Initial Reflow Research Articles

ENHANCED RESTORATION OF ADENINE NUCLEOTIDES IN RAT LIVER FOLLOWING EXTENDED PRESERVATION IN UW SOLUTION BY PROVISION OF ADENOSINE DURING REPERFUSION

The extensive reduction of adenine nucleotides during preservation coupled with the loss of salvageable precursors during initial reflow may exacerbate recovery of adenine nucleotides in allograft liver following transplantation. The objective of this study was to assess whether provision of adenosine during reperfusion of rat liver stored for 20 hr in University of Wisconsin solution could enhance adenine nucleotide restoration. ATP and total adenine nucleotide content of livers perfused with an oxygenated Krebs/fluorocarbon solution containing 1 mM adenosine were restored to levels in vivo within 30 min of perfusion. Adenine nucleotide recovery in livers perfused without adenosine was only 65% of normal. Acute nutritional deprivation of the donor rats had no effect on adenine nucleotide restoration. These results indicate that a conditional deficiency of intracellular nucleotide precursors exists during initial reperfusion of liver subjected to extended storage in UW solution. Provision of supplemental adenosine to the allograft liver during initial reflow appears warranted to promote full and rapid restoration of adenine nucleotide content following extended preservation ex vivo.

Successful Alloy Attachment of GaAs MMIC's

Alloy attachment of GaAs monolithic circuits was examined after initial reflow, after environmental bake, and after a stepped series of thermal cycles from 200 to 1000 cycles (-55 to + 125°C). The variety of solders tested included both pastes and preforms. Monolithic assemblies alloyed with these solders were evaluated for changes in physical properties as well as for changes in electrical performance. It was noted during the study that via fractures due to thermal expansion differences between the alloy and the GaAs monolithic device were a common occurrence and could become an inherent reliability risk. Based on this evidence, an investigation relating the frequency of fracturing to the size and the shape of the vias was undertaken. Results led to the development of processing parameters which could minimize and control fracture occurrence.

Successful alloy attachment of GaAs MMIC's

Alloy attachment of GaAs monolithic circuits was examined after initial reflow, after environmental bake, and after a stepped series of thermal cycles from 200 to 1000 cycles (-55 to + 125°C). The variety of solders tested included both pastes and preforms. Monolithic assemblies alloyed with these solders were evaluated for changes in physical properties as well as for changes in electrical performance. It was noted during the study that via fractures due to thermal expansion differences between the alloy and the GaAs monolithic device were a common occurrence and could become an inherent reliability risk. Based on this evidence, an investigation relating the frequency of fracturing to the size and the shape of the vias was undertaken. Results led to the development of processing parameters which could minimize and control fracture occurrence.

Renal sodium reabsorption, oxygen consumption, and gamma-glutamyltransferase excretion in the postischemic rat kidney.

The effect of 30 min of renal artery occlusion on renal sodium reabsorption, oxygen consumption, and brush border integrity was studied in the immediate 1-h reflow period. Rats were studied using clearance and renal extraction measurements. Glomerular filtration rate and renal plasma flow were measured over four consecutive 15-min periods; renal venous samples were drawn via an indwelling catheter. Renal oxygen consumption (QO2) was calculated from renal blood flow, corrected for urine flow, and from blood oxygen content measured with a fuel cell analyzer. Brush border integrity was assessed by the excretion of the brush border marker enzyme gamma-glutamyltransferase as well as by morphologic observation. Ischemia induced a 10-fold rise in fractional sodium excretion in the initial 0- to 15-min period, rose to 20-fold during the subsequent two periods, 15-45 min, and then returned to the initial reflow period level. The progressive deterioration of renal function with reflow could not be attributed to an increase in the filtered Na+ load. Rather, Na+ reabsorption appeared to be related to the presence of intact brush borders at 0-15 min, their removal from the luminal surface between 15 and 45 min, and their return at 60 min of reflow. Renal QO2 was coupled to Na+ reabsorption in the initial 15-min and final 45- to 60-min reflow periods. However QO2 was significantly increased over the control level at 30-45 min of reflow. The results point to a significant role of brush border uptake in the development of functional impairment following renal ischemia and suggest that the associated rise in renal O2 consumption may be coupled to the reparation of this organelle.

The time course and characterization of myocardial hemorrhage after coronary reperfusion in the anesthetized dog.

We quantitated hemorrhage associated with reperfusion after varying periods of myocardial ischemia and examined the flow characteristics that accompany reperfusion hemorrhage. Anesthetized dogs were reperfused after 2, 6 or 24 hours of circumflex occlusion. A control group underwent coronary occlusion without reperfusion. Radioactive microspheres were injected before and 5 minutes and 24 hours after reperfusion. The papillary muscles were analyzed for hemoglobin content, flow during myocardial ischemia and flow early and 24 hours after reperfusion. Myocardial creatine kinase activity was assayed to determine the severity of myocardial necrosis in the papillary muscles. Hemorrhage into the posterior papillary muscle was dependent upon the duration of coronary artery occlusion. Posterior papillary hemoglobin averaged 14 mg/g in the 2-hour group, 28 mg/g in the 6-hour group and 36 mg/g in the group reperfused 24 hours after occlusion, compared with 8.7 mg/g in the control group. Myocardial hemorrhage was associated with severe depression in myocardial CK and marked depression in flow to the ischemic area (i.e., collateral flow) during the occlusion. Early reflow averaged 112 ml/min/100 g in the 2-hour group, 61 ml/min/100 g in the 6-hour group and only 5.8 ml/min/100 g in the 24-hour group. Therefore, myocardial hemorrhage induced by reperfusion of the acutely ischemic myocardium is associated with severe ischemia during occlusion and severe myocardial necrosis, but does not depend upon the magnitude of early reflow. Myocardial hemorrhage may occur even though initial reflow values are markedly decreased.

Release of nucleosides from canine and human hearts as an index of prior ischemia

During ischemia, myocardial adenosine triphosphate is degraded to adenosine, inosine and hypoxanthine. These nucleosides are released into coronary venous blood and may provide an index of ischemia; adenosine may also participate in the autoregulation of coronary flow. In dogs, the temporal relations between reactive hyperemic flow and nucleoside concentrations in regional venous blood were correlated after brief occlusions of a segmental coronary artery. Reactive hyperemia and adenosine release peaked together in 10 seconds, persisted for 10 to 30 seconds and then decreased in a pattern consistent with the hypothesis that they are related. During initial reflow after 45 seconds of ischemia, mean concentrations of adenosine, inosine and hypoxanthine increased, respectively, to 52, 67 and 114 nmol/100 ml plasma; after 5 minutes of ischemia, the respective levels increased to 58, 1,570 and 1,134 nmol and fell quickly.In nine patients there was a similar release of nucleosides into coronary sinus blood during reperfusion after 59 to 80 minutes of ischemic arrest during cardiac surgery. With initial reflow, adenosine, inosine and hypoxanthine levels reached 65, 655 and 917 nmol/100 ml of blood, respectively. Inosine and hypoxanthine concentrations remained high for 5 to 10 minutes after cardiac beating resumed, often when production of lactate had decreased.The results indicate that postischemic release of nucleosides reaches significant levels in man as well as animals, is parallel with the duration of ischemia, is temporary and may be a useful supplement to measurement of lactate as an index of prior myocardial ischemia.