scholarly journals The Effect of Local Infusion of Adenosine and Adenosine Analogues on Local Cerebral Blood Flow

1989 ◽  
Vol 9 (4) ◽  
pp. 556-562 ◽  
Author(s):  
David G. L. Van Wylen ◽  
T. S. Park ◽  
Rafael Rubio ◽  
Robert M. Berne

The purpose of this study was to determine the effects of local infusion of adenosine (ADO) and non-metabolized ADO analogues on local cerebral blood flow (CBF) and interstitial fluid (ISF) ADO levels. The brain dialysis technique was used to (a) deliver drugs locally to brain tissue, (b) estimate cerebral ISF ADO levels, and (c) measure local CBF (hydrogen clearance). Dialysis probes were implanted bilaterally in the caudate nuclei of ketamine-anesthetized rats. The probe on one side was perfused with artificial CSF while the contralateral probe was perfused with artificial CSF containing ADO ( n = 5), or the ADO agonists 2-chloroadenosine (2-CADO; n = 4) or 5'-N-ethylcarboxamide adenosine (NECA; n = 4). When ADO was included in the artificial CSF at 10−5, 10−4, or 10−3 M, a 30% increase in local CBF was detected only with 10−3 M ADO. During perfusion with ADO, dialysate inosine and hypoxanthine levels increased, indicating that the cells adjacent to the probe metabolized the exogenous ADO. With 2-CADO included in the artificial CSF at 10−6, 10−5, or 10−4 M, local CBF increased 18, 131, and 201%, respectively. Perfusion with artificial CSF containing 10−7, 10−6, or 10−5 M NECA resulted in a 35, 112, and 187% increase in local CBF, respectively. In a separate group of rats ( n = 6), perfusion with artificial CSF containing 10−6 M NECA resulted in a sustained twofold increase in local CBF and 40% decrease in dialysate adenosine concentration, both of which could be reversed by including 8-( p-sulfophenyl)-theophylline, an ADO receptor antagonist, in the artificial CSF. These results are consistent with the known vascular actions of ADO and ADO analogues and suggest that there is a basal level of ISF ADO that can be reduced by increased CBF and/or adenosine receptor activation.

1988 ◽  
Vol 254 (2) ◽  
pp. H250-H257
Author(s):  
H. Schrock ◽  
W. Kuschinsky

Rats were kept on a low-K+ diet for 25 or 70 days. Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were measured in 31 different structures of the brain by means of the [14C]iodoantipyrine and [14C]2-deoxy-D-glucose method. After 25 and 70 days of K+ depletion LCBF was decreased significantly in 27 and 30 structures, respectively, the average decrease being 19 and 25%. In contrast, average LCGU was not changed. Cisternal cerebrospinal fluid (CSF) K+ concentration decreased significantly from 2.65 +/- 0.02 mM in controls to 2.55 +/- 0.02 mM and 2.47 +/- 0.02 mM in the two treated groups (P less than 0.01). CSF [HCO3-], pH, and PCO2 were increased in K+-depleted animals. These data show that K+ depletion induces an increase in CSF pH and a decrease in CSF K+ concentration, both of which cause a reduction in cerebral blood flow. The increased CSF PCO2 is secondary to the reduction of blood flow, since brain metabolism and arterial PCO2 remained constant.


1994 ◽  
Vol 14 (5) ◽  
pp. 884-884

Local Cerebral Blood Flow During Hibernation, a Model of Natural Tolerance to “Cerebral Ischemia” Kai U. Frerichs, Charles Kennedy, Louis Sokoloff and John M. Hallenbeck [ originally published in Journal of Cerebral Blood Flow and Metabolism 1994;14(2):193–205] The weighted average cerebral blood flow in the brains of hibernating and nonhibernating ground squirrels appeared in three places in the article cited above. The numbers varied to some extent in each of the three places that they were displayed. The correct number for the active ground squirrel group was 62 ± 18 ml 100 g−1 min−1. The correct number for the hibernating group was 7 ± 4 ml 100 g−1 min−1. These numbers should be inserted on page 193 in the abstract so that the sentence would read, “Mean (± SD) mass-weighted CBF in the brain was 62 ± 18 ml 100 g−1 min−1 (n = 4) in the control group but was reduced to ischemic levels, 7 ± 4 ml 100 g−1 min−1 (n = 4), in the hibernating animals (p < 0.001).” The same numbers should be inserted into the sentence that begins at the bottom of page 198, “Average blood flow (± SD) in the brain as a whole in the hibernating animals was reduced to about 1/10 (7 ± 4 ml 100 g−1 min−1) of the level in active animals (62 ± 18 ml 100 g−1 min−1) (Table 4).” Finally, on page 201 at the bottom of Table 4 below “Weighted average in brain as a whole,” the readings should be 62 ± 18 for active and 7 ± 4 for hibernating.


1976 ◽  
Vol 44 (2) ◽  
pp. 215-225 ◽  
Author(s):  
Francis W. Gamache ◽  
Ronald E. Myers ◽  
Esteban Monell

✓ The authors studied local cerebral blood flow in monkeys rendered hypotensive by infusion of a ganglionic blocking agent. Application of the 14C-antipyrine method demonstrated that the blood flow: 1) normally varies reproducibly from one structure to another within the brain; 2) appears at its lowest level in all structures during the early minutes of a rapid-onset hypotension; 3) maintains the same general rank order of blood flow rate during hypotension as was present during normotension; and 4) returns to supranormal levels immediately following the rapid restoration of blood pressure. The values for local cerebral blood flow remain close-to-normal in some animals and diminish significantly in others during late recovery from hypotension. The close-to-normal values accompany uncomplicated recoveries while the diminished values appear in those animals which became neurologically depressed. Areas of the brain considered predisposed to hypotensive injury did not exhibit depressions in blood flow rate during hypotension more markedly than did other brain areas. The present results are interpreted as strong evidence against the “border zone” hypothesis.


1988 ◽  
Vol 8 (1) ◽  
pp. 121-129 ◽  
Author(s):  
Therese M. Jay ◽  
Giovanni Lucignani ◽  
Alison M. Crane ◽  
Jane Jehle ◽  
Louis Sokoloff

Local cerebral blood flow was measured in the mouse by means of the [14C]iodoantipyrine method. This method has been previously used in the monkey, dog, cat, and rat, but its application to small mammals such as the mouse requires special attention to potential sources of error. The small size of the mouse brain requires special attention to the rapid removal and freezing of the brain to minimize effects of postmortem diffusion of tracer in the tissue. Because of the relatively low diameter/length ratios of the catheters needed for arterial sampling in small animals, substantial errors can occur in the determination of the time course of the [14C]iodoantipyrine concentration in the arterial blood unless corrections for lag time and dead space washout in the catheter are properly applied. Local cerebral blood flow was measured in seven awake mice with appropriate care to minimize these sources of error. The values were found to vary from 48 ml/100 g/min in the corpus callosum to 198 ml/100 g/min in the inferior colliculus. The results demonstrate that the [14C]iodoantipyrine method can be used to measure local cerebral blood flow in the mouse and that the values in that species are, in general, somewhat higher than those in the rat.


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