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Biomedical subjects

I L Kron

Publications and source records attributed to I L Kron.

At least 91 records · Page 5Linked to original sources

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↗

Transatrial approach to posterior postinfarct ventricular septal defects.

Repair of posterior postinfarct ventricular septal defects via the transinfarct left ventriculotomy is technically challenging and can be associated with significant morbidity. A transatrial approach avoids incising through the acutely infarcted myocardium and, in selected cases, offers a safe and reliable repair of these defects.

Cardiac Surgical Procedures↗

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↗

Is clamp and sew still viable for thoracic aortic resection?

OBJECTIVE: The authors reviewed the morbidity and mortality of surgical resection of the descending thoracic and thoracoabdominal aorta using the clamp-and-sew technique. BACKGROUND: Paraplegia remains a devastating complication after thoracoabdominal aortic resection, despite many strategies for spinal cord protection. Because of its simplicity, clamp and sew has been the preferred technique at the University of Virginia for the thoracoabdominal aortic resection when proximal control is possible. METHODS: Between 1987 and 1994, the authors reviewed 91 consecutive patients who underwent thoracic aortic resection using clamp-and-sew techniques without any additional adjuncts for spinal cord protection. RESULTS: The average age of patients was 60.8 years; 57.1% were male. No intraoperative deaths occurred. In-hospital mortality was 13% (12/91), with an overall incidence of postoperative spinal cord injury manifested as paraparesis or paraplegia of 9.9% (9/91). Eighty-nine percent (81/91) of all repairs were completed with aortic clamp times of 40 minutes or less, and nearly six out of ten were completed in 30 minutes or less (53/91). Cross-clamp times were not significantly different between those patients who sustained neurologic injury and those who had no deficits. CONCLUSIONS: The authors conclude that clamp and sew is still a viable technique for thoracoabdominal aortic resection. Nearly all resections can be completed within 40 minutes of aortic occlusion. However, the "safe" duration of thoracic aortic occlusion remains unknown, and spinal cord injury can occur even with short clamp times. Reproducible, safe, and technically simple means of spinal cord protection must be developed.

Adolescent↗

Impaired bronchial healing after lung donation from non-heart-beating donors.

BACKGROUND: Bronchial viability after lung transplantation remains a concern. Modern preservation methods, surgical technique, and limited cold ischemic periods have decreased the frequency of bronchial complications. However, lungs procured from non-heart-beating donors are subjected to a mandatory period of warm ischemia. We investigated bronchial healing in a porcine survival model of left lung transplantation using organ procurement from non-heart-beating donors after a 60-minute period of warm ischemia. METHODS: Fourteen adult domestic swine underwent left lung transplantation. All lungs were preserved with cold Euro-Collins flush and stored inflated at 4 degrees C. Control lungs (n = 5) were flushed, harvested, and stored for 2 hours before implantation. Experimental lungs (n = 9) were procured from non-heart-beating donors. These lungs were subjected to 60 minutes of warm ischemia before flush and harvest, followed by 2 hours of cold storage before implantation. After 21 days of immunosuppression with prednisone, azathioprine, and cyclosporine, pulmonary function was assessed. Bronchial viability was evaluated with bronchoscopy and, at autopsy, followed by histologic analysis. RESULTS: Implantation time did not differ significantly between the control group and the experimental group (59.6 +/- 2.1 versus 64.4 +/- 2.9 minutes, p = 0.24). Control swine exhibited no evidence of ischemic injury to the donor bronchus. In contrast, six of nine lungs procured from non-heart-beating donors showed evidence of ischemic bronchial injury (p = 0.031 versus control). Findings ranged from hypovascular edematous mucosa to necrosis and sloughing of the mucosa throughout the entire donor bronchial tree. The remaining three non-heart-beating donor lungs exhibited normal lung function and bronchial healing. CONCLUSIONS: We conclude that 60 minutes of warm ischemia for lungs procured from non-heart-beating donors results in impaired bronchial viability with current preservation techniques. Thirty minutes of warm ischemia may be the acceptable limit for lung procurement from non-heart-beating organ donors.

Animals↗

Prevention of spinal cord injury after repair of the thoracic or thoracoabdominal aorta.

Spinal cord injury occurring as the result of surgical repair of thoracic and thoracoabdominal aortic disease remains a devastating complication. The incidence of postoperative neurologic deficits varies from 4% to 38%. Factors associated with a greater risk for injury include the presence of dissection or extensive thoracoabdominal disease, and a prolonged cross-clamp time. Spinal cord ischemia initiates a deleterious cascade of biochemical events that ultimately result in an increased intracellular calcium concentration. Calcium-activated proteases, lipases, and nucleases mediate the processes that cause cell injury. The accumulation of oxygen-derived free radicals and the occurrence of hyperemia during reperfusion are also contributing causes of spinal cord injury. Increasing the spinal cord blood flow with shunts, oxygenated bypass circuits, cerebrospinal fluid drainage, the intrathecal administration of vasodilators, and the reattachment of intercostal arteries has been tried in an effort to increase spinal cord perfusion. Pharmacologically based measures to prevent spinal cord injury have been pursued, and these have consisted of hypothermia, anesthetic agents, calcium channel blockers, free radical scavengers, and immune system modulation. However, no single technique has proved to be consistently effective in preventing ischemia-induced spinal cord injury.

Aorta↗

Compensatory growth of porcine right lungs after chronic rejection of transplanted left lungs.

Neonatal lung hypoplasia is frequently a fatal condition often associated with congenital diaphragmatic hernia. Unilateral lung transplantation rarely has been performed for this indication, although it is a potential solution. It is not known whether the transplant needs to function permanently or to act as a bridge until the native lung develops. It is also not known whether the native lung will grow in the face of an immunosuppressed state and chronic rejection of the transplanted lung. We therefore developed a porcine model of left lung rejection to study this. Infant swine underwent left lung transplantation. Chronic rejection occurred in all, resulting in nonfunction of the transplanted lung. The right lungs of these animals were compared with the right lungs of size-matched and age-matched control animals not given immunosuppressive treatment and not undergoing transplantation. There were no differences in terms of the functional residual capacity, airway compliance, and airway resistance among the groups. There was a significant increase in the pulmonary vascular resistance in the animals with transplanted lungs. There was also a significant increase in the lung weight in these animals. Unilateral pneumonectomies were done in 4 infant pigs to serve as controls. Three of the 4 did not survive the operation because of acute pulmonary failure. In conclusion, the study group exhibited evidence of compensatory growth that was not seen in the control animals, as shown by the increase in lung weight. This suggests that contralateral lung growth occurs in a growing animal, despite the effects of immunosuppression therapy and chronic rejection of the transplanted lung.

Animals↗

The physiologic basis of warm cardioplegia.

BACKGROUND: Advances in myocardial protection have been instrumental in making cardiac surgery safer. Debate exists over the optimal medium and the optimal temperature for cardioplegia. Currently blood cardioplegia is preferred over crystalloid; the optimal temperature, however, remains controversial. METHODS: Both warm and cold blood cardioplegia use potassium-induced electromechanical arrest, thereby reducing oxygen consumption by 90% in the working heart. Hypothermic blood cardioplegia given every 15 to 30 minutes provides a bloodless operative field and reduces oxygen consumption an additional 5% to 20%. Continuous warm cardioplegia avoids the deleterious effects of hypothermic ischemia and minimizes reperfusion injury. Perfusion is often interrupted for 5 to 10 minutes to allow adequate visualization of the operative site. Both warm and cold cardioplegia can be given either antegrade or retrograde. RESULTS: Retrospective studies from Toronto support the safety and efficacy of warm cardioplegia. Two large prospective, randomized trials of warm cardioplegia versus intermittent cold blood or cold crystalloid cardioplegia demonstrated equally low incidences of death, perioperative myocardial infarction, and need of intraaortic balloon pump support. CONCLUSIONS: Warm blood cardioplegia represents the latest development in myocardial protection. Preliminary studies support its efficacy. Additional studies are needed to determine the ideal route of delivery and to identify any risks associated with the inherent warm cardiopulmonary bypass required.

Blood↗

Reducing bleeding after replacement of the aortic root.

Bleeding after replacement of the aortic root continues to be a major surgical problem. We detail two reliable methods, which are quick and simple to perform, that minimize surgical bleeding after aortic root replacement.

Anastomosis, Surgical↗

Predicting survival after coronary revascularization for ischemic cardiomyopathy.

BACKGROUND: The success of coronary revascularization for ischemic cardiomyopathy (left ventricular ejection fraction of 0.25 or less) has been unpredictable. We and others have demonstrated that the hospital operative mortality rate for these operations has been surprisingly low, particularly if evidence of ischemia is present. We subsequently liberalized our selection criteria based on our hypothesis that coronary artery bypass grafting is safe in this subset of patients regardless of the status of their distal coronary vasculature. METHODS: To examine this hypothesis, we studied retrospectively our patients undergoing coronary artery bypass grafting from 1983 to 1993. Ninety-six patients with ejection fractions of 0.25 or lower underwent this operation, with 88 hospital survivors (mortality 8%). All of the patients had clinical symptoms of heart failure. The male to female ratio was 4.6:1. The average age was 63.1 +/- 0.9 years (mean +/- standard error of the mean). Patients were excluded if they had valvular heart disease other than mild to moderate mitral regurgitation, required resection of a ventricular aneurysm, or required an emergency operation for acute coronary occlusion. Possible predictors of death were examined retrospectively. The catheterization films were reviewed retrospectively by a cardiovascular surgeon who was blinded to patient outcome and was never involved in the clinical management of any of the patients. Vessel quality was described as good, fair, or poor. RESULTS: Increased age and poor vessel quality were the only significant predictors of poor outcome. Sex, presence or absence of angina, preoperative angina, preoperative ejection fraction, preoperative arrhythmia disorder, aortic cross-clamp time, and the number of bypass grafts had no significant effect on outcome in the perioperative period. CONCLUSION: These results demonstrate that poor vessel quality and older age are predictors of poor outcome in patients with low ejection fractions undergoing myocardial revascularization. We conclude that poor distal coronary vasculature is a contraindication to coronary artery bypass grafting in patients with an ejection fraction of 0.25 or less, even if angina is present.

Age Factors↗

Strategies for success in academic surgery.

BACKGROUND: A growing concern among university surgeons is a perceived threat to the traditional academician role. Factors that have led to this concern include (1) changes in reimbursement and patient referral patterns, both of which have resulted in reduced income; (2) mounting external pressure from the departmental chairperson/dean to generate professional fees; (3) pervasive ambiguity in the criteria for promotion and tenure; (4) intensified competition for research dollars in recent years; and (5) a perception that fellow academicians view surgeons as operating room technicians incapable of laboratory research. These cogent issues have the means to place academic goals in jeopardy. Potentially they lead to dissatisfaction, unhappiness, and eventual departure from academia. A healthy solution to the problem includes departmental recognition and reward for whichever primary role/s the academic surgeon embraces--clinical, educational, research, or administrative. Clear chairperson-faculty communication on the issues of expectation and reward is a key ingredient in the solution. METHODS: A mail survey was conducted with chairpersons of surgical departments and academic surgeons addressing the issues of retention, promotion, and benefits. RESULTS: Results revealed significant differences in perceptions, suggesting the need for improved communication between faculty and chairpersons and a team approach to help maintain academic viability in the future. CONCLUSIONS: When the quadruple threat can be mutually described as a departmental rather than individual quality, the joys and rewards of academic surgery can be considerable for faculty and chairpersons alike.

Academic Medical Centers↗