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Biomedical subjects

K I Shine

Publications and source records attributed to K I Shine.

At least 37 records · Page 2Linked to original sources
PubMed1989

Cellular K+ loss and anion efflux during myocardial ischemia and metabolic inhibition.

It has been suggested that increased K+ efflux during myocardial hypoxia and ischemia may result from efflux of intracellularly generated anions such as lactate and inorganic phosphate (Pi) as a mechanism of balancing transsarcolemmal charge movement. To investigate this hypothesis cellular K+ loss using 42K+ and K+-sensitive electrodes, intracellular potential, venous lactate and Pi, and tissue lactate and high-energy phosphates were measured in isolated arterially perfused rabbit interventricular septa during exposure to metabolic inhibitors, hypoxia, and ischemia. Selective inhibition of glycolysis caused a marked increase in K+ efflux despite a fall in lactate production and maintenance of normal cellular high-energy phosphate content. During ischemia and hypoxia net loss of lactate and Pi exceeded K+ loss by a factor of 2-6. However, removal of glucose prior to ischemia or during hypoxia increased K+ loss but reduced lactate loss without affecting Pi loss. During hypoxia, 30 mM exogenous lactate did not alter K+ loss in a manner consistent with changes in passive electrodiffusion of lactate ion. These findings inhibition which is not related to anion efflux assumes greater importance under conditions in which glycolysis is inhibited, e.g., ischemia. Under conditions in which glycolysis is not inhibited, e.g., hypoxia, K+ efflux does not parallel passive electrodiffusion of lactate ions. However, this finding does not exclude the possibility that K+ loss could be coupled to carrier-mediated lactate ion efflux.

Adenosine Triphosphate↗
PubMed1988

Myocardial sarcolemma in ischemia: a quantitative freeze-fracture study.

Freeze-fracture electron microscopy permits the visualization of the intramembrane particles (IMP). These IMPs are presumably proteins responsible for the main functions of the membrane. Quantitative techniques (Clark-Evan statistics) were applied to determine in a critical manner whether IMP pattern shifts (random, clustered, or ordered) occur under the ischemic conditions (5-45 min with and without reperfusion) and whether this change is related to the experimental condition. In each case three hearts, eight replicas/heart, one area of 0.25 micron 2 of membrane fracture face/replica was measured to give a total of 6 micron 2 of membrane counted for each condition (control vs. ischemic). A mixed effects nested model analysis of variance was performed in each variable. We found that IMP aggregation can be present in some control membranes, but the degree of aggregation was greater and more consistent in membranes made ischemic and followed by reperfusion. Most striking was the significant clustering of IMPs in membranes from hearts ischemic for only 5 min. Reperfusion after only 5 min of ischemia reversed IMP clustering. Functionally at this time there is an increase in K+ concentration in the interstitial space that reaches approximately 15 mM within 10 min and reverses on reperfusion. The structural alteration in IMPs appears to parallel the function in ischemic hearts.

Animals↗
PubMed1987

Effects of anoxia on kinetics of [13N] glutamate and 13NH3 metabolism in rabbit myocardium.

Positron emission tomography is a unique noninvasive imaging technique that provides cross-sectional images of radiotracer concentrations in myocardium and permits measurement of blood flow as well as metabolism. Ammonia and glutamate have been labeled with the positron-emitter 13N (half-life 10 minutes) for use with positron emission tomography as tracers of flow and metabolism, respectively. In order to characterize the fate of these 13N-labelled compounds in myocardium, isolated rabbit interventricular septa were used to study the kinetics of [13N] glutamate ([13N]glu) and 13NH3 under aerobic and anoxic conditions. Tissue analyses 6 minutes after injection of a [13N]glu bolus into myocardium revealed that 70% of the 13N-label was present in [13N]glu 12%, 11%, and 4% in [13N]alanine ([13N]ala), [13N]aspartate ([13N]asp), and [13N]glutamine ([13N]gln), respectively. The corresponding relative specific activities were 1.0:0.4:0.5:0.01. Anoxia resulted in a significant increase in [13N]ala with a reduction in [13N]glu. This was consistent with increased pyruvate production due to increased anaerobic glycolysis and transamination of pyruvate with [13N]glu to yield [13N]ala. In support of this, addition of 2 mM pyruvate to the perfusate under control conditions produced a tissue distribution of 13N similar to that with anoxia. Six minutes after a bolus of 13NH3 during both control and anoxic conditions, 60% of the tissue 13N-label was in [13N]gln with no detectable amounts in other amino acids. The rest of the 13N-label was in 13NH3. Time-activity curve analyses demonstrated that anoxia significantly reduced the tissue retention of 13N-label from 13NH3 but not from [13N]glu. Thus, 13N from 13NH3 and [13N]glu was retained in tissue by different mechanisms involving glutamate, which were affected differentially by anoxia. These results suggest that positron emission tomography imaging with 13NH3 and [13N]glu in combination may be useful in identifying ischemic myocardium.

Ammonia↗
PubMed1986

Nitrogen-13 flux from L-[13N]glutamate in the isolated rabbit heart: effect of substrates and transaminase inhibition.

Kinetic and biochemical parameters of nitrogen-13 flux from L-[13N]glutamate in myocardium were examined. Tissue radioactivity kinetics and chemical analyses were determined after bolus injection of L-[13N]glutamate into isolated arterially perfused interventricular septa under various metabolic states, which included addition of lactate, pyruvate, aminooxyacetate (a transaminase inhibitor), or a combination of aminooxyacetate and pyruvate to the standard perfusate containing insulin and glucose. Chemical analysis of tissue and effluent at 6 min allowed determination of the composition of the slow third kinetic component of the time-activity curves. 13N-labeled aspartate, alanine and glutamate accounted for more than 80% of the tissue nitrogen-13 under the experimental conditions used. Specific activities for these amino acids were constant, but not identical to each other, from 6 through 15 min after administration of L-[13N]glutamate. Little labeled ammonia (1.9%) and glutamine (4.7%) were produced, indicating limited accessibility of exogenous glutamate to catabolic mitochondrial glutamate dehydrogenase and glutamine synthetase, under control conditions. Lactate and pyruvate additions did not affect tissue amino acid specific activities. Aminooxyacetate suppressed formation of 13N-labeled alanine and aspartate and increased production of L-[13N]glutamine and [13N]ammonia. Formation of [13N]ammonia was, however, substantially decreased when aminooxyacetate was used in the presence of exogenous pyruvate. The data support a model for glutamate compartmentation in myocardium not affected by increasing the velocity of enzymatic reactions through increased substrate (i.e., lactate or pyruvate) concentrations but which can be altered by competitive inhibition of transaminases (via aminooxyacetate) making exogenous glutamate more available to other compartments.

Acetates↗
PubMed1986

Potassium loss from rabbit myocardium during hypoxia: evidence for passive efflux linked to anion extrusion.

To determine the effects of permeant and impermeant anions and of osmolarity on potassium (K+) exchange, the net uptake and efflux of 42K+ were recorded in the isolated arterially perfused rabbit septum. Perfusion with solution made hyperosmolar by adding NaCl (30 mM) or sucrose (60 mM) caused similar increases of 42K+ uptake which were reversible on returning to the control solution. Washout experiments showed that the loss of K+ on returning to the control perfusate was due to a decreased influx probably mediated by inhibition of the sodium pump. The effects of anions were studied by replacing chloride in the control solution with the inert and impermeant substitute isethionate (114 mM) or by loading the myocardium with sodium dimethyloxazeolidinedione (NaDMO, 30 mM) under isosmotic condition and switching to a perfusate containing sodium isethionate (30 mM). In both these conditions a reduction of 42K content could be detected and was attributable to an increased efflux. During hypoxic substrate free perfusion K+ loss was due to an increased efflux with no evidence for altered influx of potassium. The extrusion of accumulated anions from the myocardium could be the major determinant of the early potassium loss during hypoxia and ischaemia.

Animals↗
PubMed1986

Effects of heart rate on extracellular [K+] accumulation during myocardial ischemia.

The effect of heart rate on extracellular [K+] ([K+]o) accumulation during total global ischemia was investigated in the isolated arterially perfused (37 degrees C) rabbit interventricular septum using intramyocardial K+-sensitive electrodes (tip diameter, 0.3 mm) and intracellular microelectrodes. The heart rates tested were 0, 25, 75, 125, and 150 beats/min in aqueous-perfused septa and 25, 75, and 125 beats/min in blood-perfused septa. In the lower range of heart rates (0-75 beats/min) the rate and magnitude of [K+]o accumulation during 10 min of ischemia were markedly rate dependent, but in the higher range of rates (75-150 beats/min) the rate dependence was markedly attenuated in both aqueous and blood-perfused preparations. The latter finding could be largely attributed to the more rapid shortening of the action potential duration during ischemia at the higher rates and demonstrates that the amount of time the myocardium spends in the depolarized state is an important determinant of the rate of cellular K+ loss during ischemia. Progressive shortening of the action potential duration during ischemia is also a major factor determining the onset of the plateau phase of [K+]o accumulation. The findings help to resolve previous conflicting reports on the effects of heart rate on [K+]o accumulation during ischemia.

Action Potentials↗
PubMed1985

Effects of anoxia and ischemia on thallium exchange in rabbit myocardium.

We investigated the effects of anoxia and ischemia on thallium (201Tl) exchange using isolated rabbit interventricular septa. Anoxia for 20 or 40 min caused a decrease in 201Tl tissue uptake due to an increased efflux of 201Tl with a smaller increase in 201Tl influx. Between 40 and 60 min of anoxia, the increased efflux of 201Tl was reversed and the increase in 201Tl influx was absent. After 60 min of reoxygenation, septa made anoxic for 20-60 min recovered at least 95% of the Tl lost. Mechanical recovery, however, was still significantly depressed. Reperfusion after total ischemia for 20-60 min was followed by resumption of 201Tl uptake despite continued mechanical dysfunction. Efflux rates during reperfusion after ischemia were significantly different from preischemic values but not in a predictable way. This unpredictability complicates interpretation of clinical 201Tl redistribution studies. These results represent important differences from those reported previously using 42K [Am. J. Physiol. 232 (Heart Circ. Physiol. 1): H85-H94 and H564-H570, 1977]. Anoxia did not increase the influx of 42K. Also, 60 min of ischemia resulted in progressive losses of 42K. This implies there are different sensitivities and/or mechanisms for Tl compared with K uptake. Our results are consistent with 201Tl uptake by severely damaged and nonviable cells.

Animals↗
PubMed1984

Kinetic characterization of 13NH3 and [13N]glutamine metabolism in rabbit heart.

The isolated arterially perfused rabbit interventricular septum was used to study the effects of methionine sulfoximine (MSO) on 13N-labeled ammonia (13NH3) and 13N-labeled glutamine [( 13N]gln) metabolism. Tissue time-activity curves were generated from bolus injections of 13NH3 or [13N]gln delivered interarterially during control conditions and in the presence of MSO. The fraction of 13N label retained in the tissue [EF(3)] was significantly (P less than 0.01) less after a bolus of [13N]gln than 13NH3. MSO significantly (P less than 0.05) decreased the EF(3) after a bolus of 13NH3 or [13N]gln. Chemical analyses using high-pressure liquid chromatography on tissue and effluent samples obtained after bolus injections of 13NH3 and [13N]gln with or without MSO present showed the following: 1) after a bolus of 13NH3 or [13N]gln the tissue 13N label is predominantly in [13N]gln at 6 min after injection, and 2) MSO significantly decreases the synthesis of [13N]gln after an 13NH3 bolus. Thus it would appear that the glutamine synthetase reaction is primarily responsible for the retention of the 13N label from 13NH3 as [13N]gln in rabbit myocardium.

Ammonia↗
PubMed1984

Role of acidosis in early contractile dysfunction during ischemia: evidence from pHo measurements.

To investigate the contribution of acidosis to contractile dysfunction during early myocardial ischemia, miniature intramyocardial pH electrodes (0.2 mm tip diam) were used to correlate changes in extracellular pH (pHo) with tension in the isolated arterially perfused rabbit interventricular septum. A number of findings argue against acidosis as the major cause of contractile failure during early ischemia. During hypoxia without glucose present, the rate and pattern of tension decline was very similar to total ischemia, suggesting that a common mechanism is involved. Throughout the initial period in which tension declined by 50%, however, pHo increased in the six of eight preparations during hypoxia without glucose. During hypoxia with glucose present, tension fell less rapidly than during hypoxia without glucose despite a significantly greater fall in pHo in the former case. The maximal rate of relaxation (-dT/dt) was markedly more sensitive to ischemia, hypoxia, or exposure to inhibitors of aerobic metabolism (2,4-dinitrophenol and Na azide) than the maximal rate of force development (+dT/dt). In contrast, +dT/dt and -dT/dt decreased almost symmetrically during exposure to respiratory acidosis. During ischemia, the change in pHo associated with 50% reduction in tension was 0.11 +/- 0.04 units. During respiratory acidosis, this value was 0.45 +/- 0.02 units. From these observations we concluded that acidosis is unlikely to be a major factor in the early decline of tension during ischemia.

Acidosis↗