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Biomedical subjects

S Steen

Publications and source records attributed to S Steen.

At least 37 records · Page 2Linked to original sources
PubMed1998

HeartMate left ventricular assist device as bridge to heart transplantation.

BACKGROUND: Because of the limited supply of donor hearts, prospective recipients continue to die while on the waiting list for heart transplantation. Use of long-term mechanical circulatory support devices as a bridge to transplantation may reduce this mortality. However, with the present state of technology, continued clinical evaluation of the various long-term, mechanical circulatory support devices available is mandatory. METHODS: Sixteen patients were bridged with the HeartMate left ventricular assist device (LVAD) to heart transplantation for New York Heart Association functional class IV cardiac failure. Twelve pneumatic and six electric devices were used. The mean cardiac index and the mean pulmonary vascular resistance of the patient cohort were 1.71 x min(-1) x m(-2) and 3.1 Wood units, respectively. RESULTS: The mean LVAD support time per transplanted patient was 237 days, with a cumulative LVAD support time of about 7.2 years. Bleeding was the main operative and postoperative complication. Two patients suffered from neurologic complications and there were two major incidents of device malfunction. Twelve patients (75%) now have received a transplant, 3 (19%) are awaiting a transplant, and in 1 patient (6%), the device was explanted after spontaneous left ventricular recovery. Eleven of the 12 patients who received a transplant are alive and doing well. The HeartMate LVAD gave adequate circulatory support over extended periods of time and reversed the vital organ dysfunction. Since the start of the LVAD program, only 1 patient has died on our heart transplantation waiting list, compared to nine deaths in the 2 preceding years. CONCLUSIONS: The HeartMate LVAD bridge to heart transplantation can be performed with low post-LVAD implantation and posttransplantation mortality and offers 1- and 2-year posttransplantation actuarial survival rates comparable to those for nonbridged heart transplant recipients.

Actuarial Analysis↗
PubMed1998

Function of adult pig hearts after 2 and 12 hours of cold cardioplegic preservation.

BACKGROUND: Most cardioplegic solutions have been developed using the classic Langendorf heart perfusion model, which only allows a short experimental follow-up. Our aim was to investigate hearts after prolonged storage by using a physiologic model including prolonged perfusion with normal, fresh blood. METHODS: Sixteen hearts from 60-kg pigs were preserved with dextran-enriched (dextran-40, 35 g/L) St. Thomas' solution for 2 or 12 hours after which they were continuously reperfused for 12 hours with normal blood, supplied by a support pig. A flexible balloon, fixed to an artificial valve apparatus connected to a circuit system, was inserted in the left ventricle for obtaining measurements of hemodynamic performance. RESULTS: During the first 3 to 4 hours of reperfusion there was no significant difference in left ventricular developed pressure, cardiac output, minute work output, or oxygen consumption between the two groups. After this time left ventricular developed pressure (p < 0.001), cardiac output (p < 0.01), minute work output (p < 0.01), and oxygen consumption were significantly lower in the 12-hour group. Coronary flow was higher (p < 0.01) and coronary vascular resistance lower (p < 0.01) during the first 5 to 6 hours of reperfusion in the 12-hour group. After 12 hours of reperfusion coronary vascular resistance was significantly higher (p < 0.01) in the 12-hour group. CONCLUSIONS: High-degree and long-lasting coronary hyperemia at the beginning of reperfusion can be a sign of unsatisfactory preservation of the heart. This investigation shows the importance of reperfusion with normal blood and a long follow-up period after postischemic reperfusion when studying the effect of cardioplegic solutions.

Animals↗
PubMed1998

Lung transplantation at the University of Lund 1990-1995. Analysis of the first 39 consecutive patients.

Between 1990 and 1995 39 patients were lung transplanted at the University Hospital in Lund. This is a retrospective review of survival and lung function in these patients. There were 17 single-lung transplants (SLT), 21 double-lung transplants (DLT) and 1 heart-lung transplant (HLT). Seven patients died during the period, giving an overall survival of 82%. One-year survival according to Kaplan-Meier survival analysis was 87%, and 2-year survival was 83%. Vital capacity and forced expiratory volume in 1 s (FEV1) 1 year after transplantation were 91% and 100% of predicted, respectively, in the DLT group and 60% and 50% in the SLT group. Bronchiolitis obliterans syndrome (BOS) developed in 11 of the 35 patients (31%) surviving more than 6 months, 2/21 in the DLT group and 8/13 in the SLT group and in the patient with HLT. The median time until detection of BOS was 11 months after the operation (range 6-18 months). Working capacity 1 year after transplantation was 60% of predicted in the DLT group and 47% of predicted in the SLT group. Ventilatory capacity was no longer function limiting. Lung transplantation today is a therapeutic option with a good medium-term survival and good functional results in selected patients with severe lung disease.

Adolescent↗
PubMed1997

Addition of calcium to Euro-Collins solution is essential for 24-hour preservation of the vasculature.

BACKGROUND: Genuine Euro-Collins solution is calcium free. The aim of this study was to investigate whether the addition of calcium would improve its capacity to preserve the vasculature. METHODS: The infrarenal aorta of Sprague-Dawley rats was investigated in organ baths: as fresh controls, after 24 hours of cold (4 degrees C) storage in Euro-Collins solution, or in Euro-Collins solution with the addition of calcium in amounts ranging from 0.05 to 1.5 mmol/L. The thromboxane analogue U-46619 was used to investigate contractility. Endothelium-dependent relaxation was tested by cumulative addition of acetylcholine. Papaverine was used to elicit endothelium-independent relaxation. Investigation by transmission electron microscopy was also performed. RESULTS: Storage of rat aorta for 24 hours in genuine Euro-Collins solution almost abolished smooth muscle function, and severe edema was found in the endothelial cells. However, if calcium was added, the rat aorta could be stored for 24 hours without affecting smooth muscle function, and endothelium-dependent relaxation was only slightly reduced. Furthermore, only slight edema could be demonstrated in the endothelial cells. CONCLUSIONS: If calcium is added to Euro-Collins solution in amounts ranging from 0.4 to 1.5 mmol/L, it allows good preservation of rat aorta for 24 hours. Without calcium, this solution destroys both the function and morphology of the vessels.

Animals↗
PubMed1997

Successful transplantation of lungs topically cooled in the non-heart-beating donor for 6 hours.

BACKGROUND: The aim of this study was to transplant lungs that had been topically cooled in the non-heart-beating donor for 6 hours, using the most challenging evaluation method possible, namely single-lung transplantation followed by immediate contralateral pneumonectomy. METHODS: Domestic pigs were used (6 donors and 6 recipients) with a mean body weight of 59 +/- 3 kg. Ventricular fibrillation was induced, and after 1 minute, cardiac massage was started and heparin (5 mg/kg body weight) was given via a central venous catheter. Cardiac massage was continued for 10 minutes, during which the pig was ventilated with 50% oxygen. The pleural cavities were opened and the tracheal tube disconnected from the ventilator, with the result that both lungs deflated. Saline slush was placed in both pleural cavities so that it completely covered the lungs. Within 40 minutes the lung core temperature was less than 10 degrees C, and it was kept around 8 degrees C for 6 hours by adjusting the amounts of ice slush. The left lung was then harvested and transplanted into a prepared recipient, followed by right pneumonectomy within 46 +/- 4 minutes, thus making the recipient pig 100% dependent on the transplanted cadaver lung. RESULTS: The mean ischemic time for the cadaver lungs was 8 hours and 2 minutes (range, 7 hours and 25 minutes to 8 hours and 59 minutes). All animals remained in excellent condition throughout the 24-hour observation period, with arterial oxygen tensions of approximately 225 mm Hg, or 30 kPa (inspired oxygen fraction, 0.5). CONCLUSIONS: Lungs from non-heart-beating donors may be used for transplantation if heparinization and topical cooling can be initiated within minutes of irreversible cardiac arrest.

Animals↗
PubMed1997

Effect of flush-perfusion on vascular endothelial and smooth muscle function.

BACKGROUND: The aim of this study was to investigate how much perfusion pressure an artery can tolerate without significant loss of endothelium-dependent relaxation (EDR) and vascular contractility. METHODS: The abdominal aortas of 396 Sprague-Dawley rats were used. One hundred twenty aortas were flush-perfused for 1 or 5 minutes with cold St. Thomas' Hospital cardioplegic (STHC) solution or with the same solution but modified by the addition of 3.5% dextran 40. Three perfusion pressures were tested: 50, 100, and 150 mm Hg. Two hundred eighty vessels were subjected to pressures of 50, 150, or 300 mm Hg using saline or STHC solution at 22 degrees C or STHC solution at 4 degrees C, for 10 or 60 seconds. The vessels were investigated in organ baths. Contractility was tested with the thromboxane analogue U-46619, acetylcholine was used to investigate EDR, and papaverine to elicit endothelium-independent relaxation. RESULTS: Flush-perfusion with cold STHC solution for 5 minutes at a perfusion pressure of 50 or 100 mm Hg affected neither contractility nor EDR. Vessels exposed to a flush-perfusion pressure of 150 mm Hg for 1 or 5 minutes lost 39% (p < 0.001) and 53% (p < 0.001) of their contractility, respectively. Flush-perfusion at 150 mm Hg for 1 minute did not affect EDR, whereas 5 minutes' perfusion caused a reduction of 7% (p < 0.05). A repetition of these experiments using STHC solution with 3.5% dextran 40 added gave no significantly different results. The impairment in contractility and EDR seen after perfusion at 150 mm Hg for 5 minutes disappeared after transplantation and reperfusion for 7 days. The vessels could be distended with saline or STHC solution at a pressure of 150 mm Hg without affecting contractility at 22 degrees C. At 4 degrees C, however, this pressure was harmful to contractility. Distention at a pressure of 300 mm Hg almost abolished contractility and 7 days after transplantation there had not yet been any recovery of contractility, but 30 days after transplantation the grafts had regained their normal contractility. CONCLUSIONS: Cold STHC solution, with or without dextran 40, can be used with a perfusion pressure of 100 but not 150 mm Hg without impairing EDR or vascular smooth muscle function.

Animals↗
PubMed1997

Contradictory effects of dopamine at 32 degrees C in pigs anesthetized with ketamine.

BACKGROUND: In critically ill patients who were surface cooled to 33 +/- 2 degrees C, we have observed that dopamine sometimes causes a substantial decrease in blood pressure. The present study was designed to compare the effects of dopamine in normothermia to those seen after surface cooling to 32 degrees C. METHODS: Seven pigs with a mean body weight of 21 kg were anesthetized with ketamine and muscle relaxation was induced with pancuronium. They were mechanically ventilated and given dopamine infusions (5 and 12 micrograms.kg-1.min-1)in normothermia and after surface cooling by cold water immersion to a central blood temperature of 32.0 degrees C (range 31.6-32.6 degrees C). RESULTS: In normothermia, dopamine at a dose of 5 micrograms.kg-1.min-1 increased mean arterial blood pressure (MAP) by 16% (P < 0.01) and cardiac output (CO) by 9% (P = 0.051); at 12 micrograms.kg-1.min-1 dopamine increased MAP by 26% (P < 0.01) and CO by 18% (P < 0.01). In hypothermia, MAP and CO did not change at an administration rate of 5 micrograms.kg-1.min-1; at 12 micrograms.kg-1.min-1 CO was unchanged but MAP was significantly reduced by 15% (P < 0.01). CONCLUSION: Dopamine increased CO and MAP in normothermia but not at 32 degrees C, where there was even a significant reduction of MAP in this porcine model.

Anesthesia, Intravenous↗
PubMed1996

Importance of calcium in long-term preservation of the vasculature.

BACKGROUND: The aim was to investigate the effect of calcium in organ preservation solutions with respect to 36-hour preservation of vascular smooth muscle function and endothelium-dependent relaxation. METHODS: The infrarenal aortas of 60 Sprague-Dawley rats were studied in organ baths as fresh controls and after 36 hours of cold (4 degrees C) storage in different preservation solutions with and without calcium. The thromboxane A2 analogue U-46619 was used to study contractility. Endothelium-dependent relaxation was tested by the cumulative addition of acetylcholine. Papaverine hydrochloride was used to elicit endothelium-independent relaxation. RESULTS: Krebs solution was the only solution able to fully preserve contractility. Krebs solution without calcium gave poor preservation. After the addition of 1.5 mmol/L of calcium to University of Wisconsin solution and to Perfadex, both these solutions became fully able to preserve contractility. None of the solutions (with or without calcium) were fully able to preserve endothelium-dependent relaxation, although University of Wisconsin solution gave good preservation and Perfadex, fair preservation. Euro-Collins solution and K+ (124 mmol/L)-enriched Krebs solution were not able to preserve smooth muscle function or endothelium-dependent relaxation. CONCLUSIONS: Calcium is essential for long-term preservation of vascular smooth muscle function but not for long-term preservation of endothelium-dependent relaxation.

Acetylcholine↗
PubMed1996

Effect of temperature in long-term preservation of vascular endothelial and smooth muscle function.

BACKGROUND: In clinical transplantation the donor organ is perfused with a cold preservation solution to obtain quick core cooling and a suitable environment for the tissue cells. Without good preservation of the vasculature, progressive deterioration of the blood flow during reperfusion may ultimately lead to the no-reflow phenomenon, even though the function of the other cells in the organ may be adequately preserved. The aim of this study was to find the optimal storage temperature for preservation of the vasculature. METHODS: The infrarenal aorta of 126 Sprague-Dawley rats were studied in organ baths: as fresh controls, after 36 hours of storage at 0.5 degrees C, 4 degrees C, 8.5 degrees C, and 22 degrees C in University of Wisconsin solution, and after 36-hour storage followed by transplantation and a lapse of 2 hours, 24 hours, and 7 days. The thromboxane analogue U-46619 was used to test contractility. Acetylcholine was used to elicit endothelium-dependent relaxation (EDR), and papaverine to elicit endothelium-independent relaxation. RESULTS: Storing the vessels at 0.5 degree C proved best regarding preservation of contractility, with a nonsignificant decrease, whereas storage at 4 degrees C and 8.5 degrees C resulted in a significant decrease after 36 hours. The contractility did not recover within 24 hours of in vivo reperfusion, but full recovery was seen after 7 days. Regardless of the preservation temperature used, a significant impairment in EDR was seen after 36 hours of storage. Two hours after transplantation, vessels stored at 4 degrees C and 8.5 degrees C showed no significant impairment in EDR, whereas those stored at 0.5 degrees C demonstrated a significant loss of EDR. After 24 hours and after 7 days, EDR was normal in all groups. CONCLUSIONS: Endothelium-dependent relaxing factor function is best preserved at 4 degrees C and 8.5 degrees C, whereas preservation of vascular smooth muscle function is best preserved at 0.5 degrees C.

Animals↗
PubMed1996

Inhaled nitric oxide reveals and attenuates endothelial dysfunction after lung transplantation.

BACKGROUND: Maintaining endothelial function within transplanted organs may be critical to successful preservation. In this study we have evaluated the relationship between the effect of inhalation of nitric oxide and the degree of endothelial dysfunction after lung transplantation. METHODS: A left lung, which had been preserved for 24 hours, was transplanted and a right pneumonectomy was performed in 5 pigs. After a 24-hour observation period the pigs inhaled 5, 20, and 80 ppm nitric oxide, and pulmonary vascular resistance was recorded continuously. From the same donors preserved pulmonary arteries from the contralateral lung were studied simultaneously in organ baths. Acetylcholine chloride was used to elicit endothelium-dependent relaxation in vessel segments contracted with the thromboxane A2 analogue U-46619. RESULTS: Maximal endothelium-dependent relaxation decreased in the preserved lungs and correlated to the pulmonary vascular resistance in the simultaneously transplanted lungs. Inhalation of nitric oxide in the pigs that had received transplants caused the pulmonary vessels to dilate in proportion to the endothelial dysfunction. CONCLUSIONS: Preservation of lung for transplantation induces an endothelial dysfunction, and the degree of the decrease in pulmonary vascular resistance caused by nitric oxide inhalation may be an indication of the degree of this endothelial damage. The vasodilation caused by inhaled nitric oxide increases as the endothelial function deteriorates.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Prostanoid release after lung transplantation.

BACKGROUND: Increased pulmonary vascular resistance is frequently seen after lung transplantation. Thromboxane A2 is a potent vasoconstrictor of pulmonary arteries. Thromboxane-elicited vasoconstriction can ben counteracted by prostacyclin. The effects of lung transplantation on the biosynthesis of these substances were investigated. METHODS: Pulmonary artery flush perfusion with a low-potassium dextran glucose solution was performed in six donor pigs. After a 24-hour storage period, the left lung was transplanted into a recipient, followed by right pneumonectomy, making the recipient's survival entirely dependent on the transplanted lung. A sham operation (bilateral thoracotomy, right pneumonectomy) ws done in six pigs. the urine contents of the stable thromboxane A2 metabolite 2,3-dinor-thromboxane B2 and the stable prostacyclin metabolite 2,3-dinor-6-keto-protaglandin F1 alpha were measured with a gas chromatography-mass spectrometry method. RESULTS: One to four hours after reperfusion, thromboxane A2 production reached its maximum in both groups: it ws fivefold the basal value in the transplanted group, but only twofold in the sham-operated group, the difference being significant (p < 0.005). Twenty to twenty-four hours after reperfusion, thromboxane A2 production had stabilized at about twofold the basal value in both the transplanted and in the sham-operated group. Four to eight hours after reperfusion, prostacyclin production reached 15 times the basal value in the transplanted group and twofold in the sham-operated group, the difference being significant (p < 0.05). Twenty to twenty-four hours after reperfusion, prostacyclin production was 18-fold the basal value in the transplanted group and sevenfold in the sham-operated group. No correlation was found between the thromboxane or prostacyclin production and the pulmonary vascular resistance or the mean pulmonary arterial pressure. CONCLUSIONS: The thromboxane A2 production increased fivefold after lung transplantation, with a concomitant 15-fold increase in prostacyclin synthesis, which might have counteracted the vasoconstrictor effect of thromboxane.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

The Linköping-Lund surgical experience with the HeartMate left ventricular assist system.

Four transplant candidates fulfilling the Food and Drug Administration criteria for a permanent left ventricular assist device received a pneumatic HeartMate system as a bridge to heart transplantation. All patients survived and were fully rehabilitated at the time of transplantation, which was carried out 2 to 6 months after the initial operation. There were no major complications associated with the procedures. We are impressed by the effectiveness and safety of the device.

Adult↗
PubMed1995

Long-term preservation of vascular endothelium and smooth muscle.

This study was performed in organ baths on 400 ring segments of infrarenal aorta taken from 40 Sprague-Dawley rats that had been randomized into five groups. Contractility was tested with the thromboxane analogue U-46619. Acetylcholine was used to elicit endothelium-dependent relaxing factor (EDRF). The results obtained from vessels preserved at 4 degrees C for 6, 12, 24, and 36 hours were compared with those from autologous vessels studied immediately after harvesting. Vessels preserved in Euro-Collins solution showed a 46% (p < 0.01) decrease in contractility after 12 hours of storage; after 24 hours only weak contractions could be elicited, and after 36 hours they had lost their ability to contract. The EDRF function was slightly reduced after 12 hours and could not be investigated after 24 and 36 hours. With the University of Wisconsin solution (UW) and the low-potassium-dextran-glucose solution Perfadex no decrease in contractility was seen in the first 24 hours, but at 36 hours the vessels preserved in UW had lost 40% (p < 0.01) and those preserved in Perfadex 30% (p < 0.05) of their contractility. The EDRF function was significantly reduced by about 15% after 6, 12, and 24 hours in both the UW and the Perfadex groups. At 36 hours, vessels stored in Perfadex had lost 41% (p < 0.001) and those stored in UW 17% (p < 0.01) of their EDRF function.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1995

Perfadex is superior to Euro-Collins solution regarding 24-hour preservation of vascular function.

BACKGROUND: The aim of this study was to compare Perfadex with Euro-Collins solution regarding 24-hour preservation of endothelium-dependent relaxation and vascular smooth muscle function. METHODS: The infrarenal aorta of 72 isogenic rats was studied in organ baths as fresh controls, after 24 hours of cold (4 degrees C) storage, and after 24-hour storage followed by transplantation and examination after 7 or 30 days. The thromboxane A2 analogue U-46619 was used to test contractility. Acetylcholine chloride was used to elicit endothelium-dependent relaxation and papaverine hydrochloride, to elicit endothelium-independent relaxation. RESULTS: With both solutions, all grafts were patent after 7 and 30 days. Vessels preserved in Euro-Collins solution for 24 hours lost 95% (p < 0.001) of their contractility compared with fresh controls; 7 days after transplantation, they had regained 40% of initial contractility, and after 30 days, there was no significant decrease in contractility. Vessels preserved in Perfadex manifested no significant decrease in contractility at any time. Endothelium-dependent relaxation could not be evaluated in vessels stored for 24 hours in Euro-Collins solution because they had lost almost all contractility; 7 days after transplantation, endothelium-dependent relaxation was reduced by 65% (p < 0.001), but at 30 days after transplantation, there was no significant decrease in endothelium-dependent relaxation. Vessels preserved in Perfadex for 24 hours lost 17% (p < 0.05) of endothelium-dependent relaxation, but 7 and 30 days after transplantation, there was no significant decrease in endothelium-dependent relaxation. CONCLUSIONS: Perfadex, but not Euro-Collins solution, has the capacity to preserve vascular function after 24 hours of storage followed by in vivo reperfusion.

Animals↗
PubMed1995

Trypsinogen is not activated during cardiac surgery with extracorporeal circulation.

Amylase, immunoreactive cationic trypsin(ogen) and complexes of cationic trypsin and alpha 1-proteinase inhibitor were analysed in plasma samples from 41 patients following cardiac surgery with extracorporeal circulation. Postoperative hyperamylasaemia was seen in seven patients (17%). In 10 patients there were elevated levels (> 100 micrograms 1(-1)) of immunoreactive cationic trypsin(ogen) on the first postoperative day. After gelfiltration, samples from these 10 patients were analysed for trypsin-alpha 1-proteinase inhibitor complexes, with a solid-phase, double-antibody enzyme-linked immunoassay. The median preoperative level of trypsin-alpha 1-proteinase inhibitor complexes was 4.5 micrograms 1(-1) (range 3.3-11.9) and the median value on the first postoperative day was 5.5 micrograms 1(-1) (range 2.6-14). The ratio between complexes and immunoreactive trypsin(ogen) decreased (p < 0.05) showing that activation of trypsinogen did not occur. This fact argues against the development of protease-mediated subclinical pancreatitis during cardiac surgery with extracorporeal circulation.

Adult↗
PubMed1994

Endothelium-dependent relaxation after short-term preservation of vascular grafts.

As the integrity of graft endothelium seems to be essential to successful long-term patency in coronary operations, its preservation demands the utmost care. The aim of the present study was to investigate the effects of currently used solutions on endothelium-dependent relaxation after short-term storage of vessels at room temperature or at 4 degrees C. The infrarenal rat aorta was selected for study because its use enabled standardization of the investigation, which was performed in organ baths on 672 vessel segments from 112 Sprague-Dawley rats. Stable vasoconstriction was obtained with the thromboxane analogue U-46619. Acetylcholine was used to elicit endothelium-dependent relaxation. The results obtained for vessels preserved for 2 hours were compared with those for autologous vessels studied immediately after harvesting. Vessel contractility was unaffected by the preservation solutions, except in the Ringer's acetate group, where it was reduced by 50% (p < 0.05). Endothelium-independent relaxation, tested with papaverine, was unaffected in all groups. Ringer's lactate, Krebs solution, and Perfadex (a low-potassium-dextran-glucose solution) did not significantly affect endothelium-dependent relaxation either at room temperature or at 4 degrees C, although a tendency to impaired relaxation was seen in these three groups after cold storage. Standard Ringer's solution and fresh heparinized blood each significantly reduced endothelium-dependent relaxation in vessels stored at room temperature (p < 0.05), but not in those stored at 4 degrees C. Endothelium-dependent relaxation was significantly reduced after storage in normal saline solution (p < 0.05) and in Ringer's acetate (p < 0.01), both at room temperature and at 4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗