The Journal of thoracic and cardiovascular surgery
-
J. Thorac. Cardiovasc. Surg. · Sep 1996
Neutrophil endopeptidase inhibitor improves pulmonary function during reperfusion after eighteen-hour preservation.
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. ⋯ 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.
-
J. Thorac. Cardiovasc. Surg. · Sep 1996
Comparative StudyEffects of oxygen, positive end-expiratory pressure, and carbon dioxide on oxygen delivery in an animal model of the univentricular heart.
Respiratory manipulations are a mainstay of therapy for infants with a univentricular heart, but until recently little experimental information has been available to guide their use. We used an animal model of a univentricular heart to characterize the physiologic effects of a number of commonly used ventilatory treatments, including altering inspired oxygen tension, adding positive end-expiratory pressure, and adding supplemental carbon dioxide to the ventilator circuit. ⋯ This model demonstrated the value of estimating the pulmonary/systemic flow ratio before initiating therapy. When the initial ratio was greater than about 0.7, interventions that decreased the ratio increased oxygen delivery and were beneficial. When the initial pulmonary/systemic flow ratio was below 0.7, interventions that decreased the ratio decreased oxygen delivery and were detrimental. We conclude by presenting a framework to guide therapy based on the combination of arterial and venous oxygen saturations and the estimate of the pulmonary/systemic flow ratio that they provide.
-
J. Thorac. Cardiovasc. Surg. · Sep 1996
Comparative StudyCanine double-lung transplantation with cadaveric donors.
If lungs could be retrieved from cadavers after circulatory arrest, the critical shortage of donors for lung transplantation might be alleviated. To assess gas exchange after transplantation of lungs from cadaveric donors, we performed double-lung transplantation through sequential thoracotomies in 12 dogs. Donors were sacrificed by intravenous pentobarbital injection and then ventilated with 100% oxygen. ⋯ Donor lungs retrieved at 2 and 4 hours postmortem afford similar recipient outcomes. Improvement in alveolar-arterial oxygen gradient and reduction in extravascular lung water during the study period imply that the ischemia-reperfusion injury induced by this model is reversible. If this approach could be safely introduced to clinical practice, substantially more transplant procedures could be performed.
-
J. Thorac. Cardiovasc. Surg. · Sep 1996
Comparative StudyLasting beneficial effect of short-term inhaled nitric oxide on graft function after lung transplantation. Paris-Sud University Lung Transplantation Group.
The combination of ischemia and reperfusion after lung transplantation is characterized by endothelial damage, neutrophil sequestration, and decreased release of endothelial nitric oxide. Because nitric oxide has been shown to selectively dilate the pulmonary vasculature, abrogate neutrophil adherence, and restore endothelial dysfunction, we hypothesized that inhaled nitric oxide given for 4 hours during initial reperfusion might attenuate reperfusion injury in a porcine model of left single-lung transplantation. We tested hemodynamic and gas exchange data, lung neutrophil sequestration, and pulmonary artery endothelial dysfunction after 4 and 24 hours of reperfusion in 12 pigs randomly assigned to nitric oxide and control groups. ⋯ This effect is probably mediated by a decrease in neutrophil sequestration. A protective effect on the contralateral lung was also observed. Inhaled nitric oxide may be a suitable agent when an acute reperfusion phenomenon is anticipated.
-
J. Thorac. Cardiovasc. Surg. · Sep 1996
Protective effects of dimethyl amiloride against postischemic myocardial dysfunction in rabbit hearts: phosphorus 31-nuclear magnetic resonance measurements of intracellular pH and cellular energy.
The effects of 5-(N,N-dimethyl)amiloride, a potent and specific Na(+)-H+ exchange inhibitor, were investigated in isolated perfused rabbit hearts subjected to ischemia and reperfusion. Phosphorus 31-nuclear magnetic resonance spectroscopy was used to monitor intracellular pH, creatine phosphate, beta-adenosine triphosphate, and inorganic phosphate. After cardioplegic arrest with St. ⋯ The creatine phosphate resynthesis and inorganic phosphate reduction during reperfusion were also unaffected. These findings suggest that Na(+)-H+ exchange plays an important role not only during reperfusion but also during ischemia for the development of postischemic cardiac dysfunction most likely by inducing primary Na+ and secondary Ca2+ overload. Specific Na(+)-H+ exchange inhibitors like dimethyl amiloride would have a potential therapeutic profile in cardiac surgery, especially if added before ischemia.