Biomedical subjects

T Sjöberg

Publications and source records attributed to T Sjöberg.

At least 19 recordsLinked to original sources

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

A prospective double blind randomized study comparing the need for blood transfusion with terlipressin or a placebo during early excision and grafting of burns.

INTRODUCTION: Early excision and skin grafting has become the standard of good burn management, but it is associated with major blood loss. AIM: To determine the haemostatic effect of terlipressin compared with placebo. MATERIAL AND METHODS: Fifty-one patients with burns of 10-20% total body surface area had early excision and split skin grafting of deep burns. The surface area of the burn wound and of the healed graft were measured by planimetry. The patients were randomly allocated to medication, either terlipressin or placebo. Blood loss and number of transfused units of blood were recorded. RESULTS: Twenty-one patients received terlipressin, 13 received terlipressin late (cross-over) and 17 received placebo. Six out of 21 patients exposed to terlipressin were transfused with eleven units of packed red blood cells. Seven out of 13 patients crossed over from placebo to terlipressin (late terlipressin) were transfused with 17 units of blood. Eight out of 17 patients exposed to the placebo were transfused with 22 units of blood (P < 0.05). Graft healing was 1055 +/- 609 cm2 out of 1452 +/- 11 cm2 in terlipressin and 914 +/- 633 cm2 out of 1288 +/- 720 cm2 in the placebo group (n.s.). CONCLUSION: Terlipressin reduced the need for blood transfusion by a factor of 2.5 compared to a placebo without impairment of graft healing.

Adolescent↗

PubMed2004

Immune response in burn patients in relation to HIV infection and sepsis.

The post-burn immune dysfunction predisposes patients to sepsis and multiple organ failure leading to increased mortality. HIV infection also results in a depressed immune response. The combination of burn injury and HIV might therefore lead to an increased morbidity and mortality as compared to non-HIV infected burn patients. Twenty burn patients and 10 healthy volunteers were included in a prospective study. To evaluate their immune status, CD4+ and CD8+ T-lymphocyte counts were determined in peripheral blood. HIV serology samples were obtained on admission. Bacteriological cultures were obtained from wound surface samples and wound tissue biopsies. Six burn patients were HIV infected. Clinical signs of sepsis were observed in 10 patients. The number of CD4+ T-lymphocytes were lower in burn patients compared to healthy volunteers (P < 0.05). HIV infected burn patients had lower CD4+ lymphocyte counts than non-HIV infected patients (P < 0.05). Patients with clinical signs of sepsis had lower CD4+ counts compared to patients without sepsis (P < 0.05). There was no difference in the mortality rate or the length of hospitalisation between patient groups. Burn injury, HIV infection and sepsis independently result in immunosuppression.

Adult↗

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↗

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↗

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↗

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

Inhalation of nitric oxide after lung transplantation.

BACKGROUND: Pulmonary hypertension is a postoperative complication that may adversely affect the outcome of lung transplantation. The effect of nitric oxide (NO) inhalation on pulmonary hemodynamic indices after lung transplantation was studied and compared with findings in control pigs. METHODS: Varying concentrations of NO were inhaled by 5 pigs after left lung transplantation and right pneumonectomy and by 5 controls after right pneumonectomy at an inspired oxygen fraction of 0.21 and 0.5. Hemodynamic data were recorded continuously, and fast circulatory courses were analyzed. RESULTS: Inhalation of NO reduced pulmonary vascular resistance and mean pulmonary arterial pressure in all pigs, but the decrease was pronounced and dose dependent only at an inspired oxygen fraction of 0.21 in the pigs that had transplantation. These were the only pigs that became hypoxic. With the termination of NO, there was a dose-independent rebound pulmonary vasoconstriction in the controls, especially at an inspired oxygen fraction of 0.21, but not in the pigs that had transplantation. This response was transient and could be blunted with a higher inspired oxygen fraction. CONCLUSION: Inhalation of NO reduced pulmonary vascular resistance in the transplanted lung and may be useful in the treatment of pulmonary hypertension after lung transplantation. The rebound pulmonary vasoconstriction with the termination of NO inhalation stresses the need to be aware of this effect and to wean NO carefully in clinical situations. This study showed oxygen dependency, which has to be taken into consideration in dose-response studies involving NO inhalation.

Administration, Inhalation↗

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

Contractile endothelin-B (ETB) receptors in human small bronchi.

Endothelins (ETs) are a family of novel regulatory peptides and various lines of evidence suggest an important role for ETs in regulating pulmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA receptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of small bronchi in the pathogenesis of airway disease. In the present paper, improved methodology was used which enables in vitro studies of small human bronchi down to a diameter of 0.5-1.0 mm. Using the new methodology we have tried to further characterize this receptor. Small bronchi from the distal parts of the bronchial tree were obtained from pulmonary tissue removed from 15 patients with lung cancer. They were dissected and cut into ring segments, in which isometric tension was recorded. ET-1, ET-2 and ET-3 elicited strong concentration-dependent contractions of the human small bronchus. Basically, the three peptides were equipotent with about the same maximal response. Upon reapplication, they all showed the same tachyphylaxis pattern, reaching half the initial contraction. Comparative analysis of IRL 1620, a selective ETB receptor agonist, revealed that the effect of the ETB agonist was, in all respects, similar to the responses induced by the ETs. PD 145065, a combined ETA/ETB receptor antagonist competitively inhibited the contractions induced by IRL 1620, whereas FR139317, a selective ETA receptor antagonist, was without effect. In conclusion, the present study shows that accurate measurements can be made in vitro on small human bronchi and all present data are in favour of an ETB receptor mediating endothelin-induced contraction of human bronchi smaller than 1.0 mm.

Acetylcholine↗