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Biomedical subjects

Irving L Kron

Publications and source records attributed to Irving L Kron.

At least 19 recordsLinked to original sources
PubMed2006

Attenuation of lung reperfusion injury by modified ventilation and reperfusion techniques.

BACKGROUND: High ventilation and perfusion pressures after lung transplantation may have deleterious effects. We hypothesized that using combined protective approaches for ventilation and perfusion would be optimal for reducing injury and improving function after ischemia-reperfusion. METHODS: Using an isolated, blood-perfused, rabbit lung model, lungs underwent 120 minutes of reperfusion either immediately (Sham) or after 18 hours of cold ischemia (IR). Groups Sham-P and IR-P underwent protective ventilation and reperfusion, and Groups Sham-C and IR-C underwent conventional ventilation and reperfusion. Protective ventilation involved gradually increasing the flow rate during 5 minutes to 1.8 liters/min, and conventional ventilation entailed immediate initiation of flow at 1.8 liters/min. Protective reperfusion involved gradually increasing perfusion during 5 minutes to 60 ml/min, and conventional reperfusion entailed immediate perfusion at 60 ml/min. Two other groups underwent either protective ventilation with conventional perfusion or vice versa. Airway pressure, pulmonary artery pressure, and arterial blood gases were measured throughout reperfusion. Wet/dry weight, highest oxygenation index, and bronchoalveolar lavage (BAL) protein were also measured. RESULTS: Protective ventilation and perfusion after ischemia (IR-P) resulted in significant improvements in lung function as measured by increased Po(2) and decreased Pco(2), airway pressure, and highest oxygenation index compared with conventional reperfusion (IR-C). Injury was significantly reduced in IR-P lungs as measured by reduced edema (wet/dry weight) and vascular leakage (BAL protein). In most cases, IR-P lungs performed better, with less injury than protective ventilation or perfusion alone. CONCLUSIONS: This protective approach of ventilation and perfusion after ischemia may improve lung function after transplantation, a simple method that could easily be applied clinically.

Administration, Inhalation↗
PubMed2006

An unusual case of cardiac dysfunction after left ventricular reconstruction.

This report describes an unusual cause of low cardiac output after coronary artery bypass grafting and left ventricular remodeling. It details left ventricular remodeling techniques and discusses the most recent advances and outcomes. As well, significant attention is paid to the issues surrounding failure to separate from cardiopulmonary bypass.

Aged↗
PubMed2006

Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury.

Lung ischemia-reperfusion (I/R) injury is a biphasic inflammatory process. Previous studies indicate that the later phase is neutrophil-dependent and that alveolar macrophages (AMs) likely contribute to the acute phase of lung I/R injury. However, the mechanism is unclear. AMs become activated and produce various cytokines and chemokines in many inflammatory responses, including transplantation. We hypothesize that AMs respond to I/R by producing key cytokines and chemokines and that depletion of AMs would reduce cytokine/chemokine expression and lung injury after I/R. To test this, using a buffer-perfused, isolated mouse lung model, we studied the impact of AM depletion by liposome-clodronate on I/R-induced lung dysfunction/injury and expression of cytokines/chemokines. I/R caused a significant increase in pulmonary artery pressure, wet-to-dry weight ratio, vascular permeability, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-2 expression, as well as decreased pulmonary compliance, when compared with sham lungs. After AM depletion, the changes in each of these parameters between I/R and sham groups were significantly attenuated. Thus AM depletion protects the lungs from I/R-induced dysfunction and injury and significantly reduces cytokine/chemokine production. Protein expression of TNF-alpha and MCP-1 are positively correlated to I/R-induced lung injury, and AMs are a major producer/initiator of TNF-alpha, MCP-1, and MIP-2. We conclude that AMs are an essential player in the initiation of acute lung I/R injury.

Acute Disease↗
PubMed2006

Comparison of systemic and retrograde delivery of adenosine A2A agonist for attenuation of spinal cord injury after thoracic aortic cross-clamping.

BACKGROUND: Paraplegia remains a devastating complication of thoracic aortic surgery, which has been attenuated by retrograde adenosine and systemic adenosine A2A receptor activation. We hypothesized that despite retrograde spinal perfusion of an adenosine A2A agonist (ATL-146e), systemic therapy produces superior spinal cord protection with reduced inflammation. METHODS: Forty pigs underwent 30-minute thoracic aortic cross-clamping. Pigs received: no therapy (control); retrograde saline (retrograde control); retrograde ATL-146e; systemic ATL-146e; systemic ATL-146e with retrograde saline; or systemic and retrograde ATL-146e. Retrograde therapies were given during ischemia. Systemic ATL-146e (0.06 microg.kg(-1).min(-1)) was given intravenously for 3 hours at reperfusion. At 24 hours, motor function was assessed using the Tarlov scale. Tissue was analyzed for neuronal viability, microtubule-associated protein-2 expression, and neutrophil sequestration (myeloperoxidase activity). RESULTS: Four pigs received retrograde barium showing both radiographic and histologic spinal cord perfusion. Tarlov scores at 24 hours were significantly improved versus both control groups in all ATL groups except the combined ATL-146e group (all p < 0.05). Neuronal viability by hematoxylin and eosin stain was significantly preserved in systemic ATL groups compared with both control groups (all p < 0.05). Microtubule-associated protein-2 expression was significantly preserved compared with both control groups in all systemic ATL groups. Systemic ATL significantly lowered myeloperoxidase activity versus both control groups (p < 0.01). CONCLUSIONS: Both retrograde and systemic ATL-146e therapies attenuate ischemic spinal cord injury, but combining the two routes was less effective. Given comparable results between the two routes and the simplicity of systemic delivery, peripheral venous ATL-146e at reperfusion should be preferred for spinal cord protection in thoracic aortic surgery.

Adenosine A2 Receptor Agonists↗
PubMed2006

Endothelial nitric oxide synthase is essential for postpneumonectomy compensatory vasodilation.

BACKGROUND: After pneumonectomy, the remaining lung vasculature must vasodilate to compensate for increased blood volume. We hypothesized that endothelial nitric oxide synthase (eNOS) is essential for compensatory vasodilation after pneumonectomy. METHODS: Adult, wild-type C57BL6 (WT) and eNOS knockout (eNOS-/-) mice underwent left pneumonectomy and recovered under normoxic conditions. Animals were lightly anesthetized at 1, 3, 7, or 14 days after pneumonectomy, and closed chest, systolic right ventricular pressure (RVP) was recorded using fine-needle cannulation. The right ventricle to left ventricle plus septum weight ratios were measured as an index of right ventricular hypertrophy. Two additional groups of mice (WT and eNOS-/-) were recovered after pneumonectomy in inhaled nitric oxide (iNO, 10 ppm), and RVP was measured on day 7. RESULTS: The eNOS-/- mice had significantly higher preoperative RVP than did WT (17.1 +/- 0.4 versus 14.2 +/- 0.2 cmH2O, p = 0.001). Both groups exhibited transient periods of pulmonary hypertension after pneumonectomy. On day 1, RVP was 80% above baseline in eNOS-/- mice (30.7 +/- 0.8 cmH2O) versus 42% in WT mice (20.2 +/- 0.7 cmH2O, p = 0.0001). The RVP returned to baseline in WT mice (16.3 +/- 0.2 cmH2O) but remained significantly elevated in eNOS-/- mice (28.6 +/- 0.9 cmH2O) at day 3 and at each time thereafter (p = 0.0001). The iNO significantly reduced RVP in eNOS-/- animals to 15.2 +/- 0.3 cmH2O (p = 0.0001) while having no effect in WT animals. Right ventricular hypertrophy was not observed in any group. CONCLUSIONS: Pneumonectomy results in a transient increase in RVP. Under normal circumstances, these pressures return to baseline within 3 days. The eNOS-/- mice failed to display compensatory vasodilation yet could be rescued with iNO. These results suggest that eNOS is essential for postpneumonectomy compensatory vasodilation.

Administration, Inhalation↗
PubMed2006

Does preoperative ejection fraction predict operative mortality with left ventricular restoration?

BACKGROUND: Ischemic cardiomyopathy and aneurysmal disease have been treated surgically with coronary artery bypass grafting in the past. The Dor technique for left ventricular restoration has demonstrated improved outcomes in patients with ischemic, akinetic ventricles. Our hypothesis was that even marked reduction in preoperative cardiac function (ejection fraction < .25) would not correlate with worse outcomes since the ventricle would be reshaped to improve function. METHODS: A retrospective analysis was performed on all patients who had undergone ventricular restoration with the Dor procedure from January 1996 through September 2005. Patients with a preoperative ejection fraction (EF) < .25 and those with a EF > or = .25 were compared. All Society of Thoracic Surgeons database characteristics, mortality, length of stay (LOS), and need for intraaortic balloon pump (IABP) were analyzed. RESULTS: The study included 89 patients (69 men, 20 women), 28 of whom had preoperative EFs < .25 (mean, .183 +/- .035; range, .08 to .25) and 61 had an EF > or = .25 (mean, .334 +/- .074; mean, .25 to .45). Overall operative mortality was 3.4% (3/89), with no statistically significant difference between the two groups (3.6% versus 3.3%). LOS was 7.4 +/- 3.6 days versus 8.9 +/- 15.6 days (p = NS), and need for IABP was 39.2% versus 8.1% (p < 0.05). Overall 5-year survival was 82%. Five-year survival in the EF < .25 cohort was 69.6% versus 88.3% in the EF > or = .25 cohort (p = 0.066). CONCLUSIONS: Ventricular restoration with the Dor technique is a safe procedure. Marked reduction in ejection fraction is not a contraindication to left ventricular restoration; however, increased usage of IABP should be anticipated.

Adult↗
PubMed2006

Lung transplantation in patients 60 years and older: results, complications, and outcomes.

BACKGROUND: Advanced recipient age is reported to negatively affect survival after lung transplantation (LTX). We hypothesized that LTX in patients aged > or = 60 years could be performed with acceptable outcomes. METHODS: We identified 182 consecutive LTX recipients from 1995 to 2005. Outcomes were analyzed and survival compared with results in recipients aged < 60, as well as with United Network for Organ Sharing (UNOS) registry outcomes for the same age and study period. Actuarial survivals were calculated by the Kaplan-Meier method. RESULTS: During the study period, 29% (52/182) of LTX recipients were > or = 60 years old (range, 60 to 69 years). Median follow-up was 2.9 years (range, 0 to 10 years). All patients but one received a single lung. Indications included chronic obstructive pulmonary disease in 63% (33/52), idiopathic pulmonary fibrosis in 27% (14/52), and other in 10% (5/52). In-hospital mortality was 12% (6/52) for those aged > or = 60 compared with 7% (9/130) for those aged < 60 (p = NS). Complications included reoperation in 10% (5/52), requirement for extracorporeal membrane oxygenation in 6% (3/52), renal failure in 12% (6/52), and stroke in 4% (2/52). Actuarial survivals at 30 days, and 1, 3, and 5 years were 90% (82, 98), 86% (76, 96), 71% (56, 85), and 55% (37, 73), respectively. No significant difference in survival was observed between age cohorts for our institutional data by Kaplan-Meier analysis (p = 0.34) or by Cox proportional hazard model (p = 0.15). A significant survival advantage was noted for our institution compared with UNOS for this cohort (p = 0.018). CONCLUSIONS: In carefully selected recipients > or = 60 years of age, LTX offers acceptable outcomes and survival.

Adolescent↗
PubMed2006

Early repair of complete atrioventricular septal defect is safe and effective.

BACKGROUND: Surgical repair of complete atrioventricular septal defect (CAVSD) is a well-established procedure performed on young children. Our hypothesis is that with modern techniques, the current risks of CAVSD repair in children aged younger than 3 months and in children older than 3 months are equal. METHODS: This was a retrospective review of 65 infants and children with a mean age of 10.9 months (range, 1 month to 15.5 years) who underwent CAVSD repair from 1990 to 2004. Twenty-six repairs (40%) were done on or before 3 months of age (group A) and 39 repairs (60%) were done after 3 months of age (group B). In all patients, the ventricular septal defect was repaired with an individualized approach according to each patient's specific anatomy: direct suturing without a patch, interposition of a small pericardial patch with a running suture, or both. The atrioventricular commissure was closed with interrupted sutures, and all atrial defects were closed with a pericardial patch. Data were analyzed using the chi2 analysis and the Fisher exact test. RESULTS: Three hospital deaths occurred (<30 days), 2 in group A and 1 in group B (7.7% vs 2.6%, respectively, p = 0.33). One death in group A occurred during another noncardiac surgery. Early reoperation (<1 year of initial surgery) for residual ventricular septal defect or significant mitral regurgitation, or both, occurred in 3 group A patients and in 4 group B patients (11.5% versus 10.3% respectively, p = 0.68). CONCLUSIONS: These results suggest that repair of CAVSD defects in children 3 months of age or younger had similar outcomes compared with those who underwent surgical repair after 3 months of age.

Adolescent↗
PubMed2006

Endoscopic versus open saphenous vein harvest for femoral to below the knee arterial bypass using saphenous vein graft.

BACKGROUND: Although the use of endoscopic vein harvest (EVH) in coronary artery bypass grafting is accepted, few studies have documented the implementation of EVH in peripheral vascular disease surgery. We hypothesized that EVH improves outcomes compared with open vein harvest (OVH) in patients undergoing femoral to below the knee arterial bypass surgery. METHODS: The charts of 144 consecutive patients undergoing infrainguinal bypass surgery over the course of 27 months were reviewed. A femoral to below the knee arterial bypass with saphenous vein was done in 88 patients (29 had EVH, 59 had OVH). The preoperative characteristics evaluated were age, gender, renal function, history of diabetes, hypertension, tobacco use, and previous infrainguinal bypass surgery on the affected side. End points included wound complications, length of hospital stay, operative time, angiographic and operative interventions for graft occlusion, patency rates, limb salvage, acute renal failure, myocardial infarction, and death. RESULTS: Patient characteristics and demographics were similar in the EVH and OVH groups. No operative intervention for occlusion was required in the EVH group (0/29) compared with 13.4% in the OVH group (8/59) (P = .03). At the mean follow-up time of 21 months, primary patency rate was 92.8% in the EVH group and 80.6% in the OVH group (P = .12). No significant differences were found between the EVH and OVH groups in postoperative complications, length of hospital stay, operative time, patency rates, limb salvage, and death. CONCLUSION: Despite our initial concerns of damaging the venous conduit with a minimally invasive approach to saphenous vein harvest, EVH in our experience has resulted in a trend toward improved patency rates and decreased infectious wound complications while affording the benefit of improved cosmesis. An endoscopic approach results in smaller incisions, decreased interventions for occlusion, and improved outcomes compared with OVH. EVH is the procedure of choice for harvesting saphenous vein for femoral to below the knee arterial bypass surgery.

Endoscopy↗
PubMed2006

Functional and cytoarchitectural spinal cord protection by ATL-146e after ischemia/reperfusion is mediated by adenosine receptor agonism.

BACKGROUND: ATL-146e protects the spinal cord from ischemia/reperfusion injury, presumably via adenosine A(2A) receptor activation, but this relationship remains unproven. We hypothesized that spinal cord functional and cytoarchitectural preservation from ATL-146e would be lost with simultaneous administration of the specific adenosine A(2A) antagonist ZM241385 (ZM), thus proving that adenosine A(2A) receptor activation is responsible for the protective effects of this compound. METHODS: New Zealand White rabbits underwent 45 minutes of infrarenal aortic cross-clamping. Groups (n = 10) included sham, ischemia, ischemia plus ATL-146e (ATL-146E), ischemia plus ZM, or ischemia with both compounds (agonist-antagonist). Tarlov scores were recorded every 12 hours. After 48 hours, the spinal cord was fixed for histology and microtubule-associated protein 2 immunohistochemistry. RESULTS: Tarlov scores at 48 hours were significantly better in the sham and ATL-146E groups (5.0 and 3.9, respectively) compared with the other three groups (all < or =1.3; P < .001). On hematoxylin and eosin, neuronal viability was higher in the sham, ATL-146E, and agonist-antagonist groups compared with the control and ZM groups (P < .05). Microtubule-associated protein 2 expression was preserved in the sham and ATL-146E groups but was lost in the ATL + ZM, ZM241385, and control groups. CONCLUSIONS: ATL-146e preserves the spinal cord in terms of both cytoarchitecture and function after reperfusion of the ischemic spinal cord, but this preservation is not completely blocked by competitive adenosine A(2A) receptor antagonism. Although ATL-146e does seem to partially function through activation of the adenosine A(2A) receptor, the neuroprotective mechanism may not be limited to this particular receptor.

Adenosine A2 Receptor Agonists↗
PubMed2006

Thoracic aortic endografting is the treatment of choice for elderly patients with thoracic aortic disease.

OBJECTIVE: To assess the effect of age on outcomes following thoracic aortic endografting. SUMMARY BACKGROUND DATA: Endograft therapy for thoracic aortic disease is rapidly evolving. This therapy is less invasive, and elderly patients with significant medical comorbidities are more frequently referred for endografting. We hypothesized that elderly patients over the age of 75 have worse outcomes after thoracic endografting than patients under the age of 75. METHODS: We retrospectively reviewed the charts of the first 42 patients who underwent endografting for thoracic aortic pathology. Charts were reviewed for demographics, comorbid conditions, perioperative complications and death, endoleaks, and results at 3, 6, and 12 months. Preexisting medical conditions were also evaluated to determine if any patient characteristics were associated with adverse outcomes. Perioperative morbidity included cardiac, pulmonary, renal, hemorrhagic, and neurologic (stroke and spinal cord injury) complications. RESULTS: Twenty-four patients were under the age of 75, and 18 patients were 75 or older. Baseline demographics and comorbidities were similar between the 2 groups. There were no differences in operative time, length of stay, perioperative mortality, or the incidence of significant complications between the 2 age groups. Gender, however, was associated with a statistically significant difference between the occurrence of complications, with more women experiencing complications than men (P = 0.026, relative risk = 2.36). One patient (age >75 years) in the entire cohort of 42 (2.4%) suffered a spinal cord injury. At 3 months, endoleaks were more common in the older age group (P = 0.059). CONCLUSION: Endograft therapy for thoracic aortic disease can be performed safely in elderly patients with no significant increase in perioperative morbidity or mortality compared with younger patients. Female gender is associated with a higher likelihood of perioperative complications, regardless of age. The overall incidence of spinal cord injury is very low. Endograft therapy, when anatomically possible, is the treatment of choice for thoracic aortic disease in elderly patients.

Adult↗
PubMed2006

A comparison of adenosine A2A agonism and methylprednisolone in attenuating neuronal damage and improving functional outcome after experimental traumatic spinal cord injury in rabbits.

OBJECT: Steroid agents remain the lone pharmacological treatment in widespread use for acute spinal cord injury (SCI), although their utility remains in dispute in the neurotrauma literature. Adenosine A2A receptor activation with ATL-146e, a selective A2A agonist, has shown potential benefit in treating SCI; however, it has not been compared with the gold standard, methylprednisolone. The authors of this study evaluated ATL-146e and methylprednisolone for their ability to preserve neuronal viability and motor function in experimental SCI. METHODS: New Zealand White rabbits sustained SCI or sham injury via the Allen weight-drop technique. Ten minutes postinjury, animals received ATL-146e (ATL group, 0.06 microg/kg/min intravenously for 3 hours), methylprednisolone (steroid group, 30 mg/kg intravenously), or saline (trauma control group). Hindlimb motor function was recorded every 12 hours using the Tarlov motor grading scale (0, paralysis-5, normal hop). At 48 hours, fixed spinal cord tissue was evaluated for neuronal viability. Hindlimb motor function in animals treated with ATL-146e was equivalent to that of sham-injured animals and was significantly better than that of trauma control animals at all time points and that of steroid-treated animals at 12 hours (p = 0.05). Motor function in steroid-treated animals was worse than in those given ATL-146e and better than that of trauma control animals at later time points, but was not statistically significant (both p > 0.05). Neuronal viability (measured in neurons/hpf) was significantly higher in both treatment groups compared with the trauma control group (12.1 +/- 1.4 neurons/hpf for the ATL and 13.3 +/- 1.4 neurons/hpf for the steroid group compared with 7.5 +/- 1.5 neurons/hpf for the trauma control group; both p < 0.04). Neuronal viability did not differ among ATL-146e-treated, steroid-treated, and sham-injured groups. CONCLUSIONS: The use of ATL-146e is at least as effective as methylprednisolone in preserving function and is equivalent to methylprednisolone in preserving the structure of spinal cord tissue after blunt SCI. Adenosine A2A receptor activation may be an effective treatment for acute SCI while avoiding the adverse effects of steroid agents.

Animals↗
PubMed2005

Adenosine A2A receptor agonist improves cardiac dysfunction from pulmonary ischemia-reperfusion injury.

BACKGROUND: Ischemia-reperfusion (IR) injury negatively impacts patient outcome in lung transplantation. Clinically, we observed that lung transplant patients with ischemia-reperfusion injury tend to have cardiac dysfunction. Previous studies have shown that ATL-146e (4-{3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester), a selective adenosine A2A receptor agonist, reduces lung inflammation after ischemia-reperfusion. We hypothesized that pulmonary ischemia-reperfusion causes secondary heart dysfunction and ATL-146e will improve this dysfunction. METHODS: We utilized an in vivo rabbit lung ischemia-reperfusion model. The Sham group underwent 120 minutes single lung ventilation. The IR and ATL groups underwent 90 minutes right lung ischemia with 30 minutes right lung reperfusion. The ATL-146e was given intravenously to the ATL group during reperfusion. Cardiac output and arterial blood gases were monitored, and neutrophil sequestration was measured by myeloperoxidase activity. RESULTS: Upon reperfusion, cardiac output (mL/min) significantly dropped in the IR and ATL groups. By 15 minutes reperfusion, cardiac output in the ATL group improved significantly over the IR group and remained significant thereafter. Lung myeloperoxidase activity was significantly reduced by ATL-146e. Although never hypoxemic, arterial oxygenation was lower in the IR and ATL groups while central venous pressures and mean arterial pressures were similar among groups. A separate experiment demonstrated that reperfusion with the antioxidant N-(2-mercaptopropionyl)glycine prevented cardiac dysfunction. CONCLUSIONS: Pulmonary ischemia-reperfusion causes cardiac dysfunction independent of preload, afterload, and oxygenation. The ATL-146e improves this dysfunction presumably by the antiinflammatory effects of adenosine A2A receptor activation on neutrophils. One likely mechanism involves the release of oxidants from the ischemic lung upon reperfusion, which has immediate negative effects on the heart.

Adenosine A2 Receptor Agonists↗
PubMed2005

Acute sleep deprivation in the thoracic surgical resident does not affect operative outcomes.

BACKGROUND: There is an increasing trend toward work hour restrictions for doctors world wide. These reforms have been inspired, in part, by the assertion by some that the fatigued physician is more prone to making errors. Interestingly, there is very little in the way of objective data with regard to the effects of sleep deprivation on patient outcomes. We have recently studied this in attending surgeons. The present study focused on thoracic surgical residents. Our hypothesis was that acute sleep deprivation would not lead to an increase in operative times or complications. METHODS: A retrospective review of all cases performed by thoracic surgical residents at the University of Virginia from January 1994 to March of 2004 was done. Complication rates of cases performed by "sleep deprived" (SD) residents were compared with cases done when the residents were "not sleep deprived" (NSD). A resident was deemed sleep deprived if he or she performed a case the previous evening that started between 10 pm and 5 am or ended between the hours of 11 pm and 7:30 am. RESULTS: A total of 7,323 cases were recorded in the STS database over the 10-year period examined. Two hundred and twenty-nine of these cases (3%) were performed by SD residents. Mortality rates for coronary artery bypass operations showed no significant differences (2.1% [SD = 3 of 141 patients] vs 3.1% (NSD = 143 of 4452 patients), p = 0.63). A comparison of operative, neurologic, renal, infectious, and pulmonary complications as well as cardiopulmonary bypass times, cross-clamp times, the use of blood products, and length of stay also demonstrated no significant differences between groups. CONCLUSIONS: Acute sleep deprivation in thoracic surgical residents does not affect operative efficiency, morbidity, or mortality in cardiac surgical operations.

Cardiac Surgical Procedures↗
PubMed2005

Hyperinflation during lung preservation and increased reperfusion injury.

BACKGROUND: Reperfusion injury after lung transplantation remains a perplexing and unpredictable problem. Most surgeons preserve the lung inflated, but the amount of inflation that should be used is not well documented. Therefore, we studied the effect of high inflation during organ preservation on lung function during reperfusion. Our hypothesis is that donor lung hyperinflation during storage contributes to early allograft dysfunction during reperfusion. METHODS: To test our hypothesis we used an isolated, blood-perfused, ventilated rabbit lung model. Group I lungs (control) underwent immediate reperfusion after harvest. Group II lungs (low-inflation, maintained at 6 mmHg airway pressure) and group III lungs (high-inflation, maintained at 20 mmHg airway pressure) were stored for 4 h in 4 degrees C Euro-Collins solution after harvest. All lungs were then reperfused with whole blood for 1 h, and measurements of arterial oxygenation (PO2, mmHg), pulmonary artery pressure (PAP, mmHg), peak inspiratory pressure (PIP, cm H2O), and wet-to-dry weight ratio (WTD) were obtained. RESULTS: Throughout the 1 h reperfusion period group III lungs had significantly lower oxygenation compared to groups I and II. In addition, throughout reperfusion, group III lungs showed significantly higher PAP and PIP compared to group II. WTD did not differ significantly between groups, however, there was a trend toward increased edema in group III. CONCLUSIONS: These results indicate that high inflation during cold storage results in acute pulmonary dysfunction. Careful monitoring of airway inflation pressure during storage, especially to prevent hyperinflation, should be maintained in the current practice for lung transplantation.

Animals↗
PubMed2005

Adenosine A2A receptor activation reduces inflammation and preserves pulmonary function in an in vivo model of lung transplantation.

BACKGROUND: Reperfusion injury continues to significantly affect patients undergoing lung transplantation. Isolated lung models have demonstrated that adenosine A 2A receptor activation preserves function while decreasing inflammation. We hypothesized that adenosine A 2A receptor activation by ATL-146e during the initial reperfusion period preserves pulmonary function and attenuates inflammation in a porcine model of lung transplantation. METHODS: Mature pig lungs preserved with Viaspan (Barr Laboratories, Pomona, NY) underwent 6 hours of cold ischemia before transplantation and 4 hours of reperfusion. Animals were treated with (ATL group, n = 7) and without (IR group, n = 7) ATL-146e (0.05 microg kg -1 . min -1 ATL-146e administered intravenously for 3 hours). With occlusion of the opposite pulmonary artery, the animal was maintained for the final 30 minutes on the allograft alone. Recipient lung physiology was monitored before tissue evaluation of pulmonary edema (wet-to-dry weight ratio), myeloperoxidase assay, and tissue tumor necrosis factor alpha by means of enzyme-linked immunosorbent assay. RESULTS: When the ATL group was compared with the IR group, the ATL group had better partial pressure of carbon dioxide (43.8 +/- 4.1 vs 68.9 +/- 6.3 mm Hg, P < .01) and partial pressure of oxygen (272.3 +/- 132.7 vs 100.1 +/- 21.4 mm Hg, P < .01). ATL-146e-treated animals exhibited lower pulmonary artery pressures (33.6 +/- 2.1 vs 47.9 +/- 3.5 mm Hg, P < .01) and mean airway pressures (16.25 +/- 0.08 vs 16.64 +/- 0.15 mm Hg, P = .04). ATL-146e-treated lungs had lower wet-to-dry ratios (5.9 +/- 0.39 vs 7.3 +/- 0.38, P < .02), lower myeloperoxidase levels (2.9 x 10 -5 +/- 1.2 x 10 -5 vs 1.3 x 10 -4 +/- 4.0 x 10 -5 DeltaOD mg -1 . min -1 , P = .03), and a trend toward decreased lung tumor necrosis factor alpha levels (57 +/- 12 vs 96 +/- 15 pg/mL, P = .06). The ATL group demonstrated significantly less inflammation on histology. CONCLUSION: Adenosine A 2A activation during early reperfusion attenuated lung inflammation and preserved pulmonary function in this model of lung transplantation. ATL-146e and similar compounds could play a significant role in improving outcomes of pulmonary transplantation.

Adenosine A2 Receptor Agonists↗