Low-dose sodium nitroprusside reduces pulmonary reperfusion injury

BACKGROUND: Reperfusion injury is a significant cause of early allograft dysfunction after lung transplantation. We hypothesized that direct pulmonary arterial infusion of an intravascular nitric oxide donor, sodium nitroprusside (SNP), would ameliorate pulmonary reperfusion injury more effectively than inhaled nitric oxide without causing profound systemic hypotension. METHODS: Using an isolated, ventilated, whole-blood-perfused rabbit lung model, we studied the effects of both inhaled and intravascular nitric oxide during lung reperfusion. Group I (control) lungs (New Zealand White rabbits, 3 to 3.5 kg) were harvested en bloc, flushed with Euro-Collins solution, and then stored inflated for 18 hours at 4 degrees C. Lungs were then reperfused with whole blood and ventilated with 60% oxygen for 30 minutes. Groups II, III, and IV received pulmonary arterial infusions of SNP at 0.2, 1.0, and 5.0 micrograms.kg-1.min-1, respectively, whereas group V was ventilated with 60% oxygen and nitric oxide at 80 ppm during reperfusion. RESULTS: Pulmonary arterial infusions of SNP even at 0.2 microgram.kg-1.min-1 (group II) showed significant improvements in pulmonary artery pressure (31.35 +/- 0.8 versus 40.37 +/- 3.3 mm Hg; p < 0.05) and pulmonary vascular resistance (38,946 +/- 1,269 versus 52,727 +/- 3,421 dynes.s/cm-5; p < 0.05) when compared with control (group I) lungs after 30 minutes of reperfusion. Infusions of SNP at 1.0 microgram.kg-1.min-1 (group III) showed additional significant improvements in dynamic airway compliance (1.98 +/- 0.10 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05), venous-arterial oxygenation gradient (116.00 +/- 24.4 versus 34.43 +/- 2.5 mm Hg; p < 0.05), and wet-to-dry ratio (6.9 +/- 0.9 versus 9.1 +/- 2.2; p < 0.05) when compared with control (group I) lungs. Lungs that received inhaled nitric oxide at 80 ppm (group V) were significantly more compliant (1.82 +/- 0.13 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05) than control (group I) lungs. CONCLUSIONS: Pulmonary arterial infusion of low-dose SNP during lung reperfusion significantly improves pulmonary hemodynamics, oxygenation, compliance, and edema formation. These effects were achieved at doses of SNP that did not cause profound systemic hypotension. Direct intravascular infusion of SNP via pulmonary arterial catheters could potentially abate reperfusion injury immediately after allograft implantation.     

Therapeutic implications of thymic uptake of radioiodine in thyroid carcinoma

BACKGROUND: NPC18915, a member of new antiinflammatory agent called nactins (neutrophil activation inhibitors), has been shown to reduce reperfusion injury in rat lung transplantation at high dosage. In vitro studies have demonstrated effectiveness of this compound even at low dosage. We hypothesized that this compound ameliorates lung ischemia reperfusion injury even at low dosage levels if administration is optimally timed. The aim of this study was to determine the efficacy and the best timing for administration of low-dose NPC18915. METHODS: Forty syngeneic rat left lung transplantations were performed. All isografts were flushed with low-potassium dextran-1% glucose solution 20 ml and preserved for 18 hours at 4 degrees C. Animals were divided into four groups. Group I animals (n = 10) served as control subjects. In groups II (n = 10), III (n = 10), and IV (n = 10), NPC18915 (0.04 mg) was added to the flush solution and was administered intravenously (0.4 mg/kg) immediately before reperfusion (group II) and 60 minutes (group III) and 120 minutes (group IV) after reperfusion. Pulmonary function was assessed 24 hours after reperfusion. RESULTS: In group III, oxygenation improved in comparison to group I (247.2 +/- 59.8 versus 76.6 +/- 16.0 mm Hg, p < 0.002). Wet-to-dry weight ratio and graft myeloperoxidase activity were significantly improved (group III versus group I, 6.02 +/- 0.21 versus 7.19 +/- 0.41, p = 0.013) (group III versus group I, 0.093 +/- 0.019 versus 0.207 +/- 0.023 delta optical density/min/mg, p < 0.002). There were no significant differences in CD11b expression. CONCLUSION: These data suggest that delayed administration of NPC18915, 60 minutes after reperfusion, dramatically improves pulmonary graft function.     

In vivo cyclin E expression as a marker for early cervical neoplasia

BACKGROUND: Heat shock has been associated with the acquisition of tolerance to a wide variety of stressful conditions, including ischemia. This is partly mediated by the production of various heat shock proteins (HSP), including HSP70. One novel approach to the reduction of ischemia-reperfusion injury after lung transplantation is the induction of HSP70 by heat pretreatment of the donor. The purpose of this study was to investigate the feasibility of this approach in an animal model of lung transplantation. METHODS: Animals were divided into six main groups, with groups I to III representing transplanted animals: In groups I and II, donor animals were anesthetized and then underwent heat stress 6 and 12 hours before organ harvest, respectively. Control animals underwent general anesthesia but no heat stress. After harvest, left lungs from groups I to III were preserved for 18 hours at 40 degrees C and then implanted into isogeneic recipients, which were killed 24 hours after reperfusion to assess graft function. Group IV and V animals underwent heat stress followed by a recovery period of 6 and 12 hours, respectively. Lungs were collected both at the time of harvest (right lungs) and after 18 hours of cold preservation (left lungs). Group VI served as nontransplanted controls. Groups IV to VI did not undergo lung transplantation. RESULTS: At the time of harvest but before implantation, HSP70 was significantly increased in heat-shocked nontransplanted donor lungs (groups IV and V) compared with group VI controls. After 18 hours of cold preservation, HSP70 levels were higher in group IV compared with group V and group VI controls. At 24 hours after reperfusion, mean arterial oxygenation was significantly higher in group I compared with group II and group III controls (290.25+/-24.5 vs 154.5+/-23.9 and 119.6+/-11.3 mm Hg, respectively; P < .001). Myeloperoxidase activity was improved in group I compared with group III controls (0.048+/-0.018 vs 0.137+/-0.036 deltaOD/mg/min, respectively; P < .05). The wet/dry weight ratio was also improved in group I compared with group III controls (6.2+/-0.3 vs. 7.8+/-0.4, respectively; P < .05). CONCLUSIONS: Heat pretreatment of the donor 6 hours before harvest results in increased synthesis of HSP70, which offers a dramatic protective effect against subsequent ischemia-reperfusion injury in the lung isograft.     

Donor treatment with the lazeroid U74389G reduces ischemia-reperfusion injury in a rat lung transplant model

BACKGROUND: Antioxidant treatment with lazeroids has proven beneficial for the amelioration of reperfusion injury in experimental lung transplantation. This study compares the effect of donor versus recipient treatment on immediate postoperative graft function. METHODS: A model of acute double-lung transplantation in rats was used to assess graft function. Transplanted controls after 2 (group I) and 16 hours of ischemia (group II) were compared to a recipient (group III; 16-hour ischemia) and a donor treatment group (group IV; 16-hour ischemia) using the lazeroid U74389G (6 mg/kg). Serial assessment of alveolar-arterial oxygen difference, dynamic lung compliance, airway and pulmonary vascular resistance was obtained during a 2-hour reperfusion period. Final analysis included survival, weight gain, and histologic examination. RESULTS: Graft function was significantly better after 2 hours of ischemia than in any of the three 16-hour ischemia groups (II, III, IV). After 16 hours of ischemia, donor treatment provided superior graft function with respect to dynamic lung compliance, airway resistance, and alveolar-arterial oxygen difference when compared with groups II and III. The pulmonary vascular resistance was significantly higher in group III when compared with groups II and IV. Graft weight increase reflecting edema was highest in groups III (104%) and II (98%). CONCLUSIONS: After prolonged ischemia only donor treatment with the lazeroid U74389G was able to significantly reduce ischemia-reperfusion-related graft dysfunction.     

Expression of endothelin-1 and effects of an endothelin receptor antagonist, TAK-044, at reperfusion after cold preservation in a canine lung transplantation model

BACKGROUND: Rapid increase of pulmonary vascular resistance (PVR) early after reperfusion remains a major issue in clinical lung transplantation. A potent vasoconstrictor peptide, endothelin- plays an important role in various pulmonary pathophysiologic conditions and might induce increased PVR. We investigated the expression and influence of endothelin-1, and the effects of an ETA and ETB nonselective endothelin receptor antagonist, TAK-044, at reperfusion after cold preservation in a canine lung transplantation model. METHODS: Left single lung allotransplantation procedures were performed in three groups of animals. In group I (n=5) lungs were preserved for 12 hours; in group II (n=5) lungs were preserved for 18 hours; and in group III (n=6) lungs were also preserved for 18 hours, and TAK-044 (5 mg/kg) was administered just before reperfusion. All donor lungs were flushed and preserved with low-potassium dextran glucose solution at 4 degrees C. RESULTS: Six hours after reperfusion, arterial oxygen tension (mm Hg, inspired oxygen fraction=1.0) was 512.9+/-34.7 in group I, 152.4+/-46.7 in group II, and 509.6+/-29.0 in group III; PVR index (dyne x sec x cm(-5) x m2) was 1130+/-142 in group I, 1820+/-142 in group II, and 1287+/-191 in group III. Plasma endothelin-1 level was elevated significantly, and endothelin-1-like immunoreactivity was found in a variety of pulmonary vascular tissue and was seen less with immunohistochemical evaluation in group II in bronchial tissue. Conclusions: These results suggest that endothelin-1 is expressed as a result of ischemia-reperfusion injury and may worsen early graft function. TAK-044 is beneficial in protecting the graft from high pulmonary vascular resistance and pulmonary edema during the early posttransplantation stage.     

Controlled reperfusion after lung ischemia: implications for improved function after lung transplantation

OBJECTIVES: Despite improvements in organ preservation, reperfusion injury remains a major source of morbidity and mortality after lung transplantation. This pilot study was designed to investigate the effects of controlled reperfusion after lung ischemia. METHODS: Twenty adult pigs underwent 2 hours of warm lung ischemia by crossclamping the left bronchus and pulmonary artery. In five (group 1), the clamp was simply removed at the end of ischemia (uncontrolled reperfusion). The 15 other pigs underwent modified reperfusion using blood from the femoral artery to perfuse the lung through the pulmonary artery (pressure 40 to 50 mm Hg) for 10 minutes before removing the pulmonary artery clamp. In five (group 2), the blood was mixed with crystalloid, resulting in a substrate-enriched, hypocalcemic, hyperosmolar, alkaline solution. In five (group 3), the blood was circulated through a leukocyte-depleting filter, and the last five (group 4) underwent reperfusion with both a modified solution and white blood cell filter. Lung function was assessed 60 minutes after reperfusion, and biopsy specimens were taken. RESULTS: Controlled reperfusion with both a white blood cell filter and modified solution (group 4) completely eliminated the reperfusion injury that occurred with uncontrolled reperfusion (group 1), resulting in complete preservation of compliance (98% +/- 1% vs 77% +/- 1%; p < 0.001, and arterial/alveolar ratio (97% +/- 2% vs 27% +/- 2%; p < 0.001); no increase in pulmonary vascular resistance (106% +/- 1% vs 198% +/- 1%; p < 0.001); lowered tissue edema (82.1% +/- 0.4% vs 84.3% +/- 0.2%; p < 0.001), and myeloperoxidase activity (0.18 +/- 0.02 vs 0.35 +/- 0.02 deltaOD/min/mg protein; p < 0.001). In contrast, using either a white blood cell filter or modified solution separately improved but did not avoid the reperfusion injury, resulting in pulmonary function and tissue edema levels that were intermediate between group 1 (uncontrolled reperfusion) and group 4 (white blood cell filter and modified solution). CONCLUSION: After 2 hours of warm pulmonary ischemia, (1) a severe lung injury occurs after uncontrolled reperfusion, (2) controlled reperfusion with either a modified reperfusion solution or white blood cell filter limits, but does not avoid, a lung reperfusion injury, (3) reperfusion using both a modified reperfusate and white blood cell filter results in complete preservation of pulmonary function. We therefore believe surgeons should control the reperfusate after lung transplantation to improve postoperative pulmonary function.     

Controlled reperfusion and pentoxifylline modulate reperfusion injury after single lung transplantation

OBJECTIVE: Rodent models have suggested that initial low-pressure reperfusion of transplanted lungs reduces injury after ischemia. We investigated this phenomenon and the use of pentoxifylline in a porcine model of left single lung transplantation. METHODS: Donor lungs were preserved with Euro-Collins solution for a mean ischemic time of 18.4 hours. Neutrophil trapping in the graft, pulmonary artery pressure, and gas exchange were assessed over a 12-hour period. Partial occlusion of the contralateral pulmonary artery allowed manipulation of the pulmonary artery pressure in the transplanted lung. Group A (n = 5) was perfused at a mean pulmonary artery pressure of 20 mm Hg, group B was reperfused at a mean pulmonary artery pressure of 45 mm Hg for 10 minutes before reducing the pressure to the same as group A, and group C was reperfused at a mean pressure of 20 mm Hg for 10 minutes, then increased to a mean of 45 mm Hg for the remainder of the experiment. Group D was reperfused as in group A with the addition of intravenous pentoxifylline. RESULTS: Leukocyte sequestration was observed in the first 10 minutes after reperfusion in groups A, B, and C, with maximal sequestration at 2 minutes. Significantly more sequestration was observed in the first 6 minutes in group B than in groups A and C, which were similar. Pentoxifylline significantly reduced leukocyte sequestration. Pulmonary venous oxygen tension in the allograft lung was worst in group B. Groups A and C were similar, but group D was superior to all other groups (p < 0.001). CONCLUSIONS: Low-pressure reperfusion, even when limited to the first 10 minutes, modulates reperfusion injury possibly through a leukocyte-dependent mechanism. The addition of pentoxifylline in the recipient confers significant additional benefit.     

Endoleak after endovascular graft repair of experimental aortic aneurysms: does coil embolization with angiographic "seal" lower intraaneurysmal pressure?

PURPOSE: To investigate the relation between endoleaks and intraaneurysmal pressure (IAP) and the effect of coil embolization in the management of endoleaks. METHODS: The infrarenal aorta of a dog (n = 15) was replaced by a polytetrafluoroethylene aneurysm containing a pressure transducer. Group I (n = 4) had untreated aneurysms. Group II (n = 4) had endovascularly excluded aneurysms without an endoleak. Group III (n = 7) had aneurysms excluded by means of grafts with a defect that represented the source of an endoleak. After 4 weeks of follow-up study, the endoleaks in group III dogs were subjected to coil embolization. Systolic IAP was measured daily and expressed as a ratio of systolic blood pressure obtained from a forelimb cuff. Arteriography, duplex ultrasonography, and spiral contrast computed tomography were performed to evaluate endoleaks. RESULTS: In group I, the LAP remained close to systolic blood pressure (ratio of 0.96 +/- 0.06), whereas in group II the IAP ratio showed a decline to 0.34 +/- 0.16 (p = 0.0009 group I versus II). After an initial decrease, the IAP ratio in group III stabilized at 0.75 +/- 0.18 (p = 0.003, group II versus III). Aneurysms with an endoleak remained pulsatile with a pulse pressure of 30 +/- 16 mm Hg, which was less than that of untreated aneurysms (62 +/- 15 mm Hg; p < 0.0001 group I versus III). Arteriography and computed tomography revealed "sealing" of endoleaks after coil embolization, but IAP ratio did not decrease (0.76 +/- 0.14) after coil embolization. CONCLUSIONS: Incomplete endovascular aneurysm exclusion caused by an endoleak fails to reduce IAP ratio and may subject the aneurysm to a continued risk for rupture. Although coil embolization resulted in angiographic and computed tomographic sealing, it failed to reduce IAP ratio.     

Deleterious effects of cardiopulmonary bypass on early graft function after single lung allotransplantation: evaluation of a heparin-coated bypass circuit

Clinical lung transplantation may necessitate the use of cardiopulmonary bypass during the procedure, resulting in increased morbidity with more severe early graft dysfunction and increased blood loss. A heparin surface-coated cardiopulmonary bypass circuit is now available with improved biocompatibility and reduced systemic heparin requirements and may offer advantages compared with standard uncoated cardiopulmonary bypass circuits. This study investigates in a canine model of single-lung allotransplantation whether cardiopulmonary bypass adversely affects early graft function and whether a heparin-coated cardiopulmonary bypass circuit with reduced systemic heparin dosage improves results compared with standard uncoated cardiopulmonary bypass systems. Fifteen dogs underwent left single-lung allotransplantation with occlusion of the contralateral pulmonary artery and bronchus 1 hour after reperfusion. In one group, five animals underwent the procedure without cardiopulmonary bypass. In the group with uncoated circuits, five animals underwent the procedure with the use of standard uncoated cardiopulmonary bypass circuits with full systemic heparin dosage. In the group with heparin-coated circuits, five animals underwent the procedure with the use of heparin-coated cardiopulmonary bypass circuits and reduced systemic heparin dosage. Early graft function was evaluated by arterial oxygenation, pulmonary mechanics, lung water measurements, and histologic analysis. Hemodynamics and postoperative blood loss were also measured. Two hours after reperfusion, partial pressure of oxygen in arterial blood on an inspired oxygen fraction = 1.0 was significantly greater (p < 0.001) in the group without cardiopulmonary bypass (467 +/- 58 mm Hg) than in the group with uncoated circuits (114 +/- 90 mm Hg) and the group with heparin-coated circuits (193 +/- 105 mm Hg), with no significant difference between the groups undergoing bypass procedures. Lung compliance decreased and lung water increased in all transplanted lungs without significant differences between groups. Histologic analysis did not differentiate between the groups. After reperfusion, cardiac index and mean arterial pressure were significantly reduced in the groups with uncoated circuits and with heparin-coated circuits compared with the group that did not undergo cardiopulmonary bypass (p < 0.001). Postoperative blood loss was significantly less (p < 0.002) in the group that did not undergo cardiopulmonary bypass (90 ml +/- 38 ml) compared with both the group with uncoated circuits (750 +/- 15 ml) and the group with heparin-coated circuits (690 +/- 387 ml), with no significant difference between the groups that underwent bypass. The use of cardiopulmonary bypass with systemic heparinization is detrimental to early graft function in this canine model of left single-lung allotransplantation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Therapeutic time window for the 21-aminosteroid, U-74389G, in global cerebral ischemia

A novel 21-aminosteroid (U-74389G), a new potent antioxidant, was evaluated for its protective effect on transient global cerebral ischemia. Ischemia was induced by 20 minutes of four-vessel occlusion in adult male Wistar rats. Injection of 21-aminosteroid (U-74389G, 5 mg/kg intraperitoneally injected) was repeated three times. The second injection was performed 30 minutes after the first injection, and the third injection was performed 210 minutes after that. Experimental animals were divided into five groups according to the time drug administration was initiated. Group I (n = 8) began vehicle administration 30 minutes before occlusion. Group II (n = 9) started 21-aminosteroid administration 30 minutes before occlusion. Drug administration in Group III (n = 9) began at the time of reperfusion, in Group IV (n = 8), 30 minutes after reperfusion, and in Group V (n = 6), 60 minutes after reperfusion. Animals in the control group (n = 5) underwent sham operations. One week after ischemia, the number of viable pyramidal neurons was counted in the hippocampal CA1 subfield. The results were as follows: the number of living neurons in Group I was 18.8 +/- 8.7; in Group II, was 44.7 +/- 9.5; in Group III, was 46.4 +/- 9.4; in Group IV, was 40.3 +/- 6.6; in Group V, was 10.2 +/- 2.5; and in the control group was 131 +/- 3.3. Groups II, III, and IV demonstrated significantly higher numbers of living neurons compared with Group I (P < 0.05). The present study revealed that U-74389G attenuated delayed neuronal death in global cerebral ischemia when it was administered before or soon after the ischemic episode.     

Oculoplastic surgery with a contact Nd:YAG laser silica scalpel. A case report

The purpose of this study was to evaluate the efficacy of local immunosuppression with intraportal administration of cyclosporine (CsA) in liver transplantation. Mongrel dogs weighing 12-18kg were used. Orthotopic liver transplantation was performed, and animals were divided to the following groups. Group I (n = 7): no treatment, group II (n = 7): CsA 5mg/kg/day intermittent iv, group III (n = 5): CsA 3mg/kg/day continuous iv and group IV (n = 8): CsA 3mg/kg/day continuous portal infusion. Immunosuppressive treatments were carried out for two weeks postransplant. Median survival time (MST) of group IV was significantly prolonged (MST = 18 days, range 10-85 days; p < 0.025) compared with group I (7 days, range 6-13), group II (10 days, range 7-16) and group III (7 days, range 6-10). Data of blood chemical analyses showed that hepatic dysfunction was significantly diminished in group IV compared with other groups (p < 0.05). Blood concentration of CsA on the 5th day (mean +/- SEM) was significantly lower in group IV (238 +/- 22ng/ml) than in group III (438 +/- 113ng/ml). Histologic findings showed that rejection reaction was effectively suppressed in group IV, although SG2M% (mean +/- SEM) of peripheral mononuclear cells of group IV (10.6 +/- 3.3%) was equal to that of group III (11.3 +/- 1.7%). In conclusion, local immunosuppression could achieve prominent effect in preventing hepatic graft rejection with limited systemic immunosuppression.     

The role of leukocyte depletion in reducing injury to myocardium and lung during cardiopulmonary bypass

Activated leukocytes and oxygen free radicals have been implicated in the pathogenesis of heart and lung injury after reperfusion and during cardiopulmonary bypass. This study was designed to determine whether leukocyte depletion prevents injury to the heart and lung during cardiopulmonary bypass. Twenty-eight open heart surgeries were performed in this study. In Group F, leukocyte depletion was performed with an LG-6 arterial line filter after aortic declamp (n = 14). Leukocyte depletion was not performed during cardiopulmonary bypass in Group C (n = 14). Thereafter, cardiac and lung function were assessed in the 24 hr after reperfusion. The total catecholamine dose used for 24 hr after reperfusion (r) was 61.9 +/- 13.4 in Group C and 43.9 +/- 19.2 in Group F (p < 0.05). CK-MB at 3 and 6 hr after reperfusion was 65.9 +/- 13.5 and 64.8 +/- 15.8 in Group C and 45 +/- 11.8 and 38 +/- 10.8 in Group F, respectively (p < 0.05). The pulmonary index after reperfusion at 3 and 6 hr was 1.7 +/- 0.5 and 1.3 +/- 0.4 in Group C and 0.7 +/- 0.3 and 0.6 +/- 0.4 in Group F, respectively (p < 0.05). There was significantly better preserved lung function in Group F. In conclusion, leukocyte depletion was significantly effective in preserving heart and lung function during cardiopulmonary bypass.     

Interferon-gamma-inducing factor gene transfection into Lewis lung carcinoma cells reduces tumorigenicity in vivo

The operative mortality and morbidity in patients with severe left ventricular dysfunction who undergo coronary artery bypass grafting (CABG) remain high. The low ejection fraction is the major risk factor for operative mortality. However, ejection fraction (EF) alone may not necessarily be an accurate predictor of operative mortality. We studied the correlation between indices of left ventricular volume and operative mortality. One thousand patients undergoing isolated coronary bypass operations were divided into three groups according to their preoperative ejection fraction. Fifty patients (group I) had severe left ventricular dysfunction (EF < or = 0.3), 56 patients (group II) had moderately left ventricular dysfunction (0.3 < EF < or = 0.4) and 894 patients (group III) had good left ventricular function (EF > 0.4). We analyzed the relationship between hospital mortality and left ventricular volume in 106 patients with an EF < or = 0.4. RESULTS: Cardiac index was not significantly different among the three groups. The left ventricular end-diastolic pressure (LVEDP) and mean pulmonary artery pressure in groups I an II were higher than those in group III. The left ventricular end-diastolic volume (LVEDV) was 146 +/- 44 ml/m2 in Group I, 112 +/- 31 ml/m2 in Group II and 82 + 30 ml/m2 in Group III, respectively (Group I versus II, p < 0.05, Group I and II versus III, p < 0.01). The left ventricular end-systolic volume (LVESV) was 111 +/- 38 ml/m2 in Group I, 72 +/- 21 ml/m2 in Group II and 30 +/- 14 ml/m2 in Group III, respectively (Group I versus II, p < 0.05, Group I and II versus III, p < 0.01). The LVEDV and LVESV were higher in Group I than in Group II and both in Groups I and II were higher than in Group III. The hospital mortality of any cause before discharge was 8.0% (4/50) in Group I, 3.6% (2/56) in Group II, and 2.0% (18/894) in Group III. The mortality in Group I was higher than that in Group III, but the mortality between Groups I and II was not different. We assessed correlations between large left ventricle with left ventricular dysfunction and operative mortality in 106 patients with ejection fractions of < or = 0.4. The hospital mortality in patients with both under fraction 0.4 and an LVESV > or = 140 ml/m2 was 50% (4/8). This rate was higher than in patients with an LVESV between 80 and 140 ml/m2 (1.8%, 1/55) (p = 0.0006) and an LVESV less than 80 ml/m2 (2.3%, 1/43), (p = 0.0013). The hospital mortality in patients with an LVEDV > or = 200 ml/m2 was 67% (4/6). It was also higher than that in patients with an LVEDV between 200 and 120 ml/m2 (1.7%, 1/58), (p = 0.0001), and an LVEDV less than 120 ml/m2 (2.4%, 1/42), (p = 0.0004). We conclude that patients with a low ejection fraction and an elevated LVESV or LVEDV are at increased risk for hospital death following CABG.     

Reversibility of cardiac dysfunction after valve replacement in elderly patients with severe aortic stenosis

BACKGROUND: The role of aortic valve replacement for aortic stenosis has not been fully defined in terms of the postoperative reversibility of cardiac dysfunction and pulmonary hypertension in elderly patients. METHODS: Cardiac function, assessed by radioisotope ventriculography and catheterization data, was evaluated before and after operation, and their results were compared between preoperative and postoperative data in each group of younger patients (<69 years, group I, n = 29) and elderly patients (> or =70 years, group II, n = 21). RESULTS: One month postoperatively the peak ejection rate determined by radioisotope ventriculography improved significantly in comparison with the preoperative value in elderly patients (preoperatively, 228 +/- 38 versus postoperatively, 319 +/- 116% end-diastolic volume per second, p < 0.05), although their preoperative peak ejection rate was severely depressed. The postoperative peak filling rate of the elderly group was not completely reversible to almost normal value, whereas that of the younger group was completely reversible. Early diastolic peak filling rate (one-third peak filling rate) was not reversible in both two groups. Pulmonary hypertension in the elderly patients was reversible to postoperative almost normal pulmonary artery pressure despite the severity of aortic stenosis (systolic pulmonary artery pressure preoperatively, 37 +/- 16 mm Hg versus postoperatively, 25 +/- 5 mm Hg, p < 0.02; diastolic pulmonary artery pressure preoperatively, 15 +/- 6 mm Hg versus postoperatively, 10 +/- 4 mm Hg, p < 0.05). CONCLUSIONS: Both cardiac dysfunction, reflected by reduction of peak ejection rate, and pulmonary hypertension in elderly patients with severe aortic stenosis were reversed, reaching almost normal values 1 month after operation.     

Neuronal protection from cerebral ischemia by synthetic fibronectin peptides to leukocyte adhesion molecules

Leukocytes play an important role in the development of ischemia/reperfusion injury. Recent work in our laboratory has demonstrated that a mixture of synthetic fibronectin peptides to leukocyte adhesion molecules reduces ischemic brain damage after transient focal cerebral ischemia. The purpose of this study was to evaluate the efficacy of the individual peptides on leukocyte accumulation, infarct size, and neurological outcome in rats subjected to 1 h of cerebral ischemia and 48 h of reperfusion. Thirty-five animals were divided into five groups: transient ischemia without treatment (Group I), treatment with arginyl-glycyl-aspartic acid (RGD) peptide (Group II), connecting segment (CS)-1 peptide (Group III), fibronectin (FN)-C/H-V peptide (Group IV), and scrambled FN-C/H-V peptide (Group V). Groups III and IV showed a significant decrease in the degree of leukocyte infiltration in the lesion and in the infarct size (p < 0.05) when compared to Groups I, II, and V. The neurological grade of Groups III and IV was significantly better than in Groups I, II, and V at 48 h after reperfusion (p < 0.01). Thus, in addition to demonstrating the potential efficacy of synthetic peptides as therapeutic agents for ischemia-reperfusion, these results also offer new insights into the mechanisms of leukocyte arrest and recruitment in ischemia/reperfusion injury.     

Measurement of pulmonary status and surfactant protein levels during dexamethasone treatment of neonatal respiratory distress syndrome

PURPOSE: To study the effect of epidural buprenorphine on minimum alveolar concentration (MAC) of volatile anaesthetics, duration of analgesia and respiratory function in the perioperative period. METHODS: One hundred and twenty patients, ASA I-II undergoing gynaecological surgery were randomly divided into three studies. The forty patients in each study were randomly divided into four groups depending on the dosage; Group I (control), Group II (80 micrograms. kg-1 morphine), Group III (4 micrograms. kg-1 buprenorphine), Group IV (8 micrograms. kg-1 buprenorphine). The MAC of halothane was measured following epidural administration of the agents in each group. The duration of analgesia was assessed by the first request for pentazocine. Postoperative analgesic effects were assessed by the total dosage of pentazocine required for the 48 hr after surgery. Respiratory rate (RR), minute volume (MV), and PaCO2 were measured during surgery and the postoperative period. The MAC of halothane was reduced in Group IV (P < 0.01). The duration of analgesia was 10.0 +/- 5.1 hr (Mean +/- SE) in Group I, 37.7 +/- 4.7 hr in Group II, 27.1 +/- 7.1 hr in Group III, and 44.4 +/- 4.1 hr in Group IV. Total dosage of pentazocine was lower in Group IV (P < 0.05) than in the other groups. The decrease of RR, MV and the increase of PaCO2 were observed within 60 min in Group III and IV dose dependently. CONCLUSION: Epidural buprenorphine administered in a dose of 4 or 8 micrograms. kg-1 provides postoperative analgesia that is no less effective than that of morphine.     

Mechanics of breathing in patients with atrial septal defect

Mechanics of breathing and pulmonary diffusing properties were investigated in 24 adult patients with atrial septal defect. The patients were divided into 3 groups according to mean pulmonary artery pressure: less than 19 mm Hg (group I), 20 to 24 mm Hg (group II), and greater than 25 mm Hg (group III). The only change observed in group I was a marked increase in diffusing capacity. Patients of group II showed not only an increase in diffusing capacity, but also an overt decrease in maximal expiratory flow at all lung volumes and at any given driving pressure. For these two groups, a highly significant inverse correlation was found between changes in diffusing and elastic lung properties (r = -0.71; P less than 0.001). In patients of group III, the expiratory flow remained clearly decreased; furthermore, lung compliance and lung volumes were sharply reduced, airway resistance was elevated, and diffusing capacity was normal. Finally, from group I to group III, the lung elastic recoil became progressively diminished at small lung volumes. These results suggest that an increased pulmonary blood volume induces an increase in diffusing capacity and a slight decrease in lung compliance. Simultaneous existance of high intravascular pressure strengthens the effects of increased pulmonary blood volume on lung mechanics and results in significant abnormalities in the lung mechanical behavior. It is postulated that these effects are due to a competition for space between vessels and airways within the bronchovascular sheaths, with a subsequent compression of small airways.     

Eosinophil surface antigen expression and cytokine production vary in different ocular allergic diseases

OBJECTIVES: Improving methods of donor heart preservation may permit prolonged storage and remote procurement of cardiac allografts. We hypothesized that continuous, sanguineous perfusion of the donor heart in the beating, working state may prolong myocardial preservation. METHODS: We developed a portable perfusion apparatus for use in donor heart preservation. Contractile, metabolic, and vasomotor functions were monitored simultaneously in an isolated swine heart. The metabolic state was monitored by myocardial tissue pH. Vasomotor function was assessed in isolated coronary ring chambers. Hearts were randomized into 3 groups: group I (n = 5), cardioplegic arrest, 12-hour storage at 4 degrees C with modified Belzer solution, and 2-hour sanguineous reperfusion in the working state; group II (n = 6), 12-hour continuous perfusion in the beating working state, 30 minutes of arrest (to simulate re-implantation time), and 2 hours of reperfusion, as above; group III (n = 7), coronary ring control hearts. RESULTS: At 2 hours of reperfusion, left ventricular developed pressure in group II was higher than in group I (mean +/- standard deviation: 90 +/- 6 mm Hg, 53 +/- 15 mm Hg, P = .005). Significantly less myocardial edema was observed in group II than in group I (73% +/- 4%, 80% +/- 1% water content, P = .01). Significantly less myocardial acidosis was noted in group II than in group I during preservation (pH 7.3 +/- 0.01, 6.1 +/- 0.03, P < .001) and reperfusion (pH 7.3 +/- 0.008, 6.8 +/- 0.05, P < .001). Coronary endothelial vasomotor function was better preserved in group II than in group I as evidenced by dose-response relaxation of coronary rings to 10(-8) mol/L bradykinin (37%, 55% delta baseline, P = .01). CONCLUSION: This new method extends the current preservation limit and avoids time-dependent ischemic injury, thereby allowing for distant procurement of donor organs.     

Rehabilitation of patients admitted to a respiratory intensive care unit

OBJECTIVE: Pulmonary rehabilitation has been shown to be of benefit to clinically stable patients with chronic obstructive pulmonary disease (COPD). This study examined the effect of pulmonary rehabilitation on some physiologic variables in COPD patients recovering from an episode of acute respiratory failure. DESIGN: A prospective, randomized study. SETTING: A respiratory intensive care unit (RICU). PATIENTS: Eighty COPD patients recovering from an episode of acute respiratory failure were randomized in a 3:1 fashion to receive stepwise pulmonary rehabilitation (group A, n=60 patients) or standard medical therapy (group B, n=20 patients). MAIN OUTCOME MEASURES: Improvements in exercise tolerance, sense of breathlessness, respiratory muscle function, and pulmonary function test values were measured, respectively, by exercise capacity (6-minute walking distance [6MWD]), dyspnea score (Visual Analog Scale [VAS]), maximal inspiratory pressure (MIP), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). INTERVENTIONS: Group A received pulmonary rehabilitation that consisted of passive mobilization (step I), early deambulation (step II), respiratory and lower skeletal muscle training (step III), and if the patients were able, complete lower extremity training on a treadmill (step IV). Group B received standard medical therapy plus a basic deambulation program. RESULTS: Sixty-one of 80 patients were mechanically ventilated at admission to the unit and most of them were bedridden. Twelve of the 60 group A patients and 4 of the 20 group B patients died during their RICU stay, and 9 patients required invasive mechanical ventilation at home after their discharge. The total length of RICU stay was 38+/-14 days for patients in group A versus 33.2+/-11 days for those in group B. Most patients from both groups regained the ability to walk, either unaided or aided. At discharge, 6 MWD results were significantly improved (p < .001) in Group A only. MIP improved in Group A only (p < .05), while VAS scores improved in both groups, but the improvement was more marked in group A (p < .001) than in group B (p < .05). CONCLUSIONS: COPD patients who were admitted to a RICU in critical condition after an episode of acute respiratory failure and who, in most cases, required mechanical ventilation benefited from comprehensive early pulmonary rehabilitation, compared with patients who received standard medical therapy and progressive ambulation.     

Aprotinin and recombinant human erythropoietin reduce the need for homologous blood transfusion in cardiac surgery

The effects of low dose aprotinin (Trasylol) and preoperative administration of recombinant human erythropoietin (EPO) were evaluated in 144 patients undergoing cardiopulmonary bypass divided into four groups. Group I (n = 43) received a subcutaneous administration of EPO (18,000 U) one week before operation and intraoperative administration of low-dose aprotinin (mean; 1.38 +/- 0.26 x 10(6) kallikrein inactivator units; KIU) from extracorporeal circulation, group II (n = 39) received only preoperative administration of EPO, group III (n = 28) received only intraoperative administration of low-dose aprotinin (mean; 1.46 +/- 0.25 x 10(6) KIU), and group IV (n = 34) were not administered either drug. Compared with group IV, the intraoperative blood loss was significantly lower in group I (p < 0.01), and in group II or III (p < 0.05). The postoperative drainage in 24 hours was significantly lower in groups I and III receiving aprotinin than in the other groups. The mean volume of total homologous blood transfusion and the percentage of cases not requiring a homologous blood transfusion in each group was, respectively, 74 +/- 235 ml and 88.4% in group I, 282 +/- 1289 ml and 87.2% in group II, 414 +/- 584 ml and 60.7% in group III, and 976 +/- 1931 ml and 44.1% in group IV. Significant differences were recognized between group I and group IV (p < 0.05). These findings indicate that when used in combination, both drugs reduce blood loss and the need for a homologous blood transfusion more effectively than either drug alone.