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Biomedical subjects

S Javaheri

Publications and source records attributed to S Javaheri.

At least 55 records · Page 3Linked to original sources
PubMed1987

Acetazolamide and cerebrospinal fluid ions in dogs with normal acid-base balance.

The purpose of these experiments was to study the effects of acetazolamide, a carbonic anhydrase inhibitor, on cisternal cerebrospinal fluid (CSF) ions during normal acid-base balance. We measured blood and CSF acid-base variables in two groups (n = 6 in each) of anesthetized, paralyzed and mechanically ventilated dogs with bilateral ligation of renal pedicles. After baseline samples were obtained, acetazolamide was administered intravenously within 10 min (group II); group I received equal volume (20 ml) of half-normal saline. During the next 6 h, in both groups arterial blood acid-base variables and plasma strong ions remained relatively normal. In group I, mean values for cisternal CSF PCO2 were 45.3 and 49.3 mm Hg at 0 and 6 h; respective values for CSF [HCO-3] were 24.1 and 22.7 mEq/L. In group II, corresponding values for PCO2 and [HCO-3] were 46.4 and 51.9 mm Hg, and 23.8 and 23.7 mEq/L, respectively. Comparing the two groups, related mean values were not significantly different from each other. Furthermore, acetazolamide had no significant effect on CSF Na+, K+ and Cl- concentrations. Based on the results of this study and those reported previously, we conclude that under normal acid-base balance, acetazolamide does not change ionic composition of cisternal CSF, choroidal CSF or brain extracellular fluid.

Acetazolamide↗
PubMed1987

Effects of acetazolamide on cerebrospinal fluid ions in metabolic alkalosis in dogs.

We hypothesized that inhibition of carbonic anhydrase in the central nervous system by acetazolamide should limit the rise in cisternal cerebrospinal fluid (CSF) [HCO3-] observed in metabolic alkalosis. To test this hypothesis, isosmotic isonatremic metabolic alkalosis was produced in two groups of anesthetized, paralyzed, and mechanically ventilated dogs (8 in each group). Group II animals received 50 mg/kg of acetazolamide intravenously 1 h before induction of metabolic alkalosis of 5-h duration. Renal effects of acetazolamide were eliminated by ligation of renal pedicles. In both groups cisternal CSF [Na+] remained relatively constant during metabolic alkalosis. In group I CSF [Cl-] decreased 3.6 and 8.2 meq/l, respectively, 2.5 and 5 h after induction of metabolic alkalosis. Respective increments in CSF [HCO3-] were 3.4 and 6.0 meq/l. In acetazolamide-treated dogs, during metabolic alkalosis, increments in CSF [HCO3-] (4.8 and 7.2 meq/l, respectively, at 2.5 and 5 h) and decrements in CSF [Cl-] (9.1 and 13.3 meq/l) were greater than those observed in group I. We conclude that, in dogs with metabolic alkalosis and bilateral ligation of renal pedicles, acetazolamide impairs CSF regulation of HCO3- and Cl- ions; acetazolamide not only failed to impede HCO3- rise but actually appeared to increase it. The mechanisms for these observations are discussed.

Acetazolamide↗
PubMed1987

Ventral medullary extracellular fluid pH and PCO2 during hypoxemia.

We designed experiments to study changes in ventral medullary extracellular fluid (ECF) PCO2 and pH during hypoxemia. Measurements were made in chloralose-urethan-anesthetized spontaneously breathing cats (n = 12) with peripherial chemodenervation. Steady-state measurements were made during normoxemia [arterial PO2 (PaO2) = 106 Torr], hypoxemia (PaO2 = 46 Torr), and recovery (PaO2 = 105 Torr), with relatively constant arterial PCO2 (approximately 44 Torr). Mean values of ventilation were 945, 683, and 1,037 ml/min during normoxemia, hypoxemia, and recovery from hypoxemia, respectively. Ventilatory depression occurred in each cat during hypoxemia. Mean values of medullary ECF PCO2 were 57.7 +/- 7.2 (SD), 59.4 +/- 9.7, and 57.4 +/- 7.2 Torr during normoxemia, hypoxemia, and recovery to normoxemia, respectively; respective values for ECF [H+] were 60.9 +/- 8.0, 64.4 +/- 11.6, and 62.9 +/- 9.2 neq/l. Mean values of calculated ECF [HCO3-] were 22.8 +/- 3.0, 21.7 +/- 3.3, and 21.4 +/- 3.1 meq/l during normoxemia, hypoxemia, and recovery, respectively. Changes in medullary ECF PCO2 and [H+] were not statistically significant. Therefore hypoxemia caused ventilatory depression independent of changes in ECF acid-base variables. Furthermore, on return to normoxemia, ventilation rose considerably, still independent of changes in ECF PCO2, [H+], and [HCO3-].

Acid-Base Equilibrium↗
PubMed1987

Effects of hypohydration on lung functions in humans.

We studied lung function tests during euhydration (Days 1 and 2), hypohydration (Days 3 and 4), and rehydration (Days 5, 6, and 7) in 6 normal subjects. Hypohydration was induced by administering chlorthalidone, and this resulted in a 4.5% loss of body weight. During hypohydration, lung volumes increased significantly. Interestingly, ventilatory lung function tests including peak expiratory flow rate, FEV1, maximal voluntary ventilation, and flow rates at low lung volumes also increased significantly and returned to normal upon rehydration. Diffusing capacity for carbon monoxide remained unchanged. The improvement in ventilatory lung function tests during hypohydration was surprising, and it is suggested that this was related to loss of water within and/or around the airways. This mechanism is opposite to that which occurs in pulmonary edema with excess lung water where reduction in flow rates occurs.

Adult↗
PubMed1986

Hypoxemia lowers cerebrovascular resistance without changing brain and blood [H+].

We designed the present study to see whether, during acute moderate isocapnic hypoxemia, changes in cerebral vascular resistance (CVR) and brain extracellular fluid (ECF) [H+] can or cannot be dissociated from each other. In seven anesthetized and paralyzed dogs we measured brain ECF pH with surface electrodes (n = 4) or double-barreled microelectrodes (n = 3) with tip diameters of less than 30 micron inserted 5 mm below the surface. Cerebral blood flow (CBF) was measured by radioactive microspheres during normoxemia and moderate hypoxemia, whereas brain ECF pH was measured continuously. In six of the seven dogs brain pH did not change during moderate hypoxemia of 4-20 min duration. In these six animals the mean arterial O2 partial pressure decreased from 84.8 +/- 12.9 (SD) to 46.7 +/- 10.2 Torr during hypoxic gas breathing, resulting in a significant drop in CVR from 3.88 +/- 1.88 to 3.27 +/- 1.97 Torr X ml-1 X min X 100 g and a rise in CBF from 31.7 +/- 12.7 to 47.8 +/- 31.5 ml X min-1 X 100 g-1. The mean brain ECF [H+] was 57.4 +/- 8.2 nmol/l (pH = 7.24) during normoxemia and did not change significantly during hypoxic gas breathing [56.6 +/- 7.7 nmol/l (pH = 7.25)]. Furthermore, arterial and sagittal venous blood and cisternal cerebrospinal fluid (CSF) pH did not change significantly during hypoxic gas breathing. We conclude that during acute moderate hypoxemia reduction in CVR can occur independently from increases in brain ECF, cisternal CSF, and arterial and sagittal venous blood [H+] and PCO2.

Animals↗
PubMed1986

Cerebrospinal fluid ions in metabolic acidosis in dogs: effects of acetazolamide.

We hypothesized that, during isosmotic isonatremic HCl acidosis with maintained isocapnia in cisternal cerebrospinal fluid (CSF), acetazolamide, by inhibiting carbonic anhydrase (CA) in the central nervous system (CNS), should produce an isonatric hyperchloric metabolic acidosis in CSF. Blood and CSF ions and acid-base variables were measured in two groups of anesthetized and paralyzed dogs with bilateral ligation of renal pedicles during 5 h of HCl acidosis (plasma [HCO3-] = 11 meq/l). Mechanical ventilation was regulated such that arterial PCO2 dropped and CSF Pco2 remained relatively constant. In group I (control group, n = 6), CSF [Na+] remained unchanged, [HCO3-] and strong ions difference (SID) fell, respectively, 6.1 and 5 meq/l, and [Cl-] rose 3.5 meq/l after 5 h of acidosis. In acetazolamide-treated animals, (group II, n = 7), CSF [Na+] remained unchanged, [HCO3-], and SID fell 11 and 7.1 meq/l, respectively, and [Cl-] rose 7.1 meq/l. We conclude that during HCl acidosis inhibition of CNS CA by acetazolamide induces an isonatric hyperchloric metabolic acidosis in CSF, which is more severe than that observed in controls.

Acetazolamide↗
PubMed1985

Premorbid ventilatory response to hypercapnia is not related to resting arterial carbon dioxide tension in hamsters with elastase-induced emphysema.

Marked variability in resting steady-state arterial PCO2 (PaCO2) values are observed among patients with chronic obstructive pulmonary disease (COPD), independent of severity of their obstructive airways defect. The reasons for the development of hypercapnia in some but not in the others remain unclear. One hypothesis states that the level of morbid resting PaCO2 may be related to the premorbid hypercapnic ventilatory response (HCVR); accordingly, subjects who were relatively insensitive to CO2 breathing (low responders) develop CO2 retention in the face of lung disease. The present study investigated this hypothesis in the hamster model of elastase-induced emphysema. After obtaining steady-state HCVR in 19 unanesthetized unrestrained hamsters, emphysema was induced by intratracheal instillation of pancreatic elastase. Forty-five days later, minute ventilation and PaCO2 measurements were done, and lung function tests were obtained. The slopes of HCVR and morbid PaCO2 values varied from -0.09 to 2.36 ml/min/mmHg inspired PCO2 and 48.7 to 63.1 mmHg, respectively. There were no significant correlations between morbid PaCO2 values and premorbid HCVR or lung function test abnormalities caused by emphysema. These animal model studies do not support the hypothesis that the level of PaCO2 in patients with COPD is related to their premorbid HCVR.

Animals↗
PubMed1984

Effect of amiloride on cisternal fluid [HCO3-] in acute respiratory acidosis.

In the present study we investigated if an amiloride inhibitable Na+ -H+ exchange mechanism may also be involved in the regulation of cisternal cerebrospinal fluid (CSF) [HCO3-] during acute respiratory acidosis (ARA). In anesthetized, paralyzed and ventilated dogs either mock CSF (group I, control) or mock CSF containing amiloride (group II) was injected into the cerebral lateral ventricles and ARA was induced by 8-10% CO2 breathing during 4 1/2 hours. During hypercapnia arterial PCO2 and plasma [HCO3-] rose respectively by about 35 mm Hg and 3 mmol/L in both groups. The rise in cisternal CSF PCO2 (about 40 mm Hg) was similar. However, changes in CSF [HCO3-] were significantly different between the two groups; in the control group, mean CSF [HCO3-] rose by 2.4, 4.1 and 4.4 mmol/L respectively, 1 1/2, 3 and 4 1/2 h after induction of ARA. In the amiloride group the respective rise was only 1.1, 2.5 and 2.5 mmol/L. The differences in CSF [HCO3-] could not be ascribed to differences in CSF lactate concentration. We conclude that an amiloride inhibitable Na+ -H+ exchange may play a role in the regulation of CSF [HCO3-] during acute respiratory acidosis in dogs.

Acidosis, Respiratory↗
PubMed1984

Effects of 'DIDS', an anion transport blocker, on CSF [HCO3-] in respiratory acidosis.

During acute respiratory acidosis increments in cisternal cerebrospinal fluid (CSF) [HCO3-] approximate decrements in CSF [Cl-] with CSF [Na+] remaining unchanged; the mechanisms mediating this reciprocal anionic relationship are unclear. In the present study we investigated the effects of DIDS (4,4'-diisothiocyano-disulfonic stilbene), a known inorganic anion exchange blocker, on CSF ionic regulation in acute respiratory acidosis. In two groups of anesthetized paralyzed dogs we injected either mock CSF (group I, n = 8) or mock CSF containing DIDS (group II, n = 9) into the lateral cerebral ventricles. After 45 min, acute respiratory acidosis was induced for 6 h. During acute respiratory acidosis, CSF PCO2 rose in average by 38 mm Hg in both groups; increments in CSF [HCO3-], however, were significantly lower by about 2 mEq/L in DIDS-treated animals than in controls throughout the experimental period. Such differences were not due to changes in CSF lactate concentration which were similar in both groups. Furthermore, CSF [Na+] remained unchanged in both groups. Since disulfonic stilbene derivatives combine selectively with the carrier involved in anion transport and inhibit inorganic anion exchange, the data in the present study suggest that in the central nervous system a DIDS-inhibitable carrier is involved in the rise of CSF [HCO3-] observed during acute respiratory acidosis.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1984

Respiration of chemodenervated goats in acute metabolic acidosis.

In awake goats before and after ablation of carotid bodies (CBx) we studied the effect of acute metabolic acidosis (AMA) produced by intravenous infusion of HCl on composition of arterial blood and CSF, and on ventilatory responsiveness to hyperoxic CO2 rebreathing AMA caused decrease in PaCO2 (breathing air at rest) indicating that alveolar ventilation was increased relative to CO2 production; position of CO2 response curves was shifted toward lower values of PCO2. These changes were similar before and after CBx, though the levels of PCO2 in arterial blood during air breathing at rest, and in expired gas at a given level of ventilation during CO2 rebreathing, were higher after CBx. We conclude that a respiratory adaptation to AMA does occur in goats deprived of peripheral chemoreceptors, and is probably mediated by the central chemoreceptors.

Acidosis↗
PubMed1984

Effects of acetazolamide on ionic composition of cisternal fluid during acute respiratory acidosis.

We studied the effects of intravenous acetazolamide (50-200 mg/kg) on cerebrospinal fluid (CSF) electrolytes and pH regulation in 10 anesthetized and nephrectomized dogs (group II): acetazolamide was injected at -1 h, and respiratory acidosis was induced at zero time for 6 h. A control group of 10 animals (group I) was treated similarly except that an equal volume of 0.45% saline was injected intravenously instead of acetazolamide. The mean CSF PCO2 values in group I were 49.7 +/- 3.4 (SD), 50.2 +/- 3.6, 92.3 +/- 7.0, 100.3 +/- 8.1, and 97.8 +/- 7.3 Torr, respectively, at -1, 0, 3, 4.5, and 6 h; respective values in group II were 49.8 +/- 2.0, 55.2 +/- 5.2, 95.8 +/- 6.4, 103.1 +/- 16.7, and 104.9 +/- 14.1 Torr. During acute respiratory acidosis CSF [HCO3-] rose progressively with time in group I, and the mean values were 28.1 +/- 1.4 (SD), 29.2 +/- 1.7 and 30.1 +/- 1.9 mmol/l, respectively, 3, 4.5, and 6 h after induction of acidosis; respective values in group II were 28.2 +/- 1.1, 28.3 +/- 0.9, and 28.5 +/- 1.4 mmol/l. Acetazolamide at various doses administered inhibited any further rise in CSF [HCO3-] beyond the 3rd h of acidosis. The lower rise in CSF [HCO3-] in group II could not be ascribed to differences in CSF lactate concentration which changed similarly in both groups. Increments in CSF K+ and phosphate concentrations were significantly higher in the acetazolamide group than in the control group, the former presumably reflecting efflux of K+ from intracellular to extracellular fluid compartment. We conclude that in nephrectomized dogs during acute respiratory acidosis intravenously administered acetazolamide diminishes the rise in CSF [HCO3-], impairs CSF H+ regulation, and increases CSF K+ and phosphate concentrations.

Acetazolamide↗
PubMed1984

Effects of SITS, an anion transport blocker, on CSF ionic composition in metabolic alkalosis.

Disulfonic stilbenes combine with the carrier protein involved in anion transport and inhibit the exchange of Cl- for HCO3- in a variety of biomembranes. Our aim was to determine whether such a mechanism is operative in the regulation of cerebrospinal fluid (CSF) [HCO3-] in metabolic alkalosis. In anesthetized, curarized, and artificially ventilated dogs either mock CSF (group I, 9 dogs) or mock CSF containing SITS, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (group II, 7 dogs) was periodically injected into both lateral cerebral ventricles. During 6 h of isocapnic metabolic alkalosis, produced by intravenous infusion of Na2CO3 solution, plasma [HCO3-] was increased by approximately 14 meq/l in both groups. In SITS-treated animals the mean cisternal CSF [HCO3-] increased by 7.7 meq/l after 6 h, and this was significantly higher than the respective increment, 3.5 meq/l, noted in the control group. Increments in CSF [HCO3-] in both groups were reciprocated by decrements in CSF [Cl-] with CSF [Na+] remaining unchanged. Cisternal CSF PCO2 and lactate concentrations showed similar increments in both groups. It is hypothesized that in metabolic alkalosis a carrier transports HCO3- out of cerebral fluid in exchange for Cl- and that SITS inhibits this mechanism. The efflux of HCO3- out of CSF in metabolic alkalosis would minimize the rise in CSF [HCO3-] brought about by HCO3-] influx from blood into CSF and therefore contributes to the CSF [H+] homeostasis.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1984

Single-unit pH-sensitive double-barreled microelectrodes for extracellular use.

The purpose of this study is to systematically describe the construction of pH-sensitive double-barreled microelectrodes for extracellular use. The most important advantages of these microelectrodes are as follows: the reference and the pH barrels are next to each other, and therefore the measured pH is not affected by asymmetric or slowly spreading direct current potential. The diameter of the tip of the microelectrodes is between 7 and 35 micron. These pH-sensitive microelectrodes are generally stable and Nernstian. They can be used repeatedly both in vivo and in vitro to measure tissue extracellular fluid pH. Some applications are described.

Animals↗
PubMed1983

Changes in the brain surface pH and cisternal cerebrospinal fluid acid-base variables in respiratory arrest.

Using flat-surface pH electrodes we continuously measured changes in the brain surface pH during respiratory arrest in anesthetized and paralyzed dogs which were previously ventilated with pure oxygen. Respiratory arrest was induced by halting the respirator. The mean arterial PO2 fell from 502.7 +/- 15.9 (1 SD) to 23.7 +/- 18.5, and the mean arterial PCO2 rose from 36.4 +/- 3.5 to 80.4 +/- 7.1 mm Hg, 10 min after asphyxia. The arterial blood pressure increased gradually over several minutes but fell relatively abruptly and profoundly at the end, due to circulatory failure. Initially, and as long as the arterial blood pressure and, therefore, cerebral blood flow were upheld (phase 1), changes in the brain surface pH were small (delta pH/delta t= -0.026 pH unit/min) in spite of severe hypercapnia. When cerebral perfusion pressure fell due to circulatory failure (phase 2), cerebral ischemia occurred and there was an abrupt fall in brain surface pH (delta pH/delta t= -0.067 pH unit/min). Changes in cisternal CSF [H+] grossly underestimated the magnitude of brain surface acidosis during the period of respiratory arrest; the initial difference between the mean brain surface fluid and cisternal CSF [H+] which was 8.9, rose to 15.1 and 47.4 nmol/L, respectively, 5 and 10 min after asphyxia. Changes in sagittal venous blood acid-base variables were more pronounced than those observed in the arterial blood or cisternal CSF; 5 min after respiratory arrest, arterial and sagittal venous blood and cisternal CSF and brain surface pH were 7.20, 7.09, 7.19 and 7.11, respectively. We conclude that (1) in the course of respiratory arrest cerebral outcome can potentially be determined by circulatory failure as evidenced by simultaneous changes in the arterial blood pressure and brain surface pH; (2) cisternal CSF acid-base changes lag behind those on the brain surface and CSF analyses provide unreliable information about the severity of brain acid-base changes during asphyxia; (3) changes in cerebral venous blood acid-base variables best represent the severity of metabolic aberrations in the brain during respiratory arrest.

Acid-Base Equilibrium↗
PubMed1983

Changes in brain ECF pH during metabolic acidosis and alkalosis: a microelectrode study.

We used pH-sensitive double-barreled microelectrodes to measure brain extracellular fluid (ECF) pH in anesthetized dogs during isocapnic infusion acidosis (HCl) and alkalosis (Na2CO3) of 45-60 min duration. The diameter of the tips of these electrodes varied from less than 1 to 27 micron and were placed 5 mm below the surface of the parietal cortex. In group I (metabolic acidosis, n = 5) mean plasma and brain ECF pH fell significantly by 0.221 and 0.025, respectively, with changes in brain ECF pH being 11.3% of those noted in plasma. In group II (metabolic alkalosis, n = 5) mean plasma and brain ECF pH rose significantly by 0.170 and 0.049, respectively, with changes in brain ECF pH being 28.8% of those noted in plasma. Mean arterial and sagittal venous PCO2 and cisternal cerebrospinal fluid (CSF) acid-base variables did not change significantly during acid or base infusion. We conclude that during transients of isocapnic metabolic acid-base perturbations ionic gradients exist between brain ECF and CSF and that changes in brain ECF pH measured by microelectrodes follow the changes in plasma pH. These pH changes may play an important role in respiratory adaptations of acute metabolic acidosis and alkalosis.

Acidosis↗
PubMed1982

Pulmonary ventilation and blood gas values in emphysematous hamsters.

Emphysema is known to progress in severity during the year after its induction by pancreatic elastase. A barometric chamber and indwelling aortic cannulas were used to evaluate the effects of worsening emphysema on pulmonary ventilation and arterial blood gases. Unanesthetized, unrestrained hamsters were studied 1, 5, and 13 months after panlobular emphysema was induced by intratracheal injection of porcine pancreatic elastase (0.2 mg in 0.5 ml of 0.15 M NaCl solution/100 g body weight). Lung volumes were subsequently measured in the anesthetized animals and the lungs were examined histologically and stereologically. The pattern of breathing in the 1-month emphysematous hamsters (n = 12) wsa the same as that of untreated control animals (n = 28) but the 5-month (n = 7) and 13-month (n = 6) animals breathed more deeply and slowly; there were no changes in mean inspiratory flow rate of proportion of time per breath occupied by inspiration. The PaO2 for all elastase-treated groups was significantly lower than the control but hypoxemia did not progress significantly with advancing age of the animals. The hematocrit was elevated for the 1-month and 5-month treated animals but not for the 13-month emphysematous animals. The arterial pH and PaCO2 values were not significantly different from control values in any of the three groups of emphysematous animals. We conclude that as hamsters with emphysema age their breathing becomes slower and deeper, that hypoxemia is present from 1 month onwards and does not progress and that hypercapnia is not found at any time.

Aging↗