 min after morphine injection, MAP fell significantly to about 50 mmHg (below 50% of the control value). CI was reduced to about 50% of the control value because of significant decreases in both SVI and HR. The calculated SVRI was unchanged after morphine. Within 30 min some of the initially changed parameters had returned to control levels. Central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) increased immediately after sufentanil, but decreased after morphine. With time, both parameters returned towards control values. Peak left ventricular dP/dt decreased by about 25-50% after both analgesics. The rate-pressure products (RPP) were significantly decreased to less than one half of the control values after both analgesics. Mixed venous oxygen tension (PVO2), oxygen transport and oxygen consumption were significantly lowered in the sufentanil group, whereas immediate decreases after morphine were followed by gradual increases towards control values. We conclude that the use of high doses of sufentanil in dogs is safe. Apart from initial, transient changes, a stable cardiovascular state characterizes the high-dose sufentanil anesthesia, while morphine causes fluctuations in several hemodynamic parameters. Compared to morphine anesthesia, sufentanil anesthesia appears to be an attractive alternative which deserves further evaluation in humans.

Analgesics, Opioid↗

High-dose analgesic anesthesia with morphine or sufentanil in propranolol-treated dogs.

In propranolol-pretreated dogs (2 mg . kg -1) the immediate cardiovascular effects of sufentanil (0.01 mg . kg -1) or morphine (4 mg . kg -1) were compared. Besides a 40% decrease in cardiac index (CI), sufentanil and morphine initiated quite different hemodynamic changes. Sufentanil did not significantly change mean arterial pressure (MAP), central venous pressure (CVP) and mean pulmonary artery pressure (MPAP), while the pulmonary capillary wedge pressure (PCWP) increased by 50%. After morphine, MAP declined significantly by about 65%, and significant decreases in MPAP (14%) and PCWP (33%) were also observed. Propranolol reduced heart rate by 16%, and morphine caused no further reduction in HR. A significant decrease of about 30% was seen in HR after sufentanil. Sufentanil significantly raised systemic vascular resistance index (SVRI) by 15%, whereas morphine decreased it by 32%. Pulmonary vascular resistance index (PVRI) was unchanged after sufentanil, but significantly increased after morphine. Right ventricular stroke work index (RVSWI) was unaffected by both analgesics, and morphine decreased left ventricular work index (LVSWI) significantly by 80%. Oxygen transport index declined significantly after both analgesics. Sufentanil reduced oxygen consumption by 20%, while morphine left this parameter unaffected. We conclude that the administration of high-dose sufentanil leads to a stable circulation, even when a total beta-blockade exists.

Analgesics, Opioid↗

Thiopentone-nitrous oxide-halothane anaesthesia and suxamethonium: pretreatment with pancuronium and gallamine.

Eighty healthy adult patients randomly allocated to four groups received pancuronium 0.01, 0.015, 0.02 mg kg-1 or gallamine 0.3 mg kg-1 i.v. 3 min before induction. Just before induction of anaesthesia, the patients were examined for signs and symptoms of neuromuscular blockade. After induction of anaesthesia with thiopentone, suxamethonium 1.5 mg kg-1 was administered i.v. Five minutes later the second dose was injected. No serious arrhythmia was seen in any of the four groups following the repeated dose of suxamethonium. However, the highest dose of pancuronium (0.02 mg kg-1) caused an unacceptably high frequency of partial neuromuscular blockade.

Adolescent↗