University of Wisconsin solution provides superior myocardial preservation compared with Stanford cardioplegic solution.

The efficacy of the University of Wisconsin solution to safely prolong preservation times for kidney, pancreas, and liver transplantation is established, but its efficacy in enhancing myocardial preservation is not yet clear. We studied the effects of Stanford cardioplegic solution and the University of Wisconsin solution both in preserving the myocardium and in protecting it from the effects of reperfusion injury after 6 hours of preservation. In 28 rat hearts we measured changes in high-energy phosphate content (with magnetic resonance spectroscopy) and histologic changes (edema, endothelial changes, myocyte architecture) during preservation and changes in high-energy phosphate content, histologic status, and performance (aortic systolic and diastolic pressure, heart rate, rhythm) in Langendorff and working hearts during reperfusion. No significant differences in the kinetics of high-energy phosphate changes were noted between the two cardioplegic solutions during preservation. However, at the end of 6 hours of preservation, hearts in the Stanford cardioplegic solution group were more edematous (p < 0.01) than those in the University of Wisconsin group. During reperfusion, no significant differences in the kinetics of high-energy phosphates were noted between the two cardioplegic solutions. None of the hearts in the University of Wisconsin solution group developed ventricular fibrillation at the start of reperfusion, but all hearts in the Stanford group did so. Once sinus rhythm was established no significant differences in developed pressure or heart rate were found between the two solutions. After 2.5 hours of reperfusion, hearts in the Stanford group were more edematous (p < 0.002) and had a greater disruption of myocyte architecture (p < 0.002) and greater arteriolar endothelial injury (p < 0.004). In conclusion, the University of Wisconsin solution better protects the myocardium in this rat model than does Stanford solution. The mechanism for this beneficial effect of the University of Wisconsin solution appears to be due to its better preservation of the microvasculature rather than differences in preservation of high-energy phosphates.

Moderate hyperglycemia affects ischemic brain ATP levels but not intracellular pH.

We used 31P nuclear magnetic resonance (NMR) spectroscopy to study the effect of moderate hyperglycemia on brain ATP and intracellular pH in a model of severe incomplete forebrain ischemia. Plasma glucose in the hyperglycemic rats was 277 +/- 9 mg/100 ml compared with 115 +/- 10 mg/100 ml in the normoglycemic rats at the onset of ischemia. After 15 min of ischemia, brain ATP levels decreased to 31 +/- 8% in normoglycemic rats vs. 63 +/- 11% in hyperglycemic rats (P < 0.05). Phosphocreatine levels were 31 +/- 9 and 55 +/- 8% for normoglycemic and hyperglycemic rats, respectively. Intracellular pH decreased to the same level (approximately 6.5) in both normoglycemic and hyperglycemic animals after 15 min of ischemia. In summary, we found that moderate hyperglycemia during severe incomplete forebrain ischemia significantly increases ischemic brain ATP levels but does not have a significant effect on intracellular pH. These results support the hypothesis that alterations in brain ATP and adenosine concentrations may be important in the pathogenesis of ischemic tissue injury under moderate hyperglycemic conditions, whereas alterations in tissue pH may be less important.

The effects of prophylactic expiratory positive airway pressure on the resolution of oleic acid-induced lung injury in dogs.

It is not known whether positive end-expiratory airway pressure (PEEP) merely improves gas exchange in patients with the adult respiratory distress syndrome (ARDS) or if it also affects the resolution of their lung injury. The present investigation was performed to determine whether expiratory positive airway pressure (EPAP), a form of PEEP, is prophylactic in preventing the lung injury induced by oleic acid in dogs or in enhancing its resolution. Arterial and mixed venous blood gases and functional residual capacity (FRC) were measured in 14 pairs of mongrel dogs with indwelling catheters and permanent tracheostomies. One member of each pair was treated with 10 cm H2O EPAP through a valve attached to the tracheostomy tube. Both dogs received 0.06 ml/kg oleic acid intravenously at hour 0. Measurements were made at three, 12, and 24 hours, when EPAP was discontinued, and over the next six days. Five dog pairs were sacrificed at 72 hours; the other surviving animals were sacrificed at 168 hours. FRC was higher at three, 12, and 24 hours in dogs receiving EPAP than in the untreated dogs. The arterial oxygen tension (PaO2) was higher and the venous admixture (Qva/Qt) was lower at three and 12 hours in the dogs receiving EPAP than in the untreated dogs. However, after 24 hours, no differences were noted between the two groups in FRC, PaO2, Qav/Qt, mortality, final lung compliance to initial lung compliance differences, lung water to dry lung weight ratios, or histology. It is concluded that EPAP improves gas exchange during its administration, but has no demonstrable prophylactic effect on the resolution of lung injury in the oleic acid model of human ARDS.

The effects of expiratory positive airway pressure on the resolution of oleic acid-induced lung injury in dogs.

It is not known whether positive end-expiratory pressure (PEEP) merely improves gas exchange in patients with the adult respiratory distress syndrome or also affects the resolution of their lung injury. We examined the effects of expiratory positive airway pressure (EPAP), a form of PEEP, on 13 pairs of spontaneously breathing mongrel dogs with permanent tracheostomies that were subjected to acute lung injury from oleic acid. One member of each pair was treated with 10 cm H2O EPAP by means of a special valve attached to its tracheostomy tube; the other member breathed through the tracheostomy tube alone. The EPAP was applied 3 h after an intravenous injection of 0.06 ml/kg oleic acid and continued for a total of 21 h. Functional residual capacity (FRC) was increased to preinjury values in the EPAP-treated dogs at 3, 12, and 24 h compared with that in the untreated dogs. The PaO2 was higher and the venous admixture (Qva/QT) was lower in the EPAP-treated dogs compared with that in the untreated dogs at 3 and at 12 h. However, over the 7 days after removal of EPAP no significant differences were noted between the 2 groups in FRC, PaO2, Qva/QT, inert gas elimination profiles, mortality, final lung compliance to initial lung compliance differences, lung water to dry lung weight ratios, or histologic features. We conclude that EPAP improves gas exchange during its administration but has no demonstrable effect on the resolution of lung injury induced by oleic acid in dogs.

The effects of 50% oxygen on the resolution of pulmonary injury.

We studied the effects in dogs of long-term inhalation of 50% oxygen on an 8-day course of pulmonary injury caused by intravenous oleic acid. After lung injury, the experimental animals were placed in an environmental chamber where the inspired oxygen fraction (FIO2) was maintained at 0.5 (N = 12) or 0.21 (N = 12). Oleic acid caused a marked increase in venous admixture and a decreae in PaO2, which persisted at about the same concentration for 3 days after injury. These variables gradually returned toward preinjury values at 8 days. There was no significant difference in the clinical course, gravimetric lung water measurements, or lung histologic findings between oxygen-treated and air-breathing control animals. We concluded that 50% oxygen does not affect either the extent or resolution of lung injury induced by a sublethal dosage of oleic acid.

Effects of methylprednisolone on experimental pulmonary injury.

We studied the effects of methylprednisolone on pulmonary function of unanesthetized dogs with oleic acid induced pulmonary edema observed over a four day period. Methylprednisolone (30 mg/kg) was administered to 11 dogs three and 24 hours after pulmonary injury. Eleven animals were untreated after pulmonary injury and served as controls. There was no difference between the two groups until 72 hours after injury, when the venous admixture of the steroid treated animals was 11 +/- 3% (SD) compared to 22 +/- 8% (p less than 0.001) in the untreated with respective PaO2 values of 76 +/- 6 torr and 64 +/- 8 torr (p less than 0.001). Light microscopic examination of the lungs 96 hours after injury revealed a marked proliferation of Type II pneumocytes in the methylprednisolone treated animals. We conclude that, in the oleic acid or fat embolism model of pulmonary injury, methylprednisolone significantly increases resolution of the pulmonary injury presumably by stimulation of active proliferation and maturation of Type II pneumocytes.