SUMMARY The effects of respiratory and metabolic acidosis on myocardial contractility and energy production have been investigated in the perfused rat heart. Respiratory acidosis, produced by increasing the Pco 2 , caused an 80% inhibition of pressure development at pH 6.7. When artificial buffers (plus HCI) were used in place of bicarbonate and CO 2 , only a 30% inhibition of pressure development was observed at pH 6.7. Respiratory acidosis produced a greater intracellular acidosis than artificial buffer acidosis at the same extracellular pH. We conclude that both intracellular and extracellular H + impair myocardial function but by separate mechanisms. Intracellular acidosis per se was shown to have little effect on the balance between energy production and energy utilization, and energy stores were relatively well maintained under these conditions. The contribution of intracellular acidosis to ischemic heart failure was examined using an ischemia model in which the coronary flow was decreased during diastole. Consequent restricted oxygen delivery produced a pattern of heterogeneous oxygenation. A fall in effluent pH was concomitant with the decline in myocardial performance, and the intracellular pH fell as the extracellular space became more acidotic. The data suggest that the fall of intracellular and extracellular pH were the principal determinants of the decline of pressure development in the tissue as a whole during the early stages of ischemia. We conclude that mechanical function is depressed in ischemia not only in anoxic regions of the heart but also in adjacent aerobic regions because of the pH change.ALTHOUGH it is well documented that decreased oxygen delivery and accumulation of metabolic end products are components of ischemia, the relative contribution of acidosis and hypoxia to ischemic heart failure has not been properly delineated. Myocardial performance is impaired by either anoxia, produced by equilibrating the perfusate with nitrogen instead of oxygen while maintaining the coronary flow, Previous experiments have demonstrated depression of myocardial contractility by acidosis, but the relative importance of intracellular and extracellular pH has not been unequivocally determined. Initially, it was suggested that extracellular pH was the principal determinant of cardiac work,"' 8 but more recently the importance of intracellular pH has been recognized."" 13 A role for intracellular pH was based on the assumption that there is a greater decline in intracellular pH during respiratory acidosis, produced by increasing the Pco 2 , than during metabolic acidosis, produced by decreasing the bicarbonate concentration. This difference is considered to be due to the high permeability of the sarcolemma to CO 2 and its relatively low permeability to protons or bicarbonate. Because metabolic acidosis causes a smaller negative inotropic effect than respiratory acidosis at the same extracellular pH, l3il4 it was concluded that intracellular pH is an important determinant of myocardial contractility. Howe...

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Three-way light guides containing one or more strands of 25-micron or 80-micron diameter optical fibers in each channel have been constructed and used to measure the NADH fluorescence and UV reflectance from mitochondrial suspensions, the perfused, hemoglobin-free rat liver, and the perfused beating interventricular septum of the rabbit. The optical changes measured with these so-called micro-light guides, which have channels containing one or several strands of optical fibers less than 100 micron, are comparable in magnitude with those measured using much larger conventional light guides. The effect of light scattering on the fluorescence channel has been determined and an empirical equation for correcting the fluorescence channel for light scattering has been obtained for mitochondrial suspensions. A mathematical equation characterizing the optical behavior of a two-way micro-light guide has been derived and has been shown to account satisfactorily for reflectance and fluorescence measurements of a mat surface in air.

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The ultrastructure of the Ca-depleted myocardial sarcolemma (via Ca-free and Ca-free plus EGTA perfusion at 28 degree C and 37 degree C) was studied in the vascularly perfused interventricular septum of the rabbit. Thin-section and freeze-fracture electron microscopy was used. Two major structural defects in the sarcolemma were found. (1) Ninety percent of the Ca-depleted cells have between 30 and 40% of their glycocalyx separated from the bilayer. With tannic acid staining, the separation is seen to occur between the external lamina and the surface coat. (2) Freeze-fracture data showed an apparent decrease in intramembrane particles on the P face of unidirectionally shadowed replicas. Quantitation of rotary-shadowed replicas showed no decrease in density of intramembrane particles. It was concluded from this that there was no loss of intramembrane particles, but rather a reorientation in the plane of the bilayer after Ca depletion. Both glycocalyx and bilayer changes were present after perfusion of the heart for only 5 minutes (37 degree C) with Ca-free perfusate. With low temperature and Cd substitution, separation of the glycocalyx occurred in less than 1% of the cells. After Ca depletion at 18 degree C, the density of intramembrane particles on the P face was not significantly different from controls. Cd substitution did not prevent the decrease total intramembrane particles per square micron, but the larger intramembrane particles had similar densities (154/micrometer2) as control (181/micrometer2), and as Ca-depletion with hypothermia (180/micrometer2). These findings indicate that structural changes in the glycocalyx and the bilayer can be totally prevented by hypothermia. Cd, on the other hand, prevents glycocalyx separation and affords protection only to the large intramembrane particles. Upon reperfusion with Ca, the intramembrane particles undergo the further alteration of aggregation, while numerous vesicles can be seen in the fracture plane of the membrane.