Biomedical subjects

John W Hoffman

Publications and source records attributed to John W Hoffman.

3 recordsLinked to original sources

PubMed2004

Optimizing donor heart outcome after prolonged storage with endothelial function analysis and continuous perfusion.

BACKGROUND: By minimizing tissue ischemia, continuous perfusion (CP) during organ transport may increase the safety of "marginal donors." My colleagues and I investigated whether an analysis of donor heart viability predicts recovery of grafts challenged with a 24-hour preservation interval. METHODS: Dog hearts underwent cold static storage (CS) for 8 hours (n = 8) or 24 hours (n = 2) or CP for 24 hours with cold asanguinous, oxygenated solution (n = 8). Myocardial systolic and diastolic function and oxygen and lactate consumption were assessed at base line, during CP, and after Langendorff blood reperfusion. Base line endothelial function was evaluated by the percentage transcoronary change ([coronary sinus - aorta]/aorta) in myeloperoxidase and by platelet function and coronary flow reserve after 20 seconds of coronary artery occlusion. During CP, the endothelium was assessed by transcoronary protein release and coronary resistance. Edema was assessed by weight gain and histology. RESULTS: Base line systolic and metabolic functions showed no relation to post-Langendorff function. Compared with CS, CP resulted in a greater recovery in systolic function (87% +/- 35% vs 65% +/- 15% of baseline; p = 0.05) and a shorter interval required for lactate consumption to exceed production (7.0 +/- 6.8 minutes vs 15.0 +/- 8.9 minutes; p = 0.06). Endothelial function was heterogeneous: coronary flow reserve, 2.7 +/- 0.7; percentage change in myeloperoxidase, -8.4% +/- 6.8%; and change in platelet function, 4.3% +/- 3.5%, as determined by thromboelastography angle at base line. Protein release during CP for 24 hours was 8.3 +/- 7.1 g. Two factors predicted more than 75% systolic pressure generation recovery: use of CP and normal endothelial function (p = 0.05; Fisher's exact test). However, CP led to edema according to histology, weight gain (72 +/- 29 g), and impaired diastolic function versus CS (end-diastolic pressure-volume relationship, 1.4 +/- 0.4 mm Hg/mL vs 0.8 +/- 0.3 mm Hg/mL; p = 0.08). CONCLUSIONS: Better systolic function despite 16 hours' more preservation than cold storage corroborates the idea that CP supports aerobic metabolism at physiologically important levels. Viability analysis focused on endothelial function and identified organs that were able to tolerate this 24-hour preservation interval.

Aerobiosis↗

PubMed2004

Myocardial reperfusion injury: etiology, mechanisms, and therapies.

Reperfusion of ischemic myocardium is required for tissue survival; however, reperfusion elicits pathologic consequences. Myocardial reperfusion injury is a multifarious process that is mediated in part by oxygen free radicals, neutrophil-endothelium interactions, apoptosis, and intracellular calcium overload. The oxygen paradox describes the contradictory need to delivery oxygen to ischemic tissue and the resultant reduction of oxygen to form free radicals that are involved in macromolecule oxidation, membrane disfunction, apoptosis, and damaged calcium sequestering ability, which results in hypercontracture. These cell-damaging crises are amplified by the excessive activation of neutrophils, which promote the formation of proinflammatory mediators, oxygen radicals, and the reduction of endothelial nitric oxide formation, leading to increased neutrophil-endothelium interactions and capillary occlusion. Neutrophil action is twofold, however, because it is required for necrotic debris removal after severe ischemia. The oxygen radicals produced by neutrophils, endothelium, and myocytes may also play a role in activating the apoptotic cascade. Although the role of apoptosis in reperfusion injury is controversial, apoptotic cells are found in infarcted tissue. One of the key mediators may be increased inner mitochondrial membrane permeability, resulting in reduced ATP formation, release of cytochrome c, and caspase activation, which is key to promotion of apoptosis. Increased mitochondrial membrane permeability occurs during exposure to supraphysiological calcium concentrations. This occurs because of compensatory Na+/Ca2+ exchange to remove the excess intracellular sodium resulting from decreased Na+/K+ pumping during ischemia and increased Na+/H+ exchange following reperfusion. Supraphysiological calcium elicits hypercontracture and cellular damage. The various therapies being developed to diminish myocardial reperfusion injury involve inhibition of the processes described above as well as others. Although single therapies have shown some promise, the complexity of the response to reperfusion has made dramatic improvement elusive. Effective treatment will most likely require multifaceted antagonism of the numerous pathological cascades initiated by reperfusion.

Antioxidants↗

PubMed2002

Nonheparinized partial cardiopulmonary bypass for repair of traumatic aortic rupture.

Traumatic aortic rupture requires rapid, definitive repair for optimal outcome, particularly with respect to distal neurologic function. Over the past 10 years, the R Adams Cowley Shock Trauma Center of the University of Maryland has used partial cardiopulmonary bypass without systemic heparization exclusively for all repairs of the descending aorta. A heparin-bonded circuit allows for controlled distal perfusion and obviates the need for heparinization. Excellent outcome with minimal morbidity has been achieved using this technique. Our protocol and perfusion apparatus are discussed within.

Aorta, Thoracic↗