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Biomedical subjects

S Steen

Publications and source records attributed to S Steen.

At least 19 recordsLinked to original sources
PubMed2006

Levosimendan cardioprotection reduces the metabolic response during temporary regional coronary occlusion in an open chest pig model.

BACKGROUND: Inotropic and myocardial anti-ischemic effects have been demonstrated with levosimendan. The comparison of levosimendan started before an ischemia-reperfusion event as compared with levosimendan started during ischemia has not been studied. METHODS: In anesthetized pigs, a major branch of the circumflex artery was completely occluded for 30 min and then reperfused. The metabolism in the ischemic myocardium and in non-ischemic control myocardium was studied with microdialysis concomitantly with monitoring of global hemodynamics and coronary artery flow in the chosen artery. In the protection group (PRO, n= 6), a levosimendan infusion was started 30 min before coronary artery occlusion, and in the treatment group (TRE, n= 6), a levosimendan infusion was started 10 min after the coronary artery occlusion with a loading dose of 13.3 microg/kg followed by an infusion of 0.67 microg/kg/min. A two-way repeated measures ANOVA completed with Bonferroni's multiple comparison procedure was applied to the data. A P < 0.05 was considered significant. RESULTS: During the ischemic period, the cardiac output and contractility (dp/dt(max)) were higher in the PRO as compared with the TRE and the systemic vascular resistance was lower. The myocardial microdialysate glucose concentration in the ischemic area during ischemia was higher in the PRO as compared with the TRE, and the lactate/pyruvate ratio and the lactate concentration were lower. The differences in the metabolites persisted into the first 10 min of reperfusion. No differences were found for the non-ischemic areas. CONCLUSION: Levosimendan used throughout myocardial ischemia-reperfusion might have a cardioprotective affect on the response to myocardial ischemia as compared with levosimendan started during the ischemia.

Animals↗
PubMed2006

Myocardial glycerol release, arrhythmias and hemodynamic instability during regional ischemia-reperfusion in an open chest pig model.

BACKGROUND: To develop cardioprotection against peri-operative myocardial ischemia-reperfusion injury, we need animal models where the local metabolism and blood flow are studied concomitantly with the global circulatory consequences during regional coronary occlusion. METHODS: In six anesthetized domestic pigs, the largest branch of the circumflex artery was occluded for 30 min. Microdialysate was sampled from the ischemic and non-ischemic myocardium along with continuous measurements of local coronary artery flow, global hemodynamics and registration of arrhythmias, from baseline through to 30 min of ischemia and 180 min of reperfusion. RESULTS: During ischemia, the microdialysate glucose concentration decreased, the glycerol concentration increased and the lactate/pyruvate ratio increased significantly. For glycerol, there was a further increase at reperfusion. During ischemia, cardiac output was unchanged; however, during reperfusion there was a significant drop lasting for several minutes, longer than the period in which an increased number of arrhythmias were registered. CONCLUSION: The present study demonstrates deranged circulation and arrhythmias corresponding to ischemic metabolism after regional myocardial ischemia and reperfusion. Reperfusion induced more pronounced circulatory changes than the actual ischemia. A substantial increase in myocardial glycerol release seems to be a marker of ischemic metabolism and may prove to be an indicator of reperfusion injury.

Animals↗
PubMed2005

The negative inotropic effect of esmolol on isolated cardiac muscle.

OBJECTIVE: Esmolol is an ultra-short-term acting beta adrenergic blocker for intravenous use. The most common side effect is hypotension, which is often manageable by careful titration of the dose. We speculated whether esmolol had a direct negative inotropic effect on the cardiac muscle. DESIGN: Papillary muscles and trabeculae were excised from guinea pig and pig hearts. Force production was recorded together with action potentials. Membrane currents were recorded in isolated myocytes. The effects of two concentrations of esmolol were tested (55 and 110 micromol/L). RESULTS: Esmolol reduced action potential duration and plateau voltage, and decreased force production of isolated cardiac muscle. Voltage-clamp experiments from a holding potential of -40 mV and a step change to 0 mV showed a reduction in the inward current due to esmolol. CONCLUSION: Apart from being a beta adrenergic blocker esmolol also exerts a direct negative inotropic effect on cardiac muscle due to its inhibition of the calcium current during the action potential.

Adrenergic beta-Antagonists↗
PubMed2004

Disastrous physiological effects of saline on the cell membrane demonstrated in cardiac cells.

OBJECTIVE: Saline is not an ideal storage solution. It has a low pH, no buffering capacity, and lacks other ions and nutrients. The objective was to explore the effects of storing cardiac muscle in saline. DESIGN: Guinea pig papillary muscles and ventricular myocytes were exposed to saline. The effects on action potential, membrane current, contraction and cell shortening were recorded in vitro at 35-37 degrees C. RESULTS: Saline caused transient hyperpolarization of the resting potential (-140 mV), prolonged duration of the action potential, and increased contraction amplitude, which was later reversed. The membrane resting potential depolarized after a few minutes to about -15 mV and the preparations became unexcitable. The depolarized preparations remained slightly contracted. Upon reperfusion both papillary muscles and cells became unstable and spontaneously active. Storing myocytes in saline for only 2 h resulted in excessive cell death. CONCLUSION: Saline is disastrous for the function of the heart muscle and leads to depolarization, sustained contraction and unexcitable tissue. Saline should not be used as a storage medium, even for short periods of time.

Action Potentials↗
PubMed2001

Transplantation of lungs from a non-heart-beating donor.

BACKGROUND: In animals, we have previously done successful lung transplantations using organs from non-heart-beating donors. We have also developed an ex-vivo system of assessing the function of such organs before transplantation. The next stage was to try the technique in human beings. Bearing in mind the sensitive ethical issues involved, our first aim was to find out what procedures would be acceptable, and to use the results to guide a clinical lung transplantation from a non-heart-beating donor. METHODS: The ethical acceptability of the study was gauged from the results of a broad information programme directed at the general public in Sweden, and from discussions with professionals including doctors, nurses, hospital chaplains, and judges. The donor was a patient dying of acute myocardial infarction in a cardiac intensive-care unit after failed cardiopulmonary resuscitation. The next of kin gave permission to cool the lungs within the intact body, and intrapleural cooling was started 65 min after death. Blood samples were sent for virological testing and cross matching. The next of kin then had time to be alone with the deceased. After 3 h, the body was transported to the operating theatre and the heart-lung block removed. The lungs were assessed ex vivo, and the body was transported to the pathology department for necropsy. RESULTS: No contraindications to transplantation were found, and the right lung was transplanted successfully into a 54-year-old woman with chronic obstructive pulmonary disease. The donor lung showed excellent function only 5 min after reperfusion and ventilation, and during the first 5 months of follow-up, the function of the transplanted lung has been good. INTERPRETATION: About half the deaths in Sweden are caused by cardiac and cerebrovascular disease. This group could be a potential source of lung donors. When all hospitals and ambulance personnel in Sweden have received training in non-heart-beating lung donation, we hope that there will be enough donor lungs of good quality for all patients needing a lung transplant.

Cadaver↗
PubMed2001

Effects of dopamine on porcine myocardial action potentials and contractions at 37 degrees C and 32 degrees C.

BACKGROUND: Little information exists on the effects of drugs with cardiovascular action in hypothermia, and some findings have indicated paradoxic effects of dopamine in this setting. As we have not found any data on the electrophysiologic and contractile effects of dopamine on the heart in hypothermia, we decided to study this in pig myocardium, since pigs have a cardiovascular system more similar to that of humans than other animals. METHODS: Excised muscle strips from pig ventricular septum were mounted in an organ bath. After 45 min of equilibration at 37 degrees C or 32 degrees C, resting and action potentials, time to peak contraction and contractile force were recorded during pacing with a frequency of 60/min. Dopamine at 4 microM or 8 microM was added and new recordings were made after 15 min. RESULTS: Cooling to 32 degrees C caused a prolongation of contraction by 48% and the contractile force increased by 39%. The membrane action potential duration at 50% and 90% repolarization levels increased at 32 degrees C by 28% and 16% respectively. Dopamine significantly (P<0.05) increased the contractile force and membrane action potential duration at 50% and 90% repolarization levels both in normothermia and in hypothermia, whereas the duration of the contraction was not significantly changed. CONCLUSION: Cooling to 32 degrees C significantly prolongs the myocardial action potential and the contraction duration. Dopamine increases the contractile force and prolongs the action potential both at 37 degrees C and at 32 degrees C.

Action Potentials↗
PubMed2000

The effects of epinephrine/norepinephrine on end-tidal carbon dioxide concentration, coronary perfusion pressure and pulmonary arterial blood flow during cardiopulmonary resuscitation.

End-tidal CO2 concentration correlates with pulmonary blood flow during cardiopulmonary resuscitation and has been claimed to be a useful tool to judge the effectiveness of chest compression. A high concentration of end-tidal CO2 has been related to a better outcome. However, most authors have noticed a decrease in end-tidal CO2 concentration after administration of epinephrine, concomitant with an increase in coronary perfusion pressure and an increased incidence of return of spontaneous circulation. This study was performed to evaluate changes in end-tidal CO2 concentration after injection of vasopressors during cardiopulmonary resuscitation and to investigate the time-course of the response and possible explanations for it. After 1 min of electrically induced cardiac arrest and 5 min of chest compressions, 18 pigs were randomly assigned to receive 0.045 mg kg(-1) epinephrine, 0.045 mg kg(-1) norepinephrine or no drug. After another 4 min of chest compressions the pigs were defibrillated. End-tidal CO2, pulmonary blood flow and coronary perfusion pressure decreased immediately after the induction of cardiac arrest, increased slightly during chest compressions and increased initially to supernormal levels after the return of spontaneous circulation. Injection of epinephrine or norepinephrine during chest compressions decreased end-tidal CO2 51 +/- 2%, (mean +/- S.E.M.), and 43 +/- 1%, respectively, and pulmonary blood flow by 134 +/- 13 and 125 +/- 16%, respectively, within 1 min, simultaneously increasing coronary perfusion pressure from 10 +/- 2 to 45 +/- 5 mm Hg and from 11 +/- 1 to 38 +/- 5 mm Hg, respectively. The coronary perfusion pressure slowly fell, but the effects on end-tidal CO2 and pulmonary blood flow were prolonged. In conclusion, vasopressors increased coronary perfusion pressure and the likelihood of a return of spontaneous circulation, but decreased end-tidal CO2 concentration and induced a critical deterioration in cardiac output and thus oxygen delivery in this model of cardiopulmonary resuscitation.

Animals↗
PubMed2000

Bronchial healing, lung parenchymal histology, and blood gases one month after transplantation of lungs topically cooled for 2 hours in the non-heart-beating cadaver.

BACKGROUND: The aim of this study was to investigate, in an experimental survival model, the functional and morphologic results of lung transplantation using lungs from non-heart-beating donors. METHODS: Left lungs, topically cooled to 25 degrees C for 2 hours in situ after 5 minutes of circulatory arrest followed by 26 minutes of unsuccessful cardiopulmonary resuscitation, were transplanted into syngeneic rats. Five weeks after the transplantation, right pneumonectomy was performed and blood gases measured after 60 minutes. In a control group, fresh donor lungs were used for transplantation and comparison was made with the cadaver group and a group of normal rats after right pneumonectomy. Morphologic changes were evaluated by semiquantitative scoring of 13 different parameters to obtain a total histologic index for each rat. RESULTS: Computerized tomography scans of the chest made during the third post-operative week showed normal lung parenchyma in both groups, and at 5 weeks there were no significant differences in blood gases. The bronchial anastomoses showed normal healing in all cases. The histologic changes in the lung parenchyma were generally mild and focal, primarily consisting of interstitial and perivascular mononuclear inflammation, bronchial inflammation and athelectasis. Surprisingly, the transplanted controls demonstrated the most pronounced changes, although only the difference in total histologic index between groups was significant. CONCLUSIONS: Lungs from non-heart-beating donors, topically cooled in the cadaver for two hours after failed resuscitation, showed normal bronchial healing and favorable parenchymal histology compared to transplanted control lungs 5 weeks after transplantation.

Animals↗
PubMed2000

Platelet retention in coronary artery bypass surgery with and without a heart-lung machine. Cause of thrombosis in coronary artery bypass surgery.

The aim of this study was to examine platelet function after coronary artery bypass grafting (CABG) with and without the use of extracorporeal circulation (ECC). Sixteen male patients scheduled for CABG with (n = 8) and without (n = 8) ECC were included in the study. Platelet retention, as measured with a glass-bead retention test, was examined daily during the first postoperative week. Von Willebrand factor (vWF), ristocetin co-factor (Rcof) and prothrombin fragment (PF 1 + 2) were analyzed the day after the operation. We found a significant increase (p < 0.0001) in platelet retention during the first postoperative week after CABG. There was a tendency (not statistically significant) towards a more pronounced increase in the group operated on without ECC. This increase occurred despite the fact that all patients were treated with aspirin (75 mg daily) from the first postoperative day. The median time to maximal postoperative platelet retention was 2 days. In 3 patients platelet retention increased to more than 6 times the basal level.

Adult↗
PubMed2000

Spectromicroscopy of boron in human glioblastomas following administration of Na2B12H11SH.

Boron neutron capture therapy (BNCT) is an experimental, binary treatment for brain cancer which requires as the first step that tumor tissue is targeted with a boron-10 containing compound. Subsequent exposure to a thermal neutron flux results in destructive, short range nuclear reaction within 10 microm of the boron compound. The success of the therapy requires than the BNCT agents be well localized in tumor, rather than healthy tissue. The MEPHISTO spectromicroscope, which performs microchemical analysis by x-ray absorption near edge structure (XANES) spectroscopy from microscopic areas, has been used to study the distribution of trace quantities of boron in human brain cancer tissues surgically removed from patients first administered with the compound Na2B12H11SH (BSH). The interpretation of XANES spectra is complicated by interference from physiologically present sulfur and phosphorus, which contribute structure in the same energy range as boron. We addressed this problem with the present extensive set of spectra from S, B, and P in relevant compounds. We demonstrate that a linear combination of sulfate, phosphate and BSH XANES can be used to reproduce the spectra acquired on boron-treated human brain tumor tissues. We analyzed human glioblastoma tissue from two patients administered and one not administered with BSH. As well as weak signals attributed to BSH, x-ray absorption spectra acquired from tissue samples detected boron in a reduced chemical state with respect to boron in BSH. This chemical state was characterized by a sharp absorption peak at 188.3 eV. Complementary studies on BSH reference samples were not able to reproduce this chemical state of boron, indicating that it is not an artifact produced during sample preparation or x-ray exposure. These data demonstrate that the chemical state of BSH may be altered by in vivo metabolism.

Borohydrides↗
PubMed1999

Cardiovascular effects of induced hypothermia after lung transplantation.

BACKGROUND: Induced hypothermia may be used to reduce metabolism in acute respiratory failure. Hypothermia is accompanied by an increase in pulmonary vascular resistance, as also seen in the early period after lung transplantation. It was our concern that the combination of the two would lead to an increased workload on the right ventricle. METHODS: To test this hypothesis we induced hypothermia to 32 degrees C in two groups of pigs. In one group we performed left single-lung transplantation combined with right pulmectomy (TRANSP group); in the other group, only right pulmectomy was performed (PULMEC group). RESULTS: During hypothermia, there was a significant increase in both groups in pulmonary vascular resistance (TRANSP group, 77%, p<0.05; PULMEC group, 54%, p<0.05) and a significant decrease in cardiac output (TRANSP group, 41%, p<0.05; PULMEC group, 34% p<0.05). Mean pulmonary artery pressure was unchanged, and the work done by the right ventricle was reduced (TRANSP group, 39%, p<0.05; PULMEC group, 31%). CONCLUSIONS: Induced hypothermia to 32 degrees C after lung transplantation resulted in a significant decrease in the work done by the right ventricle despite a significant increase in pulmonary vascular resistance.

Animals↗
PubMed1999

Effects of cardioplegic flushing, storage, and reperfusion on coronary circulation in the pig.

BACKGROUND: The aim of the study was to investigate how flush-perfusion of the heart with cold cardioplegic solution, 2 or 12 hours of cold ischemic storage, and 24 hours of reperfusion affect coronary endothelial function and coronary vascular resistance. METHODS: Porcine coronary arterial endothelial and smooth muscle function was studied in organ baths. An adult porcine working heart model was used to investigate coronary vascular resistance after 24 hours of reperfusion. RESULTS: Flushing the heart with 1 L of St. Thomas' cardioplegic solution, using a perfusion pressure of 60 to 65 mm Hg, significantly reduced endothelium-dependent relaxation. Flushing followed by 12 hours of storage gravely impaired endothelium-dependent relaxation, and 24 hours of reperfusion worsened it still more. CONCLUSIONS: Flushing the heart with cold cardioplegic solution impairs endothelium-dependent relaxation, as does prolonged cold ischemic storage. Reperfusion of injured coronary endothelium may injure it still more. A correlation was found (p < 0.001) between high coronary vascular resistance and low endothelium-dependent relaxation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Gas exchange function one month after transplantation of lungs topically cooled for 2 hours in the non-heart-beating cadaver after failed resuscitation.

BACKGROUND: If lungs from subjects dying of heart attacks could be used for transplantation, the lung donor shortage could be radically reduced. The aim of this study was to investigate, in an experimental survival model, the results of lung transplantation using lungs from non-heart-beating donors. METHODS: The left lung, topically cooled to 25 degrees C for 2 hours in situ after 5 minutes of circulatory arrest and 26 minutes of unsuccessful cardiopulmonary resuscitation, was transplanted into a syngeneic rat. Five weeks after the transplantation, right pneumonectomy was performed and blood gases measured every 10 minutes for 1 hour. Comparison were made with two control groups, one where fresh donor lungs were transplanted and another where only right pneumonectomy was done. RESULTS: All animals survived and were in good condition at the end of the observation period. There was no statistically significant difference in arterial oxygen or carbon dioxide tension between the groups. The bronchial anastomoses showed normal healing in all cases. CONCLUSION: Lungs from non-heart-beating donors topically cooled in situ to 25 degrees C for 2 hours before being harvested showed excellent gas exchange and bronchial healing 5 weeks after transplantation.

Animals↗
PubMed1999

Vascular function in the cadaver up to six hours after cardiac arrest.

BACKGROUND: The aim of the study was to evaluate how well vascular function is retained in a cadaver kept in a room with a temperature of 21 degrees C. METHODS: The aorta and pulmonary artery of rats were investigated in organ baths as fresh controls and after 1, 2, 3, or 6 hours' storage in the cadaver. Six-hour-old cadaver aortas were transplanted and investigated after 24 hours and 60 days. RESULTS: After 3 hours' storage there was no significant decrease in smooth muscle contractile function in either aorta or pulmonary artery. After 6 hours' storage both the aorta and the pulmonary artery demonstrated a significant decrease in smooth muscle contractile function, 30% (p < 0.05) and 44% (p < 0.001), respectively, compared to fresh controls. Storing the aorta for 2 hours and the pulmonary artery for 6 hours caused no significant decrease in endothelium-dependent relaxing function. In aorta segments investigated after 3 and 6 hours there was a significant decrease in endothelium-dependent relaxation, 12% (p < 0.05) and 29% (p < 0.001), respectively. Six-hour-old cadaver aortas transplanted and investigated after 24 hours or 60 days demonstrated no significant changes in endothelium-dependent relaxation and smooth muscle function compared to fresh controls. CONCLUSION: The pulmonary artery can tolerate 3 hours of warm ischemia in the nonheart-beating cadaver without loss of endothelium-dependent relaxation and smooth muscle function. The dysfunction seen in 6-hour-old cadaver aortas was normalized after transplantation and 24 hours of reperfusion.

Animals↗
PubMed1999

Effects of dopamine in lung-transplanted pigs at 32 degrees C.

BACKGROUND: We have used hypothermia successfully in patients with acute respiratory failure after lung transplantation. However, we have observed that dopamine may cause a substantial decrease in mean arterial pressure (MAP) in hypothermic subjects. Furthermore, a dopamine-induced increase in pulmonary vascular resistance (PVR) has been reported in the literature, and this could aggravate the increase in PVR which is often seen both in the early postoperative phase after lung transplantation, and during hypothermia. We thus hypothesized that dopamine would decrease MAP and increase PVR in hypothermic lung-transplanted subjects. METHODS: Left single lung transplantation combined with right pneumonectomy was performed in 6 pigs anesthetized with ketamine and midazolam and muscle relaxed with pancuronium. After an observation period of 24 h, the effect of dopamine infused at 5 and 12 microg x kg(-1) x min(-1) was studied in normothermia (38 degrees C) and after cooling by cold-water immersion to 32 degrees C. RESULTS: Systemic vascular resistance index (SVRI) increased and cardiac index (CI) decreased in hypothermia. Dopamine decreased SVRI and increased CI, both in normothermia and at 32 degrees C. MAP decreased during infusion of dopamine in hypothermia. Dopamine had no effect on the pulmonary vascular resistance index (PVRI). CONCLUSION: The results suggest that dopamine may be used to increase cardiac output after lung transplantation in moderate hypothermia as well as in normothermia, but one should be aware that dopamine may cause a substantial decrease in blood pressure, depending on the prevailing hemodynamic conditions at the start of its administration.

Animals↗
PubMed1999

Molecular characterization and human T-cell responses to a member of a novel Mycobacterium tuberculosis mtb39 gene family.

We have used expression screening of a genomic Mycobacterium tuberculosis library with tuberculosis (TB) patient sera to identify novel genes that may be used diagnostically or in the development of a TB vaccine. Using this strategy, we have cloned a novel gene, termed mtb39a, that encodes a 39-kDa protein. Molecular characterization revealed that mtb39a is a member of a family of three highly related genes that are conserved among strains of M. tuberculosis and Mycobacterium bovis BCG but not in other mycobacterial species tested. Immunoblot analysis demonstrated the presence of Mtb39A in M. tuberculosis lysate but not in culture filtrate proteins (CFP), indicating that it is not a secreted antigen. This conclusion is strengthened by the observation that a human T-cell clone specific for purified recombinant Mtb39A protein recognized autologous dendritic cells infected with TB or pulsed with purified protein derivative (PPD) but did not respond to M. tuberculosis CFP. Purified recombinant Mtb39A elicited strong T-cell proliferative and gamma interferon responses in peripheral blood mononuclear cells from 9 of 12 PPD-positive individuals tested, and overlapping peptides were used to identify a minimum of 10 distinct T-cell epitopes. Additionally, mice immunized with mtb39a DNA have shown increased protection from M. tuberculosis challenge, as indicated by a reduction of bacterial load. The human T-cell responses and initial animal studies provide support for further evaluation of this antigen as a possible component of a subunit vaccine for M.tuberculosis.

Adolescent↗
PubMed1998

Induced hypothermia in critical respiratory failure after lung transplantation.

Primary graft failure after lung transplantation is a serious complication with high mortality. We present 2 cases of critical respiratory failure after lung transplantation treated with surface cooling to 32 degrees and 35 degrees C, respectively, as an adjunct to conventional intensive care. Both patients were discharged from the hospital in good clinical condition. Surface cooling may be an effective mode of treatment in patients with critical respiratory failure after lung transplantation and should be considered before extracorporeal membrane oxygenation treatment is initiated.

Adult↗