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Biomedical subjects

C G Tribble

Publications and source records attributed to C G Tribble.

At least 73 records · Page 4Linked to original sources

Use of over-sized mature pulmonary lower lobe grafts results in superior pulmonary function.

BACKGROUND: Mature lobar transplantation will increase the pediatric donor organ pool; however, issues regarding size discrepancy between donor grafts and recipient lungs remain unresolved. We hypothesized that an oversized mature pulmonary lobar allograft implanted into an immature recipient would provide adequate longterm pulmonary function versus a size-matched mature lobar graft or an immature whole lung. METHODS: We investigated our hypothesis in a porcine orthotopic left lung transplant model in which 19 immature animals made up one control and three recipient groups. Group I underwent sham left thoracotomy (control, n = 4). Group II received age- and size-matched immature whole left lung transplant (n = 6). Group III received mature size-matched left upper lobe transplants (n = 4). Group IV received mature over-sized left lower lobe transplants (n = 5). Twelve weeks after implantation, data were collected after the native right lung was excluded. RESULTS: Graft weight was significantly elevated in group IV as compared with the explanted lung (72.4 +/- 6.8 versus 38.3 +/- 4.5 g; p = 0.003). Pulmonary artery pressure and pulmonary vascular resistance were significantly elevated in group III as compared with the over-sized mature lower lobe transplants (51.8 +/- 2.2 versus 40.4 +/- 2.5 mm Hg [p < 0.0001] and 1,605.9 +/- 117.5 versus 857.6 +/- 133.6 dynes.s.cm-5 [p < 0.0005], respectively). A trend toward decreased oxygenation was identified in group II. CONCLUSIONS: Over-sized mature lobar grafts provide improved hemodynamics as compared with size-matched grafts. Mature left lower lobe grafts are superior to size-matched upper lobe grafts in this model, probably as a result of an augmented vascular bed.

Age Factors↗

Acellular low-potassium dextran preserves pulmonary function after 48 hours of ischemia.

BACKGROUND: We previously have shown that extracellular preservation solutions provide superior pulmonary protection after 18 hours of cold ischemia at 4 degrees C in an isolated, whole-blood-perfused, rabbit lung model. We also reported that the addition of 20% whole blood to a low-potassium dextran solution (BLPD) conferred no discernible advantage over low-potassium dextran (LPD) alone in this same model. Our current study was aimed at documenting the importance of blood in buffering extracellular preservation solutions during 24 to 48 hours of hypothermic ischemia. METHODS: We studied three groups of lungs using an isolated, whole-blood-perfused, ventilated, rabbit lung model. Lungs were flushed with Euro-Collins, LPD, or BLPD solution, and then were reperfused after 24, 36, or 48 hours of hypothermic storage at 4 degrees C. Continuous measurements of pulmonary artery pressure, pulmonary vascular resistance, left atrial pressure, tidal volume, and dynamic airway compliance were obtained. Fresh, non-recirculated venous blood was used to determine single-pass pulmonary venous-to-arterial O2 gradients. RESULTS: The 24-hour Euro-Collins group could not be completed because of immediate reperfusion failure. The 36-hour LPD group oxygenated significantly better than the 36-hour BLPD group (363.3 +/- 65.1 versus 145.3 +/- 40.3 mm Hg, respectively; p = 0.015). The 48-hour LPD group also experienced significant improvements in oxygenation when compared with the 48-hour BLPD group (pulmonary venous-arterial O2 difference of 239.4 +/- 48.4 versus 70.7 +/- 19.5 mm Hg, respectively; p = 0.012). The 48-hour LPD group also displayed significant improvements in pulmonary artery pressure (34.72 +/- 0.96 versus 55.52 +/- 7.37 mm Hg, respectively; p = 0.031) and pulmonary vascular resistance (39,737 +/- 1,291 versus 67,594 +/- 9,467 dynes.s.cm-5, respectively; p = 0.027) when compared with the 48-hour BLPD group. There were no significant differences between the three LPD groups. CONCLUSIONS: Extracellular solutions provide improved pulmonary preservation in an isolated rabbit lung model after 48 hours of cold ischemia. The addition of blood to extracellular preservation solutions diminishes pulmonary function when combined with ischemic periods of 36 to 48 hours.

Animals↗

Resection of multiple mediastinal paragangliomas with cardiopulmonary bypass.

The case of a patient who underwent simultaneous resection of two separate mediastinal paragangliomas is presented. The tumors were located in the aortopulmonary window and in the right atrioventricular groove. The patient had previously undergone resection of a glomus vagale tumor. The mediastinal lesions were removed with the aid of cardiopulmonary bypass, and the patient is doing well postoperatively.

Adult↗

Sodium nitroprusside exacerbates myocardial ischemia-reperfusion injury.

BACKGROUND: The role of nitric oxide in myocardial ischemia-reperfusion is controversial. Although many studies claim that nitric oxide ameliorates reperfusion injury, others suggest that it exacerbates such injury, possibly through peroxynitrite production. These discordant results may be attributable to a dose-dependent phenomenon. METHODS: Isolated rabbit hearts sustained sequential periods of blood perfusion (20 minutes), warm ischemia (30 minutes), and reperfusion (20 minutes). During reperfusion, four groups underwent intracoronary infusion of saline solution (n = 6), or the nitric oxide donor sodium nitroprusside (100 nm/min [SNP100, n = 6], 1 nmol x L(-1)/min(-1) [SNP1, n = 6], or 0.01 nmol x L(-1) x min(-1) [SNP0.01]). Left ventricular-developed pressure and oxygen consumption were measured after preischemic perfusion and reperfusion. Levels of myocardial nitrotyrosine, a marker for peroxynitrite, were measured after reperfusion with an immunoradiochemical assay. RESULTS: Postischemic-developed pressure and myocardial oxygen consumption were significantly higher in the saline group than all nitroprusside-reperfused groups (p < 0.01 for both parameters). However, there were no differences in either parameter between SNP100, SNP1, or SNP0.01. Nitrotyrosine levels were similar among the four groups (p = 0.43). CONCLUSIONS: Nitroprusside exacerbates myocardial ischemia-reperfusion injury over a wide range of doses, although the mechanism does not appear to be mediated by peroxynitrite.

Animals↗

Mature pulmonary lobar transplants grow in an immature environment.

OBJECTIVE: Mature lobar transplantation will increase the pediatric donor organ pool, but it remains unknown whether such grafts will grow in a developing recipient and provide adequate long-term support. We hypothesized that a mature pulmonary lobar allograft implanted in an immature recipient would grow. METHODS: We investigated our hypothesis in a porcine orthotopic left lung transplant model using animals matched by the major histocompatibility complex to minimize the effects of chronic rejection. Twenty-three immature animals (< 12 weeks of age and < 10 kg total body weight) received either sham left thoracotomy (SH control, n = 4), left upper lobectomy to study compensatory growth (UL control, n = 4), age-matched immature whole left lung transplants (IWL TXP, n = 6), mature (donor > 1 yr in age and > 40 kg in total body weight) left lower lobe transplants (MLL TXP, n = 5), or mature left upper lobe transplants (MUL TXP, n = 4). Twelve weeks after implantation, functional residual capacity of the left lung was measured and arterial blood gas samples were obtained after the native right lung had been excluded. The graft was excised and weighed, and samples for microscopy and wet/dry ratios were collected. RESULTS: Initial and final graft weights were as follows: IWL TXP group (34.6 +/- 1.5 and 107.8 +/- 5.9 gm, p < 0.0001), MLL TXP group (72.4 +/- 6.8 and 111.4 +/- 8.7, p < 0.001), and MUL TXP group (32.8 +/- 1.3 and 92.8 +/- 7.1 gm, respectively, p < 0.004). No significant differences between groups were demonstrated when functional residual capacity, wet/dry ratios, or oxygenation were compared. Immunohistochemical staining for the nuclear antigen Ki-67 demonstrated dividing pneumocytes. CONCLUSIONS: We conclude that a mature lobar graft implanted into an immature recipient grows by pneumocyte division in this model. Mature lobar transplants can be expected to grow and provide adequate long-term function in developing recipients.

Aging↗

Minimally invasive coronary artery bypass grafting decreases hospital stay and cost.

OBJECTIVE: The authors performed a retrospective cost analysis for patients undergoing revascularization of their left anterior descending (LAD) coronary artery either by standard coronary artery bypass grafting (CABG), percutaneous transluminal coronary angioplasty (PTCA), or minimally invasive coronary artery bypass grafting (MICABG). SUMMARY BACKGROUND DATA: Minimally invasive CABG has become a safe and effective alternative treatment for single-vessel coronary artery disease. However, the acceptance of this procedure as a routine alternative for the treatment of coronary artery disease will depend on both long-term graft patency rates as well as a competitive market cost. METHODS: The authors conducted a retrospective analysis of three patient groups undergoing LAD coronary revascularization from January 1995 to July 1996. Ten patients were selected randomly from this period after PTCA of an LAD lesion with or without stenting. Nine patients underwent standard CABG on cardiopulmonary bypass with a left internal mammary artery. Nine patients received MICABG via a limited left anterior thoracotomy and left internal mammary artery to LAD grafting without the use of cardiopulmonary bypass. RESULTS: Percutaneous transluminal coronary angioplasty (n = 10) was unsuccessful in two patients. One patient in the MICABG group (n = 9) was converted successfully to conventional CABG because of an intramyocardial LAD and dilated left ventricle. There was no operative morbidity or mortality in any group. Average length of stay postprocedure was decreased significantly for both the MICABG and PTCA groups when compared with that of conventional CABG (n = 9) (2.7 + 0.26, p = 0.009, and 2.6 + 0.54, p = 0.006, vs. 4.8 + 0.46, respectively). Total hospital costs for the MICABG and PTCA groups were significantly less when compared with those of standard CABG ($10,129 + 1104, p = 0.0028, and $9113 + 3,039, p = 0.0001, vs. $17,816 + 1043, respectively). There were no statistically significant differences between the MICABG and PTCA groups. CONCLUSIONS: The final role of minimally invasive CABG is unclear. This procedure is clearly cost effective when compared with that of PTCA and conventional CABG. The long-term patency rates for MICABG will determine its overall efficacy.

Angioplasty, Balloon, Coronary↗

Median arcuate ligament syndrome: a possible cause of idiopathic gastroparesis.

The median arcuate ligament syndrome (MALS) is characterized by abdominal pain, nausea, and vomiting attributed to compression of the celiac axis by a fibrous band (the median arcuate ligament) connecting the diaphragmatic crura. The pathophysiologic origin of these symptoms is not clearly understood. Theories invoking either a neurogenic or vascular origin for the clinical features associated with MALS have been proposed, but objective evidence to support these theories is lacking. We describe the clinical course and gastric myoelectrical features of a patient with postprandial epigastric pain, weight loss, gastroparesis, and gastric dysrhythmias in whom a diagnosis of MALS was established. Surgical decompression of the celiac axis in our patient resulted in resolution of abdominal pain, return to a full diet within 4 weeks without nausea or vomiting, improvement in radionuclide gastric emptying, and restoration of the gastric electrical rhythm to a normal 3 cycle/min conduction rate. This is the first demonstration of altered gastric myoelectrical activity in a patient with MALS. The regularization of the gastric electrical rhythm in our patient after surgical decompression of the celiac axis would support a neurogenic basis for the symptoms associated with MALS. MALS should be excluded in patients with idiopathic gastroparesis and unexplained epigastric pain.

Abdominal Pain↗

Knot performance of polypropylene sutures.

A mechanical performance test using an Instron Tensile Tester demonstrated the superior handling characteristics of Surgipro suture as compared to Prolene suture that facilitated knot construction without suture breakage. For both granny and square knots, the knot run down forces for the Surgipro sutures were significantly less than those encountered for comparable knots for Prolene sutures. This propensity of the two-throw knots of Surgipro sutures to advance without breakage considerably facilitated knot construction.

Materials Testing↗

Low-potassium solution for lung preservation in the setting of high-flow reperfusion.

BACKGROUND: We previously demonstrated that standard preservation using Euro-Collins solution impairs lung function in the setting of high-flow reperfusion because of potassium-induced vasoconstriction. Preservation strategies for single-lung transplantation are an important factor in patients with pulmonary hypertension. This study investigates the hypothesis that low-potassium preservation solution will improve function of lungs subjected to high-flow reperfusion. METHODS: Twenty-one New Zealand white rabbit lungs were harvested and studied on an isolated, blood-perfused model of lung function after 4 hours of cold ischemia at 4 degrees C. Control lungs were preserved with 50 mL/kg of cold saline solution flush (group I). Experimental lungs were preserved with low-potassium solution (group II) or Euro-Collins solution (group III) at similar temperatures and volumes. RESULTS: The pulmonary arteriovenous oxygen gradient at the end of the 30-minute high-flow reperfusion period was significantly higher in group II compared with group III (121.3 +/- 19.2 mm Hg versus 31.1 +/- 4.2 mm Hg; p < 0.001). The pulmonary vascular resistance was significantly lower in group II than in group III (46.3 +/- 1.8 x 10(3) dynes x s x cm(-5) versus 79.8 +/- 8.4 x 10(3) dynes x s x cm(-5); p < 0.01. The percent decrease in dynamic airway compliance in group III was significantly greater than in group I and II (-51.0% +/- 13.3% versus -10.2% +/- 3.4% and -11.2% +/- 2.8%, respectively; p < 0.001). Similarly, the wet to dry ratio of the lungs in group III was significantly greater than in groups I and II (13.9 +/- 2.3 versus 5.9 +/- 0.2 and 6.0 +/- 0.4, respectively; p < 0.001). CONCLUSIONS: These data demonstrate that a low-potassium preservation solution yields improved lung function after high-flow reperfusion in an ex vivo rabbit lung model. Lung preservation should be aimed at the clinical setting.

Animals↗

Thromboxane receptor blockade improves oxygenation in an experimental model of acute lung injury.

BACKGROUND: Adult respiratory distress syndrome remains a major cause of morbidity and mortality. We investigated the role of thromboxane receptor antagonism in an experimental model of acute lung injury that mimics adult respiratory distress syndrome. METHODS: Three groups of rabbit heart-lung preparations were studied for 30 minutes in an ex vivo blood perfusion/ventilation system. Saline control (SC) lungs received saline solution during the first 20 minutes of study. Injury control (IC) lungs received an oleic acid-ethanol solution during the first 20 minutes. Thromboxane receptor blockade (TRB) lungs received the same injury as IC lungs, but a thromboxane receptor antagonist (SQ30741) was added to the blood perfusate just prior to study. Blood gases were obtained at 10-minute intervals, and tidal volume, pulmonary artery pressure, and lung weight were continuously recorded. Oxygenation was assessed by measuring the percent change in oxygen tension over the 30-minute study period. Tissue samples were collected from all lungs for histologic evaluation. RESULTS: Significant differences were found between SC and IC lungs as well as TRB and IC lungs when comparing pulmonary artery pressure (SC = 33.1 +/- 2.2 mm Hg, TRB = 35.4 +/- 2.1 mm Hg, IC = 60.4 +/- 11.1 mm Hg; p < 0.02) and percent change in oxygenation (SC = -20.6% +/- 10.3%, TRB = -24.2% +/- 9.5%, IC = -57.1% +/- 6.2%; p < 0.03). None of the other variables demonstrated significant differences. CONCLUSIONS: Thromboxane receptor blockade prevents the pulmonary hypertension and the decline in oxygenation seen in an experimental model of acute lung injury that mimics adult respiratory distress syndrome.

Animals↗

Non-heart-beating donors: a model of thoracic allograft injury.

4ACKGROUND. Non-heart-beating donors (NHBDs) have been proposed for the critical shortage of donors for cardiac and pulmonary transplantation. We determined the effects of prearrest hypoxia and postarrest warm ischemia on cardiac and pulmonary allografts procured from NHBDs undergoing hypoxic arrest. METHODS. Rabbit hearts and lungs were procured from separate donors and placed on isolated blood perfusion circuits. Controls were excised and perfused without ischemia. Heart from NHBDs underwent either prearrest hypoxic perfusion alone or consecutive periods of prearrest hypoxic perfusion and 20 minutes of postarrest warm ischemia. A third group of hearts underwent 30 minutes of warm, global ischemia alone. Two groups of pulmonary allografts were studied using similar hypoxic perfusion/20-minute ischemia and 30-minute ischemia donors. RESULTS. Prearrest hypoxic perfusion clearly causes significant dysfunction of cardiac allografts from NHBDs compared with nonischemic controls. Prearrest hypoxic perfusion combined with postarrest ischemia results in an additive degree of dysfunction more severe than a similar period of warm ischemia alone. Both groups of experimental lungs displayed function similar to that of nonischemic controls in terms of pulmonary hemodynamics, airway resistance, and oxygenation potential. CONCLUSIONS. We conclude that prearrest hypoxic perfusion significantly contributes to the dysfunction of NHBD cardiac allografts. Pulmonary allografts may be more amenable to procurement of NHBDs.

Animals↗

Controlled reperfusion of cardiac grafts from non-heart-beating donors.

BACKGROUND: Hearts harvested from non-heart-beating donors sustain severe injury during procurement and implantation, mandating interventions to preserve their function. We tested the hypothesis that limiting oxygen delivery during initial reperfusion of such hearts would reduce free-radical injury. METHODS: Rabbits sustained hypoxic arrest after ventilatory withdrawal, followed by 20 minutes of in vivo ischemia. Hearts were excised and reperfused with blood under conditions of high arterial oxygen tension (PaO2) (approximately 400 mm Hg), low PaO2 (approximately 60 to 70 mm Hg), high pressure (80 mm Hg), and low pressure (40 mm Hg), with or without free-radical scavenger infusion. Non-heart-beating donor groups were defined by the initial reperfusion conditions: high PaO2/ high pressure (n = 8), low PaO2/high pressure (n = 7), high PaO2/low pressure (n = 8), low PaO2/low pressure (n = 7), and high PaO2/high pressure/free-radical scavenger infusion (n = 7). RESULTS: After 45 minutes of reperfusion, low PaO2/ high pressure and high PaO2/low pressure had a significantly higher left ventricular developed pressure (63.6 +/- 5.6 and 63.1 +/- 5.6 mm Hg, respectively) than high PaO2/high pressure (40.9 +/- 4.5 mm Hg; p < 0.0000001 versus both). However, high PaO2/high pressure/free-radical scavenger infusion displayed only a trend toward improved ventricular recovery compared with high PaO2/ high pressure. CONCLUSIONS: Initially reperfusing nonbeating cardiac grafts at low PaO2 or low pressure improves recovery, but may involve mechanisms other than decreased free-radical injury.

Animals↗

Intratracheal surfactant administration preserves airway compliance during lung reperfusion.

BACKGROUND: Decreased airway compliance after lung transplantation has been observed with severe ischemia-reperfusion injury. Further, it has been shown that the surfactant system is impaired after lung preservation and reperfusion. We hypothesized that surfactant replacement after allograft storage could preserve airway compliance during reperfusion. METHODS: Rabbit lungs were harvested after flush with 50 mL/kg of cold saline solution. Immediate control lungs were studied with an isolated ventilation/perfusion apparatus using venous rabbit blood recirculated at 40 mL/min, room-air ventilation at 20 breaths/min, and constant airway pressure (n = 8). Twenty-four-hour control lungs were preserved at 4 degrees C for 24 hours and then similarly studied (n = 7). Surfactant lungs underwent similar harvest and preservation for 24 hours, but received 1.5 mL/kg of intratracheal surfactant 5 minutes before reperfusion (n = 10). Airway pressure and flow were recorded continuously during 30 minutes of reperfusion. Tidal volume and airway compliance were calculated at 30 minutes. RESULTS: Tidal volume was 33.67 +/- 0.57, 15.75 +/- 5.72, and 29.83 +/- 1.07 mL in the immediate control, 24-hour control, and surfactant groups, respectively (p = 0.004, surfactant versus 24-hour control). Airway compliance was 1.94 +/- 0.27, 0.70 +/- 0.09, and 1.46 +/- 0.10 mL/mm Hg in the immediate control, 24-hour control, and surfactant groups, respectively (p = 0.002, surfactant versus 24-hour control). CONCLUSIONS: We conclude that surfactant administration before reperfusion after 24 hours of cold storage preserves tidal volume and airway compliance in the isolated ventilated/perfused rabbit model of lung reperfusion injury.

Animals↗

Both blood and crystalloid-based extracellular solutions are superior to intracellular solutions for lung preservation.

OBJECTIVE: Lung transplantation remains limited by donor organ ischemic time, inadequate graft preservation, and reperfusion injury. We evaluated lung preservation with use of an extracellular solution, with or without the addition of blood, as compared with preservation with the intracellular Euro-Collins solution. METHODS: With use of an isolated, whole blood perfused/ventilated rabbit lung model, we studied three groups of animals. Lungs were flushed with Euro-Collins, low-potassium dextran, or 20% blood-low-potassium dextran solution. Lungs were harvested en bloc, stored inflated at 4 degrees C for 18 hours, and then reperfused at 60 ml/min with whole blood. Continuous measurements of pulmonary artery pressure, pulmonary vascular resistance, and dynamic airway compliance were obtained. Fresh, nonrecirculated venous blood was used to determine the single-pass pulmonary venous-arterial oxygen gradient. RESULTS: Lungs preserved with Euro-Collins solution demonstrated elevated pulmonary artery pressure and pulmonary vascular resistance when compared with those preserved with low-potassium dextran and 20% blood-low-potassium dextran solutions (pulmonary artery pressure: 40.8 +/- 2.2 mm Hg vs 28.9 +/- 2.4 mm Hg and 28.3 +/- 1.5 mm Hg, respectively, p < 0.001; pulmonary vascular resistance: 46.0 +/- 3.1 x 10(3) dynes x sec x cm(-5) vs 29.0 +/- 4.2 x 10(3) dynes x sec x cm(-5) and 28.8 +/- 2.3 x 10(3) dynes x sec x cm(-5), respectively, p < 0.001). Euro-Collins solution-preserved lungs demonstrated a significant drop in compliance when compared with those preserved with low-potassium dextran and 20% blood-low-potassium dextran (-21.9% +/- 4.7% vs 1.8% +/- 3.3% and 1.4% +/- 6.2%, respectively; p = 0.002). Oxygenation was improved with low-potassium dextran and 20% blood-low-potassium dextran solutions as compared with that with Euro-Collins solution (296.3 +/- 54.6 mm Hg and 290.2 +/- 66.4 mm Hg, respectively, vs 37.2 +/- 4.6 mm Hg; p = 0.001). CONCLUSIONS: Extracellular solutions provided superior preservation of pulmonary function in this rabbit lung model of ischemia-reperfusion. However, the addition of blood does not confer any demonstrable advantage over low-potassium dextran solution alone with use of an 18-hour period of cold ischemia.

Animals↗

Neutrophil endopeptidase inhibitor improves pulmonary function during reperfusion after eighteen-hour preservation.

BACKGROUND: Reperfusion injury remains a significant problem after lung transplantation and is thought to be in part mediated by neutrophils. Ulinastatin inhibits release of elastase and cathepsin G from neutrophil granules. We hypothesized that inhibition of these neutrophi endopeptidases (proteases) would attenuate pulmonary reperfusion injury. METHODS: With an isolated, whole blood-perfused, ventilated rabbit lung model, we studied the effects of ulinastatin. All lungs were flushed with cold Euro-Collins solution, harvested en bloc, stored inflated at 4 degrees C for 18 hours, and reperfused with whole blood. The 18-hour control lungs (n = 8) were stored and reperfused. Low-dose (n = 8) and high-dose (n = 7) groups were treated with total doses of ulinastatin of 25,000 and 50,000 units, respectively, during flush and reperfusion. An additional control group of lungs (n = 8) was harvested, flushed, and immediately reperfused. RESULTS: The pulmonary artery pressure was significantly lower in the high-dose group than in the 18-hour control group (36.7 +/- 1.8 vs 44.8 +/- 2.9 mm Hg, p = 0.034). The percentage decrease in dynamic airway compliance was significantly less in the high-dose group than in the 18-hour control group (-13.8% +/- 4.4% vs -25.1% +/- 3.7%, p = 0.032). Both low-dose and high-dose ulinastatin treatments did not result in a significant improvement in oxygenation with respect to the 18-hour control group (72.2 +/- 25.8 vs 32.5 +/- 4.9 mm Hg, p = 0.21). CONCLUSIONS: Ulinastatin diminishes reperfusion injury after 18 hours of hypothermic pulmonary ischemia, with resultant improvements in pulmonary artery pressure and airway compliance. Improvement in pulmonary function after preservation and reperfusion with a neutrophil endopeptidase inhibitor confirms the role of endopeptidases in reperfusion injury and suggests an intervention to reduce their detrimental effects on early graft function.

Animals↗

Euro-Collins solution exacerbates lung injury in the setting of high-flow reperfusion.

Single-lung transplantation has been abandoned for the treatment of pulmonary hypertension by many centers because of overperfusion of the graft following implantation. Euro-Collins solution is currently used for lung preservation despite the vasoconstrictive effect of this intracellular-type solution. We hypothesized that high-flow reperfusion, alone or in combination with Euro-Collins-induced vasoconstriction, may cause lung dysfunction. Twenty-eight New Zealand White rabbit lungs were harvested and studied in an isolated, blood-perfused model of lung function after 4 hours of cold ischemia. Control lungs were preserved with 50 ml/kg cold saline solution flush and reperfused at either normal flow (60 ml/min) or high flow (120 ml/min). Experimental lungs were preserved with 50 ml/kg cold Euro-Collins solution and reperfused at normal or high flow rates. The arteriovenous oxygen gradient at the end of the 30-minute reperfusion period was significantly lower in the high-flow versus the low-flow experimental group (31.1 +/- 4.2 vs 130.6 +/- 41.6 mm Hg, p < 0.05). The pulmonary vascular resistance was increased in the high-flow groups and the experimental groups, with a statistically significant difference between low-flow experimental and control groups (64374.4 +/- 5722.6 vs 37041.5 +/- 2110.9 dynes x sec x cm(-5), p < 0.001). The percentage decrease in dynamic airway compliance in the high-flow experimental group was markedly different from that in the high-flow control group (-51% +/- 13.3% vs -10.15% +/- 3.4%, p < 0.05). Similarly, the wet/dry ratio of the lungs in the high-flow experimental group (13.92 +/- 2.32) was significantly greater than that in the low-flow experimental group (6.27 +/- 0.19, p < 0.01) and than that in the high-flow control group (5.88 +/- 0.23, p < 0.001). These data demonstrate that high-flow reperfusion and preservation with Euro-Collins solution are deleterious to lung function, both individually and in combination, in an ex vivo rabbit lung model. Lung preservation with Euro-Collins solution may not be optimal when high-flow reperfusion is anticipated, as in the setting of unilateral lung transplantation for pulmonary hypertension.

Animals↗

Safe ex vivo coronary angiography with isosmotic contrast agent.

Plain-film coronary angiography of the cardiac explant on the operating table should be considered when conventional cardiac catheterization is desired but unavailable. We compared the effects of three contrast solutions on cold-preserved, isolated guinea pig hearts. Hearts were excised, perfused for 30 minutes, and arrested with Plegisol solution at 7 degree C. Twenty minutes after arrest, experimental hearts were perfused with one of three solutions: hyperosmolar Hexabrix solution (n = 6), hyperosmolar Renografin-76 solution (n = 6), or diluted, isosmotic Omnipaque solution (n = 8). The hearts were flushed with cold Plegisol solution 5 minutes later. Control hearts received no contrast during arrest (n = 9). The hearts were reperfused after 1 hour of arrest, and coronary blood flow (in millimeters per minute), left ventricular developed pressure (in millimeters of mercury), and rate of developed pressure (in millimeters of mercury per second) were measured. Endothelium-dependent smooth muscle relaxation to bradykinin administration and endothelium-independent relaxation to sodium nitroprusside administration were also assessed. No significant difference in myocardial or endothelial function was noted between control hearts and hearts perfused with Omnipaque solution. Hearts perfused with Renografin solution or Hexabrix solution, however, were found to have significantly impaired endothelial and myocardial function. We conclude that an isosmotic contrast solution should be used for ex vivo coronary angiography in cold-preserved hearts to avoid impairment of endothelial and myocardial function.

Animals↗

Enhanced isolated lung function after ischemia with anti-intercellular adhesion molecule antibody.

The binding of leukocytes to intercellular adhesion molecules expressed on endothelial surfaces during ischemia and subsequent reperfusion initiates leukocyte-mediated reperfusion injury. Interruption of this leukocyte-endothelium interaction may therefore prevent reperfusion injury. In an isolated, ventilated, blood-perfused rabbit lung preparation, we studied the effect of a monoclonal anti-intercellular adhesion molecule antibody on lung function during reperfusion. Lungs were harvested with 50 ml/kg cold Euro-Collins flush and 30 micrograms prostaglandin E1 before storage for 18 hours at 4 degrees C. Experimental groups received low-dose (100 micrograms) or high-dose (200 micrograms) anti-intercellular adhesion molecule antibody added to the pulmonary flush at harvest and to the initial reperfusate. Eighteen-hour control preparations were preserved for 18 hours and received saline solution vehicle. Immediate control preparations were harvested and immediately reperfused. The oxygen tension in the recirculated pulmonary venous effluent was measured after 30 minutes of reperfusion. Histologic specimens were graded by blinded observers for degree of leukocyte infiltration (0, normal, to 4, severe infiltration). The mean oxygen tensions (+/-standard error of the mean) were 138.29 +/- 6.23, 58.86 +/- 9.14, 86.87 +/- 11.32, and 139.33 +/- 16.15 mm Hg in immediate control preparations, 18-hour control preparations, low-dose antibody group, and high-dose antibody group, respectively (p = 0.0001). The leukocyte grades (mean +/- standard error of the mean) were 1.5 +/- 0.723, 3.0 +/- 0.955, 1.9 +/- 0.899, and 1.2 +/- 0.834, respectively (p = 0.0002). We conclude that anti-intercellular adhesion molecule antibody added to the pulmonary flush and initial reperfusate results in a dose-dependent enhancement of the reperfused lung's ability to oxygenate blood, possibly as a result of decreased leukocyte sequestration.

Animals↗